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Introduction Recent evidence suggests that complement activation is important in the pathogenesis of pauci-immune (PI) vasculitis. This is a retrospective investigation of the frequency of hypocomplementemia at pauci-immune glomerulonephritis (PIGN) diagnosis, in relation to vasculitic manifestations, renal histopathology, and treatment outcomes. Methods A total of 115 patients with biopsy-proven PIGN were categorized based on their serum complement C3 (sC3). Histopathology evaluation included activity and chronicity indexes. The primary outcome of interest was treatment resistance, defined as a progressive decline in kidney function, with persistently active urine sediment, leading to dialysis dependency or vasculitis-related death. Results In all, 20.9% of patients had low sC3 levels associated with more advanced renal impairment (P < 0.01), requiring acute dialysis (P < 0.01) more frequently compared to patients with normal sC3. Within 1 year, 85.7% of patients with normal sC3 responded to therapy, versus 58.3% of those with low sC3 (P = 0.001). The probability of treatment resistance was strongly associated with low sC3 (P = 0.004), high serum creatinine (P < 0.001), acute dialysis requirement (P < 0.001), and high histopathological score of chronicity (P < 0.01). Advanced histopathological activity was related to more intense interstitial leukocyte infiltration (P = 0.005) and higher likelihood of fibrinoid necrosis documentation in a vessel wall (P = 0.02). The probability of treatment resistance was higher in patients with low sC3 (odds ratio [OR] = 6.47, 95% confidence interval [CI] 1.47−28.35, P = 0.013), oliguria (OR = 29.57, 95% CI = 4.74−184, P < 0.0001), and high chronicity score (OR = 1.77, 95% CI = 1.23−2.54, P = 0.002). Conclusion Low sC3 is emerging as an independent predictor of treatment resistance in patients with PIGN associated with higher index of histopathological activity at diagnosis compared to normal sC3., Graphical abstract

There are several known mechanisms by which monoclonal Igs (MIg) or their subunits can cause kidney disease: (i) deposition in 1 or more kidney compartments, resulting in distinct clinicopathologic lesions, such as Ig-related amyloidosis, monoclonal Ig deposition disease, and a variety of glomerulonephritides, including cryoglobulinemic glomerulonephritis type I and II, immunotactoid glomerulonephritis, and proliferative glomerulonephritis with monoclonal immunoglobulin deposits; (ii) precipitation in tubular lumina (e.g., myeloma cast nephropathy); (iii) activation of the alternative pathway of complement (e.g., C3 glomerulopathy associated with monoclonal gammopathy, thrombotic microangiopathy associated with monoclonal gammopathy); (iv) cytokine activation (e.g., POEMS syndrome); and (v) crystallization in the renal vasculature (e.g., crystalglobulin-induced nephropathy).1, 2 Here, we describe an unusual case of monoclonal gammopathy of renal significance (MGRS)–associated crystalline nephropathy that does not conform to any of the previously described patterns of kidney involvement by monoclonal gammopathy.

When renal biopsy reveals crescentic glomerulonephritis, differential diagnosis is wide and includes 3 immunopathologic categories of disease: immune-complex–mediated glomerulonephritis (such as IgA nephropathy, lupus nephritis, and bacterial infection–associated glomerulonephritis, particularly infectious endocarditis-associated glomerulonephritis), anti–glomerular basement membrane nephritis, and pauci-immune crescentic glomerulonephritis (associated with antineutrophil cytoplasmic antibody seropositivity in most patients). Careful integration of immunofluorescence and ultrastructural findings with the serologic tests and medical history is essential to determine the underlying cause. Rarely, crescentic glomerulonephritis occurs concomitantly with granulomatous interstitial nephritis, and the differential diagnosis in this scenario includes granulomatosis with polyangiitis and sarcoidosis. Here we report an unusual case of pauci-immune crescentic and necrotizing glomerulonephritis concurrent with granulomatous interstitial nephritis due to disseminated histoplasmosis.

Coronavirus disease 2019 (COVID-19) is a pandemic caused by a novel coronavirus that has been identified to belong to the β-coronavirus family.1 As the COVID-19 pandemic continues to evolve, more aspects of this illness are being defined and described. In the United States, the incidence of acute kidney injury (AKI) in patients hospitalized with COVID-19 has been reported to be around 37%.2 Different autopsy and kidney biopsy series have revealed acute tubular injury (ATI) to be the most common renal pathology lesion in these patients.3,S1 Although cases of collapsing glomerulopathy and thrombotic microangiopathy (TMA) with COVID-19 have been reported,4,5 an association between COVID-19 and crescentic glomerulonephritis (GN) has rarely been described.6 Herein, we report 2 cases of pauci immune GN with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, who clinically improved with treatment of COVID-19 and cautious use of immunosuppressants.

Heleen Ameye, Sabine Fransis, Evelyne Lerut, Christoph Metalidis and Ben Sprangers Department of Nephrology, University Hospitals Leuven, Leuven, Belgium; Department of Pathology, Ziekenhuis OostLimburg Hospital, Genk, Belgium; Department of Morphology and Molecular Pathology, University Hospitals Leuven, Leuven, Belgium; Department of Nephrology, Ziekenhuis Oost-Limburg Hospital, Genk, Belgium; and Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium