TY  - JOUR
AB  - Introduction: Anemia is a common and clinically significant complication observed in patients with chronic kidney disease (CKD), resulting from complex interactions between renal dysfunction, erythropoietin (EPO) deficiency, and altered iron metabolism. In murine CKD models, red blood cell (RBC) death or eryptosis, characterized by exposure of phosphatidylserine (PS) on the outer membrane of RBCs, was observed to drive anemia. However, there is limited research that has investigated this phenomenon in patients with non–dialysis-dependent CKD (NDD-CKD). Methods: In this cross-sectional cohort study, we describe the relationship between RBC death and anemia in all stages of NDD-CKD (n = 122). Blood samples from 133 healthy blood donors were additionally analyzed as controls. Results: Patients with CKD had a significantly lower hemoglobin (Hb) concentration (12.4 [interquartile range: 11.1–13.7] g/dl) when compared with the healthy group (13.8 [13.0–14.8] g/dl, P < 0.001). Hb concentrations exhibited a significant positive correlation with the estimated glomerular filtration rate (eGFR) across the entire cohort (r = 0.5, P < 0.001). RBC death rates, quantified by the binding of freshly isolated RBCs to the ligand annexin V using flow cytometry (FACS), were significantly increased by approximately 1.4-fold in patients with CKD compared with the RBC death rates in healthy blood donors. RBC death correlated with the glomerular filtration rate (GFR) stage but not with the albuminuria stage of CKD, the degree of anemia, and serum iron concentration. Using multiple linear regression, eGFR was identified as the sole independent predictor of RBC death with an inverse relationship. Conclusion: RBC death is stimulated in progressive NDD-CKD, possibly contributing to the development of renal anemia.
AU  - Bissinger, R.*
AU  - Schaefer, L.*
AU  - Bohnert, B.N.
AU  - Schork, A.
AU  - Hörber, S.
AU  - Peter, A.
AU  - Qadri, S.M.*
AU  - Birkenfeld, A.L.
AU  - Heyne, N.
AU  - Bakchoul, T.*
AU  - Wieder, T.*
AU  - Artunc, F.
C1  - 73182
C2  - 56814
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 730-742
TI  - GFR is a key determinant of red blood cell survival in anemia associated with progressive CKD.
JO  - Kidney Int. Rep.
VL  - 10
IS  - 3
PB  - Elsevier Science Inc
PY  - 2025
SN  - 2468-0249
ER  - 

TY  - JOUR
AB  - Introduction: Monogenic kidney diseases, though rare, exhibit a wide spectrum of clinical manifestations. The clinical and genetic diversity and potential biases in patient referrals and identification present challenges in accurately estimating prevalences based solely on phenotype. Our aim was to determine the calculated lifetime risk associated with autosomal recessive kidney diseases (ARKDs) using population-based genotype data. Methods: We conducted a comprehensive literature review to compile a list of 149 genes associated with ARKDs, including 31 glomerulopathies, 16 tubulopathies, 87 ciliopathies, and 15 congenital anomalies of the kidney and urinary tract (CAKUT). Disease-causing variants were collected from ClinVar, HGMD, LOVD, and our in-house database and evaluated for inclusion. Minor allele frequencies of 12,912 variants were then obtained from the Genome Aggregation Database (gnomAD) and the in-house database to estimate the lifetime risk. Results: The combined estimated lifetime risk was 27.49 per 100,000 (19.35–39.65) based on the European gnomAD dataset. The 3 disorders with the highest lifetime risk (>1.5 per 100,000), accounted for 24% of the overall lifetime risk and were caused by PKHD1 (autosomal recessive polycystic kidney disease), SLC12A3 (Gitelman syndrome), and COL4A3 (Alport syndrome) variants. Extrapolating to all modes of inheritance, the overall lifetime risk for monogenic kidney disease ranged from 1 in 611 to 1 in 498. Conclusion: This study offers a comprehensive population-genetic assessment of the lifetime risk associated with ARKDs focusing on European populations, shedding light on previously underestimated prevalences and diagnostic probabilities. Consequently, these findings provide crucial insights for optimizing resource allocation towards therapy development, enhancing public health strategies, and guiding future biomedical research endeavors.
AU  - Braunisch, M.C.*
AU  - Großewinkelmann, C.M.*
AU  - Menke, M.*
AU  - Hannane, N.*
AU  - Berutti, R.*
AU  - Ćomić, J.*
AU  - Günthner, R.*
AU  - Renders, L.*
AU  - Schmaderer, C.*
AU  - Heemann, U.*
AU  - Riedhammer, K.M.*
AU  - Wagner, M.
AU  - Hoefele, J.*
C1  - 74687
C2  - 57558
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 2384-2393
TI  - Estimating lifetime risk of autosomal recessive kidney diseases using population-based genotypic data.
JO  - Kidney Int. Rep.
VL  - 10
IS  - 7
PB  - Elsevier Science Inc
PY  - 2025
SN  - 2468-0249
ER  - 

