Glomerular disease · KIMS Secunderabad
Multiple Myeloma and Kidney Disease — How Abnormal Proteins Damage the Kidneys
Multiple myeloma is a malignancy of plasma cells — the antibody-producing cells of the bone marrow. In myeloma, a single clone of abnormal plasma cells proliferates uncontrollably, producing vast quantities of abnormal immunoglobulin (the M-protein or paraprotein) and, critically, excess immunoglobulin light chains. It is these light chains — specifically the free light chains that escape into the bloodstream and are filtered by the kidneys — that cause kidney disease in myeloma. Kidney involvement occurs in approximately 20 to 50% of myeloma patients at diagnosis and is one of the most important prognostic factors determining treatment options and outcomes.
At KIMS, the nephrology team evaluates and manages kidney disease in myeloma in close coordination with the haematology-oncology team treating the myeloma itself. Kidney biopsy — with the KIMS NABL-accredited three-component analysis (LM, IF, EM) — is the definitive tool for identifying which mechanism of kidney damage is operating in a given patient, because the treatment differs completely depending on the mechanism.
Mechanisms of kidney damage in myeloma
Cast nephropathy (myeloma kidney) — the most common mechanism
Free light chains filtered by the glomerulus enter the tubular lumen, where they bind to Tamm-Horsfall protein (a glycoprotein produced by the loop of Henle) in the presence of high tubular sodium concentration. This binding forms dense, obstructing casts in the distal nephron — blocking individual nephrons and triggering a surrounding inflammatory response (giant cell reaction around the casts). The resulting tubulointerstitial damage is often severe and rapidly progressive. Cast nephropathy is the most common cause of AKI in myeloma — often presenting as the first manifestation of previously undiagnosed myeloma. The clinical picture: rapidly rising creatinine (often above 500 µmol/L at presentation), modest proteinuria (the majority of protein is light chains — not albumin — so the standard urine dipstick, which detects albumin, may be relatively normal despite significant protein excretion on 24-hour collection), and hypercalcaemia (calcium deposits in the tubular lumen exacerbate cast formation). The kidney biopsy shows the characteristic dense eosinophilic casts with surrounding multinucleate giant cells on light microscopy.
Light chain deposition disease (LCDD)
Light chains (predominantly kappa in LCDD, in contrast to lambda-predominant AL amyloidosis) deposit in the kidney as granular, non-fibrillar deposits — in the glomerular mesangium and tubular basement membranes. Unlike amyloid deposits, LCDD deposits do not show Congo red positivity or apple-green birefringence. On electron microscopy, LCDD shows punctate, granular electron-dense deposits — the ultrastructural distinction from amyloid fibrils (which are organised into characteristic 8 to 12nm fibrils). Clinical presentation: proteinuria (often nephrotic range), haematuria, and declining eGFR — indistinguishable from primary glomerulonephritis without biopsy.
AL amyloidosis
See the KIMS Amyloidosis page for full detail. In myeloma-associated AL amyloidosis, the same clone producing the M-protein also produces amyloidogenic light chains that deposit as amyloid fibrils in the kidneys, heart, and other organs. The kidney presents with nephrotic-range proteinuria, enlarged kidneys on ultrasound, and — on biopsy — Congo red positive amyloid deposits with apple-green birefringence and the characteristic fibrillar EM pattern.
Hypercalcaemic nephropathy
Osteolytic bone destruction by myeloma cells releases calcium from bone, causing hypercalcaemia in 15 to 20% of myeloma patients. Hypercalcaemia causes nephrogenic diabetes insipidus (the collecting duct becomes insensitive to ADH, causing polyuria and dehydration), intense renal vasoconstriction, calcium deposition in tubular cells (nephrocalcinosis), and volume depletion. The result: AKI from the combination of vasoconstriction and tubular calcium toxicity.
