INF2 and ROBO2 gene mutation in an Indian family with end stage renal failure and follow-up of renal transplantation.

BACKGROUND: Accurate genetic diagnosis of end-stage renal disease patients with a family history of renal dysfunction is very essential. It not only helps in proper prognosis, but becomes crucial in designating donor for live related renal transplant. We here present a case of family with deleterious mutations in INF2 and ROBO2 and its importance of genetic testing before preparing for kidney transplantation. CASE PRESENTATION: We report the case of a 29-year-female with end-stage renal disease and rapidly progressive renal failure. Mutational analysis revealed an Autosomal Dominant inheritance pattern and mutation in exon 4 of the INF2 gene (p. Thr215Ser) and exon 26 of the ROBO2 gene (p. Arg1371Cys). Her mother was diagnosed for CKD stage 4 with creatinine level of 4.3 mg/dL. Genetic variants (INF2 and ROBO2) identified in proband were tested in her sisters and mother. Her elder sister was positive for both heterozygous variants (INF2 and ROBO2). Her mother was positive for mutation in INF2 gene, and her donor elder sister did not showed mutation in INF2 gene and had mutation in ROBO2 gene without any clinical symptoms. CONCLUSION: This case report emphasize that familial genetic screening has allowed us in allocating the donor selection in family where family member had history of genetic defect of Chronic Kidney Disease. Information of the causative renal disorder is extremely valuable for risk-assessment and planning of kidney transplantation.

A systematic review and meta-analysis recite the efficacy of Tacrolimus treatment in renal transplant patients in association with genetic variants of CYP3A5 gene.

Tacrolimus is an immunosuppressant with a narrow therapeutic index and pharmacokinetic variability. This variability may be attributed to genetic variants in gene CYP3A5 associated with Tacrolimus metabolism. Studies focusing on genetic variants in the CYP3A5 gene associated with Tacrolimus metabolism have been published, a meta-analysis of these published articles may provide a direction that can change the future research and clinical management of renal transplant patients. In this systematic review and meta-analysis, we have reviewed and analyzed the studies and clinical trials conducted to determine the association between genetic variants of CYP3A5 and Tacrolimus metabolism from the PubMed database and clinical trials (www.clinicaltrials.gov). This meta-analysis also assessed the correlation of CYP3A5 genotype (rs776746) with concentration/dose (Co/D) of Tacrolimus in renal transplant patients. The 59 published articles on genetic association of the CYP3A5 on Tacrolimus doses were reviewed for this systematic review. Meta-analysis showed that the Tacrolimus Co/D ratio is significantly lower in the CYP3A5 expressor group as compared with non-expressor in Asian, European as well as in mixed populations at any post-transplant period (P<0.0001). Our study further confirmed that the CYP3A5 variant (rs776746) is clinically relevant for the dose determination of Tacrolimus. Variations in Tacrolimus Co/D have been found to be significantly linked to the patient's CYP3A5 genetic variant (rs776746). The addition of other genetic variants involved in the pharmacokinetic of Tacrolimus may determine efficient regimen for drug dose. Our meta-analysis confirmed that the CYP3A5 genetic variant (rs776746) analysis is relevant in personalizing the Tacrolimus dose determination in renal transplant patients.

Role of short-dwell daily ethanol-lock therapy in the management of hemodialysis tunneled cuffed catheter-related bloodstream infection.

BACKGROUND: Catheter-Related Blood Stream Infection (CRBSI) is the major limitation of using Tunneled cuffed catheter (TCC) for long-term Hemodialysis. The standard therapy of CRBSI involves systemic antibiotics with catheter replacement/removal. As antibiotic alone is rarely effective therapy for CRBSI, biofilm eradication using antimicrobial locking solutions is a promising modality for CRBSI treatment, hence catheter salvage. The present study evaluated the efficacy and safety of Ethanol-lock therapy (ELT) in combination with systemic antibiotics for the management of CRBSI associated with hemodialysis TCC. METHOD: 56 patients with CRBSI were treated with 70% ELT (1 h daily for 5 days) along with systemic antibiotics. Seventeen patients with CRBSI who didn't consent to ELT were treated with antibiotics alone. The effect of ELT was evaluated as clinical cure (fever resolution and negative surveillance cultures), infection-free TCC survival duration and adverse events of ELT among patients with CRBSI. The parameters were compared with 17 patients treated with antibiotics alone. RESULTS: ELT was successful in 50 out of 56 patients (89.28%); compared to 41.17% (seven out of 17) with antibiotics alone (p < 0.001). Mean TCC survival was also significantly higher with ELT combined with systemic antibiotics (126.23 ± 18.67 days) compared to antibiotics alone (38.76 ± 9.91) (p = 0.006). No systemic adverse effects were noted with ELT; two patients receiving ELT had catheter breakage during the study period. CONCLUSION: We conclude that short-dwell daily ELT with systemic antibiotics is an effective therapy for CRBSI in hemodialysis patients with TCC.

Outcome of post-COVID-19 fungal pyelonephritis: A single Indian tertiary center experience.

