Podocytopathies related to either COVID-19 infection or its vaccination, our experience and literature review.

Coronavirus disease 2019 (COVID-19) affects several organs including the kidney resulting in acute kidney injury (AKI) and variants of podocytopathies. From the beginning to the middle period of the COVID-19 pandemic, we have collected eight renal biopsies with various renal diseases including 4 podocytopathies. In addition, from the middle period to the near end of the COVID-19 pandemic, we have seen two of the patients who developed nephrotic syndrome following COVID-19 vaccination. Three of 4 podocytopathies were collapsing glomerulopathy (also called collapsing focal segmental glomerulosclerosis) and the fourth was a minimal change disease (MCD). Two of three collapsing glomerulopathy were found in African American patients, one of who was tested positive for having the high-risk allele APOL-1 G1. In addition, the two renal biopsies showed either MCD or replaced MCD following COVID-19 vaccination. MCD can be a rare complication following COVID-19 infection and COVID-19 vaccination, raising the question if there are similar antigens induced by the infection or by the vaccination that trigger the MCD. This article reports our experience of diagnosing podocytopathies related to either COVID-19 infection or its vaccination and provides a literature review regarding the incidence and potential pathophysiology in the field.

Primary cilia metaplasia in renal transplant biopsies with acute tubular injury.

Primary cilia are hair-like organelles singly distributed along the apical surface of proximal and distal nephron tubules as mechanosensors. The goal of this study was to use electron microscopy to systemically evaluate cilia changes in acute tubular injury (ATI) from both transplant and native renal biopsies. Three groups of cases were included: control group 1-native biopsies without major changes in renal tubules; study group 2-native biopsies with prominent ATI; and study group 3-renal transplant biopsies with prominent ATI (delayed renal function group). Extensive search for ciliary structures along renal tubules was conducted in each case, focused on proximal tubular areas with injured (diminished) apical microvilli. Singly located cilia were found in 3/19 specimens in control group 1, 4/18 in group 2 (native ATI), and 6/24 in group 3 (transplant ATI). Importantly, there were clusters of cilia in proximal tubules with markedly diminished apical microvilli in 3/24 biopsies from 2 patients in group 3, but none from groups 1 and 2. The clusters of cilia ranged from 6 to 15 individual cilia along the apical surface with diminished apical microvilli. Under high magnifications, the cilia demonstrated 9 pairs of peripheral microtubules without a central pair of microtubules, consistent with primary cilia (9 + 0) rather than motile cilia (9 + 2). In summary, the authors found clusters of cilia in proximal tubules with remarkable apical microvillar injury in 3 renal transplant biopsies with ATI, implying a reactive, or repairing, process following tubular injury, thus they name this finding "cilia metaplasia".

Increasing trend in infection-related death-censored graft failure in renal transplantation.

BACKGROUND: Advances in kidney transplantation have significantly improved early outcomes but failed to improve long-term graft survival. Despite many causes, the contribution of infection to death-censored graft failure (DCGF) is unknown. The aim of our study is to assess the impact of infections on DCGF using United Network for Organ Sharing data. METHODS: We analyzed 38,286 DCGFs among 189,110 first kidney transplants performed between January 1, 1990 and December 31, 2006. Information on infection contributing to DCGF was available in 31,326 DCGF recipients. Student's two-sample t test for normally distributed variables, Wilcoxon rank sum test for nonnormally distributed, and Chi-square test for categorical variables were used in univariable comparisons. Multivariable logistic regression analysis was performed to assess the independent contribution of variables to infection-related DCGF. RESULTS: Overall, infection accounted for 7.7% (2397/31,326) of all DCGF. The rate of infection-related DCGF increased from 6.4% in 1990 to 10.1% in 2006 and was significantly higher during 1997 to 2006 when compared with 1990 to 1996 period (9.1% vs. 6.3%, P<0.001). Over these 17 years, the trends in infection-related DCGF and rejection rates showed an inverse relationship with the former exceeding the latter starting in 2005. The risk of infection-related DCGF was higher (14.1%) in recipients older than 65 years and exceeded the rejection rate in those older than 60 years. Urological complications and polyoma infection were the most significant risk factors with odds ratios of 8.77 (confidence interval: 5.15-14.93) and 2.55 (confidence interval: 1.41-4.61), respectively. CONCLUSION: Infection is increasingly contributing to DCGF in recent years and warrant reevaluation of current immunosuppression protocols, especially in older recipients.

