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.

Predictors of disease severity and outcome of hospitalized renal transplant recipients with COVID-19 infection: a systematic review of a globally representative sample.

Introduction. COVID-19 presents a special challenge to the kidney transplant population.Methods. A systematic review of articles that examined COVID-19 in kidney transplant recipients was performed. Patients' demographics, clinical, laboratory and radiological presentations, immunosuppression modification, and COVID-19 specific management were abstracted and analyzed. COVID-19 severity was classified into mild, moderate, and severe. Disease outcome was classified by whether the patient was discharged, still hospitalized, or died.Results. 44 articles reporting individual data and 13 articles reporting aggregated data on 149 and 561 kidney transplant recipients respectively with COVID-19 from Asia, Europe and America fulfilled all inclusion and exclusion criteria. Among studies reporting case specific data, 76% of cases had severe disease. Compared to patients with mild/moderate disease, patients with severe disease had higher CRP, LDH, Ferritin, D-dimer and were more likely to have bilateral lung involvement at presentation and longer time since transplantation (P < 0.05 for all). Recipients' age, gender and comorbidities did not impact disease severity. Patients with severe disease had a more aggressive CNI reduction and more antiviral medications utilization. Outcome was reported on 145 cases, of those 34 (23%) died all with severe disease. Longer duration from transplant to disease diagnosis, hypoxia and higher LDH were associated with mortality (P < 0.05). Different immunosuppression reduction strategies, high dose parenteral corticosteroids use and various antiviral combinations did not demonstrate survival advantage. Similar finding was observed for studies reporting aggregated data.Conclusion. COVID-19 in kidney transplant patients is associated with high rate of disease severity and fatality. Higher LDH and longer time since transplantation predicted both disease severity and mortality. None of the COVID-19 specific treatment correlated with, or improved disease outcome in kidney transplant recipients.

Effect of race and ethnicity on renal transplant referral
.

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.

Urinary tract infections and antimicrobial sensitivity among diabetic patients at Khartoum, Sudan.

BACKGROUND: Patients with diabetes mellitus (DM) are more susceptible to urinary tract infection (UTI) than non-diabetics. Due to the emergence of multidrug resistant (MDR) uropathogenic strains, the choice of antimicrobial agent is restricted. This study investigated the epidemiology of UTI, antimicrobial susceptibility, and resistance patterns of bacterial isolates from adult diabetic patients. METHODS: A cross-sectional study was conducted at Khartoum Hospital, Sudan during the period of March - September 2013. Consecutive patients (men and women) were approached to participate in the study, irrespective of UTI symptoms. Socio-demographic and clinical data were obtained from each participant using pre-tested questionnaires. Clean-catch, midstream urine samples were collected and cultured for UTI diagnosis and antimicrobial susceptibility. Symptomatic bacteriuria was defined as a positive urine culture (≥10(5) colony-forming units [CFU]/mL of a single bacterial species) from patients with symptoms associated with UTI; asymptomatic bacteriuria was defined as a positive urine culture from patients without symptoms associated with UTI. RESULTS: A total of 200 diabetic patients were enrolled, 121 (60.5%) men and 79 (39.5%) women; 193 (96.5%) had type II DM. The overall prevalence of UTI was 39 (19.5%). Among the total population, 17.1% and 20.9% had symptomatic and asymptomatic bacteriuria, respectively. According to multivariate logistic regression, none of the investigated factors (age, sex, type of DM and duration) were associated with UTI. The predominant isolates were Escherichia coli (22, [56.4%]), and Klebsiella pneumoniae, [9, (23%)]. Eight of 22 E. coli, four of nine K. pneumoniae and one of five Enterococcus faecalis isolates originated from symptomatic patients. Six, four, three, and two of 22 E. coli isolates showed resistance to ampicillin, co-trimoxazole, nitrofurantoin, and amoxicillin-clavulanic acid, respectively. Two, two, one and one of nine K. pneumoniae isolates were resistant to ampicillin, co-trimoxazole, cephalexin, and amoxicillin-clavulanic acid. All 22 E. coli isolates were sensitive (100%) to gentamicin and cephalexin. All nine K. pneumoniae were sensitive to gentamicin (100%) and 88.8% were sensitive to cephalexin. CONCLUSION: In Sudan, about one-fifth of diabetic patients have UTI. E. coli is the most frequent isolate followed by K. pneumoniae.

Enteral granulocyte-colony stimulating factor and erythropoietin early in life improves feeding tolerance in preterm infants: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of enteral recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEPO) in preventing feeding intolerance. STUDY DESIGN: An interventional randomized control trial was conducted in 90 preterm infants born at ≤33 weeks gestational age. The neonates were assigned to 4 groups; 20 received rhG-CSF, 20 received rhEPO, 20 received both, and 30 received distilled water (placebo control). The test solution was given at the beginning of enteral feeding and was discontinued when enteral intake reached 100 mL/kg/day or after a maximum of 7 days, whichever came first. Feeding tolerance and adverse effects of treatment were assessed. Serum granulocyte colony-stimulating factor and erythropoietin levels were measured on days 0 and 7 of treatment. RESULTS: All neonates tolerated the treatment without side effects. Neonates who received rhG-CSF and/or rhEPO had better feeding tolerance, as reflected by earlier achievement of 75 mL/kg/day, 100 mL/kg/day, and full enteral feeding of 150 mL/kg/day with earlier weight gain and a shorter hospital stay (P < .05). The risk of necrotizing enterocolitis was reduced from 10% to 0% in all treatment groups (P < .05). There was a shorter duration of withholding of feeding secondary to feeding intolerance among neonates receiving both rhG-CSF and rhEPO compared with those receiving placebo (P < .05). Serum levels of granulocyte colony-stimulating factor and erythropoietin at 0 and 7 days did not differ across the treatment groups. CONCLUSIONS: Enteral administration of rhG-CSF and/or rhEPO improves feeding outcome and decreases the risk of necrotizing enterocolitis in preterm neonates. The mechanism may involve the prevention of villous atrophy.

Frequency of retinal detachment after cataract surgery in highly myopic patients.

OBJECTIVE: To determine the potential risk factors for retinal detachment after cataract surgery. METHODS: In this retrospective cohort study, medical records of patients operated on between 2000 and 2010 at the Department of Ophthalmology, King Abdulaziz University Hospital, Riyadh, Kingdom of Saudi Arabia were retrospectively reviewed for both demographic and clinical data. Cases were identified as having an ocular axial length >/=25 mm, while a control group of 500 eyes (axial length range; 22-24 mm) was sampled. Data were analyzed to compare both groups, and to assess potential risk factors for post-cataract retinal detachment. RESULTS: We reviewed 852 eyes of 721 patients; 352 eyes with documented high myopia were compared with 500 control eyes. After a mean follow up of 45.1 +/- 27.9 months, the postoperative mean LogMAR visual acuity significantly differed; 0.51 +/- 0.48 for cases and 0.38 +/- 0.41 for controls (p<0.0001). Controls showed significantly better postoperative vision as measured by LogMAR (0.92 +/- 0.7) than cases (0.71 +/- 0.61) (p<0.0001). Twelve eyes (1.4%) had retinal detachments postoperatively. The RD prevalence was significantly higher among cases (10 [2.8%]) than controls (2 [0.4%]) (p=0.007). High axial length was the only significant risk factor for retinal detachment (p=0.005) even after multivariate adjustment (p=0.019). CONCLUSION: High axial length among myopic cataract patients may increase the risk of postoperative retinal detachment.