Introduction: COVID-19 pandemic is associated with secondary opportunistic fungal infections. These have an aggressive course with a high mortality rate. We present our experience of seven cases of post-COVID-19 fungal pyelonephritis. Methods: An observational study over a period of 8 months of May to December 2021 was carried out at our tertiary care hospital, including all patients with features of fungal pyelonephritis in post-COVID-19 setting. The patient demographics, details of previous COVID-19 infection, details of present admission and management were collected. The endpoints were either discharge from the hospital or death. Results: Seven patients were included. Mean age of presentation was 42 years (range: 20-63 years, standard deviation ± 14.2). Male-to-female ratio was 6:1. One patient was diabetic. Two patients were asymptomatic, one had mild infection, and four patients had severe COVID-19 infection as per National Institute of Health criteria. In the present admission, all patients had symptomatic pyelonephritis with laboratory parameters showing elevated D dimer, C reactive protein, and total leukocyte counts. In all seven patients, ultrasound of kidney ureter bladder region showed bulky kidney, color Doppler showed main renal arterial thrombosis in two patients, segmental arterial thrombosis in another patient. Computed tomography scan was suggestive of changes of pyelonephritis in all patients with multiple renal hypodense areas. All patients required nephrectomy with biopsy suggestive of changes of necrotizing fungal inflammation. Three patients expired. Conclusion: Management of post-COVID-19 fungal pyelonephritis should be aggressive and suspicious laboratory and imaging findings should be treated by early nephrectomy.

Adult-onset nephrotic syndrome following coronavirus disease vaccination.

A 22-year-old healthy man was admitted for oedema 15 days after the first injection of the COVISHIELD coronavirus disease 2019 (COVID-19) vaccine (Oxford AstraZeneca) vaccine. Nephrotic syndrome was diagnosed and a kidney biopsy showed minimal change disease. Oral prednisolone was started at 1 mg/kg/day resulting in complete remission within 1 week.

Kidney Transplantation with ABO-Incompatible Donors: A Comparison with Matched ABO Compatible Donor Transplants.

INTRODUCTION: ABO-incompatible kidney transplantation (ABOiKTx) expands the living donor pool. There is limited long-term outcome data from India especially in comparison with ABO-compatible kidney transplantation (ABOcKTx). Here we report outcomes of the first 100 ABOiKTx compared to ABOcKTx from our center. METHODS: Between August 2013 and December 2019, 100 consecutive ABOiKTx were compared with 100 ABOcKTx done during the same period.Controls were matched for age, donor characteristics, HLA mismatches, and date of transplantation. RESULTS: Mean (SD) follow up period was 25.9 ± 20.5 and 27.2 ± 20.6 months in ABOi and ABOcKTx respectively. Patient survival at 1 and 5 years post-transplant was 93.3 and 73.5% vs. 95.4 and 93% (P = 0.03), while graft survival rates were 85 and 60% vs. 93.1 and 83% in ABOi and ABOcKTx respectively (P = 0.03). The incidence of antibody-mediated rejections was 15% vs. 4%, and that of T-cell-mediated rejections was 10 vs. 12% respectively. Infections, malignancies, and surgical complications were similar. Level of anti ABO titers, HLA mismatches, recipient age, donor age, and presence of diabetes did not impact graft survival amongst ABOiKTx. The predicted survival and incidence of acute rejections and infections in the later 50 ABOiKTx transplants were better than the first 50 ABOiKTx when compared to their respective controls. CONCLUSION: Outcomes of ABOiKTx were inferior to ABOcKTx but tends to improve as more experience is gained. Incidence of ABMR was higher but infections and surgical complications were comparable. This data provides evidence that ABOiKTx is viable option for those without a ABO compatible donor.

Adenine phosphoribosyltransferase deficiency and 2, 8-dihydroxyadenine renal stones: A preventable cause of pediatric renal stones and kidney disease.

Adenine phosphoribosyltransferase deficiency is an inherited condition presenting from infancy to late adulthood. The common features are recurrent kidney and urinary tract stones and obstructive symptoms. The stones are characteristically radiolucent. 2, 8-Dihydroxyadenine (2, 8-DHA) formation is blocked by xanthine oxidase blocker allopurinol. Here, we report the case of an eight-month-old baby girl who presented with obstructive acute kidney injury secondary to calculi which was treated with surgical removal of stone. The analysis of the calculi revealed 2, 8-DHA crystals.

Poststreptococcal glomerulonephritis with atypical hemolytic uremic syndrome: An unusual presentation.

A 14-year-old female presented with oliguric dialysis requiring kidney injury due to acute poststreptococcal glomerulonephritis (PSGN) with hypertension strongly suggestive of atypical hemolytic uremic syndrome (aHUS) with microangiopathic hemolytic anemia and elevated factor H antibody levels. Renal biopsy revealed crescentic glomerulonephritis with typical subepithelial, intramembranous and mesangial electron-dense deposits (humps) on electron microscopy. She was treated with glucocorticoids following which she recovered, remained dialysis free and her Factor H antibody levels and depressed complement 3 levels normalized. PSGN-associated HUS has rarely been described, with this patient being the 11th case reported, to the best of our knowledge. This case is unique as we describe the course and management of the first patient with PSGN-associated HUS in the era of eculizumab, without eculizumab, and plasmapheresis. This patient presented with clinical and histological features of PSGN as well as anemia and thrombocytopenia consistent with aHUS. Given that these diseases are both mediated through the alternate complement pathway, it is tempting to speculate that blockade of the terminal complement pathway through the use of eculizumab might improve outcomes. Temporally, the hematological parameters in our patient seemed to improve soon after treatment was initiated; however, none of the prior cases in the literature experienced any long-term hematological issues, suggesting that supportive management can be a reasonable alternative.