Abstract:
:Autosomal dominant polycystic kidney disease (ADPKD) is an inherited, progressive nephropathy accounting for 4-10% of end stage renal disease worldwide. PKD1 and PKD2 are the most common disease loci, but even accounting for other genetic causes, about 7% of families remain unresolved. Typically, these unsolved cases have relatively mild kidney disease and often have a negative family history. Mosaicism, due to de novo mutation in the early embryo, has rarely been identified by conventional genetic analysis of ADPKD families. Here we screened for mosaicism by employing two next generation sequencing screens, specific analysis of PKD1 and PKD2 employing long-range polymerase chain reaction, or targeted capture of cystogenes. We characterized mosaicism in 20 ADPKD families; the pathogenic variant was transmitted to the next generation in five families and sporadic in 15. The mosaic pathogenic variant was newly discovered by next generation sequencing in 13 families, and these methods precisely quantified the level of mosaicism in all. All of the mosaic cases had PKD1 mutations, 14 were deletions or insertions, and 16 occurred in females. Analysis of kidney size and function showed the mosaic cases had milder disease than a control PKD1 population, but only a few had clearly asymmetric disease. Thus, in a typical ADPKD population, readily detectable mosaicism by next generation sequencing accounts for about 1% of cases, and about 10% of genetically unresolved cases with an uncertain family history. Hence, identification of mosaicism is important to fully characterize ADPKD populations and provides informed prognostic information.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Hopp K,Cornec-Le Gall E,Senum SR,Te Paske IBAW,Raj S,Lavu S,Baheti S,Edwards ME,Madsen CD,Heyer CM,Ong ACM,Bae KT,Fatica R,Steinman TI,Chapman AB,Gitomer B,Perrone RD,Rahbari-Oskoui FF,Torres VE,HALT Progression ofdoi
10.1016/j.kint.2019.08.038subject
Has Abstractpub_date
2020-02-01 00:00:00pages
370-382issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(19)30994-9journal_volume
97pub_type
杂志文章abstract::In his hypothesis of the evolution of renal functions Homer Smith proposed that the formation of glomerular nephron and body armor had been adequate for the appearance of primitive vertebrates in fresh water and that the adaptation of homoiotherms to terrestrial life was accompanied by the appearance of the loop of He...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.220
更新日期:1996-06-01 00:00:00
abstract::Tuberous sclerosis complex is a genetic disorder characterized by hamartomatous lesions in multiple organs, frequently involving the kidney. We conducted a retrospective review of the clinical and radiographic records of 167 patients with tuberous sclerosis to determine the frequency of renal disease, the likelihood o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001853
更新日期:2006-11-01 00:00:00
abstract::The X-linked Hyp and Gy mutations are murine homologues of X-linked hypophosphatemia (XLH), a dominant disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets, hypophosphatemia and decreased renal tubular maximum for Pi reabsorption relative to glomerular filtration rate (Tmp/GFR). In Hyp a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.149
更新日期:1996-04-01 00:00:00
abstract::Endostatin (EST), an antiangiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild-type mice, aging kidneys exhibited a 2- to...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.01.030
更新日期:2016-06-01 00:00:00
abstract::Circulating parathyroid hormone (PTH) shows a complex relationship with hard outcomes in subjects with chronic kidney disease (CKD). Moreover, intervention studies directly targeting PTH failed to yield unequivocal results. Disturbed PTH metabolism, posttranslational modifications of PTH, and end-organ hyporesponsiven...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2016.06.041
更新日期:2016-12-01 00:00:00
abstract::Diabetes mellitus is associated with natriuresis, whereas estrogen has been shown to be renoprotective in diabetic nephropathy and may independently regulate renal sodium reabsorption. The aim of this study was to determine the effects of 17-beta estradiol (E(2)) replacement to diabetic, ovariectomized (OVX) female ra...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000140
更新日期:2006-02-01 00:00:00
abstract::A second generation hepatitis C virus recombinant immunoblot assay (RIBA) was used to screen stored perioperative serum from 641 renal allograft recipients. One hundred and nine (17%) were anti-HCV positive at the time of transplant. RIBA positivity was found to be an independent predictor of post-transplant liver dis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.29
更新日期:1994-01-01 00:00:00
abstract::Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. C...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.97
更新日期:2013-08-01 00:00:00
abstract::Superoxide (O2-) production and Fc alpha R antigen expression of circulating polymorphonuclear leukocytes (PMNL) isolated from patients with IgA nephropathy (IgAN) and non-IgA mesangial proliferative glomerulonephritis (PGN) and healthy volunteers were investigated to establish their biological importance in the immun...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.114
更新日期:1994-03-01 00:00:00
abstract::Few studies have examined tubular function after subtotal nephrectomy (Nx) and conservative treatments. The effects of 70% and 80% Nx (associated with dietary phosphate restriction in the latter case) on the apical brush border membrane (BBM) enzymes 5'-nucleotidase, gamma glutamyl-transferase and alkaline-phosphatase...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.485
更新日期:1997-12-01 00:00:00
abstract::Pathologic calcification is a significant cause of increased morbidity and mortality in patients with chronic kidney disease. The precise mechanisms of ectopic calcification are not fully elucidated, but it is known to be caused by an imbalance of procalcific and anticalcific factors. In the chronic kidney disease pop...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2015.12.046
更新日期:2016-05-01 00:00:00
abstract:BACKGROUND:The aim of this study was to determine the glucose-dependent regulation of the sodium-proton-antiporter (Na+/H+ antiporter) in patients with mild chronic renal failure (CRF). METHODS:We measured plasma glucose concentrations, plasma insulin concentrations, plasma C peptide concentrations, arterial blood pre...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00510.x
更新日期:1999-07-01 00:00:00
abstract::[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.319
更新日期:2009-11-01 00:00:00
