Chronic kidney disease

Introduction
 Chronic kidney disease (CKD) is a type of kidney disease in which there is gradual loss of
kidney function over a period of months to years. Initially there are generally no
symptoms; later, symptoms may include leg swelling, feeling tired, vomiting, loss of
appetite, and confusion. Complications include an increased risk of heart disease, high
blood pressure, bone disease, and anemia
 Causes of chronic kidney disease include diabetes, high blood pressure,
glomerulonephritis, and polycystic kidney disease. Risk factors include a family history
of chronic kidney disease. Diagnosis is by the estimated glomerular filtration rate
(eGFR), and a urine test to check for albumin. Ultrasound or kidney biopsy may be
performed to determine the underlying cause. Several severity-based staging systems
are in use
 Screening at-risk people is recommended. Initial treatments may include medications to
lower blood pressure, blood sugar, and cholesterol. Angiotensin converting enzyme
inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are generally first-line
agents for blood pressure control, as they slow progression of the kidney disease and
the risk of heart disease. Loop diuretics may be used to control edema and, if needed,
to further lower blood pressure
 NSAIDs should be avoided. Other recommended measures include staying active, and
certain dietary changes such as a low-salt diet and the right amount of protein.
Treatments for anemia and bone disease may also be required. Severe disease requires
hemodialysis, peritoneal dialysis, or a kidney transplant for survival
Causes

 The three most common causes of CKD in order of frequency as of 2015 are
diabetes mellitus, hypertension, and glomerulonephritis. About one of five
adults with hypertension and one of three adults with diabetes have CKD. If
the cause is unknown, it is called idiopathic
 By anatomical location:
1. Vascular disease includes large vessel disease such as bilateral kidney artery stenosis and
small vessel disease such as ischemic nephropathy, hemolytic-uremic syndrome, and vasculitis
2. Glomerular disease comprises a diverse group and is classified into:
Primary glomerular disease such as focal segmental glomerulosclerosis and IgA
nephropathy (or nephritis)
Secondary glomerular disease such as diabetic nephropathy and lupus nephritis
3. Tubulointerstitial disease includes drug- and toxin-induced chronic tubulointerstitial
nephritis, and reflux nephropathy
Obstructive nephropathy, as exemplified by bilateral kidney stones and benign prostatic
hyperplasia of the prostate gland. Rarely, pinworms infecting the kidney can cause
obstructive nephropathy
 Other:
1. Genetic congenital disease such as polycystic kidney disease or 17q12
microdeletion syndrome.
2. Mesoamerican nephropathy, is "a new form of kidney disease that could be
called agricultural nephropathy". A high and so-far unexplained number of new
cases of CKD, referred to as the Mesoamerican nephropathy, has been noted
among male workers in Central America, mainly in sugar cane fields in the
lowlands of El Salvador and Nicaragua. Heat stress from long hours of piece-rate
work at high average temperatures of about 36 °C (96 °F) is suspected, as are
agricultural chemicals
Signs and symptoms
 CKD is initially without symptoms, and is usually detected on routine screening
blood work by either an increase in serum creatinine, or protein in the urine. As
the kidney function decreases:
 Blood pressure is increased due to fluid overload and production of vasoactive
hormones created by the kidney via the renin–angiotensin system, increasing the
risk of developing hypertension and heart failure
 Urea accumulates, leading to azotemia and ultimately uremia - symptoms
ranging from lethargy to pericarditis and encephalopathy. Due to its high
systemic concentration, urea is excreted in eccrine sweat at high concentrations
and crystallizes on skin as the sweat evaporates "uremic frost“
 Potassium accumulates in the blood - hyperkalemia with a range of symptoms
including malaise and potentially fatal cardiac arrhythmias. Hyperkalemia
usually does not develop until the glomerular filtration rate falls to less than 20–
25 ml/min/1.73 m2, at which point the kidneys have decreased ability to
excrete potassium. Hyperkalemia in CKD can be exacerbated by acidemia (which
leads to extracellular shift of potassium) and from lack of insulin
 Fluid overload symptoms may range from mild edema to life-threatening
pulmonary edema.
 Hyperphosphatemia results from poor phosphate elimination in the kidney.
Hyperphosphatemia contributes to increased cardiovascular risk by causing
vascular calcification. Circulating concentrations of fibroblast growth factor-
23 (FGF-23) increase progressively as the kidney capacity for phosphate
excretion declines which may contribute to left ventricular hypertrophy and
increased mortality in people with CKD
 Hypocalcemia results from 1,25 dihydroxyvitamin D3 deficiency (caused by
high FGF-23 and reduced kidney mass)[24] and resistance to the action of
parathyroid hormone. Osteocytes are responsible for the increased production
of FGF-23, which is a potent inhibitor of the enzyme 1-alpha-hydroxylase
(responsible for the conversion of 25-hydroxycholecalciferol into 1,25
dihydroxyvitamin D3). Later, this progresses to secondary
hyperparathyroidism, kidney osteodystrophy, and vascular calcification that
further impairs cardiac function. An extreme consequence is the occurrence
of the rare condition named calciphylaxis
 Changes in mineral and bone metabolism that may cause:
1) Abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or
vitamin D metabolism;
2) Abnormalities in bone turnover, mineralization, volume, linear growth, or
strength (kidney osteodystrophy); and
3) Vascular or other soft-tissue calcification. CKD-mineral and bone disorders
have been associated with poor outcomes
 Metabolic acidosis may result from decreased capacity to generate enough
ammonia from the cells of the proximal tubule. Acidemia affects the function
of enzymes and increases excitability of cardiac and neuronal membranes by
the promotion of hyperkalemia
 Anemia is common and is especially prevalent in those requiring haemodialysis.
It is multifactoral in cause, but includes increased inflammation, reduction in
erythropoietin, and hyperuricemia leading to bone marrow suppression
 In later stages, cachexia may develop, leading to unintentional weight loss,
muscle wasting, weakness and anorexia
 Sexual dysfunction is very common in both men and women with CKD. A
majority of men have a reduced sex drive, difficulty obtaining an erection, and
reaching orgasm, and the problems get worse with age. A majority of women
have trouble with sexual arousal, and painful menstruation and problems with
performing and enjoying sex are common
 People with CKD are more likely than the general population to develop
atherosclerosis with consequent cardiovascular disease, an effect that may be
at least partly mediated by uremic toxins. People with both CKD and
cardiovascular disease have significantly worse prognoses than those with only
cardiovascular disease
Diagnosis

