Myeloma Cast Nephropathy and Paraprotein Kidney Disease
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Direct answer
Myeloma cast nephropathy is acute kidney injury in multiple myeloma, caused by free light chains that precipitate with Tamm-Horsfall protein to form obstructive tubular casts. The urinary light chain, called Bence Jones protein, is typically missed by a dipstick and needs electrophoresis or immunofixation to detect. Volume expansion, correction of hypercalcaemia and rapid reduction of the light chains are the measures that protect the kidney.
What you must remember
- Light chain cast nephropathy: the commonest renal lesion in myeloma, with obstructive casts in the distal tubule and a giant cell reaction around them.
- Precipitants: dehydration, hypercalcaemia, NSAIDs, iodinated contrast and high-dose chemotherapy all worsen the injury.
- Bence Jones proteinuria: free light chains in urine, detected by urine electrophoresis or immunofixation rather than by the dipstick.
- Serum free light chains: an abnormal kappa to lambda ratio supports a clonal plasma cell disorder and helps follow response.
- CRAB features: hypercalcaemia, renal failure, anaemia and bone lesions define symptomatic myeloma.
- Fanconi-type tubulopathy: light chains can damage the proximal tubule, causing glycosuria, phosphaturia and renal tubular acidosis.
- Light chain deposition disease: monoclonal light chains deposit along basement membranes, causing nephrotic-range proteinuria and nodular glomerulosclerosis.
- AL amyloidosis: Congo red positive deposits with apple-green birefringence, typically presenting with nephrotic syndrome.
Where the examiner tries to catch you
Paraprotein questions often test the test that will be missed and the drug that makes the kidney worse.
- Trap: using a dipstick to screen for Bence Jones proteinuria. Correct: the dipstick detects albumin poorly for light chains, so electrophoresis, immunofixation or a free light chain assay is required.
- Trap: treating light chain cast nephropathy with diuretics. Correct: diuretics worsen volume depletion and promote cast formation, so intravenous volume expansion is preferred.
- Trap: giving NSAIDs or iodinated contrast to a patient with myeloma and renal impairment. Correct: these agents add to cast injury, and hydration and calcium control are the priorities.
Frequently asked questions
Why does myeloma cause acute kidney injury?
Myeloma causes acute kidney injury mainly through light chain cast nephropathy, in which free light chains precipitate with Tamm-Horsfall protein and block the distal tubule. Dehydration, hypercalcaemia and nephrotoxic drugs act as precipitants, and correcting them is the first priority.
Why is a dipstick unreliable for Bence Jones proteinuria?
Dipstick protein tests detect albumin well but detect free light chains poorly, so Bence Jones proteinuria is often missed. Urine electrophoresis, immunofixation or a serum free light chain assay is needed to identify a monoclonal light chain in suspected myeloma.
What is the first step in managing myeloma cast nephropathy?
The first step is intravenous volume expansion to maintain urine flow, together with correction of hypercalcaemia and withdrawal of nephrotoxic drugs. Loop diuretics are avoided early, because they reduce volume and promote cast formation in the tubules.
What is light chain deposition disease?
Light chain deposition disease is a paraprotein kidney disease in which monoclonal light chains deposit along glomerular and tubular basement membranes. It typically causes nephrotic-range proteinuria and nodular glomerulosclerosis, and it differs from cast nephropathy in both mechanism and histology.
How does AL amyloidosis appear on kidney biopsy?
AL amyloidosis shows Congo red positive deposits in the mesangium and capillary walls, which give apple-green birefringence under polarised light. It typically presents with nephrotic syndrome, and light chain typing of the deposits confirms the diagnosis.