Primary nonfunction of renal allograft secondary to acute oxalate nephropathy.

Primary nonfunction (PNF) accounts for 0.6 to 8% of renal allograft failure, and the focus on causes of PNF has changed from rejection to other causes. Calcium oxalate (CaOx) deposition is common in early allograft biopsies, and it contributes in moderate intensity to higher incidence of acute tubular necrosis and poor graft survival. A-49-year old male with ESRD secondary to polycystic kidney disease underwent extended criteria donor kidney transplantation. Posttransplant, patient developed delayed graft function (DGF), and the biopsy showed moderately intense CaOx deposition that persisted on subsequent biopsies for 16 weeks, eventually resulting in PNF. The serum oxalate level was 3 times more than normal at 85 µmol/L (normal <27 µmol/L). Allograft nephrectomy showed massive aggregates of CaOx crystal deposition in renal collecting system. In conclusion, acute oxalate nephropathy should be considered in the differential diagnosis of DGF since optimal management could change the outcome of the allograft.

Adjuvant role of p53 immunostaining in detecting BK viral infection in renal allograft biopsies.

BK virus infection is a significant threat to renal transplant outcome. Detecting viral infection in renal transplant biopsies using SV40 staining is less than ideal. SV40 antibody reacts with the large T-antigen of BK virus only at the early phases of infection and can miss cells in later stages of infection. As p53 is upregulated during both early and late phases of infection, this study set out to determine whether p53 staining could improve detection of BK virus infection in renal transplant patients. The control group consisted of 16 renal allograft biopsies without histologic evidence of BK virus infection, while the BK group consisted of 15 renal allograft biopsies with histologic evidence of BK virus infection. The biopsies from both groups were immunohistochemically stained with both SV40 and p53 antibodies. Dual staining with both markers was also performed to identify their nuclear co-localization. In the BK group, the percent of p53 staining (16.6 ± 4.8 %) was significantly higher than the percent of SV40 staining (5.4 ± 2.7%). BK virus infected cells revealed a unique p53 immunostaining pattern (strong nuclear staining with a central halo). Co-localization of SV40 and p53 was identified in cells that had characteristic nuclear features of BK virus infection by histology. The sensitivity and specificity for using p53 staining to identify BK infected cells was 92% and 86 %, respectively. In conclusion, p53 staining detects a higher percentage of BK virus infected cells than SV40 staining alone. Thus, for diagnosis of BK virus infection in renal allograft biopsies, p53 staining is a sensitive and specific method when used along with SV40 staining.

Exit-site care in peritoneal dialysis.

Exit-site infection (ESI), tunnel infection and associated peritonitis are major causes of morbidity and catheter loss in chronic peritoneal dialysis patients. Meticulous exit-site care is vital in preventing ESI. Avoiding trauma to the exit-site and daily cleaning of the exit-site with a dedicated antimicrobial soap is essential for the longevity of the peritoneal dialysis catheter. Antibiotics cream and disinfectant agents including povidone-iodine, chlorhexidine, electrolytic chloroxidizing solutions (Amuchina 10% - ExSept Plus, Amuchina 5% - ExSept) are useful to keep the resident micro-organisms inhibited. ESI rates in peritoneal dialysis patients treated with Amuchina 10% (ExSept Plus) and Amuchina 5% (ExSept) for the exit-site care are similar or lower compared to povidone-iodine or chlorhexidine. Electrolytic chloroxidizing (Amuchina 10% - ExSept Plus and Amuchina 5% - ExSept) solutions for exit-site care are effective for prevention and treatment of ESI.