What are the indications for a renal biopsy in adult patients with multiple myeloma and impaired renal function?

Indications for Renal Biopsy in Multiple Myeloma

Renal biopsy is not routinely necessary in multiple myeloma patients with renal impairment when proteinuria consists predominantly of light chains with high serum free light chain levels (>500 mg/L) and the cause of renal insufficiency can be clearly attributed to myeloma; however, biopsy is essential when non-selective proteinuria (mainly albuminuria) is present, involved serum free light chains are <500 mg/L, or when there is no clear explanation for the renal dysfunction. 1, 2

When Renal Biopsy Can Be Avoided

High suspicion for light chain cast nephropathy - A renal biopsy is probably not necessary when: 1

• Proteinuria consists mainly of light chains (not albumin) 1
• High serum free light chain levels are present (>500 mg/L) 2
• The clinical picture clearly points to myeloma as the cause of renal impairment 1
• There is a high urine M-spike (>200 mg/day) with albuminuria <10% 3

In these scenarios, the diagnosis of light chain cast nephropathy can be made clinically, and immediate antimyeloma therapy should be initiated without delay for biopsy. 1

Mandatory Indications for Renal Biopsy

Perform renal biopsy when: 1, 2

• Non-selective proteinuria is present (predominantly albuminuria rather than light chains) - this suggests alternative diagnoses like AL amyloidosis or monoclonal immunoglobulin deposition disease (MIDD) 1, 2

• Involved serum free light chains are <500 mg/L despite renal impairment - the low light chain level makes cast nephropathy less likely 2

• Albuminuria >1 g/24 hours is present - this pattern is inconsistent with typical cast nephropathy and suggests glomerular pathology 4

• Renal insufficiency without high levels of free light chains - when the degree of renal dysfunction seems disproportionate to the light chain burden 1

• Coexisting conditions such as diabetes mellitus or chronic hypertension are present - these may contribute to or be the primary cause of renal impairment 1

• No clear and complete explanation for the renal insufficiency exists after initial workup 1

Specific Pathologies Requiring Biopsy for Diagnosis

AL amyloidosis - Suspect when: 1, 5

• Nephrotic-range proteinuria is present (typically >3.5 g/24h) 5
• Albuminuria comprises >50% of total proteinuria 5
• Absence of acute kidney injury at presentation 5
• Lambda light chain predominance (more common in amyloidosis) 5, 6

Note: Subcutaneous fat pad or rectal biopsy may show amyloidosis and can be attempted first, but renal biopsy provides definitive diagnosis and assesses extent of kidney involvement. 1

Monoclonal immunoglobulin deposition disease (MIDD) - Suspect when: 1, 5

• Nephrotic syndrome or significant proteinuria without proportionally elevated light chains 5
• Younger age at presentation (MIDD patients tend to be younger than those with cast nephropathy or amyloidosis) 5
• Hematuria is present (more common in MIDD than amyloidosis) 5

Membranoproliferative glomerulonephritis or other glomerular pathology - Consider when clinical features don't fit typical cast nephropathy. 1

Clinical Context and Pitfalls

The spectrum of renal lesions in multiple myeloma is more heterogeneous than traditionally recognized, with approximately 25% of renal biopsies showing non-paraprotein-associated lesions such as acute tubular necrosis, hypertensive nephrosclerosis, or diabetic nephropathy. 5

Critical distinction: Cast nephropathy and light chain tissue deposition (amyloidosis/MIDD) tend to occur in mutually exclusive fashion. 6 Patients with cast nephropathy typically have:

• Free light chains as the predominant urinary protein 6
• Few glomerular lesions 6
• Acute presentation with rapidly rising creatinine 5

In contrast, tissue deposition diseases show:

• Diffuse, non-selective proteinuria (not just light chains) 6
• Nephrotic-range proteinuria in most cases 6
• More gradual onset of renal dysfunction 5

Important caveat: Do not delay antimyeloma therapy while awaiting biopsy results if light chain cast nephropathy is strongly suspected clinically. 1 The negative impact of renal impairment on mortality is most pronounced in the first 6 months, and rapid reduction of light chains is essential for renal recovery. 1 Bortezomib-based regimens should be initiated immediately in suspected cases. 1

Diagnostic Workup Before Deciding on Biopsy

All patients require: 1, 2

• Serum creatinine and estimated GFR (using CKD-EPI or MDRD formula) 1, 2
• 24-hour urine collection for total protein, electrophoresis, and immunofixation 1, 2
• Serum protein electrophoresis and immunofixation 1
• Serum free light chain measurement with kappa/lambda ratio 1, 2

The pattern of proteinuria (light chain-predominant vs. albumin-predominant) and the serum free light chain level are the key determinants of whether biopsy is needed. 1, 2