Other mechanisms — urate, contrast, drug nephrotoxicity
Hyperuricaemia and tumour lysis — uric acid from myeloma cell breakdown or chemotherapy-induced tumour lysis precipitates in tubules (urate nephropathy). Contrast nephropathy — myeloma patients receiving IV contrast for CT or angiography have a higher risk of contrast-induced AKI because free light chains in the tubules sensitise them to ischaemic and contrast-related injury. Drug nephrotoxicity — NSAIDs, bisphosphonates (particularly zoledronic acid — which can cause focal segmental glomerulosclerosis), and some antimyeloma agents (high-dose melphalan) can cause kidney injury.
Diagnosis at KIMS
Serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP)
Identifies the M-protein band. The M-protein may be IgG, IgA, IgM, or light chain only (Bence Jones protein). SPEP alone misses 20% of myeloma cases (light chain only myeloma) where no intact immunoglobulin is produced — UPEP is essential.
Serum free light chain (sFLC) assay
Measures free kappa and lambda light chain concentrations and their ratio. Sensitive for light chain myeloma and for monitoring response to treatment. An elevated kappa:lambda ratio above 100 is a high-risk finding associated with very high light chain burden and severe cast nephropathy risk.
Kidney biopsy with NABL LM + IF + EM at KIMS — Cast nephropathy
LM shows tubular casts with giant cell reaction. IF shows light chain restriction (kappa or lambda) within the casts. EM confirms dense tubular cast material. Diagnosis directs rapid bortezomib-based therapy to reduce light chain production and clear the obstructing casts.
Kidney biopsy — Light chain deposition disease (LCDD)
LM shows mesangial expansion. IF shows granular kappa (or lambda) deposits in glomerular and tubular basement membranes. EM shows granular, non-fibrillar electron-dense deposits — the definitive distinction from AL amyloidosis. Performed in-house at KIMS NABL laboratory.
Kidney biopsy — AL amyloidosis
Congo red positive, apple-green birefringence under polarised light. IF shows lambda (or kappa) light chain restriction. EM shows 8–12nm amyloid fibrils — distinguishing AL amyloidosis from LCDD and cast nephropathy. See KIMS Amyloidosis page for further detail.
Treatment — joint nephrology and haematology-oncology
Cast nephropathy treatment
Rapid and aggressive myeloma treatment to reduce light chain production — bortezomib-based regimens achieve light chain reduction within 1 to 2 weeks, faster than other antimyeloma regimens. Aggressive hydration to increase tubular flow and reduce cast formation. Avoidance of contrast, NSAIDs, and nephrotoxins. Correction of hypercalcaemia with IV bisphosphonates (zoledronic acid) and hydration. CRRT or haemodialysis for severe AKI — at KIMS, dialysis supports the patient while bortezomib reduces light chain production. Kidney function improves in approximately 50% of cast nephropathy patients with effective myeloma treatment.
LCDD treatment
Same antimyeloma chemotherapy (bortezomib-based) to suppress light chain production. Response assessed by sFLC normalisation and kidney function improvement.
AL amyloidosis treatment
See Amyloidosis page — bortezomib-based or daratumumab-based regimens targeting the plasma cell clone.
Hypercalcaemia
IV fluids + IV bisphosphonates (zoledronic acid — used cautiously given nephrotoxicity risk in severe AKI) + calcitonin for rapid hypercalcaemia correction.
Book a Nephrology Consultation for Myeloma Kidney Disease at KIMS
Frequently Asked Questions — Multiple Myeloma and Kidney Disease
Multiple myeloma damages the kidneys primarily through free light chains — the excess immunoglobulin components produced by the abnormal plasma cell clone that escape into the bloodstream, are filtered by the kidneys, and then cause damage in different ways depending on their properties. The three main mechanisms: cast nephropathy (light chains bind to tubular proteins and form obstructing casts), light chain deposition disease (light chains deposit as granular deposits in the glomerular and tubular basement membranes), and AL amyloidosis (light chains misfold and deposit as amyloid fibrils). Hypercalcaemia from bone destruction adds a fourth mechanism. Kidney biopsy at KIMS identifies which mechanism is responsible in each patient.
