ACUTE KIDNEY FAILURE

Specific causes of acute kidney failure

▪   Prerenal failure and acute tubular necrosis
▪   Vascular causes of acute kidney failure
▪   Nephrotoxic causes of acute kidney failure
▪   Glomerulonephritic and vasculitic causes of
    acute kidney failure
▪   Interstitial nephritis as a cause of acute
    kidney failure
▪   'Haematological' causes of acute kidney failure
▪   Hepatokidney Syndrome
▪   Tropical

'Haematological' causes of acute kidney failure

Haemolytic uraemic syndrome and idiopathic postpartum kidney failure

The haemolytic uraemic syndrome (HUS) is a condition, or group of conditions, in which acute kidney failure, characterized on biopsy by thrombosis and necrosis of intrakidney vessels, occurs together with thrombocytopenia, haemolytic anaemia, and red cell fragmentation. A similar picture developing immediately (or up to several weeks) after an entirely uneventful pregnancy and delivery is termed 'idiopathic postpartum acute kidney failure'.

Myeloma

Acute kidney failure complicates about 7 per cent of cases of myeloma, often being the presenting feature, and subacute progressive kidney failure is even commoner, affecting 14 to 61 per cent of cases. The cause of kidney failure is often multifactorial, with varying contribution from the reversible factors of dehydration, infection, hypercalcaemia, and hyperuricaemia, and with kidney damage caused by free immunoglobulin light chains. The reason why some patients with myeloma develop kidney failure and others do not remains a mystery. There has been much speculation as to whether variation in the isoelectric point of light chains, and hence their capacity for reabsorption by the kidney tubules, might be responsible. However, individual patients with light chains of very similar physicochemical properties can present totally different clinical pictures, varying from no perceptible renal involvement to irreversible kidney failure.

In a patient with acute kidney failure, a history of bone pain, the findings of clumping of erythrocytes on the blood film, or of gross and unexpected elevation of the erythrocyte sedimentation rate, are clues that myeloma might be the underlying diagnosis. Such clues may be absent when excess production of monoclonal light chains is the predominant problem, hence all patients with unexplained acute or subacute kidney failure should undergo investigation both of serum for a monoclonal immunoglobulin component (with immunoparesis) and of their urine (if available) for free _ or l light chains.

The kidney biopsy appearances are of tubulointerstitial nephritis, with fractured casts in the tubular lumina, tubular atrophy, interstitial oedema/fibrosis, and an interstitial infiltrate that may contain multinucleate giant cells. However, the definitive test for myeloma is a bone marrow biopsy for immunochemical analysis of the plasma-cell population, and this should be performed whenever myeloma is a likely or possible cause of acute kidney failure.

The first priority in management is to deal promptly with those factors that can be reversed— dehydration, infection, hypercalcaemia, and hyperuricaemia. Volume resuscitation should be given, along with broad-spectrum antimicrobials (after appropriate cultures have been taken) if there is any suspicion of infection. After the intravascular volume has been restored, then (assuming adequate urine output) hypercalcaemia can be treated rapidly and effectively using a two-pronged approach: a diuresis provoked by infusion of 0.9 per cent saline (1 litre every 4–6 h) and furosemide (40 mg as necessary), and intravenous bisphosphonate (for example, disodium pamidronate, 15–60 mg as a single dose, maximum of 90 mg over 2–4 days). It has been suggested that alkalinization of the urine using intravenous sodium bicarbonate may be advantageous in promoting light-chain excretion, but it is unclear whether this is better than adequate rehydration with saline alone.

If there is a clear precipitant for the decline in kidney function, then the prospects for kidney recovery in patients with myeloma are good; if not, then the kidney outlook is less favourable. Although some report that aggressive treatment with cytotoxic agents and/or plasmapheresis can restore kidney function in such cases, this is not everyone's experience, and renal recovery seems to be the exception rather than the rule.

The prognosis for patients with myeloma and established kidney failure requiring dialysis is poor: 50 per cent 1-year survival, 30 per cent at 2 years. However, many patients will have few symptoms from their myeloma, excepting kidney failure, and these patients should certainly be offered the opportunity of kidney replacement therapy. In those with considerable extrarenal manifestations the situation is much more difficult, and it may not be appropriate or kind in such circumstances to offer aggressive haematological regimens, producing considerable side-effects, and/or dialysis. The decisions to be made are rarely straightforward: they will substantially depend on an assessment of the overall burden to the patient of their disease and a realistic appraisal of what benefits treatment might produce.