Glomerular disorders: an overview of nephritic and nephrotic syndrome

Focal segmental glomerulosclerosis is a podocytopathy causing segmental glomerular scarring on biopsy, presenting with nephrotic-range proteinuria and accounting for up to 40% of primary nephrotic syndrome in adults. Diagnosis requires kidney biopsy, and primary disease is treated with high-dose glucocorticoids followed by calcineurin inhibitors for resistant cases.

HIV-associated nephropathy is the collapsing variant of focal segmental glomerulosclerosis seen in HIV infection, driven largely by the high-risk APOL1 genotype, and confirmed by kidney biopsy. Antiretroviral therapy started immediately, plus a tenofovir alafenamide-based regimen and RAS blockade, is the cornerstone of management.

Membranous nephropathy is the leading cause of nephrotic syndrome in white adults, most often a primary autoimmune disease driven by anti-PLA2R antibodies against a podocyte antigen, diagnosed by kidney biopsy or noninvasively by anti-PLA2R serology. Patients with persistent nephrotic-range proteinuria after a period of conservative observation are treated with cyclical glucocorticoid-cyclophosphamide, a calcineurin inhibitor, or rituximab.

Membranoproliferative glomerulonephritis is a rare chronic glomerulonephritis divided into immune-complex forms, most often driven by hepatitis C virus infection, and complement-mediated C3 glomerulopathies from alternative-pathway dysregulation, diagnosed by kidney biopsy with immunofluorescence. Treatment targets the underlying cause plus immunosuppression for nephrotic-range proteinuria or kidney dysfunction, and more than half of patients progress to end-stage kidney disease within 15 years.

IgA nephropathy is the most common primary glomerular disease worldwide, caused by galactose-deficient IgA1 immune complexes depositing in the mesangium, presenting classically with synpharyngitic gross hematuria in young adults and confirmed by kidney biopsy showing dominant mesangial IgA deposits. First-line therapy is renin-angiotensin system blockade, since roughly 40% of patients progress to end-stage kidney disease within 15 years despite treatment.

Poststreptococcal glomerulonephritis (PSGN) is an immune-complex nephritic syndrome that follows group A streptococcal pharyngitis or skin infection by 1 to 4 weeks, presenting with cola-colored urine, edema, and hypertension in school-aged children. Diagnosis is typically clinical, supported by low complement (C3) and elevated antistreptolysin O/anti-DNase B titers, and treatment is supportive; children recover completely far more often than adults.

Rapidly progressive glomerulonephritis is a clinical syndrome defined by at least a 50% decline in glomerular filtration rate over days to weeks with extensive glomerular crescents on biopsy, most often from ANCA-associated, anti-glomerular basement membrane, or immune-complex glomerulonephritis. Untreated disease progresses to dialysis within days to weeks, so kidney biopsy and etiology-directed immunosuppression must begin urgently.

Anti-glomerular basement membrane (anti-GBM) disease is a rare, rapidly progressive glomerulonephritis caused by circulating antibodies against the alpha-3 chain of type IV collagen, presenting with hematuria, acute kidney injury, and, in over half of patients, pulmonary hemorrhage (Goodpasture syndrome). Kidney biopsy showing crescentic glomerulonephritis with linear IgG staining plus a positive serum anti-GBM antibody confirms the diagnosis, and outcome depends critically on early treatment with plasma exchange, pulse glucocorticoids, and cyclophosphamide before dialysis dependence and diffuse crescents set in.

Hematuria is present in urine when at least 3 erythrocytes per high-power field are seen on microscopy, and the first branch point is glomerular versus nonglomerular bleeding, based on erythrocyte morphology and casts. Gross hematuria always requires urologic evaluation and cystoscopy, asymptomatic microscopic hematuria is risk-stratified by American Urological Association criteria to select repeat testing, imaging, or cystoscopy, and glomerular hematuria is treated with disease-specific immunosuppression after biopsy.