Problem 3.

12
Study Guide 1
Causes of renal failure
1. Discuss the causes of acute (pre-renal, renal and post-renal) and chronic renal failure
Renal failure refers to failure of excretory functions of kidney. It is usually, characterized by decrease in
glomerular filtration rate (GFR). If 50% of the nephrons are affected, GFR decreases only by 20% to 30%. It
is because of the compensatory mechanism by the unaffected nephrons. The renal failure may be either
acute or chronic.
Acute renal failure is the abrupt or sudden stoppage of renal functions. It is often reversible within few
days to few weeks. Acute renal failure may result in sudden life-threatening reactions in the body with the
need for emergency treatment. No time for the body to adjust to loss of kidney function
Causes:
Prerenal (70% of community-acquired acute kidney injury [AKI])
○ Volume loss (bleed, vomiting and diarrhoea, diuretics, primary hypoaldosteronism etc.)
○ ↓ cardiac output (AMI, cardiomyopathy, valvular cardiac disease, beta-blockers, high-output cardiac
failure etc.)
○ ↓ perfusion (renal artery and small vessel disease)
– Malignant hypertension, embolic disease, cyclosporin, transplant rejection, haemolytic uraemic
syndrome (HUS), vasculitis, ↑ calcium
Intrinsic renal (acute tubular necrosis [ATN] = 70% of hospital-acquired AKI)
○ Tubular disease (ATN, nephrotoxins, rhabdomyolysis)
○ Interstitial disease (sarcoid, SLE, infection, nephritis)
○ Glomerular disease (glomerulonephritis—Goodpasture's, SLE, post infections GN)
○ Vascular disease (malignant hypertension, scleroderma, HUS, PAN, renal vein thrombosis)
drug toxicity (e.g., aminoglycosides, amphotericin, cisplatin), and iodinated radiocontrast-induced
nephropathy. Contrast-induced nephropathy is the third most common cause of new-onset AKI in
hospitalized patients.
Postrenal
○ Urethra/bladder (benign prostatic hyperplasia [BPH], phimosis, stricture, cancer, nephrogenic bladder,
clot, trauma)
○ Ureter (vesicoureteral reflux, calculi, papillary necrosis, cancer, fibrosis, stricture, AAA, pregnant, IBD,
clot, trauma)
○ Infrarenal (crystals, protein casts)
Chronic renal failure:
Chronic renal failure is the progressive, long standing and irreversible impairment of renal functions. When
some of the nephrons loose the function, the unaffected nephrons can compensate it. However, when
more and more nephrons start losing the function over the months or years, the compensatory mechanism
fails and chronic renal failure develops.
CAUSES:
1. Chronic nephritis
2. Polycystic kidney disease
3. Renal calculi (kidney stones)
4. Urethral constriction
5. Hypertension
6. Atherosclerosis
7. Tuberculosis
8. Slow poisoning by drugs or metals.
2. Discuss the various stages of chronic kidney disease
and their clinical implications
The Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes
(KDIGO)guidelines state that CKD is defined by the presence of kidney damage or decreased kidney
function for three or more months, irrespective of the cause.
-Major marker of kidney damage or disease is micro albuminuria, most commonly used to assess
abnormal if albumin-to-creatinine ratio (ACR) is 30 mg/g (3.4 mg/mmol) or greater
-Glomerular filtration rate (GFR) is generally considered to be the best index of overall kidney function,
and declining GFR is the hallmark of progressive kidney disease. Dec GFR is <60ml/min per 1.73m2
Newer staging (up-to-date)
. In patients who are diagnosed with CKD using the criteria described above, staging of the CKD is done
according to :
●Cause of disease
Identifying the cause of kidney disease (eg, diabetes, drug toxicity, auto-immune diseases, urinary tract
obstruction, kidney transplantation, etc.) enables specific therapy directed at preventing further injury. In
addition, the cause of kidney disease has implications for the rate of progression and the risk of
complications
●Six categories of GFR (G stages)
●Three categories of albuminuria (A stages)
The addition of albuminuria staging to GFR staging is new since the original KDOQI classification scheme
was published . Albuminuria staging has been added because of the graded increase in risk for mortality,
progression of CKD, and ESKD at higher levels of albuminuria, independent of eGFR, without an apparent
threshold value (table at end with implication)
Older classification:mostly based on GFR levels (lecture)

Purpose and implication;

The staging system for CKD is intended to aid clinicians in the management of patients with CKD by
identifying those with the most severe disease who are, therefore, at greatest risk for progression and
complications.
Staging according to cause, GFR, and albuminuria allows for a more complete description of risk for the
major adverse outcomes of CKD.
CKD staging is not meant to imply that there are GFR or albuminuria thresholds in CKD severity, or that all
patients in the same GFR and albuminuria category will have the same prognosis. As an example, a patient
with a GFR of 15 mL/min per 1.73 m2 likely has more severe kidney disease, and may be at higher risk for
complications, than someone with a GFR of 29 mL/min per 1.73 m2, even though both patients have GFR
stage G4.
Patients with already diagnosed CKD can now be staged according to the cause of kidney disease and then
into 18 separate categories with differing degrees of risk for progression to all-cause mortality,
cardiovascular mortality, ESKD, CKD progression, and acute kidney injury.
Based upon these findings, a "heat map" can be constructed that divides patients with CKD into the
following three broad risk categories based upon the likelihood of developing future kidney and
cardiovascular complications (eg, ESKD, cardiovascular death;
●Moderate risk (yellow) –
●High risk (orange) –
●Very high risk (red) –

-These three broad risk categories may help clinicians decide whether or not to refer their patients to a
nephrologist or specialist with expertise in caring for patients with CKD, and to develop a clinical action
plan

Stage 3mostly symptomatic then B4 no

Stage 4refer to nephrologist + consider transplant
Stage 5dialysis

3. Compare and contrast acute versus chronic renal failure

4.Differentiate azotaemia from uraemia

Azotemia is a biochemical abnormality, defined as elevation, or buildup of, nitrogenous products (BUN-
usually ranging 7 to 21 mg/dL), creatinine in blood, and other secondary waste products within the body
Azotemia associated with clinical signs, symptoms and biochemical abnormalities is Uremia. A complication
related to elevated BUN levels is mostly associated with excess nitrogenous waste production from renal
failure. The toxic effects of such waste can cause uremia. Uremic complications include platelet
dysfunction and bleeding, encephalopathy, peripheral neuropathy, acidosis, nausea, vomiting,
hypothermia, and itching.
Uremia most commonly occurs in the setting of chronic and end-stage renal disease, but may also occur as
a result of acute kidney injury

Epidemiology of renal failure in the Pacific. Prevention of kidney failure: what can be
done, and what are the limitations?
5.Discuss the major causes of renal failure in the surveys published in literature from the
pacific.
A questionnaire was sent to various countries in the Asian Pacific region and 10 countries responded. Data
from Australia and New Zealand was obtained from their registry report. The questionnaire requested
information on incidence, prevalence, transplantation rate, demographic data, causes of ESRD, causes of
death, and mortality rates for the years 1998 to 2000.
Diabetic nephropathy was the most common cause of ESRD in 9 of the 12 countries surveyed and 6 of the
12 countries had greater than 35% of their dialysis patients age 60 years and older

Australia 2000 New Zealand 2000

Glomerulonephritis 38% Diabetic nephropathy 44%
Diabetic nephropathy 22% Glomerulonephritis 20%
Hypertension 12% Hypertension 13%
Polycystic kidney disease 7%

6.Compare the major causes of renal failure, found in the survey done twenty years ago
and from the survey done more recently
ACUTE
1. Dr. Ram’s – 1885
Medical causes of ARF (CWM hospital 1968 – 84)

Dr. Buadromo’s study - 2001

Study of SLE cases from central division between Jan 1996 to 2000;
  Total of 64 cases of SLE; death - 63% had renal diseases
CHRONIC
Prevalence study – 1983 (Ram et al.)
Causes of CRF:
 Chronic glomerulonephritis (>50%)
 Hypertensive nephropathy
 Diabetic nephropathy
 Chronic pyelonephritis
Retrospective case review (Lautoka Hospital – 1998)
 A total of 65 chronic renal failure cases identified in 6 months of 1998; Major causes of CRF was
diabetes
Fiji Incidence Study of ESKD ( Dr. A Krishnan) - 1st January 2012 to 31st December 2012

7.Discuss reasons for the change in causes of renal failure over the last 20 years.
It has been argued that all industrializing societies undergo various "epidemiological transition" stages in
which the transition from Stage Two to Stage Three involves a change from "receding pandemics" to"
degenerative and lifestyle diseases". Continued globalization will mean that more populations in the
Pacific, and throughout the world, are adopting Westernized diets and lifestyles
The early studies by Prior and colleagues from throughout the Pacific Islands beginning in the 1960s clearly
showed that while diabetes was virtually non-existent in Polynesian populations maintaining a traditional
lifestyle, the reverse was true for the urbanized Polynesian populations
Due to rapid changes in lifestyle, risk factors such as obesity, unhealthy diets and physical inactivity have
become widespread throughout the region. This is particularly evident in the populations with the greatest
social and economic changes.
1983leptospirosis 1st AGN 2nd (ARF), CRFCGN, HTN, DM
1998DM 1st cause

8. Propose strategies to prevent end-stage renal disease, in terms of primary, secondary,

and tertiary prevention.
Primary prevention

 Identification of people at risk -Early identification and management

o Evaluation/screening of high risk: - diabetes type 2 and hypertension
o post renal causes
o Hypervolemia (dehydration, blood loss, septicemia etc.)
o Infectious diseases – leptospirosis, septicemia etc.
 Effective control of blood glucose and blood pressure
 Life style modification
 Management of reversible causes
 Prevention of acute glomerulonephritis
 Cautious use of nephrotoxic agents
Secondary prevention

 Effective control of blood glucose and blood pressure

 Management of dyslipidemia
 Smoking cessation
 Reduction in protein intake
 Prevention of malnutrition
 Prevention of CV events
Tertiary

 Renal replacement therapy: Dialysis (peritoneal dialysis or hemodialysis) or renal transplant

 Prevent or control complications of CRF (metabolic acidosis, infection, anemia, malnutrition, etc.)

