The COVID-Kidney Controversy: Can SARS-CoV-2 Cause Direct Renal Infection?

Context: Determining whether SARS-CoV-2 causes direct infection of the kidneys is challenging due to limitations in imaging and molecular tools. Subject of Review: A growing number of conflicting kidney biopsy and autopsy reports highlight this controversial issue. Second Opinion: Based on the collective evidence, therapies that improve hemodynamic stability and oxygenation, or dampen complement activation, are likely to ameliorate acute kidney injury in COVID-19. At this time, whether inhibition of viral infection and replication directly modulates kidney damage is inconclusive.

Download Full-text

Granulomatous interstitial nephritis in a patient with SARS-CoV-2 infection

BMC Nephrology ◽

10.1186/s12882-020-02213-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Katarzyna Szajek ◽

Marie-Elisabeth Kajdi ◽

Valerie A. Luyckx ◽

Thomas Hans Fehr ◽

Ariana Gaspert ◽

...

Keyword(s):

Acute Kidney Injury ◽

Interstitial Nephritis ◽

Kidney Biopsy ◽

Kidney Diseases ◽

Case Reports ◽

Kidney Injury ◽

Maculopapular Rash ◽

Tubular Injury ◽

Granulomatous Interstitial Nephritis ◽

First Case

Abstract Background Acute kidney injury (AKI) associated with severe coronavirus disease 19 (COVID-19) is common and is a significant predictor of morbidity and mortality, especially when dialysis is required. Case reports and autopsy series have revealed that most patients with COVID-19 – associated acute kidney injury have evidence of acute tubular injury and necrosis - not unexpected in critically ill patients. Others have been found to have collapsing glomerulopathy, thrombotic microangiopathy and diverse underlying kidney diseases. A primary kidney pathology related to COVID-19 has not yet emerged. Thus far direct infection of the kidney, or its impact on clinical disease remains controversial. The management of AKI is currently supportive. Case Presentation The patient presented here was positive for SARS-CoV-2, had severe acute respiratory distress syndrome and multi-organ failure. Within days of admission to the intensive care unit he developed oliguric acute kidney failure requiring dialysis. Acute kidney injury developed in the setting of hemodynamic instability, sepsis and a maculopapular rash. Over the ensuing days the patient also developed transfusion-requiring severe hemolysis which was Coombs negative. Schistocytes were present on the peripheral smear. Given the broad differential diagnoses for acute kidney injury, a kidney biopsy was performed and revealed granulomatous tubulo-interstitial nephritis with some acute tubular injury. Based on the biopsy findings, a decision was taken to adjust medications and initiate corticosteroids for presumed medication-induced interstitial nephritis, hemolysis and maculo-papular rash. The kidney function and hemolysis improved over the subsequent days and the patient was discharged to a rehabilitation facility, no-longer required dialysis. Conclusions Acute kidney injury in patients with severe COVID-19 may have multiple causes. We present the first case of granulomatous interstitial nephritis in a patient with COVID-19. Drug-reactions may be more frequent than currently recognized in COVID-19 and are potentially reversible. The kidney biopsy findings in this case led to a change in therapy, which was associated with subsequent patient improvement. Kidney biopsy may therefore have significant value in pulling together a clinical diagnosis, and may impact outcome if a treatable cause is identified.

Download Full-text

Immunotherapy‐related acute kidney injury: Kidney biopsy or not?

Nephrology ◽

10.1111/nep.13687 ◽

2020 ◽

Vol 26 (1) ◽

pp. 89-90 ◽

Cited By ~ 1

Author(s):

Sophie Chatterton ◽

Sarah Williams ◽

Kazi Nahar ◽

Alexander M. Menzies ◽

Muh G. Wong

Keyword(s):

Acute Kidney Injury ◽

Kidney Biopsy ◽

Kidney Injury

Download Full-text

Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2104347118 ◽

2021 ◽

Vol 118 (37) ◽

pp. e2104347118

Author(s):

Ravi Shankar Keshari ◽

Narcis Ioan Popescu ◽

Robert Silasi ◽

Girija Regmi ◽

Cristina Lupu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hemolytic Anemia ◽

Complement Activation ◽

Inflammatory Responses ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Multiple Organ ◽

