What is the diagnosis and management plan for a patient with impaired renal function, presenting with 73% obsolescent glomeruli, tubular atrophy, and interstitial fibrosis on renal biopsy, with a history of possible hypertension and/or diabetes?

Diagnosis: Advanced Hypertensive/Ischemic Nephrosclerosis with Possible Superimposed Light Chain-Mediated Kidney Disease

This patient requires immediate hematologic workup for monoclonal gammopathy given the pseudolinear IgG/kappa/lambda staining pattern on immunofluorescence, despite the Congo red negativity, as this pattern suggests possible early or atypical monoclonal immunoglobulin deposition that may be contributing to the severe chronic kidney damage. 1

Primary Pathologic Diagnosis

The biopsy demonstrates severe chronic kidney disease with a chronicity index of 9-10 out of 10 (73% obsolescent glomeruli, 60-70% tubular atrophy/interstitial fibrosis, marked vascular sclerosis), indicating nonviable renal parenchyma with minimal potential for functional recovery. 1

Key Histologic Features:

• Vascular pathology is the dominant finding: Marked hyperplastic changes in interlobular arteries and arterioles with hyaline arteriolosclerosis showing near-luminal occlusion strongly suggests long-standing, poorly controlled hypertension as the primary driver of kidney injury. 2, 3

• The 73% obsolescent glomeruli with global sclerosis and hyalinosis, combined with severe arteriosclerosis, is consistent with advanced hypertensive/ischemic nephrosclerosis. 2, 3

• Segmental sclerosis in 5 viable glomeruli with moderate mesangial matrix expansion suggests superimposed focal segmental glomerulosclerosis (FSGS), likely secondary to hyperfiltration injury in remaining nephrons. 1, 4

• The 60-70% tubular atrophy and interstitial fibrosis with mononuclear infiltrates indicates severe chronic tubulointerstitial injury, which is the strongest predictor of irreversible renal dysfunction. 3, 5, 6

Critical Immunofluorescence Finding Requiring Action

The pseudolinear tubular basement membrane and glomerular basement membrane staining for IgG, kappa, and lambda light chains WITHOUT light chain restriction is atypical and warrants exclusion of monoclonal immunoglobulin-associated kidney disease, despite the negative Congo red stain. 1

Why This Matters:

• This staining pattern can represent: (1) nonspecific trapping of immunoglobulins in severely sclerotic tissue, OR (2) early/atypical monoclonal immunoglobulin deposition disease that has not yet formed amyloid fibrils. 1

• The presence of neutrophilic casts and granular debris in tubular lumens, combined with the IF findings, raises concern for possible light chain cast nephropathy or early light chain deposition disease superimposed on chronic vascular disease. 1, 7

• Even without detectable serum/urine monoclonal protein, proliferative glomerulonephritis with monoclonal immunoglobulin deposits can occur, and the biopsy report should recommend thorough evaluation for monoclonal gammopathy. 1

Mandatory Immediate Workup

Before finalizing the diagnosis as purely hypertensive nephrosclerosis, the following hematologic evaluation MUST be completed: 7

1. Serum protein electrophoresis (SPEP) with immunofixation electrophoresis (SIFE) - to identify any monoclonal protein. 7

2. Serum free light chain assay (SFLCA) - measuring kappa and lambda free light chains with kappa:lambda ratio (normal 0.26-1.65, or 0.34-3.10 in CKD stage 5). 7

3. 24-hour urine collection with urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) - to quantify Bence Jones proteinuria. 7

4. Complete metabolic panel - including calcium (to assess for hypercalcemia suggesting myeloma). 7

5. If any monoclonal protein is detected: Bone marrow biopsy to assess for plasma cell dyscrasia. 7

Management Plan Based on Chronicity Score

With a chronicity index of 9-10/10, this kidney is classified as nonviable, and revascularization procedures are contraindicated even if renal artery stenosis were present. 2

Stage 4-5 CKD Management Protocol:

Blood Pressure Control (Target <130/80 mmHg): 2

• ACE inhibitors or ARBs are indicated for patients with eGFR <60 mL/min/1.73 m², but must be initiated cautiously given the severe vascular disease and risk of acute-on-chronic kidney injury. 2, 8
• Monitor serum creatinine and potassium within 1-2 weeks of initiation - discontinue if creatinine rises >30% or potassium >5.5 mEq/L. 8
• Avoid NSAIDs and other nephrotoxic medications absolutely. 7, 8

Cardiovascular Risk Reduction: 2

• Statin therapy is mandatory for all CKD patients given the severe atherosclerotic burden. 2

CKD-Mineral Bone Disorder Management: 2

• Check hemoglobin, serum calcium, phosphate, intact PTH, and 25-hydroxyvitamin D. 2
• Treat secondary hyperparathyroidism and vitamin D deficiency per KDIGO guidelines. 2

Immediate Nephrology Referral: 2

• This patient meets multiple criteria for urgent nephrology referral: eGFR likely <30 mL/min/1.73 m² (given 73% obsolescent glomeruli), uncertainty about etiology (possible monoclonal immunoglobulin disease), and need for preparation for renal replacement therapy. 2

If Monoclonal Gammopathy is Confirmed

If serum/urine studies reveal monoclonal protein or abnormal free light chain ratio: 7

• Initiate bortezomib-containing regimen immediately (bortezomib/dexamethasone can be given without dose adjustment in severe renal impairment). 7
• Goal: ≥50-60% reduction in free light chains by day 12 of treatment. 7
• Consider adding cyclophosphamide, thalidomide, or daratumumab as third agent. 7
• Provide aggressive hydration and urine alkalinization. 7
• Monitor renal function closely - recovery of kidney function reverses the negative impact on overall survival. 7

Prognosis and Counseling

The severity of histopathological damage (73% obsolescent glomeruli, 60-70% tubular atrophy/interstitial fibrosis) is an independent predictor of poor renal functional outcome, with high likelihood of progression to end-stage kidney disease requiring dialysis or transplantation. 3, 5, 6

• Tubular atrophy and interstitial fibrosis are better predictors of renal outcome than glomerulosclerosis alone, and this patient has severe involvement of both compartments. 5, 6

• The marked vascular sclerosis with near-luminal occlusion indicates chronic tubular ischemia that is irreversible, further limiting any potential for functional recovery. 3, 5

• If no monoclonal protein is found and this represents pure hypertensive nephrosclerosis, the focus shifts entirely to slowing progression, managing CKD complications, and preparing for renal replacement therapy. 2