What is the best management plan for an elderly gentleman with a history of Benign Prostatic Hyperplasia (BPH), Urinary Tract Infections (UTIs), pedal edema, and Hypertension (HTN), presenting with Impaired Renal Function, proteinuria, and a renal biopsy diagnosis of Focal Segmental Glomerulosclerosis (FSGS) with moderate global glomerulosclerosis, mild chronic tubulointerstitial nephritis, and hypertensive vascular changes?

Management of FSGS with Hypertensive Nephrosclerosis in an Elderly Patient

This elderly gentleman requires aggressive blood pressure control with ACE inhibitor or ARB therapy as the cornerstone of management, with immunosuppression deferred unless proteinuria remains >4 g/day after 3-6 months of maximal conservative therapy. 1

Immediate Priority: Exclude Secondary Causes and Optimize Conservative Management

Rule Out Secondary FSGS

• A thorough evaluation must exclude secondary forms of FSGS before considering immunosuppression 2
• This patient has multiple features suggesting secondary (maladaptive) FSGS rather than primary disease:
  • History of BPH with recurrent UTIs (potential obstructive component)
  • Hypertension with vascular changes on biopsy
  • Relatively preserved serum albumin (3.86 g/dL, not severely low)
  • Moderate global glomerulosclerosis (46% obsolescent glomeruli) with hypertensive vascular changes 2
• The biopsy shows negative immunofluorescence, which is consistent with both primary and secondary FSGS but does not distinguish between them 2

Blood Pressure Management (First-Line Therapy)

• Initiate ACE inhibitor or ARB at maximally tolerated dose regardless of baseline blood pressure 1
• Target systolic blood pressure ≤125/80 mmHg or <120 mmHg using standardized measurement 2, 1
• Current BP of 160/80 mmHg is significantly above target and likely contributing to progressive kidney injury 2
• Add thiazide diuretic if blood pressure remains elevated after ACE inhibitor/ARB uptitration 1
• Loop diuretics (furosemide) are first-line for severe edema given his pedal edema 1
• Monitor serum creatinine and potassium 1-2 weeks after starting ACE inhibitor/ARB to detect hyperkalemia or acute kidney injury 3

Proteinuria Management

• Uptitrate ACE inhibitor or ARB to maximally tolerated dose as first-line therapy 2
• Current urine protein-creatinine ratio of 3.10 (approximately 3.1 g/day) is in the nephrotic range but below the threshold that mandates immediate immunosuppression 1
• Target proteinuria <1 g/day through RAS blockade and blood pressure control 2
• Consider intensifying dietary sodium restriction to <2.0 g/day if proteinuria fails to improve on maximal medical therapy 2

Address BPH and Potential Obstructive Component

Urological Evaluation

• Refer to urology for BPH management given history of recurrent UTIs and potential contribution to renal dysfunction 2
• The relatively small left kidney (8.5 x 3.2 cm) compared to right (8.6 x 4.1 cm) raises concern for chronic obstruction or ischemia 2
• Alpha-blocker therapy (e.g., tamsulosin) should be considered for BPH symptoms if present 2
• Post-void residual urine measurement should be obtained to assess for urinary retention 2

Cardiovascular Risk Reduction

Lipid Management

• Initiate statin therapy for cholesterol control given total cholesterol of 216 mg/dL and nephrotic-range proteinuria 1, 4
• Patients with nephrotic syndrome have increased cardiovascular risk and benefit from statin therapy 2

Anemia Management

• Hemoglobin of 8.4 g/dL requires evaluation for causes beyond chronic kidney disease 5
• Check iron studies, B12, folate, and consider erythropoiesis-stimulating agents if appropriate 5

Immunosuppression Decision Algorithm

Criteria for Considering Immunosuppression

Immunosuppression should ONLY be considered if ALL of the following are met: 1

1. Proteinuria remains >4 g/day (current: 3.1 g/day)
2. Proteinuria stays at >50% of baseline value despite 3-6 months of maximal conservative therapy
3. Idiopathic FSGS is confirmed (secondary causes excluded)
4. Patient has nephrotic syndrome features