9. Discuss tertiary prevention and whether or not it is a valid/achievable option for

implementation in Fiji
There are three primary treatment options for patients with ESRD: (tertiary)
1. Peritoneal dialysis (PD)
In PD, the dialysis fluid is passed directly into the patient’s body and, in contrast to HD, no blood removal
occurs. The peritoneal membrane which lines the abdominal cavity has a large surface area and a good
capillary blood supply. It is this semi-permeable membrane that is used to perform PD, and allows excess
water and waste products to be removed from the blood.
Dialysis fluid is instilled into the peritoneal cavity through a surgically inserted indwelling catheter, which
goes through the abdominal wall. The distal end of the catheter has tiny holes in it to allow the dialysis
fluid to flow freely into the peritoneal cavity. Fluid is removed from the blood by ultrafiltration down an
osmotic pressure gradient. Solutes and toxins cross the peritoneal membrane through diffusion and
solvent drag with water
Available in Fiji for chronic kidney injuries
2. Haemodialysis (HD)
HD is a process where blood is filtered to remove waste products. The patient is connected to a dialysis
machine where blood is removed from the patient’s body and filtered by passing it over an artificial, semi-
permeable membrane, into dialysis fluid. The waste products are retained within the dialysis fluid and the
blood returned into the body.
To facilitate HD, access to the patient’s bloodstream must be established, either using a surgically created
arteriovenous fistula, where an artery is joined to a vein during a minor surgical operation, a graft, and the
join between the artery and vein is made using a synthetic tube, or by inserting a permanent or temporary
central vascular catheter into a large vein, such as the subclavian, jugular, or femoral vein.
HD usually takes 3–4 hours each time and will be required, on average, 3 times a week for most patients.
The blood is removed and passed over a membrane with a large surface area, to allow solutes to be
exchanged between the blood and dialysis fluid. Dialysis membranes are sterile, disposable membranes
made of cellulose or polycarbonate materials. Pressure is applied to the blood in the machine to induce an
ultrafiltration process and allow removal of excess water in addition to the removal of toxins.
Available in Fiji for acute kidney cases  200 to 250 dollars per session
3. Kidney transplantation
Renal transplantation offers the best chance of long-term survival in ESRD and is the most cost-effective
treatment. All patients with ESRD should be considered for transplantation but many are not suitable due
to a combination of comorbidity and advanced age (although no absolute age limit applies). Active
malignancy, vasculitis and cardiovascular comorbidity are common contraindications to transplantation,
with risk of recurrence of the original renal disease (generally glomerulonephritides) being a less common
problem.
Not done in Fiji due to a smaller number of donors and many people cant afford it

Study Guide 2
1.Explain the two major aspects of renal acid-base balance and the role of the kidney in
maintaining a normal blood pH.
Every day, metabolism produces:
 Volatile acid - 13 000mmol of CO2.
 Fixed (non-volatile) acid- 50-80mmol of H+ [in the form of H2SO4, H3PO4, and NH4+].
The 2 major nephron events which regulate renal acid-base balance are:
1. Reabsorption of bicarbonate ions (HCO3 –)
2. Secretion of hydrogen ions (H+).
H+ is secreted into the lumen of proximal convoluted tubule, distal convoluted tubule and collecting duct.
Distal convoluted tubule and collecting duct have a special type of cells called intercalated cells (I cells)
that are involved in handling hydrogen and bicarbonate ions.
Secretion of H+ occurs by two pumps:
i. Sodium-hydrogen antiport pump - DCT
ii. ATP-driven proton pump – DCT & CD
About 4,320 mEq of HCO3 – is filtered by the glomeruli every day.

REMOVAL OF HYDROGEN IONS

BICARBONATE MECHANISM
Na+ is reabsorbed from the renal tubule under the influence of aldosterone. HCO3 – combines with Na+ to
form sodium bicarbonate (NaHCO3). Now, the H+ is secreted into the tubular lumen from the cell in
exchange for Na+.
PHOSPHATE MECHANISM – DCT & CD
H+, which is secreted into renal tubules, reacts with phosphate buffer system. It combines with sodium
hydrogen phosphate to form sodium dihydrogen phosphate. Sodium dihydrogen phosphate is excreted in
urine.
AMMONIA MECHANISM - PCT
In the tubular epithelial cells, ammonia is formed when the amino acid glutamine is converted into
glutamic acid in the presence of the enzyme glutaminase. Ammonia is also formed by the deamination of
some of the amino acids such as glycine and alanine
Ammonia (NH3) is secreted into tubular lumen in exchange for sodium ion. Here, it combines with H+ to
form ammonium (NH4). The tubular cell membrane is not permeable to ammonium. Therefore, it remains
in the lumen and then excreted into urine.
2. Compare and contrast pathophysiological changes occurring in the following:
 respiratory acidosis: acute and chronic
Respiratory acidosis is the acid-base disturbance initiated by an increase in PaCO2 and PH <7.35. Primary
hypercapnia is a synonymous term.
Production of carbon dioxide occurs rapidly and failure of ventilation promptly increases the partial
pressure of arterial carbon dioxide (PaCO2). The normal reference range for PaCO2 is 35-45 mm Hg.
The level of PaCO2 is determined by the interaction of two factors, the rate of carbon dioxide production
(VCO2) and the rate of alveolar ventilation (VA), as follows:
PaCO2 = K x VCO2 / VA
Alveolar Hypoventilation↑PaCO2 levels↓bicarb (used up to buffer)/PaCO2 ratio↓PH of blood
Kidneys play main compensatory role:
1. Increase HCO3- reabsorption in kidney
2. ↑ regeneration (new synthesis) of HCO3- ions.
3. Kidney excretes excess H+ ion in large amounts in the form of NH4+ and H2PO4-
Causes:
Basically there is ↑ accumulation of CO2 in blood due to
respiratory ↓ or ↑production of CO2 as ssen in seizures,
fever, ↑P.E.

Chronic Vs Acute:
Acute:
-the PaCO2 is elevated above the upper limit of the reference range (ie, >45 mm Hg) with an accompanying
acidemia (ie, pH < 7.35)
Acute respiratory acidosis is present when an abrupt failure of ventilation occurs. Causes include::
- Central nervous system disease or drug-induced respiratory depression (HYPO)
 - Inability to ventilate adequately, due to a neuromuscular disease or paralysis (eg, myasthenia
gravis, amyotrophic lateral sclerosis [ALS], Guillain-Barré syndrome, muscular dystrophy)
- Airway obstruction, usually related to asthma or chronic obstructive pulmonary disease (COPD)
Adaptation for Acute:
-Occurs within 5-10minutes
It originates exclusively from acidic titration of the body’s non-bicarbonate buffers (hemoglobin,
intracellular proteins and phosphates, plasma proteins):
CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+
H+ + Buf- ↔ HBuf
where Buf- refers to the base component and HBuf to the acid component of non-bicarbonate buffers.
On average, plasma bicarbonate concentration increases by about 0.1 mEq/L for each 1 mmHg acute
increment in PaCO2; as a result, plasma hydrogen ion concentration increases by about 0.75 nEq/L for
each mm Hg acute rise in PaCO2
Chronic:
the PaCO2 is elevated above the upper limit of the reference range, with a normal or near-normal pH
secondary to renal compensation and an elevated serum bicarbonate levels (ie, >30 mEq/L)
Chronic respiratory acidosis may be secondary to many disorders, including COPD. Hypoventilation in
COPD involves multiple mechanisms, including the following:
-Decreased responsiveness to hypoxia and hypercapnia
-Increased ventilation-perfusion mismatch leading to increased dead space ventilation
-Decreased diaphragmatic function due to fatigue and hyperinflation
Adaptation for chronic: (basically kidney kicks in)
-requires 3-5days of sustained hypercapnia for completion
-upregulation of renal acidification mechanism in both proximal and distal segments of nephrons where:
Transient ↑ in urinary acid secretion (↑ ammonium excretion)
↑bicarb reabsorption
-transient ↑ in chloride secretionthis balances the ↑in bicarb conc in plasma leading to plasma anion
gap
On average, plasma bicarbonate concentration increases by about 0.3 mEq/L for each mm Hg chronic
increment in PaCO2; as a result, plasma hydrogen ion concentration increases by about 0.3 nEq/L for
each mm Hg chronic rise in PaCO2. Thus, at a given PaCO2 value, chronic adaptation provides better
defense of systemic acidity than acute adaptation
 respiratory alkalosis: acute and chronic
Respiratory alkalosis is a disturbance in acid and base balance due to alveolar hyperventilation . Primary
hypocapnia is a synonymous term. PH > 7.45
Primary decreases in carbon dioxide production are generally attended by parallel decreases in alveolar
ventilation, thus preventing expression of respiratory alkalosis.
↑RR↓PaCO2 ↑bicarb (used up to buffer)/PaCO2 ratio↑PH

Respiratory alkalosis is the most common acid-base

abnormality observed in patients who are critically ill.