Immune Recognition ◽

Gram Positive ◽

Terminal Complement

Late-stage anthrax infections are characterized by dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to extreme bacteremia, sepsis, multiple organ failure, and, ultimately, death. Despite the bacterium being nonhemolytic, some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS) through unknown mechanisms. We recapitulated the pathology in baboons challenged with cell wall peptidoglycan (PGN), a polymeric, pathogen-associated molecular pattern responsible for the hemostatic dysregulation in anthrax sepsis. Similar to aHUS anthrax patients, PGN induces an initial hematocrit elevation followed by progressive hemolytic anemia and associated renal failure. Etiologically, PGN induces erythrolysis through direct excessive activation of all three complement pathways. Blunting terminal complement activation with a C5 neutralizing peptide prevented the progressive deposition of membrane attack complexes on red blood cells (RBC) and subsequent intravascular hemolysis, heme cytotoxicity, and acute kidney injury. Importantly, C5 neutralization did not prevent immune recognition of PGN and shifted the systemic inflammatory responses, consistent with improved survival in sepsis. Whereas PGN-induced hemostatic dysregulation was unchanged, C5 inhibition augmented fibrinolysis and improved the thromboischemic resolution. Overall, our study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and likely other gram-positive infections in which PGN is abundantly represented. Neutralization of terminal complement reactions reduces the hemolytic uremic pathology induced by PGN and could alleviate heme cytotoxicity and its associated kidney failure in gram-positive infections.

Download Full-text

Diagnostic utility of kidney biopsy in patients with sarcoidosis and acute kidney injury

International Journal of Nephrology and Renovascular Disease ◽

10.2147/ijnrd.s22549 ◽

2011 ◽

pp. 131 ◽

Cited By ~ 8

Author(s):

Ravish Shah ◽

Ravish Shah

Keyword(s):

Acute Kidney Injury ◽

Kidney Biopsy ◽

Kidney Injury ◽

Diagnostic Utility

Download Full-text

Tubulitis in a patient treated with nivolumab: Case report and literature review

Journal of Onco-Nephrology ◽

10.1177/2399369318812969 ◽

2018 ◽

Vol 2 (2-3) ◽

pp. 107-112

Author(s):

Viral Vakil ◽

Mark Birkenbach ◽

Katti Woerner ◽

Lihong Bu

Keyword(s):

Acute Kidney Injury ◽

Immune Checkpoint Inhibitors ◽

Kidney Biopsy ◽

Tubulointerstitial Nephritis ◽

Checkpoint Inhibitors ◽

Kidney Injury ◽

Programmed Death Ligand 1 ◽

Programmed Death ◽

Metastatic Urothelial Carcinoma ◽

Programmed Death 1

Kidney injury associated with use of immune checkpoint inhibitors that target the programmed death-1 molecule commonly manifests as acute tubulointerstitial nephritis on kidney biopsy. We present a case of a 66-year-old man who developed acute kidney injury at 6 months after initiation of treatment with anti-programmed death-1 antibody, nivolumab, for treatment of metastatic urothelial carcinoma. A renal biopsy showed focal moderate-to-severe lymphocytic tubulitis with minimal interstitial inflammation. Programmed death ligand-1 immunopositivity was detected only in tubules exhibiting lymphocytic tubulitis. The patient’s renal function improved to baseline with conservative management consisting of discontinuation of nivolumab followed by prednisone treatment.

Download Full-text

P0531CONTINUOUS HEMODIAFILTRATION WITH PMMA HEMOFILTER MODULATED COMPLEMENT ACTIVATION AND RENAL DYSFUNCTION IN A SWINE MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0531 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Alessandra Stasi ◽

ROSSANA FRANZIN ◽

Fabio Sallustio ◽

Chiara Divella ◽

Claudia Curci ◽

...

Keyword(s):

Gene Expression ◽

Acute Kidney Injury ◽

Complement Activation ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Kidney Injury ◽

Swine Model ◽

Complement Factor ◽

Factor B ◽

Renal Biopsies

Abstract Background and Aims Sepsis-induced acute kidney injury (AKI) is a growing health care problem, refractory to conventional treatments. This disease is characterized by an overwhelmed immune response against a primary insult that become responsible for renal dysfunction and poor outcome. Therapeutic strategies based on blood purification have been developed for the treatment of this disease. The use of polymethyl methacrylate (PMMA) membrane hemofilter in continuous hemodiafiltration (CHDF) modality showed better hemodynamic stability and efficient renal support in chronic dialysis maintenance. Here we investigated the efficacy of Hemofeel PMMA membrane (TORAY, Japan) in interfering with Complement activation and renal damage in a swine model of sepsis-induced AKI. Method After 3 hours from LPS infusion, 7 hours of PMMA-CVVH treatment or 7 hours of polysulfone (PSF)-CVVH were performed. Animals were sacrificed after 24h from LPS infusion. Histologic and renal function parameters were analyzed in all pigs. Pentraxin-3 (PTX3) and C5b-9 deposits were assessed on renal biopsies. Systemic Complement activation was evaluated by Wieslab kit. Gene expression profile was obtained from isolated PBMCs by Agilent SurePrint G3 Porcine Gene Expression Microarrays. Genespring and R software were used for the analysis. Results were validated by Real-time PCR. Results Analysis of renal biopsies from septic pigs presented increased interstitial leucocyte infiltrate, extensive collagen deposition and diffuse glomerular thrombi compared to healthy pigs (p<0.05). Confocal analysis showed extensive PTX-3 and C5-b9 deposits at tubulo-interstitial level associated with significant activation of systemic complement classical and alternative pathways (p<0.05). Interestingly, PMMA-CVVH treatment significantly reduced local and systemic complement activation, leucocyte infiltrate and tubule-interstitial fibrosis (p<0.05). On the contrary, no significant improvement was observed by PSF-CVVH treatment. Then, we compared the whole-genome gene expression profiles of swine PBMC. We identified 711 differentially expressed genes comparing PBMC before LPS infusion (LPS T0) and after 24 hours from LPS infusion (LPS T24) and 913 genes comparing gene expression profiles of LPS T24 group with that of septic pigs treated with PMMA-CVVH (PMMA T24 group) (fold change >2 ; false discovery rate <0.05). The most modulated genes were Granzime B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, SERPINB-1 and TIMP-2 that were closely related to sepsis-induced immunological process. Finally, quantitative PCR confirmed the microarray data indicating that Granzime B and Complement Factor B upregulation in PBMC was significantly hampered by PMMA treatment. Conclusion Our data suggest that LPS induced AKI is characterized by activation of Classical and alternative Complement pathways resulting in significant renal tissue damage. By interfering with complement activation and inflammatory response, PMMA membrane might prevent dysfunctional activation of resident renal cells with prevention of sepsis-induced AKI.

