What is the appropriate management for a patient with non-diabetic nodular sclerosis (Focal Segmental Glomerulosclerosis, FSGS) and impaired renal function?

Management of Non-Diabetic Nodular Sclerosis (Idiopathic Nodular Glomerulosclerosis)

Initial Diagnostic Imperative

Non-diabetic nodular sclerosis, also termed idiopathic nodular glomerulosclerosis (ING), should be managed with aggressive supportive care focused on RAS blockade, blood pressure control, smoking cessation, and lipid management—immunosuppression has no role in this condition. 1

This is a distinct vasculopathic entity that mimics diabetic nephropathy histologically but occurs without diabetes, strongly linked to hypertension and heavy smoking. 1

Classification and Differential Diagnosis

Before confirming ING, you must systematically exclude other causes of nodular glomerulosclerosis through specific testing:

• Rule out occult diabetes or prediabetes: Obtain fasting glucose, HbA1c, and oral glucose tolerance testing, as impaired glucose metabolism may be underrecognized in these patients 2
• Exclude light chain deposition disease: Perform serum and urine immunofixation electrophoresis with free light chain assay 3
• Rule out amyloidosis: Congo red staining on biopsy tissue 3
• Exclude membranoproliferative GN, fibrillary GN, and immunotactoid GN: Immunofluorescence and electron microscopy are essential 3
• Assess for chronic hypoxic/ischemic conditions: Review for cyanotic heart disease, chronic obstructive pulmonary disease, or severe vascular disease 3

Core Treatment Strategy

Blood Pressure Management

• Initiate ACE inhibitor or ARB at maximally tolerated dose regardless of baseline blood pressure if proteinuria exceeds 0.5 g/day 4
• Target systolic blood pressure <120 mmHg using standardized office measurement 4
• Add additional antihypertensive agents as needed to achieve target, prioritizing diuretics for volume management 4
• Counsel patients to hold RAS inhibitors during intercurrent illness with volume depletion risk 4

Smoking Cessation

• Mandate immediate and complete smoking cessation—continuation of smoking is the strongest predictor of progression to ESRD (p=0.0165) 1
• The typical ING patient has a 52.9 pack-year smoking history; ongoing tobacco use dramatically accelerates disease progression 1

Proteinuria Reduction

• Up-titrate ACE inhibitor or ARB to maximum tolerated dose as first-line therapy for proteinuria reduction 4
• Implement strict sodium restriction to <2.0 g/day (<90 mmol/day) 4
• Use potassium-wasting diuretics and/or potassium-binding agents if hyperkalemia limits RAS inhibitor dosing 4

Lipid Management

• Initiate statin therapy for persistent dyslipidemia, particularly given the high prevalence of hypercholesterolemia (90%) and extrarenal vascular disease (43.5%) in ING patients 4, 1
• Consider non-statin therapy if LDL goals are not met despite maximally tolerated statin dose 4

Critical Monitoring Parameters

Track these specific markers to assess disease trajectory:

• Serum creatinine and eGFR every 3 months: A 40% or greater decline in eGFR over 2-3 years indicates treatment failure and high risk for ESRD 4
• Quantify proteinuria every 3 months: Use 24-hour urine collection or spot urine protein-to-creatinine ratio 4
• Blood pressure at every visit: Ensure consistent achievement of <120/80 mmHg target 4
• Serum potassium and bicarbonate monthly initially: Treat metabolic acidosis if bicarbonate <22 mmol/L 4

Prognostic Factors and Expected Outcomes

The median time to ESRD after biopsy diagnosis is 26 months in untreated or inadequately treated patients. 1

Predictors of progression to ESRD include:

• Continued smoking (strongest predictor) 1
• Lack of angiotensin II blockade (p=0.0007) 1
• Degree of tubular atrophy and interstitial fibrosis on biopsy 1
• Severity of arteriosclerosis on biopsy 1

Common Pitfalls to Avoid

• Do not use immunosuppressive therapy: ING is a vasculopathic, not immunologic, condition—corticosteroids and other immunosuppressants have no role and expose patients to unnecessary toxicity 1
• Do not assume diabetes is absent based solely on initial glucose testing: Impaired glucose metabolism or insulin resistance may be intermittent or borderline; serial testing including HbA1c and glucose tolerance testing is warranted 2
• Do not underestimate the importance of smoking cessation: This is not optional counseling—it is the single most modifiable risk factor for disease progression 1
• Do not delay RAS blockade due to mild creatinine elevation: The renoprotective benefits outweigh concerns about initial GFR reduction, provided potassium and volume status are monitored 1