What is the diagnosis and management plan for a patient with impaired renal function, likely due to non-diabetic kidney disease, with biopsy results showing significant glomerular sclerosis, tubular atrophy, and interstitial fibrosis?

Diagnosis: Monoclonal Immunoglobulin-Associated Kidney Disease with Severe Chronic Injury

The biopsy findings of pseudolinear IgG, kappa, and lambda staining on tubular and glomerular basement membranes, combined with extensive chronic damage (73% obsolescent glomeruli, 60-70% tubular atrophy/interstitial fibrosis), indicate a monoclonal immunoglobulin-related kidney disease with severe irreversible injury requiring immediate hematologic workup and consideration for renal replacement therapy. 1

Primary Pathologic Diagnosis

Based on the Mayo Clinic/Renal Pathology Society standardized reporting framework, this case should be diagnosed as:

• Primary diagnosis: Monoclonal immunoglobulin-associated kidney disease (pattern requires further characterization with serum/urine studies) 1
• Pattern of injury: Focal segmental and global glomerulosclerosis with severe chronic tubulointerstitial injury 1
• Additional features: Extensive (73%) global glomerulosclerosis, severe (60-70%) tubular atrophy and interstitial fibrosis, severe arteriosclerosis and hyaline arteriolosclerosis 1
• Chronicity index: Severe (9-10 of 10) 1

The pseudolinear basement membrane staining for IgG with both kappa and lambda light chains is atypical and requires correlation with serum studies to determine if there is monoclonal protein present that was not detected by standard immunofluorescence 1.

Mandatory Immediate Workup

The following tests must be obtained urgently to characterize the underlying hematologic disorder: 1, 2

• Serum protein electrophoresis (SPEP) - quantitative screening for monoclonal protein 2
• Serum immunofixation electrophoresis (SIFE) - more sensitive than SPEP for identifying and typing monoclonal immunoglobulins 2
• Serum free light chain assay (SFLCA) - measures κ and λ free light chains independently with κ:λ ratio (normal 0.26-1.65) 2
• 24-hour urine collection with urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) - essential for detecting Bence Jones proteinuria 2
• Complete metabolic panel - assess current renal function and electrolyte abnormalities 2

If monoclonal protein is detected, proceed immediately with: 1, 2

• Bone marrow biopsy to assess plasma cell burden and exclude multiple myeloma 2
• Skeletal survey or whole-body low-dose CT for lytic lesions 2
• Cardiac biomarkers (troponin T, NT-proBNP) if AL amyloidosis suspected, as levels >0.06 ng/mL or >5000 ng/L respectively indicate high transplant-related mortality 2

Critical Clinical Context and Prognosis

The extensive chronic damage (73% obsolescent glomeruli, 60-70% tubular atrophy/interstitial fibrosis) indicates severe irreversible kidney injury with poor prognosis for renal recovery. 1

• The degree of tubular atrophy and interstitial fibrosis is a better predictor of renal outcome than glomerular sclerosis 3, 4
• The severe arteriosclerosis and near-occlusion of arteriolar lumens suggest chronic ischemic injury contributing to tubular atrophy 3, 5
• The chronicity index of 9-10/10 indicates minimal potential for functional recovery even with treatment of underlying hematologic disorder 1

The marked vascular changes (hyaline arteriolosclerosis with near luminal occlusion) are associated with significantly increased risk of tubulointerstitial injury and predict progression to end-stage renal disease. 4, 5

Management Algorithm

If Monoclonal Protein is Detected:

1. Light Chain Cast Nephropathy or Light Chain Deposition Disease:

• Initiate bortezomib-containing regimens immediately to decrease nephrotoxic clonal immunoglobulin production 2
• Bortezomib/dexamethasone can be administered without dose adjustment in severe renal impairment 2
• Add third agent that doesn't require dose adjustment (cyclophosphamide, thalidomide, or daratumumab) 2
• Goal: ≥50-60% reduction in free light chains by day 12 of treatment 2
• Provide adequate hydration and urine alkalinization 2
• Avoid nephrotoxic medications (NSAIDs, IV contrast) 2

2. AL Amyloidosis (if Congo red positive on repeat staining):

• Cardiac risk stratification is mandatory before treatment 2
• Bortezomib-based therapy remains first-line 2
• Consider autologous stem cell transplantation only if cardiac biomarkers permit 2

3. Proliferative Glomerulonephritis with Monoclonal Ig Deposits:

• Clone-directed therapy targeting underlying plasma cell disorder 1
• Note: Serum/urine studies may be negative in up to 50% of cases, but treatment is still indicated 1

If No Monoclonal Protein Detected:

The pseudolinear staining pattern with polyclonal immunoglobulin suggests:

• Consider repeat immunofluorescence with pronase digestion to unmask potential masked deposits 1
• Evaluate for secondary causes of chronic tubulointerstitial nephritis 1
• The extensive vascular disease and clinical impression of "non-diabetic kidney disease" may represent hypertensive nephrosclerosis, but the immunofluorescence findings are atypical for this diagnosis 6, 5

Renal Replacement Therapy Planning

Given the severe chronicity (60-70% tubular atrophy/interstitial fibrosis, 73% obsolescent glomeruli), this patient should be evaluated for renal replacement therapy regardless of underlying diagnosis. 1

• Initiate dialysis access planning (fistula placement or peritoneal dialysis catheter) 1
• Begin transplant evaluation if appropriate candidate 1
• Even with aggressive treatment of underlying hematologic disorder, renal recovery is unlikely given severity of chronic changes 3, 4

Critical Pitfalls to Avoid

Do not delay hematologic workup: The pseudolinear immunofluorescence pattern requires immediate correlation with serum/urine studies, as monoclonal gammopathy-related kidney disease is treatable but time-sensitive 1, 2

Do not assume benign hypertensive nephrosclerosis: The immunofluorescence findings are not consistent with pure hypertensive nephrosclerosis and mandate exclusion of monoclonal immunoglobulin disease 1, 6

Do not use nephrotoxic agents: Avoid NSAIDs, IV contrast, and other nephrotoxic medications in this patient with severe chronic kidney disease 2

Do not delay dialysis planning: The extensive chronic damage (chronicity index 9-10/10) indicates high likelihood of progression to end-stage renal disease regardless of treatment 1, 5