Nephrotic syndrome (NS) contributes significantly to chronic kidney disease (CKD) -related mortality worldwide. Whole Exome Sequencing (WES) was used to identify pathogenic variants associated with NS in a Tamil Nadu patient cohort, with the long-term goal of developing a region-specific diagnostic strategy. The genomic DNA was extracted from 15 patients with proteinuria and 7 healthy controls and subjected to WES. Variants were systematically filtered and annotated against GRCh38 then prioritized using multiple prediction algorithms, including CADD, SIFT, FATHMM, PredictSNP2, and ClinVar annotations. Protein stability effects were evaluated using MUPro and PremPS. The functional consequences of the variant were assessed using PANTHER cSNP. Variant distribution patterns and pathogenicity scores were visualized using multi-parametric scatter plot and genotype heat maps. A total of 266 variants were identified across 59 nuclear genes previously reported to be associated with NS, including 114 non-synonymous substitutions. Integrated computational filtering based on CADD, ClinVar, PredictSNP2, PANTHER score and protein stability, prioritized 14 variants predicted to have deleterious effects. Functional annotation highlighted three variants of particular significance: CUBN (rs139724058), FAT1 (rs3733415), and TRPC6 (rs36111323). In the present pilot study, we identified genetic variants that may contribute to NS susceptibility in this South Indian cohort. This exploratory study findings provide preliminary candidate variants that may warrant investigation in larger cohorts and functional studies to establish clinical utility and address precision medicine strategies.
A BSTRACT Infections contribute to the second most common cause of death in chronic kidney disease (CKD) patients. With the usage of intravenous cannulas, central lines, and repeated hospitalizations, patients are at risk of getting infections. This necessitates the usage of anti-microbial therapy. The antibiotic prescription should be cautious in renal patients with appropriate renal dose adjustments to avoid nephrotoxicity. The aim of this study was to estimate the impact of clinical pharmacist-driven support for antibiotic usage in patients with kidney diseases. A retrospective cross-sectional study was conducted among CKD patients from August to October 2022 in an 800-bedded hospital in South India. During this study period, a trained clinical pharmacist was actively involved in monitoring appropriate antibiotic prescriptions and dosing for all renal patients. Patient demographics, empirical therapy, antibiotic time-out, culture sensitivity, and anti-microbials after culture reports were collected from the patient’s records. The usage of empirical antibiotics, their culture correlation, and renal dose adjustments was analyzed. Out of 102 patients, almost 99.01% of patients received empirical therapy. Cefoperazone sulbactam (26.7%) was the most used drug, followed by amoxicillin clavulanate IV (25.7%) and then meropenem (22.8%). When the antibiotic time-out was checked, 21.5% stopped antibiotics and the remaining continued to have antibiotics. The renal dose adjustments were followed in 99.01% of those required dose adjustments. Successful engagement of clinical pharmacists can be achieved by integrating the pharmacist rounds with the routine clinical rounds led by physicians, which can bridge the gaps in the implementation of anti-microbial stewardship activities.
