CHRONIC KIDNEY

DISEASES
Presentation Outline.
 Definition of CKD.
 Staging of CKD.
 Pathophysiology of CKD.
 Risk Factors For CKD.
 Etiology of CKD.
 Pathophysiology & Chemistry of Uremia.
 Clinical & Lab Manifestations of CKD & Uremia.
 Management Approaches to Pts With CKD.
 References.
Chronic Renal Failure
A. Definitions
1. Azotemia - elevated blood urea nitrogen (BUN >28mg/dL)
and creatinine (Cr>1.5mg/dL)
2. Uremia - azotemia with symptoms or signs of renal failure
3. End Stage Renal Disease (ESRD) - uremia requiring
transplantation or dialysis
4. Chronic Renal Failure (CRF) - irreversible kidney
dysfunction with azotemia >3 months
5. Glomerular Filtration Rate (GFR) - the total rate of
filtration of blood by the kidney
6. Creatinine Clearance (CCr) - the rate of filtration of
creatinine by the kidney (GFR marker)
Cont…
Definition
 CKD is defined as ,
Presence of evidence of structural or functional
abnormalities of the kidneys (abnormal urinalysis,
imaging study or histology ) that persists for at
least 3 months with or with out decreased GFR
(defined as GFR less than 60ml/min/) Or,
 Decreased GFR (<60ml/min) with or with out
evidence of kidney damage.
Staging of CKD
Risk Factors
 Hypertension
 Diabetes Mellitus
 Autoimmune diseases
 African ancestry
 older age
 Family history of kidney disease
 Previous history of AKI
 Presence of protienuria,abnormal urinary sediments
and structural abnormalities of urinary tract.
Pathophysiology of CKD
 Pathophysiology of CKD involves two broad mechanisms ,
1-Initiating mechanisms specific to the underlying etiology like
.immune complex deposition Eg Glomerulonephritis
.toxin exposure Eg tubulointerstitial diseases

2-Pogressive mechanisms involving hypertrophy and

hyperfiltration of remaining viable nephrons due to loss of
renal mass. This is mediated by the RAA mechanism.
.this mechanism is initially adaptive & vital but finally
proves maladaptive and deliterious.
Etiology of CKD

 Diabetic Nephropathy-leading cause

 Hypertensive nephropathy
 Chronic glomerulonephritis
 Polycystic kidney disease.
 Other causes like obstructive uropathy and
infections etc.
Pathophysiology and Chemistry of Uremia.

 Hundreds of toxins are incriminated for the uremic

syndrome eg,
- nitrogenious excretory cpds like guanido cpds,
urates & hippurates,polyamines,myoinositols,
indols benzoates and phenols.
. Urea and Creatinine are readily measurable but are
not the only real cause of the uremic syndrome.
. In CKD, other than excretory failure ,there are also
associated metabolic & endocrine derangements.
Cont…
 Metabolic derangements lead to anemia,
malnutrition, abnormal carbohydrate, fat and protein
metabolism.
 Endocrine derangements lead to abnormalities of
PTH, insulin, glucagon, sex hormones and prolactin.
 Renal insufficiency is associated with pronounced
worsening of systemic inflammation evidenced by
increased CRP & decreased level of negative acute
phase reactants like albumin.
Cont…
 Thus pts with CKD and pronounced systemic
inflammation are prone to the malnutrition-
inflammation-atherosclerosis/calcification
syndrome which contributes to their susceptibility
to vascular problems.
 In summary, the pathophysiology of the uremic syndrome
can be divided into manifestations in three spheres of
dysfunction:
 (1) those consequent to the accumulation of toxins that
normally undergo renal excretion, including products of
protein metabolism;
 (2) those consequent to the loss of other renal functions, such
as fluid and electrolyte homeostasis and hormone regulation;
and
 (3) progressive systemic inflammation and its vascular and
nutritional consequences.
Clinical & Lab manifestations of CKD and Uremia.

 Uremia leads to disturbance of virtually every

organ system function.
 Florid manifestations are decreasing in the best set
up because of early dialysis.
 Some of these uremic syndromes even persist and
fail to revert after dialysis.
Fluid ,electrolyte and acid base disorders in CKD.