Kidneys play main compensatory role:

1. Decrease in regeneration (new synthesis) of HCO3- ions.
2. Decreased HCO3- reabsorption in kidney. So it is lost in urine.
3. Decrease in excretion of H+ ion
Acute:
In acute respiratory alkalosis, the PaCO2 level is below the lower limit of normal and the serum pH is
alkalemic
Adaptation for acute:
Within 5-10 mins from onset
-alkaline titration of non-bicarb buffers (hemoglobin, intracellular proteins and phosphates, plasma
proteins):
HBuf ↔ H+ + Buf +
HCO3- + H+ ↔ H2CO3 ↔ H2O + CO2
where HBuf refers to the acid component and Buf- to the base component of nonbicarbonate buffers.
On average, plasma bicarbonate concentration falls by about 0.2 mEq/L for each mm Hg acute decrement
in PaCO2; as a result, plasma hydrogen ion concentration decreases by about 0.75 nEq/L for each mm Hg
acute reduction in PaCO2.
Chronic:
the PaCO2 level is below the lower limit of normal, but the pH level is relatively normal or near normal due
to compensatory mechanisms.
Adaptations for chronic: (basically kidney kicks in)
-require 2- days
-down regulation of renal acidification mechanismstransient ↓ in net acid excretion (↓Ammonium
secretion + ↑ Bicarb secretion)
-↓bicarb reabsorption
-↑plasma chloride conc
On average, plasma bicarbonate concentration decreases by about 0.4 mEq/L for each mm Hg chronic
decrement in PaCO2; as a result, plasma hydrogen ion concentration decreases by about 0.4 nEq/L for
each mm Hg chronic reduction in PaCO2. Thus, at a given PaCO2 value, chronic adaptation provides better
defense of systemic acidity than acute adaptation

 metabolic acidosis
is the acid-base imbalance characterized by excess accumulation of organic acids in the body, which is
caused by abnormal metabolic processes. Organic acids such as lactic acid, ketoacids and uric acid are
formed by normal metabolism

1) Failure to excrete normally produced metabolic

acids in urine e.g. in chronic renal failure (CRF)
2) Increased production of organic acids: e.g.
diabetic ketoacidosis (DKA)
3) Loss of alkaline fluid (HCO3-) from body: e.g.
Severe diarrhea.

compensation by respiratory system: increased H+ ion stimulates respiratory

centrehyperventilationloss of CO2 pH will increase back to normal

 metabolic alkalosis
Metabolic alkalosis is the acid-base imbalance caused by loss of excess H+ resulting in increased HCO3-
concentration. Increased pH above 7.45
CAUSES:
 1) Vomiting of gastric contents, due to loss of acids from
stomach in large amounts.
2) Increase in Aldosterone: Increased H+ loss in urine

Respiratory system (main compensation):

hypoventilationgain of CO2 pH will decrease back to normal.

3. Differentiate the metabolic acidosis in a patient with renal failure from someone with
diabetic ketoacidosis (DKA)
Normally, metabolic acids which are produced during normal daily metabolic reactions are excreted by the
kidney.
These excess H+ ions combine with PO4- or NH3 in the DCT and are eliminated in the urine.
In CRF, these H+ ions cannot be excreted: for the most part this is due to an inability on the part of the
kidney to produce NH3 in the DCT, which normally binds with secreted H+ ions to form NH4+ ion, for
excretion in the urine.

Thus, the acidosis of CRF results from an inability to excrete the normal complement of acids produced.
In ketoacidosis, on the other hand, metabolic acids are produced in abnormal amounts, by formation of
ketoacids during ketosis, and by formation of lactic acid during anaerobic metabolism in tissues poorly
perfused due to hypovolemia and dehydration.
Once adequate hydration is restored and the process of ketosis halted, these excess metabolic acids may
be eliminated by normal methods of excretion in the urine (or re-metabolized to their original substrate).
 Study Guide 3
1. Discuss the physiological roles of calcium and phosphate
Calcium:
In a normal young healthy adult, there is about 1,100 g of calcium in the body. It forms about 1.5% of total
body weight. 99% of calcium is present in the bones and teeth and the rest is present in the plasma.
Approximately 99% of body calcium resides in the skeleton; the other 1% is present in the extracellular and
intracellular spaces. Normal blood calcium level ranges between 8.5 and 10.2 mg/dL/ 2.1-2.55 mmol/L or
4.1-5.2mEq/L
Types of calcium
in plasma: ionized/ diffusible (50%) vital for neural Act, muscle contraction, Cardiac activity, secretion
Non-ionize/ non-diffusibleas Ca bicarb (8-10%)
Calcium bound to albumin 40-42%
in bone: rapidly exchangeable calciumto maintain blood level
Slowly exchangeable/ stable calcium for bone remodelling
Calcium is very essential for many activities in the body such as:
1. Bone and teeth formation
2. Neuronal activity
3. Skeletal muscle activity
4. Cardiac activity
5. Smooth muscle activity
6. Secretory activity of the glands
7. Cell division and growth
8. Coagulation of blood.

Phosphate:
Phosphorus (P) is an essential mineral that is required by every cell in the body for normal function.
Phosphorus is present in many food substances, such as peas, dried beans, nuts, milk, cheese and butter.
Inorganic phosphorus (Pi) is in the form of the phosphate (PO4 ). Most of the phosphorus in the body is
found as phosphate. Phosphorus is also the body’s source of phosphate. In body, phosphate is the most
abundant intracellular anion.
IMPORTANCE OF PHOSPHATE
1. Phosphate is an important component of many organic substances such as, ATP, DNA, RNA and many
intermediates of metabolic pathways
2. Along with calcium, it forms an important constituent of bone and teeth
3. It forms a buffer in the maintenance of acid-base balance.

Total amount of phosphate in the body is 500 to 800 g. Though it is present in every cell of the body, 85%
to 90% of body’s phosphate is found in the bones and teeth. Normal plasma level of phosphate is 4 mg/dL.
2. Explain the roles of the following hormones in calcium and phosphate homeostasis
 Vitamin D3
Calcitriol is a steroid hormone synthesized in kidney. It is the activated form of vitamin D. Its main action is
to increase the blood calcium level by increasing the calcium absorption from the small intestine
Calcitriol hormone increases absorption of phosphate from small intestine

 Parathyroid hormone
The overall action of PTH is to increase plasma Ca++ levels and decrease plasma phosphate levels.
In the bone, PTH stimulates osteoclasts which break down the matrix of bone, releasing Ca2+ and PO4-
into the circulation, raising their levels.
In the intestine, PTH increases Ca2+ and PO4- absorption (as long as active vitamin D is present in
sufficient levels to facilitate this).
In the kidney, PTH stimulates reabsorption of Ca2+ and decreases reabsorption of PO4-, promoting PO4-
excretion.
The effect of this is to raise Ca2+ levels and decrease PO4- levels in the circulation.
Note that PTH also stimulates formation and release of calcitriol, the active form of vitamin D.

 Calcitonin.
Calcium: It reduces the blood calcium level mainly by decreasing bone resorption
Phosphate: Calcitonin also decreases the plasma level of phosphate by inhibiting bone resorption and
stimulating the urinary excretion.
3. For three hormones in Q2, describe the
 synthesis,
 production or secretion,
 the actions and effects on bone, intestine or kidneys
Parathyroid hormones
Produced at the parathyroid gland by CHIEF (PRINCIPAL) CELLS – non-granuler cells cell. clear cytoplasm,
large nucleus, contains mucous
Half-life and Plasma LevelParathormone has a half-life of 10 minutes. Normal plasma level of PTH is
about 1.5 to 5.5 ng/dL.
Synthesis
PTH secretion responds to small alterations in plasma Ca2+ within seconds through a unique Ca receptor
within the parathyroid cell plasma membrane senses changes in the extracellular fluid concentration of
Ca2+.
Prepro – PTH enter endoplasmic reticulum  pro – PTH  then enter Golgi body  PTH

Metabolism
Sixty to seventy percent of PTH is degraded by Kupffer cells of liver, by means
of proteolysis. Degradation of about 20% to 30% PTH occurs in kidneys and to
a lesser extent in other organs.

Bone
Parathormone enhances the resorption of calcium from the bones
(osteoclastic activity) by acting on osteoblasts and osteoclasts of the bone.
Resorption of calcium from bones occurs in two phases:
i.Rapid phase
Rapid phase occurs within minutes after the release of PTH from parathyroid glands. Immediately after
reaching the bone, PTH gets attached with the receptors on the cell membrane of osteoblasts and
osteocytes. The hormone-receptor complex increases the permeability of membranes of these cells for
calcium ions. It accelerates the calcium pump mechanism, so that calcium ions move out of these bone
cells and enter the blood at a faster rate
ii.Slow phase
Slow phase of calcium resorption from bone is due to the activation of osteoclasts by PTH. When
osteoclasts are activated, some substances such as proteolytic enzymes, citric acid and lactic acid are
released from lysosomes of these cells. All these substances digest or dissolve the organic matrix of the
bone, releasing the calcium ions. The calcium ions slowly enter the blood. PTH increases calcium resorption
from bone by stimulating the proliferation of osteoclasts also.
Along with calcium resorption, PTH also increases phosphate absorption from the bones
Kidney
PTH increases the reabsorption of calcium from the renal tubules along with magnesium ions and
hydrogen ions. It increases calcium reabsorption mainly from distal convoluted tubule and proximal part of
collecting duct. PTH also increases the formation of 1,25- dihydroxycholecalciferol (activated form of
vitamin D) from 25-hydroxycholecalciferol in kidneys
Gastrointestinal Tract
PTH increases the absorption of calcium ions from the GI tract indirectly. It increases the formation of 1,25-
dihydroxycholecalciferol in the kidneys. This vitamin, in turn increases the absorption of calcium from GI
tract. Thus, the activated vitamin D is very essential for the absorption of calcium from the GI tract. And
PTH is essential for the formation of activated vitamin D.
Parathormone increases the absorption of phosphate from GI tract through calcitriol.
Vitamin D3
Liver form 25-hydroxyl cholecalciferolhas 2 isotopes vitamin D2 and D3..so D3 has high affinity
Kidney will form 1,25-dihydroxyl cholecalciferol as well as 24/25,dihydroxyl vit Dthese 24/25 inhibit prod
of VIT D3 (1,25 DOH). Cubulin, megalinabsorbed into kidney from urine

