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Background Infants with a solitary functioning kidney (SFK) are at risk for chronic kidney injury (CKI). Lack of compensatory kidney growth (CKG) is associated with CKI, but measuring CKG is challenging since it is typically reported relative to normal kidneys. This study aims to (1) standardize SFK growth in infants, (2) investigate the relationship between standardized kidney length and clinical outcomes, and (3) use these results to develop a risk-based prediction model and local clinical pathway for SFK care. Methods This was a quality improvement study of 166 infants with an SFK. Linear regression was used to assess kidney growth from 0 to 180 days of life. Univariate binary regression analysis was used to identify kidney length to body length thresholds associated with the development of CKI, defined as the composite outcome of chronic kidney disease (eGFR < 60 mL/min/1.73 m.sup.2), hypertension, or proteinuria. Results Kidneys grew in length from 0 to 180 days, and growth was constant when standardized to body length. Over follow-up, infants with a baseline kidney length to body length [less than or equal to] 0.088 were more likely to experience CKI than the rest of the cohort (27 vs. 8%, p = 0.04). Kidney length to body length [less than or equal to] 0.088 was also significantly associated with CKI development (OR 4.17, 95% CI 1.14-15.28, p = 0.04). Conclusions In this study, kidney length to body length ratio was a stable CKG metric over 0-180 days, and a baseline ratio [less than or equal to] 0.088 was a risk factor for CKI. Results will aid in developing a practical, point-of-care risk assessment tool, and overarching risk-stratified clinical pathway for infants with an SFK. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Douglas G. Matsell [sup.1] , Carol Bao [sup.1] , Teagan Po White [sup.1] , Ella Chan [sup.1] , Eli Matsell [sup.1] , Dan Cojocaru [sup.1] , Lydia Bajno [sup.2] [...]

Background Multicystic dysplastic kidney (MCDK) disease and unilateral renal agenesis (URA) are well-known causes of a solitary functioning kidney (SFK) and are associated with long-term kidney injury. The aims of this study were to characterize the natural history of SFK at our center, define the risk factors associated with chronic kidney injury, and identify distinguishing features between URA and MCDK that predict outcome. Methods This was a retrospective cohort study of 230 SFK patients. We compared MCDK (n=160) and URA (n=70) according to clinical features at diagnosis and kidney outcomes over follow-up. Univariate and multivariate binary regression analysis was used to determine independent risk factors for chronic kidney injury, defined as the composite outcome of hypertension, proteinuria, or chronic kidney disease (eGFR Results URA had a higher prevalence of comorbid genetic syndromes (15 vs. 6%, p=0.04), non-renal anomalies (39 vs. 11%, p Conclusions In our population, URA was more likely to have associated syndromes or anomalies, and to have worse outcomes over time than MCDK. URA diagnosis was an independent risk factor for chronic kidney injury. Our results will be used to develop a standardized clinical pathway for SFK management. Graphical abstract, Author(s): Douglas G. Matsell [sup.1] , Carol Bao [sup.1] , Teagan Po White [sup.1] , Ella Chan [sup.1] , Eli Matsell [sup.1] , Dan Cojocaru [sup.1] , Marisa Catapang [sup.1] [...]

Background Small kidneys due to renal hypodysplasia (RHD) result from a decrease in nephron number. The objectives of this study were to identify clinical variables that determine long-term renal outcome in children with RHD and to define the role of kidney size as a predictor of developing end-stage renal disease (ESRD). Methods This was a single-center retrospective cohort analysis. The primary outcome was development of ESRD. We identified 202 RHD cases, with 25 (12 %) reaching ESRD at mean age of 8.9 (±6.6) years. Results Children with RHD with a known genetic syndrome had the smallest kidneys while those with posterior urethral valves (PUV) had the largest kidneys at diagnosis. Cases with bilateral RHD were most likely to develop ESRD. Younger gestational age (OR 0.8, CI 0.69-0.99, p = 0.05), smaller kidney size at diagnosis (OR 0.13, CI 0.03-0.47, p = 0.002), lower best-estimated glomerular filtration rate (eGFR) (OR 0.74, CI 0.58-0.93, p = 0.01), proteinuria (OR 1.03, CI 1.01-1.05, p < 0.001) and high blood pressure (OR 1.02, CI 1.01-1.04, p = 0.01) were associated with development of ESRD, while kidney size at diagnosis was independently associated with ESRD (HR 0.03, CI 0.01-0.72, p = 0.043). Conclusions In children with RHD, kidney size at diagnosis predicts the likelihood of developing ESRD. Electronic supplementary material The online version of this article (doi:10.1007/s00467-015-3079-5) contains supplementary material, which is available to authorized users., Author(s): Douglas G. Matsell[sup.1] [sup.2] [sup.3] [sup.4] , Dan Cojocaru[sup.1] , Eli W. Matsell[sup.1] , Allison A. Eddy[sup.1] [sup.2] [sup.3] [sup.4] Author Affiliations: (1) Department of Pediatrics, British Columbia Children's [...]

P4-ATPases flip lipids from the exoplasmic to cytoplasmic leaflet of cell membranes, a property crucial for many biological processes. Mutations in P4-ATPases are associated with severe inherited and complex human disorders. We determined the expression, localization and ATPase activity of four variants of ATP8A2, the P4-ATPase associated with the neurodevelopmental disorder known as cerebellar ataxia, impaired intellectual development and disequilibrium syndrome 4 (CAMRQ4). Two variants, G447R and A772P, harboring mutations in catalytic domains, expressed at low levels and mislocalized in cells. In contrast, the E459Q variant in a flexible loop displayed wild-type expression levels, Golgi-endosome localization and ATPase activity. The R1147W variant expressed at 50% of wild-type levels but showed normal localization and activity. These results indicate that the G447R and A772P mutations cause CAMRQ4 through protein misfolding. The E459Q mutation is unlikely to be causative, whereas the R1147W may display a milder disease phenotype. Using various programs that predict protein stability, we show that there is a good correlation between the experimental expression of the variants and in silico stability assessments, suggesting that such analysis is useful in identifying protein misfolding disease-associated variants., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)