Expanding the spectrum of APOL1-related renal disease: de novo collapsing glomerulopathy following kidney transplant

Kopp, Jeffrey B.

doi:10.1016/j.kint.2018.09.006

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…Increased susceptibility to collapsing glomerulopathy, including HIV-associated nephropathy, has been linked to risk variants of APOL1 (G1, G2), which are increased in those of African descent and are protective against trypanosomal disease. 26,[29][30][31] Our patients were Black with two risk alleles for APOL1, suggesting the possibility that COVID-19 may increase the risk of collapsing glomerulopathy in those patients with risk variants of APOL1, i.e., a "second-hit" phenomenon. In one patient, a single kidney status due to living donation more than a decade earlier likely further increased the risk of adverse response to additional hits.…”

Section: Discussionmentioning

confidence: 83%

“…Collapsing glomerulopathy has numerous etiologies including viral infections, such as HIV, cytomegalovirus, and parvovirus B19; severe ischemia; medications, such as pamidronate, anabolic steroids; and IFN. [25][26] Whereas HIV can directly infect renal parenchymal cells (tubular epithelial cells and glomerular visceral epithelial cells) in cases of HIV-associated nephropathy, 27,28 such definitive evidence for coronavirus glomerular infection is lacking. Increased susceptibility to collapsing glomerulopathy, including HIV-associated nephropathy, has been linked to risk variants of APOL1 (G1, G2), which are increased in those of African descent and are protective against trypanosomal disease.…”

Section: Discussionmentioning

confidence: 99%

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AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype

Larsen

Hernandez-Arroyo

et al. 2020

JASN

240

273

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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.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype

Larsen

Hernandez-Arroyo

et al. 2020

JASN

240

273

View full text Add to dashboard Cite

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“…This type of inflammatory response may also harm the kidney and glomerular function. Many studies have emphasized the potential involvement of interferon pathways [16,17] and a viral trigger [18][19][20][21] in glomerular injury. Podocyte dysregulation might be due to an infection-driven inflammatory response that releases cytokines or viral products; in turn, these products circulate and interact with receptors on podocytes [22].…”

Section: Discussionmentioning

confidence: 99%

Indirect effects of severe acute respiratory syndrome coronavirus 2 on the kidney in coronavirus disease patients

Couturier

Ferlicot

Chevalier

et al. 2020

Clinical Kidney Journal

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Among patients hospitalized for novel coronavirus disease (COVID-19), between 10 and 14% develop an acute kidney injury and around half display marked proteinuria and haematuria. Post-mortem analyses of COVID-19 kidney tissue suggest that renal tubular cells and podocytes are affected. Here we report two cases of collapsing glomerulopathy and tubulointerstitial lesions in living COVID-19 patients. Despite our use of sensitive reverse transcription polymerase chain reaction techniques in this study, we failed to detect the virus in blood, urine and kidney tissues. Our observations suggest that these kidney lesions are probably not due to direct infection of the kidney by severe acute respiratory syndrome coronavirus 2.

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“…In particular, APOL1 variants have been associated with increased risk for progression of different kidney diseases, as well as de novo collapsing glomerulopathy after transplantation, and their frequency is probably higher in Hispanic individuals. [34][35][36] Collapsing lesions in pregnancy have been infrequently reported, possibly because of the rarity of kidney biopsy in this setting. A common element in our 3 cases was good response to therapy, unusual in collapsing FSGS.…”

Section: Discussionmentioning

confidence: 99%

Collapsing Lesions and Focal Segmental Glomerulosclerosis in Pregnancy: A Report of 3 Cases

Guillén

Silva

González

et al. 2019

American Journal of Kidney Diseases

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The relationship between focal segmental glomerulosclerosis (FSGS) and pregnancy is complex and not completely elucidated. Pregnancy in patients with FSGS poses a high risk for complications, possibly due to hemodynamic factors, imbalance between angiogenic and antiangiogenic factors, and hormonal conditioning. Although poor clinical outcomes associated with collapsing FSGS are common outside of pregnancy, the prognosis during pregnancy is not well documented. We report 3 patients who developed collapsing FSGS during pregnancy, 2 of whom had presumed underlying FSGS. Two patients underwent biopsy during pregnancy, and 1, during the puerperium. None of the 3 patients improved spontaneously after delivery, and 1 experienced a rapid deterioration in kidney function and proteinuria after delivery. Aggressive immunosuppressive therapy led to a full response in 1 case (without chronic lesions) and to partial responses in the remaining 2 cases. These cases suggest that collapsing lesions should be considered in patients with FSGS who develop a rapid increase in serum creatinine level or proteinuria during pregnancy and that these lesions may at least partially respond to treatment.

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Expanding the spectrum of APOL1-related renal disease: de novo collapsing glomerulopathy following kidney transplant

Cited by 4 publications

References 9 publications

AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype

AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype

Indirect effects of severe acute respiratory syndrome coronavirus 2 on the kidney in coronavirus disease patients

Collapsing Lesions and Focal Segmental Glomerulosclerosis in Pregnancy: A Report of 3 Cases

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