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 osteodystrophyThis 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 biopsyControl 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.