How should chronic glomerulonephritis be evaluated and managed in patients presenting with persistent hematuria, proteinuria ≥300 mg/day, reduced glomerular filtration rate, or hypertension?

Chronic Glomerulonephritis: Evaluation and Management

Diagnostic Evaluation

Kidney biopsy remains the gold standard for diagnosing chronic glomerulonephritis and should be performed in patients with persistent proteinuria ≥0.5 g/day to establish the specific type of glomerulonephritis and guide treatment decisions. 1, 2

Initial Laboratory Assessment

• Quantify proteinuria using 24-hour urine collection in adults or first morning protein-to-creatinine ratio (PCR) in children 1
• Calculate eGFR using the CKD-EPI creatinine equation in adults or modified Schwartz equation in children 1
• Examine urine sediment for red blood cell casts, acanthocytes, and erythrocyte morphology in all patients 1
• Order serologic studies including complement levels, antinuclear antibody, ANCA, anti-GBM antibodies, hepatitis B/C serologies, HIV, and quantitative immunoglobulins to identify secondary causes 3, 4
• Perform renal ultrasound to assess kidney size and rule out obstruction 3

Risk Stratification

• Assess risk of progression by evaluating proteinuria level, blood pressure, and eGFR at diagnosis and during follow-up 1
• Recognize that proteinuria >1 g/day, uncontrolled hypertension, and reduced GFR at presentation predict adverse outcomes 1
• Use pathological features from kidney biopsy to assess prognosis, though complete clinical remission may not be possible in all forms of chronic glomerulonephritis 1

Blood Pressure and Proteinuria Management

ACE inhibitors or ARBs should be initiated and uptitrated to maximally tolerated doses as first-line therapy in all patients with chronic glomerulonephritis and proteinuria ≥0.5 g/day, regardless of blood pressure. 1

Blood Pressure Targets

• Target systolic blood pressure <120 mmHg using standardized office measurement in most adult patients 1
• For patients with proteinuria >1 g/day, aim for blood pressure <125/75 mmHg (or <130/80 mmHg if stricter targets not feasible) 1, 3
• In children, target 24-hour mean arterial pressure ≤50th percentile for age, sex, and height by ambulatory monitoring 1

ACE Inhibitor/ARB Therapy

• Uptitrate ACE inhibitor or ARB to maximally tolerated dose to achieve proteinuria <1 g/day 1
• Do not discontinue therapy if serum creatinine increases up to 30% from baseline, unless kidney function continues to worsen or refractory hyperkalemia develops 3, 5
• Use potassium-wasting diuretics and/or potassium-binding agents to maintain normal serum potassium and allow continued RAS inhibitor use 1
• Counsel patients to hold RAS inhibitors and diuretics during intercurrent illness or risk of volume depletion 1, 3

Immunosuppressive Therapy

Choose an immunosuppressive regimen that balances three priorities: averting immediate morbidity, preventing disease progression, and minimizing harmful side effects. 1

Treatment Principles

• Base intensity of induction therapy on severity of presenting symptoms and specific type of glomerulonephritis 1
• Adjust dosing based on GFR level to ensure safety 1
• Recognize that prolonged or multiple rounds of immunosuppression may be required to prevent chronic kidney disease progression 1
• Use proteinuria reduction as a surrogate endpoint for treatment efficacy 1

Pre-Treatment Screening

• Screen for latent infections including tuberculosis, hepatitis B/C, HIV, and syphilis before initiating immunosuppression 1
• Consider Strongyloides screening in patients from endemic tropical environments with eosinophilia and elevated IgE 1
• Update vaccination status including pneumococcal, influenza, and herpes zoster (Shingrix) vaccines 1
• Discuss fertility preservation options where indicated 1

Prophylaxis During Immunosuppression

• Prescribe prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose prednisone, rituximab, or cyclophosphamide 1
• Monitor therapeutic drug levels where clinically indicated 1
• Screen regularly for development of cancers and infections during prolonged immunosuppression 1

Supportive Care Measures

Edema Management

• Use diuretics as preferred agents along with dietary sodium restriction <2.0 g/day (<90 mmol/day) 1
• Add mechanistically different diuretics if initial diuretic response is insufficient 1
• Monitor closely for hyponatremia, hypokalemia, GFR reduction, and volume depletion 1

Metabolic Management

• Treat metabolic acidosis if serum bicarbonate <22 mmol/L 1
• Consider statin therapy for persistent dyslipidemia in nephrotic syndrome patients, particularly those with cardiovascular risk factors 1
• Restrict dietary protein to 0.8-1 g/kg/day in nephrotic-range proteinuria, adding up to 5 g/day to compensate for urinary protein losses 1
• Limit protein intake to 0.8 g/kg/day (avoiding <0.6 g/kg/day) in patients with eGFR <60 mL/min/1.73 m² and nephrotic-range proteinuria 1

Thromboembolism Prevention

• Provide full anticoagulation for patients with thromboembolic events occurring in nephrotic syndrome 1
• Consider prophylactic anticoagulation in nephrotic syndrome when thromboembolism risk exceeds bleeding risk 1

Nephrology Referral Criteria

Refer to nephrology for persistent proteinuria >1 g/day (ACR ≥60 mg/mmol or PCR ≥100 mg/mmol), as kidney biopsy may be indicated and immunosuppressive therapy may be required. 1, 3

Additional Referral Indications

• eGFR <30 mL/min/1.73 m² (though not automatically required based on GFR alone if stable) 1, 3
• Abrupt sustained decrease in eGFR >20% after excluding reversible causes 1, 3
• Urinary red cell casts or RBC >20 per high-power field that is sustained and unexplained 3
• Hypertension refractory to treatment with ≥4 antihypertensive agents 3
• Inability to tolerate renal protective medications (ACE inhibitors/ARBs) 1, 3
• Uncertainty about diagnosis or suspected hereditary kidney disease 1, 3

Monitoring Strategy

• Assess eGFR and proteinuria at least annually in all patients with confirmed chronic glomerulonephritis 3
• Monitor serum creatinine, potassium, and proteinuria levels frequently when initiating or uptitrating ACE inhibitor/ARB therapy 3, 5
• Recognize that a ≥40% decline in eGFR from baseline over 2-3 years suggests high risk for kidney failure 1

Critical Pitfalls to Avoid

• The vast majority of patients with stage 3 CKD die from cardiovascular causes rather than progressing to end-stage renal disease, so cardiovascular risk reduction must be prioritized alongside kidney-specific interventions. 1, 3
• Proteinuria <1 g/day can generally be managed in primary care with ACE inhibitors/ARBs, blood pressure control, and lifestyle modifications without requiring nephrology referral 1, 3
• Avoid nephrotoxins including NSAIDs, aminoglycosides, and radiocontrast agents in patients with chronic glomerulonephritis 3
• Do not abruptly discontinue immunosuppression without careful monitoring, as proteinuria frequently recurs following cessation of therapy 1