haematologic renal disease
Haematological malignancies injure the kidney through distinct mechanisms — light chain cast nephropathy (myeloma kidney), amyloid deposition (AL), direct tubular toxicity, and metabolic complications (TLS, hypercalcaemia). The dipstick-negative proteinuria of cast nephropathy vs the dipstick-positive albuminuria of amyloidosis is the single most useful bedside distinction. Aggressive volume expansion and urgent bortezomib-based chemotherapy are the cornerstones of renal rescue in paraprotein-related AKI.
light chain cast nephropathy (myeloma kidney)
The most common cause of AKI in multiple myeloma. Free light chains (FLCs) precipitate with Tamm-Horsfall protein in the distal tubule → intratubular obstruction and direct tubular toxicity.
Clues:
- AKI with dipstick-negative or trace proteinuria despite high quantitative protein on UPCR — dipstick detects albumin, not light chains (overflow proteinuria)
- Markedly elevated serum FLC ratio
- Precipitants: dehydration, NSAIDs, contrast, hypercalcaemia — volume depletion is the common thread (loop diuretics contribute primarily through volume depletion)
Light chain toxicity to proximal tubule can cause acquired Fanconi syndrome — glucosuria with normal blood glucose, hypophosphataemia, type II RTA; suspect in non-diabetic glycosuria with unexplained metabolic acidosis and a paraprotein.
Management:
- Aggressive IV crystalloid — high urine flow dilutes intratubular FLCs and reduces precipitation
- Avoid nephrotoxins (NSAIDs, aminoglycosides, contrast if avoidable)
- Treat hypercalcaemia if present (IV saline + denosumab or zoledronic acid — use denosumab if eGFR <30 mL/min)
- Urgent bortezomib-based regimen + high-dose dexamethasone — started together, not sequentially. Bortezomib needs no renal dose adjustment. Rapid FLC reduction (>50% within 21 days) is the strongest predictor of renal recovery
- High-cutoff HD membranes (Theralite) — both randomised trials (MYRE (JAMA 2017), EuLITE) failed primary endpoints; not standard of care. Chemotherapy drives FLC reduction, not mechanical removal
A “negative” urine dipstick does not exclude significant proteinuria. In myeloma, the protein is light chains (not albumin). Always request UPCR or UPEP when paraprotein-related kidney disease is suspected.
amyloidosis
AL amyloidosis
Misfolded monoclonal light chains deposit as amyloid fibrils in glomeruli, vessels, and interstitium.
- Renal presentation: nephrotic-range proteinuria (dipstick-positive — this is albuminuria), oedema, progressive CKD. Kidneys may be normal or enlarged on imaging.
- Systemic clues: restrictive cardiomyopathy (see cardiac amyloidosis), hepatomegaly, macroglossia, periorbital purpura, autonomic neuropathy
- Diagnosis: tissue biopsy — Congo Red stain with apple-green birefringence under polarised light. Abdominal fat pad aspirate is ~80% sensitive; renal biopsy if fat pad negative and suspicion persists. Mass spectrometry (or immunogold EM) is required to confirm the amyloid subtype (AL vs AA vs ATTR) before committing to chemotherapy — Congo Red alone confirms amyloid but does not type it.
- Management: daratumumab (Darzalex) + bortezomib + cyclophosphamide + dexamethasone (Dara-CyBorD) — standard of care first-line. ANDROMEDA final analysis (2026) showed OS benefit (HR 0.62) in addition to higher renal and cardiac response rates.
Cast nephropathy = dipstick-negative, AKI, high FLCs. AL amyloidosis = dipstick-positive nephrotic syndrome, insidious CKD, lower FLC burden. Both arise from clonal plasma cell disorders but require different urgency and approach.
