Parietal epithelial cells role in repair versus scarring after glomerular injury

International audiencePurpose of review: The recent years have been marked by the publication of several articles highlighting the pathophysiological role of glomerular parietal epithelial cells (PEC) and refining their phenotypic heterogeneity.Recent findings: The present review synthetizes recent findings on (i) the potential regenerative role of PEC in glomerular diseases, and (ii) the mechanisms and signaling of leading to PEC pathogenic involvement in crescentic glomerulonephritis (CGN) and focal segmental glomerulosclerosis (FSGS).Summary: The debate is still open regarding the podocyte regenerative properties of PEC in glomerular disease, whereas the pathogenic involvement of PEC activation in glomerular disease is increasingly admitted. Recent highlights on the podocyte regenerative role of PEC, on one hand, and on their pathological function, on the other hand, for sure will feed the debate in the kidney community for the next years. Nevertheless, from a therapeutic perspective, the two options, boosting cellular regeneration and blocking PECs pathogenicity, should not be seen as antagonistic but, rather, complementary

Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries

Objective. Indirect evidence suggests a role for heme oxygenase-1 (HO-1) in limiting diabetic vasculopathy. The goal of this study was to assess the role of HO-1 in the development of microvascular lesions within glomeruli during diabetes mellitus using a mouse model with specific alteration of the Hmox1 gene. Approach and Results. The effects of Hmox1 haploinsufficiency were studied as a means of assessing the intrinsic contribution of HO-1 in the development of renal microvascular lesions during diabetes. Renal function and histology were analyzed 10 weeks after diabetes induction with streptozotocin. Diabetic Hmox1+/− mice showed higher levels of albuminuria and blood urea compared to their wild-type diabetic littermates. More severe glomerular microvascular lesions were also observed in the diabetic Hmox1+/− mice. This was associated with a renal increase in the expression of the oxidative stress marker, nitrotyrosine. Conclusions. Genetic Hmox1 partial deficiency is sufficient to sensitize mice to the development of diabetic glomerular microvascular lesions. HO-1 exerts antioxidant effects in the kidney during diabetes mellitus. These have protective effects on the development of glomerular endothelial injury

Rôle pathogénique de l’expression anormale de la tétraspanine CD9 par les cellules épithéliales pariétales dans les glomérulopathies extracapillaires

International audienceNo abstract availabl

COVID-19–Related Collapsing Glomerulopathy in a Kidney Transplant Recipient

International audienceWe report a case of a kidney transplant recipient who presented with acute kidney injury and nephrotic-range proteinuria in a context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Kidney biopsy revealed collapsing glomerulopathy. Droplet-based digital polymerase chain reaction did not detect the presence of SARS-CoV-2 RNA in the biopsy fragment, and the virus was barely detectable in plasma at the time of the biopsy. SARS-CoV-2 RNAemia peaked several days later, followed by a seroconversion despite the absence of circulating CD19-positive lymphocytes at admission due to rituximab-based treatment of antibody-mediated rejection 3 months earlier. Genotyping for the 2 risk alleles of the apolipoprotein L1 (APOL1) gene revealed that the donor carried the low-risk G0/G2 genotype. This case illustrates that coronavirus disease 2019 infection may promote a collapsing glomerulopathy in kidney allografts with a low-risk APOL1 genotype in the absence of detectable SARS-CoV-2 RNA in the kidney and that podocyte injury may precede SARS-CoV-2 RNAemia

The cellular prion protein is a stress protein secreted by renal tubular cells and a urinary marker of kidney injury

International audienceEndoplasmic Reticulum (ER) stress underlies the pathogenesis of numerous kidney diseases. A better care of patients with kidney disease involves the identification and validation of ER stress biomarkers in the early stages of kidney disease. For the first time to our knowledge, we demonstrate that the prion protein PrP C is secreted in a conventional manner by ER-stressed renal epithelial cell under the control of the transcription factor x-box binding protein 1 (XBP1) and can serve as a sensitive urinary biomarker for detecting tubular ER stress. Urinary PrP C elevation occurs in patients with chronic kidney disease. In addition, in patients undergoing cardiac surgery, detectable urine levels of PrP C significantly increase after cardiopulmonary bypass, a condition associated with activation of the IRE1-XBP1 pathway in the kidney. In conclusion, our study has identified PrP C as a novel urinary ER stress biomarker with potential utility in early diagnosis of ongoing acute or chronic kidney injury