Chronic kidney disease

Overview
Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss of renal function over a period of months or years through five stages. Each stage is a progression through an abnormally low and progressively worse glomerular filtration rate, which is usually determined indirectly by the creatinine level in blood serum.

Stage 1 CKD is mildly diminished renal function, with few overt symptoms.

Stage 5 CKD is a severe illness and requires some form of renal replacement therapy (dialysis or renal transplant). Stage 5 CKD is also called end-stage renal disease (ESRD). ESRD is how the US Centers for Medicare and Medicaid Services and US federal legislation reference this stage of illness. Stage 5 CKD is also known as chronic kidney failure (CKF) or chronic renal failure (CRF).

Signs and symptoms
Initially it is without specific symptoms and can only be detected as 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 leading to hypertension and congestive heart failure
 * Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy)
 * Potassium accumulates in the blood (known as hyperkalemia with symptoms ranging from malaise to fatal cardiac arrhythmias)
 * Erythropoietin synthesis is decreased (leading to anemia causing fatigue)
 * Fluid volume overload - symptoms may range from mild edema to life-threatening pulmonary edema
 * Hyperphosphatemia - due to reduced phosphate excretion, associated with hypocalcemia (due to vitamin D3 deficiency).
 * Later this progresses to tertiary hyperparathyroidism, with hypercalcaemia, renal osteodystrophy and vascular calcification
 * Metabolic acidosis, due to decreased generation of bicarbonate by the kidney, is one of the most life threatening consequences of renal failure. Causes altered enzyme activity by excess acid acting on enzymes and also depression of the CNS by excess acid interfering with neuronal excitability.

People with CKD suffer from accelerated atherosclerosis and have higher incidence of cardiovascular disease, with a poorer prognosis.

Diagnosis
In many CKD patients, previous renal disease or other underlying diseases are already known. A small number presents with CKD of unknown cause. In these patients, a cause is occasionally identified retrospectively.

It is important to differentiate CKD from acute renal failure (ARF) because ARF can be reversible. Abdominal ultrasound is commonly performed, in which the size of the kidneys are measured. Kidneys with CKD are usually smaller (< 9 cm) than normal kidneys with notable exceptions such as in diabetic nephropathy and polycystic kidney disease. Another diagnostic clue that helps differentiate CKD and ARF 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). If these levels are unavailable (because the patient has been well and has had no blood tests) it is occasionally necessary to treat a patient briefly as having ARF until it has been established that the renal impairment is irreversible.

Numerous uremic toxins (see link) are accumulating in chronic renal failure patients treated with standard dialysis. These toxins show various cytotoxic activities in the serum, have different molecular weights and some of them are bound to other proteins, primarily to albumin. Such toxic protein bound substances are receiving the attention of scientists who are interested in improving the standard chronic dialysis procedures used today.

Stages of Chronic Kidney Disease
All individuals with a Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence of kidney damage. The rationale for including these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the adult level of normal kidney function, which may be associated with a number of complications.

All individuals with kidney damage are classified as having chronic kidney disease, irrespective of the level of GFR. The rationale for including individuals with GFR 60 mL/min/1.73 m2 is that GFR may be sustained at normal or increased levels despite substantial kidney damage and that patients with kidney damage are at increased risk of the two major outcomes of chronic kidney disease: loss of kidney function and development of cardiovascular disease.

Stage 1 CKD
Slightly diminished function; Kidney damage with normal or increased GFR (>90 mL/min/1.73 m2). Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.

Stage 2 CKD
Mild reduction in GFR (60-89 mL/min/1.73 m2) with kidney damage. Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.

Stage 3 CKD
Moderate reduction in GFR (30-59 mL/min/1.73 m2)

Stage 4 CKD
Severe reduction in GFR (15-29 mL/min/1.73 m2)

Stage 5 CKD
Established kidney failure (GFR <15 mL/min/1.73 m2, or permanent renal replacement therapy (RRT)

Causes
The most common causes of CKD are diabetic nephropathy, hypertension, and glomerulonephritis. Together, these cause approximately 75% of all adult cases. Certain geographic areas have a high incidence of HIV nephropathy.

Historically, kidney disease has been classified according to the part of the renal anatomy that is involved, as:
 * Vascular, includes large vessel disease such as bilateral renal artery stenosis and small vessel disease such as ischemic nephropathy, hemolytic-uremic syndrome and vasculitis
 * Glomerular, comprising a diverse group and subclassified into
 * Primary Glomerular disease such as focal segmental glomerulosclerosis and IgA nephritis
 * Secondary Glomerular disease such as diabetic nephropathy and lupus nephritis
 * Tubulointerstitial including polycystic kidney disease, drug and toxin-induced chronic tubulointerstitial nephritis and reflux nephropathy
 * Obstructive such as with bilateral kidney stones and diseases of the prostate

Treatment
The goal of therapy is to slow down or halt the otherwise relentless progression of CKD to stage 5. Control of blood pressure and treatment of the original disease, whenever feasible, are the broad principles of management. Generally, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as they have been found to slow the progression of CKD to stage 5.

Replacement of erythropoietin and vitamin D3, two hormones processed by the kidney, is usually necessary, as is calcium. Phosphate binders are used to control the serum phosphate levels, which are usually elevated in chronic kidney disease.

When one reaches stage 5 CKD, renal replacement therapy is required, in the form of either dialysis or a transplant.

Prognosis
The prognosis of patients with chronic kidney disease is guarded as epidemiological data has shown that all cause mortality (the overall death rate) increases as kidney function decreases. The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.

While renal replacement therapies can maintain patients indefinitely and prolong life, the quality of life is severely affected. Renal transplantation increases the survival of patients with stage 5 CKD significantly when compared to other therapeutic 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 thrice weekly hemodialysis and peritoneal dialysis.