Psychosocial Assessment of Candidates for Transplantation (PACT) Score Identifies High Risk Patients in Pediatric Renal Transplantation

Background: Currently, there is no standardized approach for determining psychosocial readiness in pediatric transplantation. We examined the utility of the Psychosocial Assessment of Candidates for Transplantation (PACT) to identify pediatric kidney transplant recipients at risk for adverse clinical outcomes.Methods: Kidney transplant patients <21-years-old transplanted at Duke University Medical Center between 2005 and 2015 underwent psychosocial assessment by a social worker with either PACT or unstructured interview, which were used to determine transplant candidacy. PACT assessed candidates on a scale of 0 (poor candidate) to 4 (excellent candidate) in areas of social support, psychological health, lifestyle factors, and understanding. Demographics and clinical outcomes were analyzed by presence or absence of PACT and further characterized by high (≥3) and low (≤2) scores.Results: Of 54 pediatric patients, 25 (46.3%) patients underwent pre-transplant evaluation utilizing PACT, while 29 (53.7%) were not evaluated with PACT. Patients assessed with PACT had a significantly lower percentage of acute rejection (16.0 vs. 55.2%, p = 0.007). After adjusting for HLA mismatch, a pre-transplant PACT score was persistently associated with lower odds of acute rejection (Odds Ratio 0.119, 95% Confidence Interval 0.027–0.52, p = 0.005). In PACT subsection analysis, the lack of family availability (OR 0.08, 95% CI 0.01–0.97, p = 0.047) and risk for psychopathology (OR 0.34, 95% CI 0.13–0.87, p = 0.025) were associated with a low PACT score and post-transplant non-adherence.Conclusions: Our study highlights the importance of standardized psychosocial assessments and the potential use of PACT in risk stratifying pre-transplant candidates

Rare variants in tenascin genes in a cohort of children with primary vesicoureteric reflux

Primary vesicoureteral reflux (PVUR) is the most common malformation of the kidney and urinary tract and reflux nephropathy is a major cause of chronic kidney disease in children. Recently, we reported mutations in tenascin XB (TNXB) as a cause of PVUR with joint hypermobility

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(−6) (Fisher exact test). Two of these SNPs—the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1—were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 controls; P=1.42×10(−17)). In the rare variant gene set–based analysis, the best signal was found in PLCG2 (P=7.825×10(−5)). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome

Steroid-sensitive nephrotic syndrome (SSNS) accounts for \u3e80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 controls; P=1.42×10(-17)). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825×10(-5)). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) accounts for \u3e80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 controls; P=1.42×10(-17)). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825×10(-5)). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome

Steroid-sensitive nephrotic syndrome (SSNS) accounts for \u3e80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 controls; P=1.42×10(-17)). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825×10(-5)). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS