CHRONIC RENAL FAILURE

Chronic renal failure (CRF) refers to an irreversible deterioration in renal function which classically develops over a period of years. Initially, it is manifest only as a biochemical abnormality (azotemia). Eventually, loss of the excretory, metabolic and endocrine functions of the kidney leads to the development of the clinical symptoms and signs of renal failure, which are referred to as uraemia. When death is likely without renal replacement therapy, it is called end-stage renal failure (ESRF).

Patients often have bilateral small kidneys at presentation, and in such a situation renal biopsy is usually inadvisable because of the difficulty in making a histological diagnosis in severely damaged kidneys and the fact that treatment is unlikely to improve renal function significantly.

Clinical assessment Renal failure may present as a raised blood urea and creatinine found during routine examination, in patients presenting with hypertension, proteinuria or anaemia. Thereafter, due to the widespread effects of renal failure, symptoms and signs may develop that are related to almost every body system. Patients may present with complaints which are not obviously renal in origin, such as tiredness or breathlessness.

There may be unusually deep respiration related to metabolic acidosis (Kussmaul's respiration), anorexia and nausea. Later, hiccoughs, pruritus, vomiting, muscular twitching, fits, drowsiness and coma ensue.

Acidosis Declining renal function is associated with metabolic acidosis, which is often asymptomatic. Sustained acidosis aggravates metabolic bone disease. Acidosis may also contribute to reduced renal function and increased tissue catabolism.

Hematological complication Anaemia is common; it usually correlates with the severity of renal failure. Several mechanisms are implicated, including: relative deficiency of erythropoietin diminished erythropoiesis due to toxic effects of uraemia on marrow precursor cells reduced red cell survival reduced dietary intake and absorption of iron and other haematinics. Platelet function is impaired and bleeding time prolonged.(increased bleeding tendency).

Cardiovascular disease and lipids Atherosclerosis is common and may be accelerated by hypertension. Pericarditis is common in untreated or inadequately treated ESRF. It may lead to pericardial tamponade and, later, constrictive pericarditis. Hypertension develops in approximately 80% of patients with CRF. this is caused by sodium retention. Chronically diseased kidneys also tend to hypersecrete renin, leading to high circulating concentrations of renin, angiotensin II and aldosterone. Hypercholesterolaemia is almost universal in patients with significant proteinuria, and increased triglyceride levels are also common in patients with CRF.

Infection Cellular and humoral immunity are impaired, with increased susceptibility to infection.

Renal osteodystrophy This metabolic bone disease which accompanies CRF consists of a mixture of osteomalacia, hyperparathyroid bone disease (osteitis fibrosa), osteoporosis and osteosclerosis. Osteomalacia results from diminished activity of the renal 1α-hydroxylase enzyme, with failure to convert cholecalciferol to its active metabolite, 1,25-dihydroxycholecalciferol(active vitamin D).

Myopathy Generalised myopathy is due to a combination of poor nutrition, hyperparathyroidism, vitamin D deficiency and disorders of electrolyte metabolism.

Neuropathy Neuropathy results from demyelination of nerve fibres, with the longer fibres being involved at an earlier stage. Sensory neuropathy may cause paraesthesiae. Motor neuropathy may present as foot drop. Uraemic autonomic neuropathy may cause delayed gastric emptying, diarrhoea and postural hypotension.

Gastrointestinal Gastrointestinal manifestations are common at low GFRs, including anorexia followed by nausea, and vomiting is commonly seen. There is a higher incidence of peptic ulcer disease in uraemic patients.

Investigations and management

At presentation the nature of the underlying disease should be determined, if possible, by history, examination, testing of biochemistry, immunology, radiology and biopsy

Control of blood pressure In many types of renal disease, (e.g. diabetic nephropathy, & other diseases with heavy proteinuria ), control of blood pressure may retard deterioration of GFR. ACE inhibitors have been shown to be more effective at retarding the progression of renal failure than other therapies which lower systemic blood pressure to a similar degree. This may be because they reduce glomerular perfusion pressure leading to reduction in proteinuria which is a good prognostic sign. Angiotensin II receptor antagonists and certain non-dihydropyridine calcium antagonists also reduce glomerular perfusion pressure.

Hyperkalaemia Hyperkalaemia often responds to dietary restriction of potassium intake. Drugs which cause potassium retention should be stopped. Occasionally it may be necessary to prescribe ion-exchange resins to remove potassium in the gastrointestinal tract. Sometimes patients present with severe hyperkalaemia which is a medical emergency.

Acidosis Correction of acidosis helps to correct hyperkalaemia and may also decrease muscle catabolism. Sodium bicarbonate supplements are often effective (4.8 g of Na+ and HCO3- daily), but may cause oedema and hypertension. Calcium carbonate (used as a calcium supplement and phosphate binder), has a beneficial effect on acidosis.

Renal osteodystrophy Hypocalcaemia is corrected by giving 1α-hydroxylated synthetic analogues of vitamin D, which also decreases PTH. Hyperphosphataemia is controlled by dietary restriction of foods with high phosphate content (milk, cheese, eggs) and the use of phosphate-binding drugs (e.g. calcium carbonate and aluminium hydroxide) administered with food. Secondary hyperparathyroidism is usually prevented or controlled by these measures but, in severe bone disease with autonomous parathyroid function, parathyroidectomy may become necessary.

anaemia Recombinant human erythropoietin is effective in correcting the anaemia of CRF. Erythropoietin is less effective in the presence of iron deficiency, or active inflammation and these factors should be corrected before treatment (e.g. Iron supplementation).