 Sodium and water homeostasis

-In CKD pts the total body water & sodium is
increased due to decreased sodium clearance
leading to expanded ECFV. This expansion may
contribute to hypertension, which itself can
accelerate the nephron injury.
-Hyponatremia is not common in CKD
 Loop> thizide diuretics ,dilaysis

 Acute on chronic
Potassium Homeostasis.
 There is risk of hyperkalemia in CKD but it doesn’t
necessarily occur because of other ways of
excreting it , GI tract & aldosterone related
excretion at the distal tuble. BUT,
 If CKD pts have additional factors like increased
dietary intake, increased protein catabolism ,
hemolysis , and are taking potassium retaining
drugs like ACE-I or spirinolactone , they can
develop hyperkalemia.
Cont…
 Hyperkalemia may appear early in some forms of
CKD due to pathological distal tubular K transport
secondary to hyporeninemic hypoaldosteronism as in
diabetic nephropathy ,TIDs and obstructive uropathy.
 Hyokalemia is uncommon in CKD & its presence
shows either decreased intake or overzealous
diuresis.
 Hypokalemia may also be due to primary K wasting
disorders like distal or proximal RTA.
Metabolic Acidosis.
 Metabolic acidosis is a common disturbance in
advanced CKD. The majority of CKD pts can
acidify the urine but produce little ammonia to
buffer the daily acid out put.
 Concomitant hyperkalemia decreases
ammoniagensis and complicates the acidosis
 Hyperkalemia and type IV RTA is common with
diabetic nephropathy ,TID and obstructive
nephropathy.
Cont…
 Early in the course of CKD ,the MA tends to be non
anion gap MA ,but with further decline in renal
function ,the MA will be of the anion gap variety.
 In CKD, the MA is usually mild and the PH is rarely
below 7.35 and can be corrected by oral sodium
bicarbonate supplementation.
 But, this seemingly mild MA may be associated with
profound protein and bone catabolism and thus alkali
therapy should be considered once bicarbonate level
falls below 20mmol/l.
Disorders of Calcium and Phosphate Metabolism.

 The complications of abnormal calcium &

phosphate metabolism in CKD pts occur in the
skeleton , vascular beds and rarely the soft tissues.
Bone manifestation of CKD
 CKD related renal osteodystrophy is of 2 types ,
1-High turn over bone disease due to high PTH.
.Osteitis fibrosa cystica –classic bone lesion of
hyperparathyroidism.
2-Low turn over bone disease due to low PTH.
.Adynamic bone disease-is due to suppressed PTH
secondary to supplementation with Vit D & Ca based
phosphate binders in ESRD pts on dialysis.
.Osteomalacia –Vit D def ,Al toxicity ,MA
Calcium ,Phosphorus and the Cardiovascular
system.

 Pts with CKD related hyperphosphatemia and

hypercalcemia are prone to calcification of the
vessels.
 The vascular calcification may involve the
coronary arteries and the heart valves.
 This is one reason why pts with CKD are at a
substantially increased risk of Cardiovascular dd.
Hematologic abnormalities.
 Normocytic normochromic anemia is observed as
early as stage 3 and is almost universal by stage 4.
 It is associated with adverse pathophysiologic
consequences like decreased tissue oxygen delivery
increased CO ,ventricular dilatation and ventricular
hypertrophy.
 Its etiology in CKD is multi factorial
Cardiovascular Abnormalities.
 Cardiovascular diseases are the leading cause of
morbidity and mortality in CKD pts followed by
infections.
 CKD pts usually succumb to CV diseases before they
reach stage 5.
 About 30-45 % of pts with CKD are already
complicated by CV diseases by the time they reach
stage 5
 CKD is currently considered as a coronary heart
disease equivalent as is diabetes.
Ischemic vascular disease.
 Any stage of CKD is an independent risk factor for
ischemic cardiovascular disease (IHD,CVA,PAD)
 This is due to the presence of both the traditional and
CKD related cardiovascular risk factors in CKD.
 Traditional risk factors
HTN,hypervolumia,dyslipidemia,hyperhomocystinemia
& increased sympathetic activity.
 CKD related risks-
anemia,hyperphosphatemia,hyperparathyroidism & the
generalized inflammation typical of CKD.
Heart Failure.
 Pts with CKD may develop heart failure due to
- Myocardial ischemia
- LVH
-Overt cardiomyopathy
- Na and water overload.
. Hypertension , LVH & pericarditis are also other
cardiovascular complications of CKD.
Other complications
 Abnormal Hemostasis
 Neuromuscular Abnormalities
 Gastrointestinal and Nutritional Abnormalities
 Endocrine-Metabolic Disturbances
 Dermatologic Abnormalities
Management approach to Pts with CKD.