Download Full-text

Eculizumab, a novel potential treatment for acute kidney injury associated with preeclampsia/HELLP syndrome

BMJ Case Reports ◽

10.1136/bcr-2018-228709 ◽

2019 ◽

Vol 12 (9) ◽

pp. e228709 ◽

Cited By ~ 11

Author(s):

Hatem Elabd ◽

Mennallah Elkholi ◽

Lewis Steinberg ◽

Anjali Acharya

Keyword(s):

Acute Kidney Injury ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Complement Activation ◽

Hellp Syndrome ◽

Kidney Injury ◽

Complement Protein ◽

Igg Antibody ◽

Elevated Liver Enzymes

The kidney is one of the major organs affected in preeclampsia. There is evidence suggesting a role for excessive complement activation in the pathogenesis of preeclampsia. We describe a case of preeclampsia with severe features, including HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and acute kidney injury (AKI) that developed following caesarian section. The patient required renal replacement therapy. A trial of daily plasma exchange was not effective. The patient received a single dose of eculizumab, a humanised monoclonal IgG antibody that binds to complement protein C5. One week post administration of eculizumab, there was significant improvement in haematologic, hepatic and renal function. Blood pressure had normalised and renal replacement therapy was discontinued. The use of eculizumab may have contributed to recovery of kidney function further supporting the role of complement activation in the pathogenesis of preeclampsia and associated AKI.

Download Full-text

Acute Kidney Injury Associated with Minimal Change Nephrotic Syndrome in an Elderly Patient Successfully Treated with both Fluid Management and Specific Therapy Based on Kidney Biopsy Findings

Case Reports in Nephrology and Dialysis ◽

10.1159/000507426 ◽

2020 ◽

Vol 10 (1) ◽

pp. 42-50 ◽

Cited By ~ 2

Author(s):

Yuko Oyama ◽

Yoichi Iwafuchi ◽

Tetsuo Morioka ◽

Ichiei Narita

Keyword(s):

Elderly Patient ◽

Acute Kidney Injury ◽

Nephrotic Syndrome ◽

Kidney Biopsy ◽

Fluid Management ◽

Kidney Injury ◽

Oral Prednisolone ◽

Minimal Change Nephrotic Syndrome ◽

Minimal Change ◽

Fluid Removal

Oliguric acute kidney injury (AKI) with minimal change nephrotic syndrome (MCNS) has long been recognized. Several mechanisms such as hypovolemia due to hypoalbuminemia and the nephrosarca hypothesis have been proposed. However, the precise mechanism by which MCNS causes AKI has not been fully elucidated. Herein, we describe an elderly patient with AKI caused by MCNS who fully recovered after aggressive volume withdrawal by hemodialysis and administration of a glucocorticoid. A 75-year-old woman presented with diarrhea and oliguria, and laboratory examination revealed nephrotic syndrome (NS) and severe azotemia. Fluid administration had no effect on renal dysfunction, and hemodialysis was initiated. Her renal function improved upon aggressive fluid removal through hemodialysis. Renal pathological findings revealed minimal change disease with faint mesangial deposits of IgA. After administration of methylprednisolone pulse therapy followed by oral prednisolone, she achieved complete remission from NS. The clinical course of this case supports the nephrosarca hypothesis regarding the mechanism of AKI caused by MCNS. Furthermore, appropriate fluid management and kidney biopsy are also important in elderly patients with AKI caused by NS.

Download Full-text