Membranoproliferative Glomerulonephritis Diagnosis and Treatment

Clinical Presentation and Diagnosis

The American Society of Nephrology recommends that nephritic syndrome may occur with hematuria, proteinuria, hypertension, and acute kidney injury 1
The Journal of the American Society of Nephrology suggests that serum creatinine, urinalysis with quantification of proteinuria, and complement levels (C3 and C4) are mandatory for diagnosis 2
The American Society of Nephrology states that protein electrophoresis to detect monoclonal proteins and hepatitis C serology, cryoglobulin titers, and antinuclear antibody testing to identify secondary causes are essential 2
Genetic screening for mutations in C3, complement factors H/I/B, CD46, and CFHR 1-5 is recommended for C3 glomerulopathy in children 1
The American Society of Nephrology recommends testing for acquired autoantibodies including C3 nephritic factor (C3Nef) and anti-factor H antibody for C3 glomerulopathy in adults 1

The Journal of the American Society of Nephrology suggests that mesangial and/or endocapillary hypercellularity with thickening of capillary walls caused by subendothelial deposits is a characteristic feature of MPGN 3
Lobular accentuation of glomerular tufts with mesangial expansion and GBM changes including double contours ("tram-tracking") are common findings 2
Documenting the percentage of globally sclerosed glomeruli and extent of tubulointerstitial fibrosis is crucial 2, 1

The American Society of Nephrology recommends that patients with idiopathic MPGN with nephrotic-range proteinuria and/or impaired renal function should be treated with oral cyclophosphamide or mycophenolate mofetil (MMF) plus low-dose alternate-day or daily corticosteroids for less than 6 months 1
Direct-acting antivirals targeting HCV are the primary treatment for hepatitis C-associated MPGN 1
Treating the underlying infection (e.g., bacterial endocarditis, cellulitis) is essential for infection-related MPGN 4, 5
The American Society of Nephrology suggests that treating the underlying hematologic disorder (e.g., Waldenström macroglobulinemia) is necessary for monoclonal Ig-associated MPGN 4, 5

The American Society of Nephrology states that patients with nephrotic-range proteinuria >3.8 g/day have a 35% risk of end-stage renal disease within 2 years 6
Nephrotic syndrome carries significant thrombotic risk with 29% incidence of renal vein thrombosis and 17-28% incidence of pulmonary embolism due to loss of anticoagulant proteins 6

Renal biopsy specimens should be evaluated by experienced nephropathologists due to the rarity and complexity of MPGN classification 7

Patients with idiopathic MPGN with nephrotic syndrome and progressive decline in kidney function should receive oral cyclophosphamide or mycophenolate mofetil (MMF) plus low-dose alternate-day or daily corticosteroids for less than 6 months, as recommended by the American Journal of Kidney Diseases 7
Indications for immunosuppressive therapy include nephrotic syndrome with or without progressive decline in kidney function, active nephritic syndrome, and rapidly progressive disease with or without crescents, according to the American Journal of Kidney Diseases 7
Patients who should not receive immunosuppression include those with normal eGFR and non-nephrotic-range proteinuria, and those with advanced CKD with severe tubulointerstitial fibrosis, small kidney size, or chronic inactive disease, as stated by the American Journal of Kidney Diseases 7

In children with MPGN and nephrotic syndrome and/or impaired renal function, alternate-day prednisone (40 mg/m²) for 6 to 12 months is warranted as first-line treatment, according to the American Journal of Kidney Diseases 7

All patients require close follow-up every 3-4 months monitoring renal function, proteinuria, and urine microscopy, as recommended by the American Journal of Kidney Diseases 7

Failing to distinguish primary from secondary MPGN, and not recognizing MPGN pattern without immune deposits, can lead to inappropriate treatment, as warned by the American Journal of Kidney Diseases 7
Treating patients with advanced chronic disease with immunosuppression is contraindicated, as stated by the American Journal of Kidney Diseases 7