25-hydroxycholecalciferol is converted into 1,25-

dihydroxycholecalciferol (calcitriol) in kidney. It is the active form
of vitamin D3. This step needs the presence of PTH.
Action

 It increases the absorption of calcium from the intestine, by

increasing the formation of calcium binding proteins in the
intestinal epithelial cells. These proteins act as carrier
proteins for facilitated diffusion, by which the calcium ions
are transported. The proteins remain in the cells for several
weeks after 1,25-dihydroxycholecalciferol has been
removed from the body, thus causing a prolonged effect on
calcium absorption
 It increases the synthesis of calcium-induced ATPase in the intestinal epithelium
 It increases the synthesis of alkaline phosphatase in the intestinal epithelium
 It increases the absorption of phosphate from intestine along with calcium
Calcitonin
Calcitonin is secreted by the parafollicular cells or clear cells (C cells)

 Ploypeptide(32 aa) , MW 35KD.

 The major stimulus of calcitonin secretion is a rise in plasma Ca ++ levels
 The target cell for calcitonin is the osteoclast.
 The major effect of calcitonin administration is a rapid fall in Ca2+ caused by inhibition of bone
resorption.
Calcitonin plays an important role in controlling the blood calcium level. It decreases the blood calcium
level and thereby counteracts parathormone.
BonesCalcitonin stimulates osteoblastic activity and facilitates the deposition of calcium on bones. At
the same time, it suppresses the activity of osteoclasts and inhibits the resorption of calcium from bones. It
inhibits even the development of new osteoclasts in bones.
Calcitonin inhibits the resorption of phosphate from bone and stimulates the deposition of phosphate on
bones.
Kidney Calcitonin increases excretion of calcium through urine, by inhibiting the reabsorption from the
renal tubules.
Calcitonin increases the excretion of phosphate through urine, by inhibiting the reabsorption from renal
tubules.
IntestineCalcitonin prevents the absorption of calcium from intestine into the blood.

4. Differentiate between calcium homeostasis and balance

Calcium balance refers to the state of the body stores of calcium at equilibrium over some extended time
period (usually days, weeks, or months). Calcium balance can be calculated as the difference between
calcium entering the body through absorption of dietary calcium and obligate losses of calcium through
urine, gastrointestinal tract, skin and bone remodelling
Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including
growth, aging, and acquired or inherited disorders.
 Children are in positive bone balance (formation > resorption), which ensures healthy skeletal
growth.
 Healthy young adults are in neutral bone balance (formation = resorption) and have achieved peak
bone mass.
 Elderly individuals are typically in negative bone balance (formation < resorption), which leads to
age-related bone loss.
Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone,
1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at
the gut, kidney, and bone. Serum calcium homeostasis has evolved to simultaneously maintain
extracellular ionized calcium levels in the physiologic range while allowing the flow of calcium to and from
essential stores.

5. Explain how renal failure can lead to problems with calcium and phosphate
homeostasis.
Phosphate excretion falls in the very early stages of CKD. Retained phosphate then results in the release of
FGF23 and other phosphaturia agents by osteocytes as a compensatory mechanism.
FGF23 causes phosphaturia to bring the plasma phosphate level to within the normal range.
FGF23 also downregulates renal 1α-hydroxylase, reducing the action of activated vitamin D in increasing
intestinal absorption of phosphate. Despite consistently elevated levels of FGF23, phosphate levels in
blood will once again rise as CKD progresses
As CKD progresses, secondary hyperparathyroidism develops:
 ↓ renal production of 1α-hydroxylase  ↓conversion of 25-(OH) 2D3 to active 1,25-(OH) 2 D 3
(1,25-dihydroxycholecalciferol).
 1,25-(OH) 2 D 3 deficiency ↓ gut calcium absorption and fall in calcium.
 ↓ activation of vitamin D receptors in parathyroid glands by 1,25-(OH) 2 D3 increases the release of
PTH.
 Retained phosphate also indirectly lowers ionized calcium (and probably directly via a putative but
unrecognized phosphate receptor), resulting in increased PTH synthesis and release.
 PTH promotes reabsorption of calcium from bone and increased proximal renal tubular
reabsorption of calcium.

6.Compare secondary hyperparathyroidism with primary hyperparathyroidism

Hyperparathyroidism (HPT) is characterized by abnormally high parathyroid hormone (PTH) levels in the
blood due to overactivity of the parathyroid glands
P-HPT is characterized by elevated parathyroid hormone and calcium levels and is usually caused by
parathyroid adenomas (or, in rare cases, by parathyroid carcinomas). Although often asymptomatic,
symptoms such as bone pain, gastric ulcers, and/or kidney stones may emerge in severe cases.
 Parathyroid gland adenoma (∼ 85%): benign tumor of the parathyroid glands
 Hyperplasia and multiple adenomas (∼ 15%)
 In rare cases, carcinomas; (∼ 0.5%) or idiopathic
S-HPT is characterized by high parathyroid hormone and low calcium levels and may be caused by kidney
failure, vitamin D deficiency, or malabsorption. sHPT is also called reactive HPT, as the increase in
(parathyroid) hormone production is a physiological response to hypocalcaemia and not caused by an
abnormality of the parathyroid glands.
 Chronic kidney disease (most frequent cause)
 Malnutrition
 Vitamin D deficiency (e.g., ↓exposure to sunlight, nutritional deficiency, liver cirrhosis)

7.Discuss the effects of renal failure on bone metabolism

PTH acts directly on the bones to stimulate Ca++ resorption and kidney to stimulate Ca++ reabsorption in
the distal tubule of the kidney and to inhibit reabosorptioin of phosphate (thereby stimulating its
excretion).
Continual resorption of bone, with osteomalacia (normal bone but mineralization is less/ affected) and
osteoporosis.
 Pathological fractures: Weakened bones are at greater risk of fracture.
 X-rays of bone may show demineralisation, and in advanced cases may show subperiosteal erosions
or bone cysts. 
 Study Guide 4
1. Discuss the effects of renal failure on fluid and electrolyte balance
Potassium
Solutes, such as phosphate, urate, and hydrogen ions, are often maintained near the normal range until
GFR falls below 20 to 30 per cent of normal. Thereafter, the plasma concentrations of these substances
rise, but not in proportion to the fall in GFR. Maintenance of relatively constant plasma concentrations of
these solutes as GFR declines is accomplished by excreting progressively larger fractions of the amounts of
these solutes that are filtered at the glomerular capillaries; this occurs by decreasing the rate of tubular
reabsorption or, in some instances, by increasing tubular secretion rates.
Urinary excretion of potassium is related primarily to distal tubular secretion mediated by aldosterone and
sodium potassium adenosine triphosphatase. In renal failure there is increased tubular secretion that
provides effective regulation until the onset of oliguria. 
With hyperkalaemia larger amounts of potassium can be eliminated through the bowel
Although nonoliguric patients can maintain potassium excretion with normal dietary intake, they are more
prone to develop hyperkalaemia with increased loading (i.e., use of salt substitutes).
Use of potassium-sparing diuretics, such as spironolactone (Aldactone), volume depletion, acute infection,
severe acidosis, or marked hyperglycaemia also may precipitate elevated levels of serum potassium.
With progression of disease to end-stage renal failure (ESRF), total body potassium can increase to life-
threatening levels and must be controlled by dietary restriction, loop diuretics, cation exchange resins, and
dialysis. 
Severe acute hyperkalaemia is treated with intravenous calcium gluconate, intravenous dextrose and
insulin, and nebulized or intravenous salbutamol (sympathetic beta2 agonist, promotes Na+-K+- ATPase
pump and intracellular movement of potassium). Renal replacement therapy may be required (support of
renal function using haemodialysis or peritoneal dialysis).
Sodium
In the case of sodium and chloride ions, their plasma concentrations are maintained virtually constant even
with severe decreases in GFR. This is accomplished by greatly decreasing tubular reabsorption of these
electrolytes. For example, with a 75 per cent loss of functional nephrons, each surviving nephron must
excrete four times as much sodium and four times as much volume as under normal conditions
Levels of sodium must be regulated within narrow limits because sodium is the major extracellular solute.
In CKD, sodium and water balance is maintained very close to normal until the development of stage 5
ESKD. This occurs because of the increased fractional excretion of sodium, particularly in the distal
nephron, in relation to decreasing GFR. Hormones including aldosterone, prostaglandins, and natriuretic
peptides also modulate sodium excretion, and their levels are elevated with progressive renal failure.
Individual variation in the underlying pathology of CKD must be considered in the management of sodium
intake or restriction. Sodium wasting may be present with tubulointerstitial causes of CKD, and there may
also be extrarenal losses of sodium from vomiting, diarrhea, or fever.
Sodium retention is more likely in ESKD, particularly in the presence of nephrotic syndrome or heart
failure. Sodium retention contributes to hypertension, edema, heart failure, and mortality. Interdialytic
water intake can cause volume overload and dilutional hyponatremia during dialysis. Management of salt
and water balance requires individual assessment, and both hyponatremia and hypernatremia require
management
Hydrogen Ions
The intake of a normal diet produces 50 to 100 mEq of hydrogen per day. These ions are secreted from the
renal tubules and excreted in the urine combined with phosphate and ammonia buffers. Metabolic
acidosis develops when GFR decreases to less than 20% to 25% of normal. The causes of acidosis are
primarily related to decreased hydrogen ion elimination and decreased bicarbonate reabsorption. With
ESRF, metabolic acidosis may be severe enough to require alkali therapy and dialysis. Bicarbonate levels
should be maintained at about 22 mEq/L. 
Calcium and phosphate
Renal failure affects Ca2+ metabolism in several ways:
1. As glomerular filtration, and tubule reabsorption and secretion, decline, excretion of PO4- is made
more difficult, and so PO4- levels ↑ in the circulation.
a. The ↑ in circulating PO4- levels itself causes a decrease in Ca2+ levels.
2. active vit. D formation in the kidneys is depressed in CRF, and so absorption of Ca2+ in the intestine
decreases, with a decrease in circulating Ca2+ levels.
3. The ↓ in serum Ca2+ stimulates release of PTH, which acts to:
a. ↑ Ca2+ reabsorption and ↑ PO4- excretion in the kidneys (which is ineffective in renal
failure)
b. ↑ bone resorption to ↑ circulating levels of Ca2+ and PO4 (which is effective in doing both).
The net result is that both Ca2+ and PO4- are liberated from bone, while the body is unable to rid itself of
the excess PO4- in the face of CRF.
Ca2+ levels remain relatively low, PO4- levels remain high, and secondary hyperparathyroidism is the
eventual outcome, with its long-term effect on bone.

