scholarly journals Collapsing glomerulopathy in a patient with APOL1 intermediate-risk genotype triggered by lupus nephritis and SARS-CoV-2 infection: lessons for the clinical nephrologist

Author(s):  
Christophe Masset ◽  
Karine Renaudin ◽  
Delphine Kervella ◽  
Agnès Chapelet ◽  
Clément Deltombe ◽  
...  
2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Carole Burger ◽  
KARRAS Alexandre

Abstract Background and Aims African ancestry is associated with more severe kidney involvement and end stage renal disease (ESRD) in lupus nephritis (LN). Two polymorphisms of the apolipoprotein L1 gene (APOL1), defining the risk allels (RA) G1 and G2, particularly frequent among subjects of African ancestry, markedly increase the risk of ESRD and the occurrence of collapsing glomerulopathy (CG) in the general population. The aim of this study was to assess the impact of ApoL1 RA on clinical, biological, and histological presentation of LN, and its prognosis. Method Patients of African ancestry with biopsy-proven LN were included between January 2017 and September 2018. Clinical, laboratory and pathology datas were retrospectively collected and ApoL1 genotyping was performed. Results Among the 53 included patients, 31 had no RA, 16 were heterozygous with only one RA and 6 had 2 RA (G1/G1 or G2/G2 or G1/G2). The population was divided in 2 groups: low risk polymorphism (LRP) group defined by the presence of 0 or 1 RA, and high risk polymorphism (HRP) group with 2 RA. At presentation, hypertension (OR 25,4 [1,3-510,3]) and acute renal failure (OR: 9,3 [1,3-65,2]), were more frequent in the HRP group when compared to the LRP group. Initial median serum creatinine was respectively 363 μmol/l (IQR 119-594) vs 64 μmol/l (IQR 55-127). After 2-year follow-up, median eGFR was 59mL/min (IQR 41-91) in the HRP group and 117mL/min (IQR 92-124mL/min) in the LRP group. Patients in the HRP group were more likely to have an impaired renal function with an estimated glomerular filtration rate (eGFR) <60mL/min compared to patients in the LRP group (OR: 13,5 [2,1-86,5]). Moreover, ESRD-free survival was worse in the HRP group (Hazard ratio: 78,8 [5,3-1124,0]) despite similar chronicity indexes on initial kidney biopsy and comparable therapeutic strategies. As for histological findings, CG was observed in 67% of patient’s kidney biopsy in the HRP group whereas it only concerned 12% of patient’s kidney biopsy in the LRP group (OR: 14,8 [2,4-84,8]). Conclusion The ApoL1 polymorphism strongly affects LN prognosis in patients with African ancestry, resulting in more severe inaugural presentation, higher risk of subsequent severe chronic kidney disease and development of collapsing glomerulopathy for subjects with 2 RA.