 Diagnosis of CKD is largely based on history, examination and urine dipstick

combined with the measurement of the serum creatinine level (see above). It is
important to differentiate CKD from acute kidney injury (AKI) because AKI can be
reversible. One diagnostic clue that helps differentiate CKD from AKI is a gradual
rise in serum creatinine (over several months or years) as opposed to a sudden
increase in the serum creatinine (several days to weeks). In many people with
CKD, previous kidney disease or other underlying diseases are already known. A
significant number present with CKD of unknown cause
 Screening those who have neither symptoms nor risk factors for CKD is not
recommended. Those who should be screened include: those with hypertension or
history of cardiovascular disease, those with diabetes or marked obesity, those
aged > 60 years, subjects with African American ancestry, those with a history of
kidney disease in the past, and subjects who have relatives who had kidney
disease requiring dialysis
 Screening should include calculation of the estimated GFR (eGFR) from the
serum creatinine level, and measurement of urine albumin-to-creatinine ratio
(ACR) in a first-morning urine specimen, as well as a urine dipstick screen for
hematuria
 Kidney ultrasonography is useful for diagnostic and prognostic purposes in
chronic kidney disease. Whether the underlying pathologic change is
glomerular sclerosis, tubular atrophy, interstitial fibrosis or inflammation, the
result is often increased echogenicity of the cortex
 The echogenicity of the kidney should be related to the echogenicity of either
the liver or the spleen. Moreover, decreased kidney size and cortical thinning
are also often seen and especially when disease progresses. However, kidney
size correlates to height, and short persons tend to have small kidneys; thus,
kidney size as the only parameter is not reliable
 Additional tests may include nuclear medicine MAG3 scan to confirm blood
flow and establish the differential function between the two kidneys.
Dimercaptosuccinic acid (DMSA) scans are also used in kidney imaging; with
both MAG3 and DMSA being used chelated with the radioactive element
technetium-99
 Renal biopsy
Uremic frost
GFR Calculator
Staging of chronic kidney disease-
National Kidney Foundation
Management

 Apart from controlling other risk factors, the goal of therapy is to slow down or
halt the progression of CKD. Control of blood pressure and treatment of the
original disease are the broad principles of management
 Blood pressure - Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin
II receptor antagonists (ARBs) are recommended as first-line agents since they
have been found to slow the decline of kidney function, relative to a more rapid
decline in those not on one of these agents
 They have also been found to reduce the risk of major cardiovascular events such
as myocardial infarction, stroke, heart failure, and death from cardiovascular
disease when compared to placebo in individuals with CKD
 ACEIs may be superior to ARBs for protection against progression to kidney failure
and death from any cause in those with CKD. Aggressive blood pressure lowering
decreases people's risk of death
 Aggressive treatment of high blood lipids is recommended
 A low-protein, low-salt diet may result in slower progression of CKD and
reduction in proteinuria as well as controlling symptoms of advanced CKD to
delay dialysis start. A tailored low-protein diet, designed for low acidity, may
help prevent damage to kidneys for people with CKD
 Anemia - A target hemoglobin level of 9–12 g/dL is recommended, raising
hemoglobin levels to the normal range has not been found to be of benefit:
Guidelines recommend treatment with parenteral iron prior to treatment with
erythropoietin.
Replacement of erythropoietin is often necessary in people with advanced disease.
It is unclear if androgens improve anemia
 Calcitriol is recommended for vitamin D deficiency and control of metabolic
bone disease
 Phosphate binders are used to control the serum phosphate levels, which are
usually elevated in advanced chronic kidney disease
 Phosphodiesterase-5 inhibitors and zinc may improve sexual dysfunction in
men
 Guidelines for referral to a nephrologist vary between countries. Most agree
that nephrology referral is required by Stage 4 CKD (when eGFR/1.73m2 is
less than 30 ml/min; or decreasing by more than 3 ml/min/year)
 It may also be useful at an earlier stage (e.g. CKD3) when urine albumin-to-
creatinine ratio is more than 30 mg/mmol, when blood pressure is difficult to
control, or when hematuria or other findings suggest either a primarily
glomerular disorder or secondary disease amenable to specific treatment
 Other benefits of early nephrology referral include proper education
regarding options for kidney replacement therapy as well as pre-emptive
transplantation, and timely workup and placement of an arteriovenous fistula
in those people with chronic kidney disease opting for future hemodialysis
 Renal replacement therapy - At stage 5 CKD, kidney replacement therapy is
usually required, in the form of either dialysis or a kidney transplant
 In CKD numerous uremic toxins accumulate in the blood. Even when ESKD
(largely synonymous with CKD5) is treated with dialysis, the toxin levels do
not go back to normal as dialysis is not that efficient. Similarly, after a kidney
transplant, the levels may not go back to normal as the transplanted kidney
may not work 100%. If it does, the creatinine level is often normal
 The toxins show various cytotoxic activities in the serum and have different
molecular weights, and some of them are bound to other proteins, primarily
to albumin. Uremic toxins are classified into three groups as small water-
soluble solutes, middle molecular-weight solutes, and protein-bound solutes
 Hemodialysis with high-flux dialysis membrane, long or frequent treatment,
and increased blood/dialysate flow has improved removal of water-soluble
small molecular weight uremic toxins. Middle molecular weight molecules are
removed more effectively with hemodialysis using a high-flux membrane,
hemodiafiltration and hemofiltration. However, conventional dialysis
treatment is limited in its ability to remove protein-bound uremic toxins
Types of dialysis
 There are three different types of dialysis;
1.Hemodialysis - is the most common type of dialysis. This process uses an artificial
kidney (hemodialyzer) to remove waste and extra fluid from the blood. The blood is
removed from the body and filtered through the artificial kidney. The filtered blood is
then returned to the body with the help of a dialysis machine. The three types of