2. Discuss the effects of renal failure on blood pressure regulation

Renal lesions that decrease the ability of the kidneys to excrete sodium and water almost invariably cause
hypertension. Therefore, lesions that either decrease GFR or increase tubular reabsorption usually lead to
hypertension of varying degrees
Hypertension can exacerbate injury to the glomeruli and blood vessels of the kidneys and is a major cause
of ESRD.  Abnormalities of kidney function can also cause hypertension
Thus, the relation between hypertension and kidney disease can, in some instances, propagate a vicious
cycle: primary kidney damage leads to increased blood pressure, which causes further damage to the
kidneys, further increases in blood pressure, and so forth, until ESRD develops.

Not all types of kidney disease cause hypertension because damage

to certain portions of the kidney causes uraemia without
hypertension. Nevertheless, some types of renal damage are
particularly prone to cause hypertension.
Once hypertension has developed, renal excretion of sodium and
water returns to normal because the high arterial pressure causes
pressure natriuresis and pressure diuresis, so that intake and output
of sodium and water become balanced once again.
Even when there are large increases in renal vascular resistance or
decreases in the glomerular capillary coefficient, the GFR may still return to nearly normal levels after the
arterial blood pressure rises. Likewise, when tubular reabsorption is increased, as occurs with excessive
aldosterone secretion, the urinary excretion rate is initially reduced but then returns to normal as arterial
pressure rises. Thus, after hypertension develops, there may be no sign of impaired excretion of sodium
and water other than the hypertension.

3. Discuss the impact of renal failure on its physiological role of excretion

The effect of complete renal failure on the body fluids depends on

 water and food intake

 the degree of impairment of renal function
Assuming, that a person with complete renal failure continues to ingest the same amounts of water and
food, the concentrations of different substances in the extracellular fluid
Important effects include
(1) generalized edema resulting from water and salt retention,
(2) acidosis resulting from failure of the kidneys to rid the body of normal acidic products,
(3) high concentration of the nonprotein nitrogen’s—especially urea, creatinine, and uric acid—
resulting from failure of the body to excrete the metabolic end products of proteins,
(4) high concentrations of other substances excreted by the kidney, including phenols, sulfates,
phosphates, potassium, and guanidine bases. This total condition is called uremia because of the
high concentration of urea in the body fluids
Uremia—Increase in Urea and Other Nonprotein Nitrogen’s (Azotemia).
The nonprotein nitrogen’s include urea, uric acid, creatinine, and a few less important compounds. These,
in general, are the end products of protein metabolism and must be removed from the body to ensure
continued normal protein metabolism in the cells. The concentrations of these, particularly of urea, can
rise to as high as 10 times normal during 1 to 2 weeks of total renal failure. With chronic renal failure, the
concentrations rise approximately in proportion to the degree of reduction in functional nephrons. For this
reason, measuring the concentrations of these substances, especially of urea and creatinine, provides an
important means for assessing the degree of renal failure.
Extra
Isosthenuria—Inability of the Kidney to Concentrate or Dilute the Urine.
One important effect of the rapid rate of tubular flow that occurs in the remaining nephrons of diseased
kidneys is that the renal tubules lose their ability to concentrate or dilute the urine. The concentrating
ability of the kidney is impaired mainly because:

 the rapid flow of tubular fluid through the collecting ducts prevents adequate water reabsorption
 the rapid flow through both the loop of Henle and the collecting ducts prevents the countercurrent
mechanism from operating effectively to concentrate the medullary interstitial fluid solutes.
Therefore, as progressively more nephrons are destroyed, the maximum concentrating ability of the kidney
declines, and urine osmolarity and specific gravity (a measure of the total solute concentration) approach
the osmolarity and specific gravity of the glomerular filtrate.
The diluting mechanism in the kidney is also impaired when the number of nephrons decreases because
the rapid flushing of fluid through the loops of Henle and the high load of solutes such as urea cause a
relatively high solute concentration in the tubular fluid of this part of the nephron. As a consequence, the
diluting capacity of the kidney is impaired, and the minimal urine osmolality and specific gravity approach
those of the glomerular filtrate. Because the concentrating mechanism becomes impaired to a greater
extent than does the diluting mechanism in chronic renal failure, an important clinical test of renal function
is to determine how well the kidneys can concentrate urine when a person’s water intake is restricted for
12 or more hours

4. Revise the role of kidney in maintaining acid-base balance and discuss the
development of metabolic acidosis in CKD
Kidneys are the body’s 3rd line of defense in maintaining Acid base balance
HCO3- is reabsorbed in PCT and regenerated in DCT
H+ secreted in DCT as H2PO4 and in PCT & DCT as NH4+
In Acidosis Kidneys play main compensatory role:
1. Increase HCO3- reabsorption in kidney
2. ↑ regeneration (new synthesis) of HCO3- ions.
3. Kidney excretes excess H+ ion in large amounts in the form of NH4+ and H2PO4-

In alkalosis Kidneys play main compensatory role:

1. Decrease in regeneration (new synthesis) of HCO3- ions.
2. Decreased HCO3- reabsorption in kidney. So it is lost in urine.
3. Decrease in excretion of H+ ion

CKD and Acidosis:

-Normally, metabolic acids which are produced during normal daily metabolic reactions are excreted by
the kidney.
-These excess H+ ions combine with PO4- or NH3 in the DCT and are eliminated in the urine.
-In CRF, these H+ ions cannot be excreted: for the most part this is due to an inability on the part of the
kidney to produce NH3 in the DCT, which normally binds with secreted H+ ions to form NH4+ ion, for
excretion in the urine.
-Thus the acidosis of CRF results from an inability to excrete the normal complement of acids produced.
5. Discuss the effects of renal failure on erythropoiesis
Normal erythropoiesis:
EPO is a glycoprotein hormone, naturally produced by the peritubular Cells
in the cortex and outer medulla of the kidneys. They synthesize
erythropoietin and release it into the bloodstream. These cells are in a
somewhat oxygen-poor region with an oxygen concentration that is rarely
affected by physiological changes in blood flow

Anaemia in CKD is typically normocytic, normochromic, and hypo-proliferative (↓EPO)

Anemia in ESRD is due to the:
- reduced production of erythropoietin by the diseased kidneys
- uremia toxic effect on BM
- a shortened half-life of red blood cellsdue to inflammatory process + Uremic toxins
- the potential loss of red blood cells in the extracorporeal dialysis circuit and the gastrointestinal
tract (related to intermittent anticoagulation for the hemodialysis procedure).
- patients with anemia and CKD may suffer from iron-deficiency anemia (IDA)as well. This is due to
both true paucity of iron stores (absolute IDA) and relative (functional) iron deficiency; the latter
being due to underlying inflammation which impairs the body’s ability to appropriately utilize the
iron sequestered in the tissues

how are iron stores affected in CKD?