abstract::The kidneys excrete the daily acid load mainly by generating and excreting ammonia but the underlying molecular mechanisms are not fully understood. Here we evaluated the role of the inwardly rectifying potassium channel subunit Kir4.2 (Kcnj15 gene product) in this process. In mice, Kir4.2 was present exclusively at t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.09.028
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Fabry disease is an X-linked generalized progressive debilitating lysosomal storage disorder. The disease usually manifests in childhood, but the diagnosis is often made following the occurrence of late-stage complications such as progressive kidney failure. In order to identify key novel renal diagnostic im...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00846.x
更新日期:2004-09-01 00:00:00
abstract::Human transitional B cells express relatively high IL-10 and low TNF-α levels, which correlate with B regulatory activity in vitro. Herein, we aim to further define B regulatory phenotype and determine whether B regulatory activity can serve as a prognostic marker for renal allograft dysfunction (graft loss or 2-fold ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.08.028
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:The "intact" parathyroid hormone (PTH) assay recognizes PTH-(1-84) as well as amino terminally truncated PTH fragments, that is, large carboxyterminal PTH fragments (C-PTH fragments). The present study investigated whether the use of the plasma PTH-(1-84)/C-PTH fragment ratio enhances the noninvasive assessm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00949.x
更新日期:2001-10-01 00:00:00
abstract:BACKGROUND:Aquaporin-2 (AQP-2) proteins are mainly expressed at the apical region of the collecting duct cells. We previously reported three different mutations in the C-terminus of AQP-2 that all-cause autosomal-dominant nephrogenic diabetes insipidus. When one of these mutant AQP-2s was expressed in Madin-Darby canin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00654.x
更新日期:2005-11-01 00:00:00
abstract::To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.201
更新日期:1996-05-01 00:00:00
abstract::Tremendous progress has been made over recent years in the understanding of the mechanisms regulating calcium, phosphorus, vitamin D, and parathyroid hormone homeostasis in the normal human body and in patients with different degrees of renal failure. In addition, some of these findings have been translated into clini...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.692
更新日期:2009-05-01 00:00:00
abstract::Recent decades have witnessed the revelation of expanding roles of the vitamin D endocrine system beyond calcium and phosphorus metabolism. Along with these non-calcemic or non-classic actions of vitamin D are newly discovered therapeutic actions of vitamin D analogs in a number of pathological conditions, including k...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.175
更新日期:2010-07-01 00:00:00
abstract::Bone-derived fibroblast growth factor-23 (FGF23) plays an important role in systemic phosphate turnover. Increased FGF23 activity results in hypophosphatemic disorders, while reduced activity is linked to hyperphosphatemic disorders. FGF23, together with klotho as co-factor, can activate FGF receptors in its target ti...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.316
更新日期:2014-12-01 00:00:00
abstract::Following 5/6 nephrectomy, 18 rats were fed a normal diet. After 30 days, serum creatinine (SCr), urine protein excretion and urine volume were increased compared to pre-nephrectomy (0.27 +/- 0.1 vs. 1.62 +/- 0.6 mg/deciliter, 17.0 +/- 10.3 vs. 257.6 +/- 13.4 mg/24 hr, and 16.6 +/- 4.4 vs. 39.2 +/- 11.7 ml/24 hr, resp...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.49
更新日期:1986-03-01 00:00:00
abstract::Staphylococcal neutral phosphatase (NPtase) is a highly cationic bacterial surface bound protein. It has significant affinity for human and rat immunoglobulins in vitro and an electrostatic interaction may be involved. Radioisotopic studies showed that NPtase had a high affinity for the polyanionic structures of the r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.314
更新日期:1996-07-01 00:00:00
abstract::The possibility that hypercalciuria could cause calcium stone formation through a mechanism other than by increasing urinary saturation of stone-forming calcium salts was explored. The effect of increasing calcium concentration on the inhibitor activity against the spontaneous precipitation of calcium oxalate was exam...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.100
更新日期:1988-05-01 00:00:00
abstract::We demonstrate that salts of diatrizoate and iothalamate, radiographic contrast agents, depress the active transport of sodium in the urinary bladder of the Columbian toad, Bufo marinus. Isolated toad bladders were incubated in isotonic Ringer's solutions with isosmolar displacement of sodium chloride by contrast medi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.11
更新日期:1975-02-01 00:00:00
abstract:BACKGROUND:Hyperuricemia has been linked to cardiovascular and renal diseases, possibly through the generation of reactive oxygen species (ROS) and subsequent endothelial dysfunction. The enzymatic effect of xanthine oxidase is the production of ROS and uric acid. Studies have shown that inhibiting xanthine oxidase wit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00273.x
更新日期:2005-05-01 00:00:00
abstract::A novel variant of the LLC-PK1 cell line was used to examine directly the mechanism whereby PGF2 alpha and TPA inhibit renal ammoniagenesis. The variant cells, which exhibit a growth pattern and morphology similar to the parent cell line, were isolated by a self selection process utilizing long-term cultures of parent...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.368
更新日期:1994-10-01 00:00:00
abstract::Many features of chronic kidney disease may be reversed, but it is unclear whether advanced lesions, such as adhesions of sclerotic glomerular tufts to Bowman's capsule (synechiae), can resolve during treatment. We previously showed, using a renal ablation model, that the renoprotective effect of the AT-1 receptor blo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.528
更新日期:2009-01-01 00:00:00
abstract::Substantial evidence implicates impaired renal excretion of sodium as the major culprit in the pathogenesis of hypertension. The key question is: How does the impairment of Na+ excretion lead to increased peripheral vascular resistance and elevation of the blood pressure? Here we describe the evidence that elevated le...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.260
更新日期:1996-06-01 00:00:00