Abstract：
:Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Connaughton DM,Kennedy C,Shril S,Mann N,Murray SL,Williams PA,Conlon E,Nakayama M,van der Ven AT,Ityel H,Kause F,Kolvenbach CM,Dai R,Vivante A,Braun DA,Schneider R,Kitzler TM,Moloney B,Moran CP,Smyth JS,Kennedy Adoi
10.1016/j.kint.2018.10.031subject
Has Abstractpub_date
2019-04-01 00:00:00pages
914-928issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(18)30839-1journal_volume
95pub_type
杂志文章,多中心研究abstract：:In six healthy males on a fixed sodium/potassium (Na/K) intake, we studied the relation between plasma K and urine K and Na excretion after an oral K load. Studies were repeated during fludrocortisone (0.5 mg bid) or spironolactone (50 mg qid), that is, after escape from the Na-retaining and Na-excreting effects of th...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1988.235
更新日期：1988-11-01 00:00:00
abstract：:Most epidemiologic data, thus far, have focused on short-term outcomes of acute kidney injury (AKI). Lo et al. correlate AKI with long-term outcomes. The concept of 'uremic memory' sheds light on the importance of AKI and its permanent imprint. The focus of research should be on prevention of an episode of AKI, when p...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2009.314
更新日期：2009-10-01 00:00:00
abstract：:Increasing evidence points to the importance of aberrant O-glycosylated immunoglobulin A1 (IgA1) in the pathogenesis of IgA nephropathy (IgAN), a disease widely considered to be a polygenic disorder. We earlier found that haplotypes in two key glycosyltransferase genes, C1GALT1 and ST6GALNAC2, were associated with sus...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.99
更新日期：2009-07-01 00:00:00
abstract：:Experiments were performed using a variety of methods to assess the functional status of different nephron populations following 45 min of renal ischemia in the rat. Micropuncture techniques revealed that SNGFR and reabsorption in the surface nephrons are only modestly reduced after ischemia, whereas kidney GFR and re...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1983.122
更新日期：1983-07-01 00:00:00
abstract：:Among Canadians starting dialysis, patients of East Asian and Indo Asian background are less likely than whites to receive a renal allograft. Although the reasons for such variation are complex, less living donation may contribute significantly. More studies are needed to confirm these differences and to evaluate stra...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/sj.ki.5002437
更新日期：2007-08-01 00:00:00
abstract：:To investigate mechanisms underlying GFR control in diabetes mellitus, renal hemodynamics and segmental tubular handling of sodium, using lithium clearance, were assessed in 41 insulin-dependent diabetics (IDD) treated by insulin for 11 +/- 8 days, and in 19 normal controls. Average GFR and effective renal plasma flow...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.95
更新日期：1990-04-01 00:00:00
abstract：:The biological action of calcitriol is mediated through a hormone-receptor complex interacting with nuclear chromatin. Interaction of the calcitriol receptor (VDR) with VDR response elements produces bioactive proteins which carry out the physiological actions of calcitriol. Since biological response to calcitriol app...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1994.252
更新日期：1994-07-01 00:00:00
abstract：BACKGROUND:Inbred miniature swine treated for 12 days with high-dose cyclosporine A develop tolerance to histocompatibility complex (MHC) class I-mismatched renal allografts. When this protocol was modified by adding thymectomy before transplant, all animals developed acute rejection. Thereafter, by day 100, one half d...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2000.00440.x
更新日期：2000-12-01 00:00:00
abstract：:Vascular calcification is recognized as a major contributor to cardiovascular disease (CVD) in end stage renal disease (ESRD) patients. Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascul...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/ki.2008.644
更新日期：2009-05-01 00:00:00
abstract：BACKGROUND:The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood d...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1046/j.1523-1755.2001.00805.x
更新日期：2001-07-01 00:00:00
abstract：:Angiotensinase A (aminopeptidase A; ATA) is an angiotensin II splitting exopeptidase, which is localized in endothelial and epithelial cells of the glomerular tuft. In order to investigate the influence of a reduction in renal mass on enzyme activity, ATA activity was measured in isolated rat glomeruli five and 14 wee...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.283
更新日期：1990-11-01 00:00:00
abstract：:Innate lymphoid cells are a recently recognized group of immune cells with critical roles in tissue homeostasis and inflammation. Regulatory innate lymphoid cells are a newly identified subset of innate lymphoid cells, which play a suppressive role in the innate immune response, favoring the resolution of intestinal i...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2019.07.019
更新日期：2020-01-01 00:00:00
abstract：:This study evaluated risk factors for end-stage renal disease (ESRD) and the prognostic significance of serum creatinine levels in a community-based mass screening. We used the registries of both community-based mass screening and chronic dialysis programs. In 1983, a total of 107,192 subjects over 18 years of age (51...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1997.119
更新日期：1997-03-01 00:00:00
abstract：BACKGROUND:The ontogeny of the renal mineralocorticoid (MR) and glucocorticoid (GR) receptors in the ovine fetus, and the effects of early exposure to synthetic or natural glucocorticoids on the expression of these genes in late gestation were examined. METHODS:A partial cDNA sequence for the ovine MR was cloned and u...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00157.x
更新日期：2002-02-01 00:00:00
abstract：:Our findings indicate that hypoaldosteronism occurs commonly (23/31 patients) in hyperkalemic patients with chronic renal insufficiency and that the deficiency of aldosterone contributes to the pathogenesis of the hyperkalemia. In most patients (83%), hypoaldosteronism could be accounted for by deficient renal secreti...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1980.11