In absolute iron deficiency, the total body iron stores are depleted, limiting the production of RBCs.
Contributing factors to absolute iron deficiency include decreased gastrointestinal absorption in patients
with CKD and increased blood loss (for example in the setting of uremia-induced platelet dysfunction and
the iatrogenic loss from serial blood draws or access-site and circuit issues during the dialysis procedure)
Functional iron deficiency occurs due to inefficient utilization of iron stores, stemming from one or both of
two main phenomena. The first of these, anemia of chronic inflammation, is known as reticuloendothelial
cell iron blockade. This may occur in the absence of EPO supplementation and can occur in inflammatory
diseases other than CKD. Specifically, reticuloendothelial cell iron blockade can be triggered by active
infection or inflammation, hypoxia, or genetic deficiencies. The second process relates to the use of
exogenous EPO. Because RBC production increases in response to ESAs, the available iron may be used
faster than the existing iron stores are able to release it, leading to a supply/demand mismatch and a
“relative” iron deficiency
CKD↑urea↑ammonia production in gutalkaline environmentiron need acidic environment for
absorption↓ iron absorption

6.Discuss chronic kidney disease related mineral and bone disorder

Once called ‘renal osteodystrophy’ but now more appropriately described as a mineral and bone disorder,
CKD-MBD encompasses:
 changes in calcium, phosphorus, PTH, FGF23 and vitamin D metabolism
 the various forms of bone disease that may develop alone or in combination in CKD
 the vascular consequences, such as arterial stiffness and calcification, that accompany it

Osteitis fibrosa cystica – Osteitis fibrosa cystica is functionally characterized by high bone turnover due to
persistently high PTH. Activated osteoclasts cause bone resorption, cortical bone destruction, and fibrous
cysts formation. Osteoclast-like giant cells and vascularized fibrous tissue might replace bone marrow
resulting in Brown tumors, which are non-neoplastic lesions
Adynamic bone disease – Adynamic bone disease is characterized by low bone turnover with reductions in
both osteoblast and osteoclast activity and the skeleton becomes inert.
Osteomalacia – Osteomalacia is primarily characterized by decreased mineralization, causing an increase in
unmineralized osteoid. High remodeling rate: excessive osteoid formation with normal/little mineralization
low remodeling rate: normal osteoid production with diminished mineralization
Mixed uremic osteodystrophy – Mixed uremic osteodystrophy (MUO) is a term used to describe bone
biopsy findings of both high bone turnover and a disproportionate decrease in mineralization resulting in
increased osteoid
Osteoporosis - is caused by an imbalance of bone resorption and bone remodeling, leading to decreased
skeletal mass
Vascular Calcification in CKD
Extra-skeletal calcification is highly prevalent in CKD
Two types of vascular calcification
 Intimal calcification leads to calcific plaques or circumferentially calcified atherosclerosis
 Medial calcification is nonocclusive and leads to vascular stiffening
Pathogenesis of Vascular Calcification
Phenotypic switch  vascular smooth muscle cells (VSMCs) osteo/chondrocytic-like cells  lay down
collagen and noncollagenous proteins (ECM)  intima or media Calcium and phosphorus incorporated
 mineralization  hydroxyapatite

7.Discuss uraemia, its clinical presentation and effects on organs

Patients presenting with uremia typically complain of nausea, vomiting, fatigue, anorexia, weight loss,
muscle cramps, pruritus, or changes in mental status
Cardiovascular
 More than 60% of patients have echocardiographic manifestations of left ventricular hypertrophy,
dilation, and systolic or diastolic dysfunction
 Metabolic consequences of CKD, including accelerated atherogenesis, contribute to metastatic
calcification in the myocardium, cardiac valves, and arteries.
 Arrhythmias may be caused by electrolyte abnormalities, cardiac structural changes or ischemic
cardiovascular disease.
 Pericarditis can occur in patients with uremia, ammonium breath
Gastrointestinal
  Patients describe a metallic taste and loss of appetite. Later, they experience nausea, vomiting, and
weight loss, and those with severe uremia may also experience stomatitis and enteritis.
 There may be gastrointestinal bleeding caused by gastritis, peptic ulceration, and arterial venous
malformations in the setting of platelet dysfunction.
Neurologic
 Lethargy, irritability, asterixis, seizures, and frank encephalopathy with coma are late
manifestations of uremia
 Peripheral neurologic manifestations appear as a progressive symmetrical sensory neuropathy in a
glove-and-stocking distribution.
 Patients have decreased distal tendon reflexes and loss of vibratory perception. Peripheral motor
impairment can result in restless legs, footdrop, or wristdrop.
Musculoskeletal
 Hypocalcaemia and secondary hyperparathyroidism are the result of phosphate retention and the
lack of α 1 -hydroxylase activity in the failing kidney
 Over time, maladaptive parathyroid hypertrophy (i.e., tertiary hyperparathyroidism) leads to bone
disease and tissue calcification.
Hematologic and Immunologic
 Erythropoietin (EPO), becomes progressively deficient as CKD progresses.
 Bleeding disorders, primarily from defects in platelet adherence and aggregation, are common in
patients with uremia.
 patients are generally immunosuppressed and susceptible to infections. This may be due to
functional abnormalities of polymorphonuclear leukocytes, lymphocytes, and other cellular host
defenses.
Endocrine and Metabolic
 A deranged pituitary-gonadal axis can result in sexual dysfunction exhibited by impotence,
decreased libido, amenorrhea, sterility, and uterine bleeding.
 Lipid abnormalities are also common in CKD. The activity of lipoprotein lipase is decreased in
uremia, with a reduction in the conversion of very-low-density lipoprotein to low-density
lipoprotein and thus hypertriglyceridemia.
Skin
 Uremic hue, a yellowish skin color, is likely the result of retained liposoluble pigments, such as
lipochromes and carotenoids.
 Nail findings of uremia include the half-and-half nail, characterized by red, pink, or brownish
discoloration of the distal nail bed, pale nails, and splinter hemorrhages.
 Other common signs and symptoms include pruritus, and ecchymoses due to disorders of bleeding.
 Calciphylaxis, or calcific uremic arteriolopathy, results in painful skin calcification and is often seen
in patients with uncontrolled hyperparathyroidism.
 Build of bilirubin also causes itchiness, urea in swear glands excreted in sweat too, also high levels
of phosphates causes itchiness
8.Discuss the risk for cardiovascular disease in patients with CKD - hypertension,
dyslipidaemia, left ventricular hypertrophy

Proinflammatory mediators, oxidative stress, altered vitamin D metabolism, and metabolic derangements
are significant contributors. Declining erythropoietin production causes anemia, which reduces oxygen
delivery to the myocardium.
Elevated renin level stimulates the secretion of aldosterone, increasing sodium and water reabsorption.
Hypertension is the result of excess sodium and fluid volume. Activation of RAAS release angiotensin 2
which is a vasoconstrictor causing further hypertension
Dyslipidaemia occurs early in CKD. CKD leads to a down regulation of lipoprotein lipase and the LDL-
receptor, and increased triglycerides in CKD are due to delayed catabolism of triglyceride rich lipoproteins,
with no differences in production rate
Atheromatous plaque and arterial calcification contribute to loss of vessel elasticity and obstruction and
are accelerated by the oxidative stress of CKD. Macrovascular disease is responsible for increased risk for
ischemic heart disease, left ventricular hypertrophy, congestive heart failure, stroke, & peripheral vascular
disease in individuals with uremia.
Pericarditis can develop from inflammation caused by the presence of uremic toxins. Accumulation of fluid
in the pericardial space can compromise ventricular filling and cardiac output.
80-90% of CKD patients develop LVH
 Study Guide 5
1. State the effects of chronic renal failure on drug absorption, distribution, metabolism
and excretion (renal and non-renal effects
Absorption: process by which unchanged drug proceeds from the site of administration into the blood.
Affected by factors such as Lipid solubility, molecular size, degree of ionization (ionized are polar), PH of
environment
CRF effect:
Uremia and gut edema may cause nausea/vomiting or diarrhoea in patientsDecreases absorption of
drug taken orally
Uremia causes increased gut ammonia production makes gut environment alkalinedecreases absorption
of drugs that require acidic medium for absorption e.g. Iron
Distribution: the process of reversible transfer of a drug between one location and another
after being absorbed into blood, a drug may be distributed to tissues, depending on:
- blood supply to tissue
- permeability of capillaries, tissue membrane and perfusion
- lipid-solubility of a drug - lipid soluble drugs can easily cross capillary membrane into tissue
some drugs are bound to plasma proteinform drug protein complex:
Acidic drugs bind to albumin Basic drugs bind to α1-Acid glycoprotein
drug-protein complex can’t cross capillary membrane (too large) → not distributed to tissue
only free (unbound) drugs can cross capillary membrane → distributed to tissue » pharmacological effect
important to considerVolume of distributionvolume in which amount of drug in the body would eed
to be uniformly distributed to produce the observed concentration in the blood

CRF effect:
-Increased fluid accumulation may increase volume of distribution of water-soluble drugsImportant to
ensure adequate loading doses are given E.g. loading doses of Penicillins, Cephalosporins need to be
increased by 25-50%
-Albuminuria: loss of albumin in urinereduction in protein binding of many acidic drugs to albuminE.g.
penicillins, cephalosporins, aminoglycosides, frusemide and phenytoin (Avoid using high doses or
prolonged treatment with such drugs)
-Basic drugs bind mainly to 1-acid glycoprotein and this process is generally unaffected by CKDE.g.
metoprolol, codeine, ephedrine, phenobarbitione etc.
-Chronic renal failure also causes azotaemia: retained N compounds compete with drugs for protein
bindingResults in increased concentration of free drugs (esp. acidic drugs like Phenytoin)
-Renal impairment may alter tissue binding of certain drugs, e.g tissue binding of Digoxin decreases, thus
VD also decreases by approx. 50%-->Loading dose will need to be reduced
Hyperkalaemia will result in Digoxin toxicity
Metabolism: Drug modification or biotransformation by enzymes
A drug metabolized by liver to
inactive metabolites is not
significantly affected by a reduction
in renal excretion
However, for many drugs,
metabolites may be active, e.g. Glibenclamide
Most drugs are cleared by a combination of renal and non-renal clearance; few drugs are eliminated
entirely unchanged by the kidney
CRF effect:
-alterations in hepatic and extra-hepatic drug metabolism and transport occur during renal failure.
Reduction, hydrolysis and conjugation are slowedMay result in increased concentration of parent drug
-Many active or toxic metabolites depend on renal function for elimination; therefore they may
accumulate in RI E.g. Pethidine is converted to NorpethidineMay cause seizures if it accumulates- best to
avoid in RI
-Accumulation of uremic toxins and inflammatory cytokines may affect activity of cytochrome P 450
metabolic enzymes and of P-glycoprotein and organic anion-transporting peptides (OATPs). E.g. Results in
increase in bioavailability of meropenem, vancomycin and erythromycin
Excretion: Loss of drug from the body