First-Line Immunosuppression Choice (If Criteria Met)

• Calcineurin inhibitors (cyclosporine preferred) should be used as first-line therapy rather than high-dose corticosteroids in elderly patients 1
• Rationale: Elderly patients have increased risk of steroid-related complications including osteoporosis, diabetes, psychiatric effects, and infections 2, 6
• Cyclosporine is preferred over tacrolimus due to lesser tendency to precipitate diabetes 1
• Starting dose: 2 mg/kg/day, gradually increased to maximum 4 mg/kg/day with careful pharmacokinetic monitoring (target C0 = 125-175 ng/mL) 2
• Long-term treatment (6-12 months) is required to achieve maximum benefit 2

Contraindications to Immunosuppression in This Patient

• Current GFR must be assessed - cyclosporine should be limited to patients with GFR >60 mL/min/1.73m² due to nephrotoxicity risk 7
• With serum creatinine 1.7 mg/dL in an elderly patient, estimated GFR is likely <60 mL/min/1.73m², making cyclosporine less favorable 7
• High-dose corticosteroids should be avoided in elderly patients when possible 6, 7

Infection Prophylaxis (If Immunosuppression Initiated)

Pre-Immunosuppression Screening

• Screen for latent tuberculosis, hepatitis B/C, and HIV before initiating immunosuppression 1
• Administer pneumococcal vaccination, annual influenza vaccination, and herpes zoster vaccination before starting immunosuppressive therapy 1

During Immunosuppression

• Trimethoprim-sulfamethoxazole prophylaxis is recommended during immunosuppression 1
• Elderly patients are particularly prone to infectious complications of immunosuppressive therapy 6, 7

Monitoring and Follow-Up

Short-Term Monitoring (First 3-6 Months)

• Repeat urine protein-creatinine ratio monthly to assess response to conservative therapy 3
• Monitor serum creatinine, potassium, and blood pressure every 2-4 weeks initially 2, 3
• Assess for medication side effects including hyperkalemia, acute kidney injury, and hypotension 2

Long-Term Monitoring

• Annual follow-up if stable on conservative therapy 2
• Nephrology referral is warranted if proteinuria worsens, kidney function declines >25%, or nephrotic syndrome persists despite maximal conservative therapy 2, 7

Prognosis and Risk Stratification

Poor Prognostic Features in This Patient

• Moderate global glomerulosclerosis (46% obsolescent glomeruli) indicates significant chronic damage 8
• Tubular atrophy and interstitial fibrosis (20-25%) predicts worse outcomes 2
• Hypertensive vascular changes suggest ongoing injury from uncontrolled hypertension 2
• Elevated ESR (106 mm/hr) may indicate active inflammation or underlying systemic disease 5

Expected Outcomes

• With proteinuria of 3.1 g/day (nephrotic range but <14 g/day), median time to end-stage renal failure is approximately 7 years without treatment 8
• Aggressive blood pressure control and proteinuria reduction can significantly slow progression 2
• The presence of significant chronic changes (46% global sclerosis, 20-25% interstitial fibrosis) limits potential for complete recovery but does not preclude benefit from therapy 2

Critical Pitfalls to Avoid

• Do not start immunosuppression prematurely - this patient requires 3-6 months of maximal conservative therapy first 1
• Do not use high-dose corticosteroids as first-line in elderly patients due to high complication rates 1, 6
• Do not overlook BPH as a contributing factor - obstructive uropathy can worsen kidney function and must be addressed 2
• Do not ignore cardiovascular risk - nephrotic syndrome increases thrombotic and cardiovascular complications requiring statin therapy and possibly anticoagulation if albumin drops below 2.0 g/dL 7
• Do not assume all FSGS requires immunosuppression - secondary forms (obesity-related, hypertensive, obstructive) should be managed conservatively 2, 4