Nephritic syndrome refers to a group of glomerular disorders characterized by hematuria and limited proteinuria (< 3.5 g/day) from inflammatory injury to the glomerulus. Most cases arise due to immune complex deposition in the subendothelial space or mesangium, triggering complement activation and subsequent inflammatory infiltrate. Nephritic syndromes can cause periorbital edema and peripheral edema (less common).
Nephritic syndrome presents with dysmorphic RBCs, RBC casts, & WBC casts in the urine. Electron microscopy shows a granular pattern on immunofluorescence. Clinically, patients often present with hematuria, oliguria, & hypertension, along with signs of renal insufficiency like increased BUN & creatinine).
Notable causes of nephritic syndrome include IgA nephropathy (Berger disease), post-streptococcal glomerulonephritis (PSGN), diffuse proliferative glomerulonephritis (DPGN) and membranoproliferative glomerulonephritis (MPGN).
IgA nephropathy is caused IgA & immune complexes deposition in the mesangium. IgA nephropathy often manifests clinically as gross hematuria following an upper respiratory or GI infection.
Post-streptococcal glomerulonephritis (PSGN) typically occurs 1-3 weeks after a group A streptococcal infection and is marked by cola-colored urine and leukocyte infiltration in the mesangium & endothelium.
DPGN and MPGN often present as nephritic syndrome and nephrotic syndrome concurrently. Diffuse proliferative glomerulonephritis (DPGN) is often associated with SLE, and occurs due to anti-DNA immune complex deposition in the subendothelial space, displaying a ‘wire-looping’ of capillaries on LM and a granular pattern on IF.
Membranoproliferative glomerulonephritis (MPGN) can be initiated by various agents, including viral & bacterial infections or autoimmune conditions. MPGN is characterized by a tram-track appearance of the GBM. Type I MPGN is associated with HBV/HCV and occurs due to immune complex deposition in the subendothelial space. Type II MPGN (dense deposit disease) results in intramembranous complex deposition and is associated with C3 nephritic factor, which stabilizes C3 convertase and persistently activated the alternative complement pathway, lowering C3 levels.
A delay in diagnosis and treatment of nephritic syndrome can result in progression to rapidly progressive glomerulonephritis (RPGN). All immune-complex mediated glomerulonephritides can lead to RPGN, resulting in accumulation of plasma proteins and fibrin deposits that form crescents within Bowman’s space, leading to segmental glomerular necrosis and breakdown in the GBM. Pauci-immune RPGN (no IC deposition) can also occur in conditions such as anti-neutrophilic autoimmune vasculitides (c-ANCA/p-ANCA associated vasculitides) and anti-GBM disease (Goodpasture’s syndrome).
Nephritic syndrome is a renal condition marked by inflammatory damage to the glomeruli. The syndrome is primarily identified by the presence of hematuria, which can be either gross or microscopic, and includes dysmorphic RBCs and RBC casts, signaling glomerular damage. Other signs may include WBC in the urine, increased levels of blood urea nitrogen (BUN) and creatinine, reduced urine output (oliguria), and elevated blood pressure due to salt and water retention. It may also manifest as periorbital and, occasionally, peripheral edema. Proteinuria is also a feature but is generally less pronounced compared to nephrotic syndrome.
Most cases of nephritic syndrome are an outcome of glomerular injury due to inflammation. The injury typically originates from antibody-antigen binding, leading to immune complex (IC) deposition which in turn triggers complement activation and ensuing inflammation. Immune complexes customarily deposit in the subendothelial space or the glomerulus mesangium. This immune complex deposition often results in a “granular” pattern on immunofluorescence microscopy and causes a subsequent complement activation leading to low serum C3.
Type II membranoproliferative glomerulonephritis involves the deposition of an unknown material in the glomerular basement membrane (GBM), transforming it into an irregular, electron-dense ribbon. This condition is associated with overactivation of the alternative complement pathway, often due to the presence of an autoantibody called C3 nephritic factor. This leads to a stabilized C3 convertase and an overactive alternative pathway, resulting in low levels of serum C3 with normal C4.
PSGN is a type of nephritic syndrome that occurs typically 1-3 weeks after a skin or pharyngeal infection with nephritogenic strains of group A strep. PSGN is associated with immune complex deposition in the mesangium, as well as both the subendothelial and subepithelial spaces. Hematuria, often described as "cola-colored," is a common manifestation of PSGN. Additionally, light microscopy shows marked leukocyte infiltration in the mesangium and endothelium and immunofluorescence microscopy reveals a granular pattern due to immune complex deposition.
Rapidly progressive glomerulonephritis (RPGN) is a severe form of glomerular disease that leads to a rapid decline in kidney function It can be a progression of immune-complex mediated glomerulonephritides (such as PSGN, diffuse proliferative glomerulonephritis, IgA nephropathy, HSP), or pauc-immune in origin. On light microscopy, the glomeruli show segmental necrosis and breaks in the glomerular basement membrane. Crescent formation is a hallmark feature, caused by epithelial cell proliferation from the capsule, leading to the obliteration of Bowman's space. Immunofluorescence often shows a granular pattern in immune complex-mediated forms of RPGN.