Major site: Kidney

Mechanism:
Passive tubular reabsorption:
- high urine flow rate – urine less concentrated »↓ lipid soluble drug reabsorption
- ↓ urine flow rate - urine more concentrated » ↑ reabsorption of lipid soluble drugs.
- water soluble drugs are never reabsorbed into blood
Note: ionized drugs are more soluble (polar) hence will dissolve in body fluids and be easily excreted and
since they are more polar (less lipid soluble), they will not be reabsorbed.
Active tubular secretion:
- occurs along proximal tubule
- Carrier mediated transport process
 - ‘acid’ and ‘base’ pump actively secrete drugs into tubule lumen
- Limited number of transporters, which can be competed for
CRF effect:
-Decreased GFR results in decreased elimination of many drugs
-Active tubular secretion of drugs is reduced. E.g. Sitagliptin, Methotrexate due to decrease in activity of
transporter proteins
-For some drugs e.g. ciprofloxacin, compensatory increases in alternative elimination pathways occur
dosage reduction may not be necessaryIn this case, monitor and dose according to physiological
responseStart with lower doses

2. Demonstrate the use of pharmacokinetic parameters in the design of a rational dosing

regimen - calculation of maintenance dose, loading dose and dosing interval
Loading Dose
For a drug with long half-life, or high volume of distribution, a loading dose is often given
This may be normal doses given more frequently at first, or a higher dose to start with
The loading dose “loads” into the second compartment allowing subsequent maintenance doses to reach
therapeutic levels in the plasma
Loading Dose = Volume of Distribution (V) X Desired Drug Concentration in Plasma
(V) changes depending on:

 age
 body composition
 disease state
 gender
Example:

 (V) of infants < 1 year old ~ 75-80% body weight

 (V) of healthy adult male ~ 60% body weight,
 (V) of healthy adult female ~ 55% body weight.
Steady State
The same formula can be rearranged as:
C = dose rate
ss
Clearance

Where; Css = concentration of drug in plasma at steady state

Thus, clearance determines Css
Loading dose rate & Maintenance dose rate need to be adjusted in renal disease patients due to small
clearance (longer t1/2)
Maintenance Dose
Maintenance dose: dose administered to maintain the desired plasma concentration in the body (e.g.,
250mg once daily)
Maintenance Dose = Dose Rate x Dosing Interval
Bioavailability (F)
Dose rate
Dose Rate: rate at which drug is being administered (e.g., 1mg/hr)
Dose Rate= Clearance x plasma conc at Css
Example
Calculations
A target plasma concentration of 10 mg/L is desired for drug X to relieve acute bronchial asthma in a
patient. If the patient is a nonsmoker and otherwise normal except for asthma, we may use the mean
clearance of 2.8 L/h/70 kg. Since the drug will be given as an intravenous infusion, F = 1, V= 35L
(I) Calculate the loading dose for this drug.
Loading dose= Vd x desired conc in plasma
= 35L x 10mg/L
= 350mg
(II) The clinician wants to maintain this plasma level using oral form of drug X, which is given every 12
hours. What would be the maintenance dose of the oral form? (Note: oral bioavailability of this drug is
0.96).
Dose rate = Cl x Drug conc at Css
= 2.8L/ hr x 10mg/L
= 28mg/hr
Maintenance dose= Dose rate x Dose interval
Bioavailability (F)
= 28mg/hr x 12hr
0.96
= 350mg every 12 hourly
Note: in this example, the loading dose and maintenance dose are same, however, the loading doses are
usually higher than maintenance doses in practice.
In the above example, if the patient develops renal failure and the Clearance decreases to 1.5L/hr, what
maintenance dose would need to be administered to ensure that plasma concentration remains same?
Dose rate = Cl x Drug conc at Css
= 1.5L/hr x 10mg/L
= 15mg/hr
Maintenance dose= Dose rate x Dose interval
 Bioavailability (F)
= 15mg/hr x 12hr
0.96
= 187.5mg
Note that the maintenance dose will need to be decreased so the plasma concentration remains stable
Half life and Clearance
T1/2 = Vd / Cl
Half-life: time taken for the plasma concentration to fall by half.
The greater the Vd, the longer the half-life
The greater the clearance the shorter the half-life

 Thus, renal disease is likely to prolong the half-life of drugs cleared by the kidneys

GFR
GFR: amount of blood plasma filtered through the kidneys per minute ~125 mL/min
used clinically to guide management or adjustment of drug dosage
Generally, there is linear correlation b/w creatinine clearance and drug clearance

 In patients with impaired renal function, dose adjustment can be based on creatinine clearance
Renal Clearance
most widely recognized formula for calculating CrCl and estimating renal function
Cockcroft-Gault formula:

 If lean body weight is not available, ideal body weight can be used.
  limitations: lack of validity in some populations, lack of reliability in severe malnutrition, obesity,
renal changes
 alternative to CrCl is the eGFR (CrCL is not equivalent to eGFR*)
Calculating Ideal Body Weight
• Females: 45.5Kg+ 0.9Kg/cm for each cm above 152cm
• Males: 50Kg+ 0.9Kg/cm for each cm above 152cm
• Add 10% for a heavy frame, subtract 10% for a light frame
Categories of Impairment
• Severe impairment CrCl <10mL/min
• Moderate Impairment CrCl 10-25mL/min
• Mild Impairment CrCl 25-50mL/min
categorization for purpose of drug dosing- NOT for classification of chronic renal diseases
Drugs mainly eliminated by renal excretion
Drugs excreted largely unchanged in the urine include:

 Frusemide, gentamicin, methotrexate, atenolol, digoxin, benzylpenicillin, cimetidine

These drugs must be used with great care in patients with impaired renal function

 E.g., elderly people, and patients with renal failure

Dosage adjustment for drugs normally eliminated largely or partly by kidneys

 Changing initial or loading dose is generally unnecessary

 For Maintenance dose: either
 Reduce each dose (e.g., by half) Or Increase intervals between doses
 Monitor therapy
 For some drugs, loading dose needs to be decreased, e.g. Digoxin dose is halved
Drugs that can aggravate renal failure
• NSAIDs
• Aminoglycosides
• Probenecid
• Cisplatin
• ACE inhibitors
• Cyclosporin
• Lithium
Avoid giving NSAID, ACEI and diuretic together
• Causes ‘triple whammy’ effect
• May increase risk of acute kidney injury
• NSAIDS also decrease efficacy of ACEI and Diuretics
 Study Guide 6
What is the medical management of chronic renal failure?
1.Describe the principles of the medical management of chronic renal failure
The aims of management in CKD are to: [Davidson]
 monitor renal function
Renal function should therefore be monitored
every 6 months in patients with stage 3 CKD, but
more frequently in patients who are deteriorating
rapidly or have stage 4 or 5 CKD.
 prevent or slow further renal damage
 limit complications of renal failure
 treat risk factors for cardiovascular disease
 prepare for RRT, if appropriate

Screening in Fiji:
Kidney health triad  BP + eGFR + Proteinuria
 On first appointment, annually thereafter.

Blood pressure control

 Target  <130mmHg systolic
Salt restriction to <5g/d [Fiji 11.7g/d avg]
ACEI/ARB dose increased every 2-4weeks to achieve maximum tolerated dose
Glycemic control
 Target HbA1c <6.5% to <8%
1st line
 Metformin
 SGLT 2 inhibitor
2nd line [eGFR<30ml/min]
 Glipizide/insulin

Cardiovascular risk reduction

Simvastatin  20mg/d / Atorvastatin  40mg/d [not initiated in dialysis dependent CKD]

Aspirin  lifelong secondary prevention for those with a known HX of CVD
Management of advanced CKD complications
Complications  eGFR<30ml/min
1.Anemia
Iron therapy IV
ESA therapy should only be prescribed by a specialist and is reserved for those who have had an
inadequate response to iron, have symptoms attributable to anaemia, would otherwise be considering a
blood transfusion, and are likely to survive long enough for meaningful benefit.
 ESAs target  Hb 10-11g/dL.
 During ESA therapy iron stores must be maintained, targeting Ferritin 500-700 mcg/L and TSAT 20-
40%.
2.Fluid Overload
Salt restriction [<5g/d] & Fluid restriction [matched to urine output]
Frusemide  can give in all stages  20-160mg/d up to 500mg/d in stage 5
 Hydrochlorothiazide  if resistance to frusemide
3.Hyperkalemia
1. First identify and correct contributing factors
a. Metabolic acidosis
b. Constipation — results in bowel potassium reabsorption
c. Hyperinsulinemia states — low carbohydrate diets, advanced diabetes
d. ACEI/ARB use
2. Promote potassium excretion
a. Potassium wasting diuretics (e.g. thiazides, frusemide) if fluid state allows
b. Resonium in short-term courses only
3. Dietary changes as described above↓ protein intake, can give aluminum salts cuz they X absorption
4. Refer immediately to the closest emergency centre if K a 6.5 mmol/L
4.Metabolic acidosis
 HCO3- <22mmol/L
Dietary changes
 ↑ fruits and vegetables – alkaline
 ↓meats/fish – acidic
Oral sodium bicarbonate crystals [target 22-26]
 HCO3 18-22  840mg 2x/d
 HCO3 <18  1680mg 2x/d
5.Mineral disorders
Hypocalcemia
Oral calcium carbonate [1.80-2.1mmol/L]
 Taken on empty stomach  prevent Ca binding to dietary phosphate
 500mg once daily
Oral calcitriol  0.25mcg once daily  ↑ dietary Ca absorption
Hyperphosphatemia
1. Dietary change
 Restrict animal products (meat, dairy, eggs) , Avoid highly processed foods
2. Oral calcium carbonate
 phosphate binder when taken with meals, thus reducing dietary phosphate absorption
 Starting dose of 500mg once or twice daily taken with largest meals of the day
Pruritis
 Topical treatments  QV intensive/ menthol 0.05% / blackmores evening primerose oil
 Gabapentin  start 100mg max 300mg (GABA mimicinhibit calcitonin gene–related peptide (a
mediator of itching) release from primary afferent neurons through a primary increase GABA)
Hyperuricemia & Gout
Reduce alcohol, sugar sweetened drinks, and reduce meats and seafood.
Allopurinolinhibit xanthine oxidase, an enzyme in the purine catabolism pathway that converts
hypoxanthine to xanthine to uric acid.
Pain management