1997 ◽  
Vol 8 (1) ◽  
pp. 70-76
Author(s):  
M Haas

Electron microscopy is routinely utilized in most centers in the evaluation of native renal biopsies. Several studies, primarily from the 1960s and early 1970s, provide justification for its use. Conducted by Siegel et al. (1), the largest study evaluated 213 consecutive renal biopsies and found that electron microscopy was needed for a correct diagnosis in 11%, as well as for confirmation or additional information in another 36%. However, nearly all of these studies were conducted before the use of immunofluorescence in renal biopsy diagnosis became widespread and before several new glomerular diseases and variants were described. In light of this situation and the expense of the procedure, the routine use of electron microscopy in native renal biopsies also examined by immunofluorescence and routine light microscopy was reevaluated. From January 1996 to June 1996, 288 native renal biopsies were received, and all were evaluated by the same pathologist. Of those, 233 met criteria for inclusion in this study, which were > or = 5 glomeruli for light microscopy, > or = 2 for immunofluorescence, and > or = 1 for electron microscopy, not including globally scarred glomeruli. Light microscopy (hematoxylin and eosin, periodic acid-Schiff stains) and immunofluorescence--for immunoglobulin (Ig) G, IgA, IgM, C3, C1q, fibrinogen; kappa/lambda when needed--were evaluated on each biopsy within 48 h of receipt, and a preliminary diagnosis was recorded if possible. Electron microscopy was then performed, and a final diagnosis was made. In 50 cases (21%), electron microscopy was needed to make the final diagnosis; in two of these cases, the preliminary diagnosis was incorrect, and in 48, a firm preliminary diagnosis could not be made. In the other cases, the preliminary diagnosis was correct, but in 48 (21%), ultrastructural study was felt to provide important confirmatory data, and in eight cases (3%), an additional, unrelated diagnosis was supported by the ultrastructural findings. Diagnoses most frequently requiring electron microscopy included minimal change nephropathy, early diabetic nephropathy, membranous lupus nephritis, membranoproliferative glomerulonephritis, postinfectious glomerulonephritis, thin basement membrane nephropathy (or exclusion of this in cases of otherwise unexplained hematuria), and human immunodeficiency virus-associated nephropathy (or exclusion of it in cases of collapsing glomerulopathy). Common diagnoses usually not requiring electron microscopy included IgA nephropathy, diffuse proliferative lupus nephritis, focal segmental glomerulosclerosis (not collapsing glomerulopathy variant), pauci-immune crescentic glomerulonephritis, acute interstitial nephritis, and amyloid nephropathy. This study confirms that, as was the case 20 to 30 yr ago, electron microscopy provides useful diagnostic information in nearly half of native renal biopsies. If electron microscopy cannot be performed routinely on all such biopsies, it is recommended that tissue for ultrastructural studies be set aside in each case.


2020 ◽  
Vol 31 (8) ◽  
pp. 1688-1695 ◽  
Author(s):  
Huijuan Wu ◽  
Christopher P. Larsen ◽  
Cesar F. Hernandez-Arroyo ◽  
Muner M.B. Mohamed ◽  
Tiffany Caza ◽  
...  

BackgroundKidney involvement is a feature of COVID-19 and it can be severe in Black patients. Previous research linked increased susceptibility to collapsing glomerulopathy, including in patients with HIV-associated nephropathy, to apo L1 (APOL1) variants that are more common in those of African descent.MethodsTo investigate genetic, histopathologic, and molecular features in six Black patients with COVID-19 presenting with AKI and de novo nephrotic-range proteinuria, we obtained biopsied kidney tissue, which was examined by in situ hybridization for viral detection and by NanoString for COVID-19 and acute tubular injury–associated genes. We also collected peripheral blood for APOL1 genotyping.ResultsThis case series included six Black patients with COVID-19 (four men, two women), mean age 55 years. At biopsy day, mean serum creatinine was 6.5 mg/dl and mean urine protein-creatinine ratio was 11.5 g. Kidney biopsy specimens showed collapsing glomerulopathy, extensive foot process effacement, and focal/diffuse acute tubular injury. Three patients had endothelial reticular aggregates. We found no evidence of viral particles or SARS-CoV-2 RNA. NanoString showed elevated chemokine gene expression and changes in expression of genes associated with acute tubular injury compared with controls. All six patients had an APOL1 high-risk genotype. Five patients needed dialysis (two of whom died); one partially recovered without dialysis.ConclusionsCollapsing glomerulopathy in Black patients with COVID-19 was associated with high-risk APOL1 variants. We found no direct viral infection in the kidneys, suggesting a possible alternative mechanism: a “two-hit” combination of genetic predisposition and cytokine-mediated host response to SARS-CoV-2 infection. Given this entity’s resemblance with HIV-associated nephropathy, we propose the term COVID-19–associated nephropathy to describe it.


Cureus ◽  
2021 ◽  
Author(s):  
Angel DeLaCruz ◽  
Haider Ghazanfar ◽  
Nayrobi Peña ◽  
Rabih Nasr

2006 ◽  
Vol 175 (4S) ◽  
pp. 86-86
Author(s):  
Makoto Sumitomo ◽  
Junichi Asakuma ◽  
Yasumasa Hanawa ◽  
Kazuhiko Nagakura ◽  
Masamichi Hayakawa

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