AA amyloidosis
Serum amyloid A deposits as amyloid fibrils during chronic inflammation (RA, chronic osteomyelitis, TB, bronchiectasis, Crohn disease, FMF). Presents with nephrotic syndrome ± progressive CKD — identical renal presentation to AL. Confirm AA subtype on mass spectrometry. Management: treat the underlying inflammatory condition (colchicine for FMF, biologics for RA/Crohn).
monoclonal immunoglobulin deposition disease (MIDD)
Light chain deposition disease (LCDD, usually kappa) is the most common form. Congo Red–negative linear light-chain deposits along tubular and glomerular basement membranes → nodular glomerulosclerosis. Kidney involved in ~96% of cases. Distinguish from AL (Congo Red–positive) — management is clone-directed therapy as for MGRS.
hyperviscosity syndrome — renal effects
Most commonly Waldenström macroglobulinaemia (IgM paraprotein). IgM macroglobulin increases serum viscosity → decreased renal perfusion → prerenal AKI. Systemic features: mucosal bleeding, blurred vision, confusion. Management: urgent plasmapheresis — do not transfuse RBCs before pheresis (further increases viscosity).
tumour lysis syndrome — renal mechanisms
See tumour lysis syndrome for full management. Two mechanisms of renal injury:
- Calcium-phosphate precipitation — hyperphosphataemia + calcium → CaPO₄ deposits in renal tubules → now the dominant cause of TLS-associated AKI. Use sevelamer for phosphate binding — avoid calcium-containing binders (calcium carbonate worsens CaPO₄ precipitation)
- Uric acid nephropathy — uric acid crystallises in tubules (acidic urine, high concentration) → intratubular obstruction. Rasburicase has made this less common; note rasburicase requires G6PD testing before administration (haemolytic anaemia risk) and is often formulary-restricted in Canadian centres
Do not replete calcium aggressively in TLS — promotes CaPO₄ precipitation in the kidney. Treat only if symptomatic (tetany, arrhythmia).
hypercalcaemia of malignancy — renal effects
Mechanisms: afferent arteriolar vasoconstriction → reduced GFR; nephrogenic DI (Ca²⁺ downregulates aquaporin-2) → polyuria → volume depletion → worsens prerenal AKI.
Causes: PTHrP (solid tumours), osteolytic (myeloma bone disease), calcitriol excess (lymphoma), PTH (parathyroid carcinoma — rare).
Management: IV normal saline (aggressive volume expansion) → denosumab preferred in renal impairment (zoledronic acid contraindicated if eGFR <30 mL/min). Calcitonin for rapid short-term reduction. See multiple myeloma for myeloma-specific management.
monoclonal gammopathy of renal significance (MGRS)
A clonal B-cell or plasma cell disorder that does not meet criteria for overt malignancy (e.g. MGUS-level clone) but produces a nephrotoxic paraprotein. The clone is “too small to treat” by haematology criteria but is destroying the kidney.
Patterns: membranoproliferative GN, C3 glomerulopathy, fibrillary GN, immunotactoid GN, proliferative GN with monoclonal Ig deposits, light chain proximal tubulopathy.
- Renal biopsy is essential — IF with full light chain subtyping, EM
- Management: clone-directed therapy guided by the nephrotoxic protein, even though the haematological burden is low
- Without treatment, progression to ESKD is common
traps
- Trusting a negative dipstick in myeloma — light chains are invisible to dipstick; order UPCR/UPEP
- Attributing nephrotic syndrome in a paraprotein patient to cast nephropathy — cast nephropathy does not cause albuminuria; consider AL amyloidosis or MGRS-associated glomerulopathy
- Giving IV contrast without preparation — dehydration + contrast + high FLC burden is a classic precipitant of cast nephropathy; volume-expand first if imaging is necessary
- Ignoring MGRS — a “benign” MGUS with unexplained renal disease is not benign; biopsy and consider clone-directed therapy
- Typing amyloid by Congo Red alone — confirms amyloid but does not distinguish AL from AA or ATTR; mass spectrometry is required before starting chemotherapy
- Repleting calcium aggressively in TLS — promotes CaPO₄ precipitation in the kidney; treat only if symptomatic (tetany, arrhythmia)