 History
-early, asymptomatic & an incidental finding.
-ask Hx of Hypertension , DM
-ask Hx of drugs eg NSAIDs ,ACE-I ,lithium
-dig Hx for uremic symptoms like appetite loss,
weight loss ,nausea ,hiccup ,muscle cramp,
pruritis and restless legs are especially helpful.
Cont...
 Physical Examination
-Blood pressure and target organ damage
precordial examination (left ventricular heave, a
fourth heart sound)
-Fundoscopy
-Edema & and sensory polyneuropathy
-Pericardial friction rub
-Uremic flap (asterixis)
Cont…
 Lab Work
-Serial BUN and creatinine
-A 24-h urine collection
-serum and urine protein electrophoresis.
-In GN –HBV and HCV screen ,ANA , ANCA ,HIV,
VDRL.
-Serum Ca , P , PTH
-Hg , Iron studies , B12 and folate level
-blood glucose etc.
Cont…
 Imaging
- Renal Ultrasound in CKD shows shrunken echogenic kidneys except
in diabetic nephropathy , amyloidosis and HIVAN. PCKD
- The diagnosis of renovascular disease can be made by doppler
sonography ,CT or MRI.
- IV contrast material is contraindicated in CKD.
- Renal biopsy is indicated
.Isolated glomerular hematuria
.Isolated non nephrotic proteinuria
.Nephrotic syndrome
.The Nephritic Syndrome
.Unexplained acute renal failure.
Establishing the Diagnosis and Etiology of CKD

 The most important initial diagnostic step in the evaluation of a

patient presenting with elevated serum creatinine is to distinguish
newly diagnosed CKD from acute or subacute renal failure
because the latter two conditions may respond to therapy specific to
the disease.
 Previous measurements of serum creatinine

 Evidence of MBD with hyperphosphatemia,

hypocalcemia, and elevated PTH and bone alkaline

phosphatase
 Normochromic, normocytic anemia

 bilaterally reduced kidney size (<8.5 cm in all but the

smallest adults)
Treatment: Chronic Kidney
Disease
 Treatments aimed at specific causes of CKD are discussed
elsewhere. Among others, these include
 optimized glucose control in diabetes mellitus,

 immunomodulatory agents for glomerulonephritis,

and
 emerging specific therapies to retard cytogenesis in

polycystic kidney disease.

 The optimal timing of both specific and nonspecific
therapy is usually well before there has been a measurable
decline in GFR and certainly before CKD is established
General Management.
 In all CKD pts , serial creatinine determination is
crucial.
 If there is an acute acceleration from the base line,
look for an acute on chronic insult,
-ECF volume depletion
-Uncontrolled HTN ,UTI , Obstructive uropathy.
-exposure to nephrotoxins
-acute flare of the primary disease ,eg SLE
Slowing The Progression of CKD.
 Reduction of intraglomerular hypertension and
protienuria.
-ACE-I and ARBs are best in decreasing
intraglomerular hypertension & protienuria.
-In the face of their side effects , one can use
calcium chanell blockers like verapamil or
diltiazem.
Cont…
 Protein restriction
-It decreases both nausea and renal progression
-Recommended = 0.60-0.75 gm/d 50 % of which
should be in the form of high biologic value.

-As pt approaches stage 5 ,they should be allowed 0.9

gm /d as spontaneous protein intake decreases.
-Sufficient energy intake is important to prevent protein-
calorie malnutrition, and 35 kcal/kg is recommended
DIABETIC Renal Disease
 the prognosis of diabetic patients on dialysis is poor, with
survival comparable to many forms of cancer. Accordingly,
it is mandatory to develop strategies whose aim is to prevent
or slow the progression of diabetic nephropathy in these
patients.
 Control of Blood Glucose
 preprandial glucose be kept in the 5.0–7.2 mmol/L

(90–130 mg/dL) range and hemoglobin A1C should

be < 7%.
 the use and dose of oral hypoglycemics needs to be
reevaluated
Treatment of fluid ,electrolyte and acid-base
disorders.