更新日期：1980-01-01 00:00:00
abstract：:The effect of the tricarboxylic acid (TCA) cycle precursor, pyruvate, on glutamine metabolism by isolated renal cortical mitochondria was assessed by quantitating its key nitrogen and carbon metabolites. When mitochondria from normal rats were incubated at pH 7.4, pyruvate (2 mM) inhibited ammonia production by almost...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1982.166
更新日期：1982-09-01 00:00:00
abstract：:Recent studies have greatly expanded our knowledge of initial events that lead to epithelial cell polarity. Epithelial polarity is defined, in part, by apical cell-cell tight junctions that separate the plasma membrane into the apical domain and the basolateral domain, as well as the zonula adherens that mediate inter...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/sj.ki.5002579
更新日期：2007-12-01 00:00:00
abstract：BACKGROUND:Hypertriglyceridemia is a result of reduced triglyceride (TG)-rich lipoprotein (TRL) catabolism and occurs in rats with nephrotic syndrome (NS) and in Nagase analbuminemic rats (NARs). While the heparin-releasable lipoprotein lipase (LpL) pool in NAR and in NS is similar, TG levels are significantly greater ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2001.00478.x
更新日期：2001-01-01 00:00:00
abstract：:The family of bone morphogenetic proteins. Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor-beta (TGF-beta) superfamily of growth factors. The first BMPs were originally identified by their ability to induce ectopic bone formation when implanted under the ...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1046/j.1523-1755.2000.00081.x
更新日期：2000-06-01 00:00:00
abstract：:Anemia can contribute to chronic allograft injury by limiting oxygen delivery to tissues, particularly in the tubulointerstitium. To determine mechanisms by which erythropoietin (EPO) prevents chronic allograft injury we utilized a rat model of full MHC-mismatched kidney transplantation (Wistar Furth donor and Lewis r...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2011.473
更新日期：2012-05-01 00:00:00
abstract：:Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic drivers has proven to...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2015.239
更新日期：2015-12-01 00:00:00
abstract：:One reason for the inadequacy of current renoprotective therapy and the persistent poor renal prognosis in diabetic nephropathy is the large interindividual variation in response to treatment. Genetic as well as non-genetic factors are known to influence treatment efficacy. This Commentary summarizes the impact of the...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/sj.ki.5000283
更新日期：2006-04-01 00:00:00
abstract：:The mechanism whereby glucocorticoid deficiency impairs renal water excretion was studied in the conscious mineralocorticoid-replaced, adrenalectomized rat. Control animals received physiologic replacement with prednisolone, and experimental animals were deprived of glucocorticoid hormone for either 1 or 14 days. The ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1980.110
更新日期：1980-07-01 00:00:00
abstract：:Experiments in rodents have demonstrated an important role for selectins in kidney ischemia-reperfusion injury (IRI). However, the relevance of this in larger mammals, as well as the impact on long-term structure and function is unknown. We tested the hypothesis that small molecule selectin ligand inhibition attenuate...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5000335
更新日期：2006-05-01 00:00:00
abstract：:Indomethacin has been used to lower proteinuria in human glomerular diseases with controversial results. The mechanism of indomethacin beneficial effects has not been established. A possible explanation is that indomethacin reduces proteinuria by inhibiting the synthesis of renal prostaglandins (PGs); however, appropr...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1987.147
更新日期：1987-06-01 00:00:00
abstract：BACKGROUND:To chart the epidemiology of primary glomerular disease by means of a prospective regional study in the southern part of The Netherlands. METHODS:Experienced renal technicians collected renal biopsies, blood, and 24-hour urine samples at the bed site in each of the participating hospitals. The material was ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2004.00835.x
更新日期：2004-09-01 00:00:00
abstract：BACKGROUND:Hyperoxaluria may be idiopathic, secondary, or due to primary hyperoxaluria (PH). Hepatic alanine:glyoxylate aminotransferase (AGT) or glyoxylate/hydroxypyruvate reductase (GR/HPR) deficiency causes PHI or PHII, respectively. Hepatic glycolate oxidase (GO) is a candidate enzyme for a third form of inherited ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00468.x
更新日期：2002-08-01 00:00:00
abstract：:Germ free rats provide a unique model in which to assess biological response to environment. In 48 germ-free male, Sprague-Dawley rats we examined the consequences of oral exposure to nordihydroguaiaretic acid (NDGA), a nephrotoxin; to Staphylococcus epidermidis and bacillus species, non-endotoxin-containing bacteria;...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1987.213
更新日期：1987-09-01 00:00:00
abstract：:Hemodynamic pressure in glomerular capillaries (GCP) and in first order peritubular capillaries (EAP) in superficial nephrons of mutant Wistar rats with surface glomeruli was measured by micropuncture with a servo-nulling device in the following conditions: 1) control;2) norepinephrine infusion (NE); 3) epinephrine in...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1976.61
更新日期：1976-06-01 00:00:00
abstract：:During online hemodiafiltration, patients are directly infused with sterile substitution solutions to maintain fluid balance. Adequate water treatment and a well-organized quality control process are essential to provide non-pyrogenic fluids with consistent optimal quality. We sought to assess water quality, the water...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.245
更新日期：2009-09-01 00:00:00
