What is the initial treatment approach for patients diagnosed with glomeronephritis?

Initial Treatment Approach for Glomerulonephritis

The initial treatment of glomerulonephritis requires immediate supportive care with ACE inhibitors or ARBs for blood pressure control and proteinuria reduction, combined with disease-specific immunosuppression only after kidney biopsy confirms the diagnosis and identifies the specific glomerulonephritis type. 1, 2

Immediate Diagnostic Steps Before Treatment

• Obtain kidney biopsy as the gold standard for diagnosis before initiating immunosuppression, as it guides specific treatment selection and determines whether immunosuppression is warranted 2, 3
• Perform urgent urinalysis with microscopy looking specifically for glomerular hematuria (dysmorphic red blood cells, acanthocytes) and red blood cell casts 3, 4
• Order autoimmune serologies (ANCA, anti-GBM, ANA, complement levels) to narrow the differential diagnosis 3, 5
• Exception: If clinical presentation strongly suggests ANCA vasculitis with positive MPO- or PR3-ANCA, do not delay immunosuppressive therapy while waiting for biopsy 3

Universal Supportive Care (Start Immediately for All Types)

Blood Pressure and Proteinuria Control

• Start ACE inhibitors or ARBs at maximally tolerated doses as first-line therapy for all patients with hypertension and proteinuria 1, 2
• Target systolic blood pressure <120 mmHg in adults using standardized office measurement 1, 2
• In children, target 24-hour mean arterial pressure at ≤50th percentile for age, sex, and height by ambulatory monitoring 1, 2
• Hold RAS inhibitors during intercurrent illnesses with volume depletion risk to prevent acute kidney injury 1

Edema Management

• Use loop diuretics (furosemide) as first-line agents for edema 1
• Add thiazide diuretics if loop diuretics alone are insufficient 1
• Monitor closely for hyponatremia, hypokalemia, GFR reduction, and volume depletion 1

Dietary Modifications

• Restrict sodium to <2.0 g/day to control hypertension and fluid retention 2
• For nephrotic-range proteinuria: prescribe 0.8-1 g/kg/day protein with additional protein up to 5 g/day to compensate for urinary losses 1, 2
• For eGFR <60 ml/min/1.73 m² with nephrotic proteinuria: limit to 0.8 g/kg/day 1
• Never restrict protein below 0.6 g/kg/day due to malnutrition risk 1

Disease-Specific Immunosuppressive Treatment (After Biopsy Confirmation)

Post-Infectious Glomerulonephritis

• Administer penicillin (or erythromycin if penicillin-allergic) even without persistent infection to decrease antigenic load 1, 2
• First-generation cephalosporins (cephalexin) are appropriate for non-anaphylactic penicillin allergies 2
• Manage nephritic syndrome with diuretics, antihypertensives, and dialysis if necessary 1
• Consider corticosteroids only for severe crescentic disease based on anecdotal evidence 1

Membranous Nephropathy

• Observe for 6 months with supportive care alone before starting immunosuppression unless severe symptoms (albumin <2.5 g/dL with thrombosis risk) or declining kidney function (creatinine rise ≥30% within 6-12 months) are present 6, 1, 2
• When immunosuppression is indicated: use 6-month course of alternating monthly cycles of oral and IV corticosteroids with oral cyclophosphamide (preferred over chlorambucil) 6, 1, 2
• Alternative for contraindications to alkylating agents: cyclosporine or tacrolimus for at least 6 months 1
• Do not use immunosuppression if serum creatinine ≥3.5 mg/dL or eGFR ≤30 ml/min/1.73 m² with small echogenic kidneys 6

Focal Segmental Glomerulosclerosis (FSGS)

• Use high-dose corticosteroids (prednisone 1 mg/kg/day or 2 mg/kg every other day, maximum 80 mg/day) for minimum 4 weeks, up to 16 weeks as tolerated or until complete remission 1, 2
• Taper corticosteroids slowly over 6 months after achieving complete remission 1, 2
• For steroid-resistant or steroid-intolerant cases: use calcineurin inhibitors (cyclosporine or tacrolimus) 1

Membranoproliferative Glomerulonephritis (MPGN)

• For HCV-associated cryoglobulinemic nephritis with diffuse MPGN: use glucocorticoids and/or immunosuppressive agents with plasma exchange as first-line, then consider antiviral therapy after stabilization 6
• For HCV-associated mesangial glomerulonephritis: use direct-acting antivirals (DAAs) as first-line since lesions are self-limiting 6
• For idiopathic MPGN with nephrotic syndrome and progressive kidney function decline: use oral cyclophosphamide or mycophenolate mofetil plus low-dose alternate-day or daily corticosteroids for <6 months 6, 1, 2
• In children with MPGN and nephrotic syndrome: consider alternate-day steroids (40 mg/m²) for 6-12 months 1

HCV-Related Glomerulonephritis

• For CKD stages 1-2: use combined pegylated interferon and ribavirin 6, 1
• For CKD stages 3-5 not on dialysis: use pegylated interferon monotherapy with dose adjustment for kidney function 6, 1
• For HCV with mixed cryoglobulinemia causing nephrotic proteinuria or progressive disease: use plasmapheresis, rituximab, or cyclophosphamide with IV methylprednisolone plus concomitant antiviral therapy 6

HBV-Related Glomerulonephritis

• Treat with interferon-α or nucleoside analogues as recommended for general population 6
• Adjust antiviral agent dosing based on degree of kidney function 6

Pre-Immunosuppression Safety Protocol

• Screen for latent tuberculosis, HIV, hepatitis B, and hepatitis C before starting immunosuppression 2, 3
• Review and update vaccination status: administer pneumococcal vaccine, influenza vaccine, and herpes zoster vaccination (Shingrix) 1, 2
• Provide prophylactic trimethoprim-sulfamethoxazole for patients receiving high-dose prednisone or other immunosuppressive agents 1
• Consider fertility preservation counseling where indicated 1

Monitoring Treatment Response

• Assess proteinuria regularly using spot urine protein-creatinine ratio as the primary marker of treatment response 1, 2, 3
• Monitor for ≥40% decline in eGFR from baseline over 2-3 years as surrogate outcome for kidney failure 1, 2, 3
• Perform repeat kidney biopsy only if rapidly deteriorating kidney function occurs (doubling of creatinine over 1-2 months) in absence of massive proteinuria (≥15 g/day) 6, 1

Critical Pitfalls to Avoid

• Do not use mycophenolate mofetil in non-Chinese patients with IgA nephropathy as it lacks efficacy 2
• Avoid prolonged or multiple rounds of immunosuppression due to cumulative toxic drug exposure 1, 2
• Do not use corticosteroids or immunosuppression for schistosomal-associated glomerulonephritis as it results from direct infection 6
• IgA-dominant postinfectious glomerulonephritis must be distinguished from idiopathic IgA nephropathy to avoid inappropriate corticosteroid treatment 1
• Do not extrapolate pediatric treatment data to adults as adults respond more slowly with higher side effect risk 2
• Monitor therapeutic drug levels for calcineurin inhibitors and watch for development of cancers or infections during immunosuppressive therapy 1, 3