Cast nephropathy — the most common mechanism — is potentially reversible if myeloma treatment is started rapidly and effectively. Bortezomib-based regimens reduce light chain production within days to weeks. If the light chain burden is reduced quickly, the obstructing casts can be cleared, the giant cell inflammatory response resolves, and tubular function recovers. Kidney function improves in approximately 50% of cast nephropathy patients who achieve a good haematological response. Recovery is less likely if treatment is delayed (more extensive tubular damage and fibrosis) or if the response to chemotherapy is incomplete. LCDD may stabilise or modestly improve with effective myeloma treatment. AL amyloidosis improves more slowly — over 6 to 18 months of sustained haematological response.
IV contrast used for CT scanning causes contrast nephropathy — AKI from direct tubular toxicity and vasoconstriction — in a small percentage of patients with normal kidneys. In myeloma patients, the risk is significantly higher because free light chains in the tubular lumen sensitise the tubular cells to ischaemic and toxic injury. The traditional advice was that contrast was absolutely contraindicated in myeloma — current evidence suggests the risk is lower than previously feared with adequate hydration and modern iso-osmolar contrast agents. However, the nephrology team should be involved in any decision to administer IV contrast to a myeloma patient with elevated creatinine or elevated free light chains.
Bence Jones protein is the historical term for free immunoglobulin light chains excreted in the urine — named after Henry Bence Jones who described the characteristic heat-precipitation properties of these proteins in 1847. In myeloma, the abnormal plasma cell clone produces excess light chains that are too small to be retained in the blood and are filtered freely by the glomerulus, appearing in the urine. Bence Jones proteinuria can be detected by urine protein electrophoresis (UPEP) and quantified by the 24-hour urine free light chain assay. Standard urine dipstick does not detect Bence Jones protein — it only detects albumin. This is why a myeloma patient can have significant Bence Jones proteinuria with a normal urine dipstick.
Dialysis supports myeloma patients through the acute kidney injury caused by cast nephropathy while myeloma treatment reduces light chain production. High-flux haemodialysis membranes can remove some free light chains directly from the blood — the MYRE and EuLITE trials investigated this approach but did not show convincing benefit over standard dialysis. CRRT at KIMS provides continuous kidney support for haemodynamically unstable patients. Most myeloma patients with cast nephropathy who achieve a complete or very good partial haematological response (marked reduction in light chains) recover enough kidney function to come off dialysis.
Both multiple myeloma and AL amyloidosis are caused by abnormal plasma cell clones producing excess light chains. In myeloma, the light chain burden is typically high and causes bone destruction, hypercalcaemia, anaemia, and kidney damage through cast nephropathy. In AL amyloidosis, the plasma cell clone is smaller but produces a specific type of light chain that misfolds into amyloid fibrils — causing organ damage through tissue infiltration rather than the direct nephrotoxicity and obstruction of cast nephropathy. Approximately 15% of AL amyloidosis patients also meet the criteria for overt myeloma. Both are treated with bortezomib-based chemotherapy targeting the plasma cell clone, but the organ damage patterns, urgency, and monitoring differ significantly.
Not every myeloma patient requires kidney biopsy — but biopsy is indicated when: the cause of kidney injury is uncertain (cast nephropathy, LCDD, and AL amyloidosis can all cause proteinuria and declining eGFR, but require different treatment approaches), nephrotic-range proteinuria is present (more likely LCDD or AL amyloidosis than cast nephropathy), or response to myeloma treatment is not accompanied by kidney function improvement as expected. At KIMS, the nephrology team and haematology-oncology team review each myeloma patient with kidney disease together to determine whether biopsy adds decision-relevant information.
KIMS Secunderabad — Dr. Aswini Dutt T (glomerular disease subspecialty), NABL-accredited kidney biopsy with LM + IF + EM (distinguishes cast nephropathy, LCDD, and AL amyloidosis — three different diagnoses with three different treatments), sFLC assay and SPEP/UPEP, CRRT 24/7 for AKI, haematology-oncology coordination for bortezomib and daratumumab-based antimyeloma treatment. Call 040-4488-5000.