Effect of race and ethnicity on renal transplant referral
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BACKGROUND: Multiple studies have revealed disparity in renal healthcare access and outcomes in racial/ethnic minorities with the socioeconomic status explaining the majority but not all of the disparity. We wanted to determine if racial/ethnic disparities existed at the first step toward renal transplantation, the renal transplant referral process. MATERIALS AND METHODS: A cohort of 200 adult end-stage renal disease patients was followed retrospectively for 2 years from January 2016 to February 2018. The study exposure was based on self-declared race/ethnicity of the patients, who were categorized as Black, White, and Hispanic. The study outcome was based on medical team patient evaluation and consisted of the patients who refused referral, who were not referred, and who were referred for transplant. Medical and demographic factors collected were age, gender, socioeconomic status, hemoglobin A1c ≥ 7, body mass index ≥ 40, left ventricular ejection fraction ≤ 40%, the presence of coronary or peripheral arterial disease, albumin level, history of smoking, cirrhosis, and cancer. The data were analyzed using univariate analyses and multinomial logistic regression. RESULTS: In the adjusted analysis, there was no difference in the likelihood of transplant referral between Black and White patients (OR = 0.71, 95% CI 0.22 - 2.3, p = 0.56). However, both Black (OR = 16, 95% CI 3.3 - 77, p = 0.0006) and White (OR = 22, 95% CI 3.4 - 150, p = 0.0013) patients were more likely to be referred for transplant when compared with Hispanic patients. Odds of transplant refusal were not different across race/ethnic groups. CONCLUSION: Hispanic patients are disadvantaged in the referral for renal transplant when compared to Black and White patients for reasons unclear at this time.

Myeloperoxidase Staining Identifies Endothelial Injury of Peritubular Capillaries and Glomeruli in Renal Antibody-Mediated Rejection.

OBJECTIVE: It remains unclear if C4d staining is related to any peritubular and glomerular injury during antibody mediated rejection (ABMR). The goal of this study was to determine if myeloperoxidase (MPO) staining can highlight endothelial injury in peritubular capillaries (PTC) and glomeruli. METHODS: The study included 12 native negative controls, 19 transplant biopsies with borderline changes (BC) as transplant controls, and one group of renal transplant biopsies with ABMR as the study group (acute/chronic, n=22). All three groups were stained for MPO immunohistochemically, and the MPO expressions in the endothelium of PTC and glomeruli were evaluated and correlated with serum creatinine (SCr). In addition, the ultrastructural layers of the PTC (an index for chronic allograft rejection) were correlated with MPO indices in PTC. RESULTS: The negative control group and the transplant controls showed no MPO expression in the endothelium of glomeruli and PTC. However, in the biopsies with ABMR, there were MPO-positive stains in the endothelial cells of glomeruli (15/21 cases, 71.4 %) and PTC (16/22 cases, 72.7 %). There were significant correlations between the peritubular MPO staining versus SCr (r=0.355 and p=0.0106) and glomerular MPO staining versus SCr (r=0.365 and p=0.0092). Furthermore, the layers of PTC by electron microscopy were significantly correlated with MPO scores in PTC (r=0.696, p=0.0001). CONCLUSION: Our data suggest that the MPO-positive endothelial injuries are most likely the cause leading to renal graft dysfunction following ABMR.

Focal Segmental Glomerulosclerosis (FSGS) Progressing to Collapsing Glomerulopathy in Renal Transplant Recipients With and Without COVID-19 Infection.

BACKGROUND: Collapsing glomerulopathy (CGN) secondary to HIV or COVID-19 infection mainly occurs in patients of African American descent due to APOL-1 gene mutations, but CGN is occasionally reported in white patients. CGNs are rarely reported in renal transplant biopsies and their association with idiopathic focal segmental glomerulosclerosis (FSGS) is unclear. METHODS AND RESULTS: Patient #1 was a 48-year-old Caucasian white man who had a renal transplant 8 years ago and was recently diagnosed with COVID-19 infection. Two weeks post infection, his serum creatinine (SCr) increased to 2.01 mg/dL from a baseline of 1.40 mg/dL, and he developed concomitant nephrotic range proteinuria. The first renal transplant biopsy showed FSGS. Four weeks later, his sCr level increased to 2.65 mg/dL with worsening proteinuria, and a second renal transplant biopsy revealed CGN. Patient #2 was a 32-year-old African American man whose native renal biopsy revealed primary FSGS. He received a renal transplant with initial post-transplant sCr level at 1.17 mg/dL. Four months later, his sCr and protein-to-creatinine ratio began to rise. Sequential biopsies revealed that the patient had developed recurrent FSGS, which progressed to show features of CGN. The CGN was further confirmed in his transplant kidney graft at autopsy later. CONCLUSIONS: This is the first case report of CGN in a white renal recipient with COVID-19 infection. The pathologic presentations of FSGS progressing to collapsing FSGS in our 2 renal transplant recipients suggest that FSGS and GGN may share a common pathophysiologic mechanism of podocytopathy.