Cost of Renal Failure: who should be treated? Is a dialysis program sustainable in Fiji? The
public health perspective.
2. Discuss the cost implications of “renal replacement therapy”. its merits and demerits.
Haemodialysis
Pros of haemodialysis
 When AV fistulas are used for vascular access, the risks complications of haemodialysis are reduced.
 AV fistulas for haemodialysis can last many years, catheters for peritoneal dialysis and other forms
of vascular access, with usually no need for additional surgical intervention.
 Haemodialysis at dialysis centres is done 3 times weekly leaving most of the week dialysis free.
 Trained staff at the centres continuously supervise and monitor patient’s health and treatments
 Haemodialysis at treatment centres allows for social interactions with people undergoing the same
process
 Haemodialysis sessions can be used for work, reading and relaxation
 Haemodialysis carries a relatively low risk of infection
 Haemodialysis can also be done at home, at your own convenience. Haemodialysis done at home is
generally done daily, with assistance from a partner.
 Nocturnal haemodialysis done at home is a relatively gentle form of treatment, leaving the patient
feeling stronger
 Nocturnal haemodialysis allows for sense of normality and for regular work/school schedules
Cons of haemodialysis
 If haemodialysis is done in a clinic, you will to travel to the clinic, and spend 3-4 hours there each
session.
 Haemodialysis schedule must be stringently kept.
 Travel is more complex, requiring advance planning and arrangements.
 Diet and fluid restrictions must be adhered to strictly.
 Fistula may seem ungainly and ugly to patient and can be at risk for infection
 If undergoing home haemodialysis, a partner must be home, and must be involved in the nursing.
 If done at home space, electrical and plumbing needs must be considered
 Possible side effects include low blood pressure, shortness of breath and nausea.
 Uses heparin  bleeding disorders

Peritoneal dialysis
Pros
 Gentler, slower dialysis with less side effects. Best option for any patients with heart disease.
 A partner is not required.
 CAPD and CCPD are interchangeable depending on your schedule.
 Can dialyze during sleep
 No need to go to centre three times a week
 Comfort of being at home for treatment
 No need to be stuck with needle each treatment like haemodialysis
 Fewer food and liquid restrictions than haemodialysis
 Don’t need to arrange for dialysis treatment at a centre when traveling
Cons
 Treatments are done seven days a week.
 Need to take have space in home to set up machine and store PD supplies
 Need to be careful to not get PD catheter infected
 PD can cause weight gain due to glucose in the dialysate (dialysis solution)
3. Discuss the challenges and complications of palliative care in renal failure patients
Integral to the precepts of palliative care is an interdisciplinary approach focusing upon physical comfort
(managing pain and other symptoms) and psychological, spiritual, and social support for the patient and
their family and community.
The goal of palliative care is to achieve the best possible quality of life by relieving suffering, controlling
symptoms, and restoring functional capacity, while maintaining sensitivity to personal, cultural, and
spiritual beliefs and practices ( to provide a support system to help patients live as actively as possible until
death)
Hospice care focuses on the care, comfort, and quality of life of a person with a serious illness who is
approaching the end of life. Like palliative care, hospice provides comprehensive comfort care as well as
support for the family, but, in hospice, attempts to cure the person's illness are stopped
The international kidney community is increasingly using the synonymous term "kidney supportive care"
rather than "kidney palliative care" to help reinforce the appropriateness of this kind of care throughout
the symptomatic illness trajectory and to distinguish it from end-of-life care
Benefits:
-experience lower symptoms burden at end of life, receive care consistent with their preference and to use
hospice services.
-palliative and hospice care in ESKD can ↓hospital care costs
Barriers:
-palliative and hospice care are underutilizedlate referral to hospice care once all treatment options are
exhaustedthis complicated transition
-uneven access to specialty palliative care services
-underdeveloped models of care for seriously ill patients with advanced CKD
-misaligned policy incentives
-In addition, nephrologists tend to be poorly trained in palliative care and often feel uncomfortable with
the care of dying patients
-patients lack understanding of the potential benefits of palliative and hospice care.
Components of kidney support care
1 Shared decision makingincorporate patients need + adapt care plans that facilitate patients life
2 Quality of life assessmentsymptom assessment regularly-3 monthly for non dialysis patients + fraility
of patients is assessed
3 Advance care planningshare personal values, life goals, and preferences regarding future medical care
and prepare them for periods of incapacity
4 Palliative and hospice care consultation
5 Terminal symptom management advance CKD have high symptom burden, As the patient's condition
deteriorates during the terminal phase, certain nonpharmacologic interventions become less realistic (eg,
exercise). Symptoms should be anticipated, with arrangement of appropriate prescriptions in place to
address symptoms as they occur.
- Painmost common complain 69%, opiods usedfentanyl, methadone
- Constipationw opioid usestool softeners, dietary changes and laxatives
- SOBpositioning of patients, fan blow at them gently, supplement oxygen, reassurance
 - Anxiety, agitation & deliriumusually due to metabolic abnormalitiesused benzodiazepines for
anxiety, trazodone for agitation
- Myoclonus, muscle twitching and seizuresdue to opioids or uremic associated
- Nausea/ vomitinguse pro-kinetic agentmetoclopramide
- Respiratory tract secretionsaccumulate cuz weak to cough
- Pruritustopical/ emollients
Other challenges faced by patients at end of life:
Painelderly unwilling to report their pain because they believe its normal symptom
Depression45% of terminally ill patients w cancer have it, can lead to suicide, it makes their illness
worse. Anxiety coexists, demoralization can also occur. These symptoms occur due to the illness itself or
the treatment
Copingpatients face challenge coping with their disease on daily basis. Bod copers display a defensive
style which may include isolation, non-compliance avoidance, denial.
Dignity(worthy of honor, respect and esteem) for many patients dignity is related to level of
independence and autonomy so in terminally ill their dignity is gone
Otherssuch as anorexia, weakness, sexual dysfunctionall these lead to suffering more
Challenges faced by clinicians involved with end of life care:
-in adequate trainingneed to learn in engaging in difficult conversations
-in sufficient compensations
- personal discomfort with death
 Study Guide 7
1.Discuss the different values of ethics
Principles or standards of behavior, one’s judgement of what Is important in life
What are the sources of Ethical Values?

 Family and cultural values – society, Religion, Education

Values
 Virtue (moral excellence) - love, compassion, selfless
 honesty
 truth-telling,
 transparency,
 showing respect for patients and families, and showing respect for patients' own values

2.Discuss the different elements to principle-based ethics

The Principle of Respect for Patients’ Autonomy
 Self rule. This principle allows people to reign/control over themselves and to make decision that
apply to their lives.
 Informed consent , respect patients decisions – their self ruling
 What is beneficial to patients cannot be determined only by the doctor – this is a joint decision
making exercise between patient and doctor
The Principle of Beneficence
 Generate the largest possible fraction of GOOD OVER EVIL. That which produce the most benefit
over risks.
 Describe various scenarios to illustrate decisions based on principle-based ethics
The Principle of Non-Maleficence
 People should choose to do no harm or Non-Harm
 If the choices are both harmful then choose to do the least harm possible to others.
The Principle of Justice
 Fairness : Equality  Human rights
 The principle of JUSTICE include decisions that are legal vs decisions that are illegal.
3.Describe various scenarios to illustrate decisions based on principle-based ethics
Its recommendations emphasize patients' wishes and best interests as well as the appropriate use of the
expensive, life-sustaining therapies of dialysis and transplantation.
Nephrologists Have Seen Chronic Dialysis Treatment As A Tremendous Success (Lowrie and Hampers,
1981). This view is based largely on the personal satisfaction of being able to provide life-sustaining
treatment to patients who would otherwise die
Patients are not obligated to undergo life-sustaining treatment (President's Commission, 1983). Others
have also observed that the prolongation of life may not always be a benefit that outweighs all burdens
The termination of treatment of incompetent patients, by contrast, should occur only after full discussion
between the patients' family, or other representatives, and the physicians
Nephrologists should be open to permitting dialysis to stop when it no longer benefits the patient. The
discussion of the decision to stop dialysis might be initiated by the patient for whom the burdens have
come to outweigh the benefits or by the physician who recognizes that the treatment goals are no longer
achievable.
In situations where the expected benefit to the patient is not clear but the patient (and/or family) wants
treatment, a time-limited trial of dialysis of I to 3 months
Legal instruments that document the patients' wishes in advance are the living will and the durable power
of attorney for health care. Physicians may also document patients' advance directives in patients' charts
after a witnessed discussion.