entrance points are:
Arteriovenous (AV) fistula. This type connects an artery and a vein. It’s the
preferred option.
AV graft. This type is a looped tube.
Vascular access catheter. This may be inserted into the large vein in your neck
Both the AV fistula and AV graft are designed for long-term dialysis treatments.
People who receive AV fistulas are healed and ready to begin hemodialysis two to
three months after their surgery. People who receive AV grafts are ready in two to
three weeks. Catheters are designed for short-term or temporary use
Hemodialysis treatments usually last three to five hours and are performed three
times per week. However, hemodialysis treatment can also be completed in shorter,
more frequent sessions
2. Peritoneal dialysis involves surgery to implant a peritoneal dialysis (PD)
catheter into the abdomen. The catheter helps filter your blood through the
peritoneum, a membrane in the abdomen. During treatment, a special fluid
called dialysate flows into the peritoneum. The dialysate absorbs waste. Once
the dialysate draws waste out of the bloodstream, it’s drained from the abdomen
This process takes a few hours and needs to be repeated four to six times per
day. There are numerous different types of peritoneal dialysis. The main ones
are:
Continuous ambulatory peritoneal dialysis (CAPD). In CAPD, the abdomen is
filled and drained multiple times each day. This method doesn’t require a
machine and must be performed while awake
Continuous cycling peritoneal dialysis (CCPD). CCPD uses a machine to cycle
the fluid in and out of the abdomen
Intermittent peritoneal dialysis (IPD). This treatment is usually performed in
the hospital, though it may be performed at home. It uses the same machine
as CCPD, but the process takes longer
3. Continuous renal replacement therapy (CRRT) - This therapy is used primarily
in the intensive care unit for people with acute kidney failure. It’s also known as
hemofiltration. A machine passes the blood through tubing. A filter then removes
waste products and water. The blood is returned to the body, along with
replacement fluid. This procedure is performed 12 to 24 hours a day, generally
every day
Prognosis
 CKD increases the risk of cardiovascular disease, and people with CKD often
have other risk factors for heart disease, such as high blood lipids. The most
common cause of death in people with CKD is cardiovascular disease rather
than kidney failure
 Chronic kidney disease results in worse all-cause mortality (the overall death
rate) which increases as kidney function decreases. The leading cause of
death in chronic kidney disease is cardiovascular disease, regardless of
whether there is progression to stage 5
 While kidney replacement therapies can maintain people indefinitely and
prolong life, the quality of life is negatively affected. Kidney transplantation
increases the survival of people with stage 5 CKD when compared to other
options; however, it is associated with an increased short-term mortality due
to complications of the surgery. Transplantation aside, high-intensity home
hemodialysis appears to be associated with improved survival and a greater
quality of life, when compared to the conventional three-times-a-week
hemodialysis and peritoneal dialysis
 People with ESKD are at increased overall risk for cancer. This risk is
particularly high in younger people and gradually diminishes with age. Medical
specialty professional organizations recommend that physicians do not
perform routine cancer screening in people with limited life expectancies due
to ESKD because evidence does not show that such tests lead to improved
outcomes
Epidemiology

 About one in ten people have chronic kidney disease. In Canada 1.9 to 2.3
million people were estimated to have CKD in 2008. CKD affected an
estimated 16.8% of U.S. adults aged 20 years and older in the period from
1999 to 2004. In 2007 8.8% of the population of Great Britain and Northern
Ireland had symptomatic CKD
 Chronic kidney disease was the cause of 956,000 deaths globally in 2013, up
from 409,000 deaths in 1990
 African, Hispanics, and South Asians, particularly those from Pakistan, Sri
Lanka, Bangladesh, and India, are at high risk of developing CKD. Africans are
at greater risk due to the number of people affected with hypertension
among them
The end

 Thank you all