hronic kidney disease (CKD), also known as chronic renal disease (CRD), is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and might include feelinggenerally unwell and experiencing a reduced appetite. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic kidney disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease, anemia or pericarditis. It is differentiated from acute kidney disease in that the reduction in kidney function must be present for over 3 months.

Chronic kidney disease is identified by a blood test for creatinine. Higher levels of creatinine indicate a lower glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products. Creatinine levels may be normal in the early stages of CKD, and the condition is discovered if urinalysis (testing of a urine sample) shows that the kidney is allowing the loss of protein or red blood cells into the urine. To fully investigate the underlying cause of kidney damage, various forms of medical imaging, blood tests and often renal biopsy (removing a small sample of kidney tissue) are employed to find out if there is a reversible cause for the kidney malfunction. Recent professional guidelines classify the severity of chronic kidney disease in five stages, with stage 1 being the mildest and usually causing few symptoms and stage 5 being a severe illness with poor life expectancy if untreated. Stage 5 CKD is often called end stage renal disease (ESRD),end stage renal failure (ESRF), or end-stage kidney disease (ESKD) and is synonymous with the now outdated terms chronic kidney failure (CKF) or chronic renal failure (CRF).

There is no specific treatment unequivocally shown to slow the worsening of chronic kidney disease. If there is an underlying cause to CKD, such as vasculitis, this may be treated directly to slow the damage. In more advanced stages, treatments may be required for anemia and bone disease. Severe CKD requires renal replacement therapy, which may involve a form of dialysis, but ideally constitutes a kidney transplant.

Signs and symptoms
CKD is initially without specific symptoms and is generally only 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 created by the kidney via the RAS (renin-angiotensin system), increasing one's risk of developing hypertension and/or suffering from congestive heart failure
• Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Urea is excreted by sweating and crystallizes on skin ("uremic frost").
• Potassium accumulates in the blood (known as hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias)
• Erythropoietin synthesis is decreased
• Fluid volume overload — symptoms may range from mild edema to life-threatening pulmonary edema
• Hyperphosphatemia — due to reduced phosphate excretion
• Hypocalcemia — due to 1,25 dihydroxyvitamin D₃ deficiency. The 1,25 dihydroxyvitamin D₃ deficiency is due to stimulation of fibroblast growth factor-23.
  • Later this progresses to secondary hyperparathyroidism, renal osteodystrophy and vascular calcification that further impairs cardiac function.
• Metabolic acidosis, due to accumulation of sulfates, phosphates, uric acid etc. This may cause altered enzyme activity by excess acid acting on enzymes and also increased excitability of cardiac and neuronal membranes by the promotion of hyperkalemia due to excess acid (acidemia)
• Iron deficiency anemia, which increases in prevalence as kidney function decreases, and is especially prevalent in those requiring haemodialysis. It is multifactoral in cause but includes increased inflammation, reduction in Erythropoietin, hyperuricemia leading to bone marrow suppression.

People with chronic kidney disease suffer from accelerated atherosclerosis and are more likely to develop cardiovascular disease than the general population. Patients afflicted with chronic kidney disease and cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter.

Sexual dysfunction is very common in both men and women with chronic kidney disease. 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 periods and problems with performing and enjoying sex are common.

Diagnosis

In many CKD patients, previous renal disease or other underlying diseases are already known. A small number present 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, in which the size of the kidneys is measured, is commonly performed. 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 from 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.

Additional tests may include nuclear medicine MAG3 scan to confirm blood flows and establish the differential function between the two kidneys. DMSA scans are also used in renal imaging; with both MAG3 and DMSA being used chelated with the radioactive element Technetium-99.

In chronic renal failure treated with standard dialysis, numerous uremic toxins accumulate. 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.

Treatment
The presence of chronic kidney disease confers a markedly increased risk of cardiovascular disease, and people with CKD often have other risk factors for heart disease, such as hyperlipidemia. The most common cause of death in people with CKD is therefore cardiovascular disease rather than renal failure. Aggressive treatment of hyperlipidemia is warranted.

Apart from controlling other risk factors, the goal of therapy is to slow down or halt the 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. Although the use of ACE inhibitors and ARBs represents the current standard of care for patients with CKD, patients progressively lose kidney function while on these medications, as seen in the IDNT and RENAAL studies, which reported a decrease over time in estimated glomerular filtration rate (an accurate measure of CKD progression, as detailed in the K/DOQI guidelines) in patients treated by these conventional methods.

Currently, several compounds are in development for CKD. These include, but are not limited to, bardoxolone methyl, olmesartan medoxomil, sulodexide, and avosentan.

Replacement of erythropoietin and calcitriol, two hormones processed by the kidney, is often necessary in people with advanced disease. Guidelines recommend treatment with parenteral iron prior to treatment with erythropoietin. A target hemoglobin level of 9-12 g/dL is recommended. Phosphate binders are also used to control the serum phosphate levels, which are usually elevated in advanced chronic kidney disease. Zerenex(TM), a very promising new drug developed by Keryx Biopharma will have the ability to treat both elevated serum phosphate levels and anemia in CKD patients likely reducing or eliminating the need for other drugs i.e. IV iron and ESA's.

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

The normalization of hemoglobin has not been found to be of any benefit to the CKD but does significantly improve the patient's quality of life in reducing symptoms such as fatigue and can improve other co-morbidities that might be present, such as chronic heart failure (CHF). Although the evidence for them is limited, phosphodiesterase-5 inhibitors and zinc show potential for helping men with sexual dysfunction.