 Salt intake should be adjusted

 Use of loop diuretics- at times high dose or in combination with
metolazone. Thiazides are not effective in stage 3-5 CKD.
 Water restriction only if there is hyponatremia
 Intractable volume overload – dialysis.
 Hyperkalemia responds to
.Decreased K intake
.Stopping K retaining drugs ACE-I,ARB,Aldactone.
.GI potassium binders
. Kaluretics like loop diuretics.
Cont…

 Refractory hyperkalemia is an indication for

dialysis.
 The early appearing RTA and the late appearing
anion gap metabolic acidosis in CKD pts respond
to an alkali therapy.
 Thus , sodium bicarbonate should be started once
the bicarbonate is < 20mmol/l
 Intractable acidosis is an indication for dialysis.
Treatment of disorders of calcium and phosphate
metabolism.

 Ca , P & PTH should be followed serially

 Hyperphosphatemia should be treated by
decreasing dietary intake and use of phosphate
binders.
 Calcium carbonate and calcium citrate are the
phosphate binders. Risk of hypercalcemia.
 Sevelamer , a non calcium containing phosphate
binder has no risk of hypercalcemia.
Cont…
 Calcitriol or vitamin D analogues directly suppress
PTH and indirectly suppress it by raising ionized
Ca.
 As a side effect, they may cause hypercalcemia and
hyperphosphatemia by augmenting their GI
absorption.
 The PTH should be kept in the range of 150-300
pg/ml.
Treatment of Cardiovascular abnormalities in CKD.

 Management of HTN
-aim is to decrease progression of kidney disease
and cardiovascular complications.
-Target BP - 130/80 for any pt with CKD
-125/75 for diabetic pts and
proteinuric pt > 1gm/day.
-Try them initially with salt restriction & diuretics.
-ACE-I and ARBs are the best choice. S/E
Cont…
 Management of cardiovascular risk factors.
-HTN ,dyslipidemia and hyperhomocystienemia all
promote atherosclerosis but are all modifiable complications of CKD.
-HTN-already discussed
-Hyperhomocystienemia-responds to vitamin therapy
with B6 ,B12 and folate.
-Dyslipidemia
-The commonest form of dyslipidemia in CKD is hypertriglyc-
eridemia.
–target LDL to <70mg/dl with statins as CKD is a CHD equiv.
Treatment of Anemia in CKD.
 EPO use has obviated the use of repeated blood
transfusions.
 Adequate iron study has to be made before EPO as
response to EPO depends on sufficient iron pool.
 Iron supplementation has to be considered in CKD.
 If the anemia is resistant to EPO in the face of good
iron store , consider other causes of anemia.
 Blood transfusion is given only if the patient is
resistant to EPO and is not recommended
Cont…
 Risk of transfusion in CKD pts are ,
-suppression of erythropoeisis,
-transfusion associated infections ,
-iron overload and
-development of alloantibodies and sensitization
of the pt for donor kidneys.
. In CKD pts , hemoglobin of 11-12 mg% should be
targeted.
Other measures in CKD.
 Nephrotoxins should be avoided.
 Dose adjustment has to be made for drugs with
primarily renal excretion.
Preparation for RRT.
 CKD pts should be serially evaluated for possible eligibility
for RRT ( maintainance dialysis or kidney transplantation).
 Clear indications for dialysis

-pericarditis or pleuritis
-progressive encephalopathy or neuropathy
-intractable muscle cramp
-persistent anorexia , nausea and vomiting.
-refractory hyperkalemia
-refractory hypervolumia
Cont…
-Clinically siginificant bleeding diathesis.
-hypertension poorly responsive to medications.
-weight loss or signs of malnutrition.
-Refractory metabolic acidosis.
-Diabetic pts with GFR<15ml/min ?
-Non diabetic pts with GFR<10ml/min ?
WHEN TO START
References.
 Harrison’s principle of Internal Medicine 18th
edition
 Uptodate 17.3
 The Kidney , Brenner and Rector’s , 8th Edition
Thank You