TY  - JOUR
AB  - Introduction: Currently, there is only limited data on monogenic causes of vertebral defects, anorectal malformations, cardiac defects, esophageal atresia or tracheoesophageal fistula, renal malformations, and limb defects (VACTERL) association. The aim of this study was to extend the spectrum of disease-causing variants in known genes, to determine the diagnostic yield of monogenic causes, and to identify candidate genes and rare variants by applying comprehensive genetic testing or rare variant burden. Methods: The total cohort comprised 101 affected individuals and their parents. Trio exome sequencing was only performed in 96 individuals and their parents because of DNA quality reasons and case-control gene and pathway burden tests were calculated and evaluated by quantile-quantile plots, principal component analysis plots and family-based association test (FBAT). Results: In 5 of 96 individuals, disease-causing variants in known genes or loci were identified to be associated with the following 4 disorders: Kabuki syndrome, Sotos syndrome, MELAS syndrome, and deletion syndrome encompassing TWIST1. In 91 individuals, no disease-causing variants were found. FBAT showed 14 significant variants, 2 significant genes (LOC645752 and ZNF417), and 8 significant pathways. Conclusion: This study shows that most individuals with VACTERL association do not have known discrete genetic syndromes, implying that pathomechanisms or variants not identifiable by exome sequencing may exist requiring further investigation.
AU  - Ćomić, J.*
AU  - Tilch, E.*
AU  - Riedhammer, K.M.*
AU  - Brugger, M.*
AU  - Brunet, T.*
AU  - Eyring, K.*
AU  - Vill, K.*
AU  - Redler, S.*
AU  - Tasic, V.*
AU  - Schmiedeke, E.*
AU  - Schäfer, F.M.*
AU  - Abazi-Emini, N.*
AU  - Jenetzky, E.*
AU  - Schwarzer, N.*
AU  - Widenmann, A.*
AU  - Lacher, M.*
AU  - Zech, M.
AU  - Grasshoff-Derr, S.*
AU  - Geßner, M.*
AU  - Kabs, C.*
AU  - Seitz, B.*
AU  - Heydweiller, A.C.*
AU  - Muensterer, O.*
AU  - Lange-Sperandio, B.*
AU  - Rolle, U.*
AU  - Schumacher, J.*
AU  - Braunisch, M.C.*
AU  - Berutti, R.*
AU  - Reutter, H.*
AU  - Hoefele, J.*
C1  - 73109
C2  - 56812
SP  - 877-891
TI  - Trio exome sequencing in VACTERL association.
JO  - Kidney Int. Rep.
VL  - 10
IS  - 3
PY  - 2025
SN  - 2468-0249
ER  - 

TY  - JOUR
AB  - INTRODUCTION: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP. METHODS: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years. RESULTS: Our analyses prioritized myofibroblasts and endothelial cells, among the total of 33 annotated cell type, as specifically involved in BP regulation (P < 0.05/33, i.e., 0.001515). Enrichment of heritability for systolic BP (SBP) was observed in myofibroblast cells in mature human kidney cortex, and enrichment of heritability for diastolic BP (DBP) was observed in descending vasa recta and peritubular capillary endothelial cells as well as stromal myofibroblast cells. The new finding of myofibroblast, the significant cell type for both BP traits, was consistent in 8 replication efforts using 7 sets of independent data, including in human fetal kidney, in East-Asian (EAS) ancestry, using mouse single-cell RNA sequencing (scRNA-seq) data, and when using another prioritization method. CONCLUSION: Our findings provide a solid basis for follow-up studies to further identify genes and mechanisms in myofibroblast cells that underlie the regulation of BP.
AU  - Ganji-Arjenaki, M.*
AU  - Kamali, Z.*
AU  - Sardari, S.*
AU  - de Borst, M.H.*
AU  - Snieder, H.*
AU  - International Consortium of Blood Pressure (Gieger, C.)
AU  - International Consortium of Blood Pressure (Peters, A.)
AU  - International Consortium of Blood Pressure (Ried, J.)
C1  - 71368
C2  - 56063
SP  - 1849-1859
TI  - Prioritization of kidney cell types highlights myofibroblast cells in regulating human blood pressure.
JO  - Kidney Int. Rep.
VL  - 9
IS  - 6
PY  - 2024
SN  - 2468-0249
ER  - 

TY  - JOUR
AU  - Lau, L.H.Y.
AU  - Wiebe, N.*
AU  - Ramesh, S.*
AU  - Ahmed, S.*
AU  - Klarenbach, S.W.*
AU  - Carrero, J.J.*
AU  - Stenvinkel, P.*
AU  - Thorand, B.
AU  - Senior, P.*
AU  - Tonelli, M.*
AU  - Bello, A.*
C1  - 68414
C2  - 54702
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 1875-1878
TI  - Prospective study of associations between testosterone, mortality, and health outcomes among adults undergoing hemodialysis.
JO  - Kidney Int. Rep.
VL  - 8
IS  - 9
PB  - Elsevier Science Inc
PY  - 2023
SN  - 2468-0249
ER  - 

TY  - JOUR
AU  - Mahling, M.
AU  - Köppen, M.*
AU  - Mühlbacher, T.
AU  - Amann, K.*
AU  - Königsrainer, A.*
AU  - Heyne, N.
AU  - Häberle, H.*
AU  - Nadalin, S.*
AU  - Guthoff, M.
C1  - 60417
C2  - 49438
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 2114-2118
TI  - Acute kidney allograft injury following vitamin C administration for septic shock.
JO  - Kidney Int. Rep.
VL  - 5
IS  - 11
PB  - Elsevier Science Inc
PY  - 2020
SN  - 2468-0249
ER  -