Abstract:
:Familial aggregation of non-diabetic end-stage renal disease (ESRD) is found in African Americans and variants in the apolipoprotein L1 gene (APOL1) contribute to this risk. To detect genetic associations with milder forms of nephropathy in the high-risk families, analyses were performed using generalized estimating equations to assess relationships between kidney disease phenotypes and APOL1 variants in 786 relatives of 470 families. Adjusting for familial correlations, 23.1, 46.7, and 30.2% of genotyped relatives possessed two, one, or no APOL1 risk variants, respectively. Relatives with two compared with one or no risk variants had statistically indistinguishable median systolic blood pressure, urine albumin to creatinine ratio, estimated glomerular filtration rate (GFR; MDRD equation), and serum cystatin C levels. After adjusting for age, gender, age at ESRD in families, and African ancestry, significant associations were detected between APOL1 with overt proteinuria and estimated GFR (CKD-EPI equation), with a trend toward significance for quantitative albuminuria. Thus, relatives of African Americans with non-diabetic ESRD are enriched for APOL1 risk variants. After adjustment, two APOL1 risk variants weakly predict mild forms of kidney disease. Second hits appear necessary for the initiation of APOL1-associated nephropathy.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Freedman BI,Langefeld CD,Turner J,Núñez M,High KP,Spainhour M,Hicks PJ,Bowden DW,Reeves-Daniel AM,Murea M,Rocco MV,Divers Jdoi
10.1038/ki.2012.217subject
Has Abstractpub_date
2012-10-01 00:00:00pages
805-11issue
7eissn
0085-2538issn
1523-1755pii
S0085-2538(15)55637-8journal_volume
82pub_type
杂志文章abstract::Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-k...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.134
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND:Dopamine (DA) is thought to regulate renal proximal transport through the inhibition of the Na+,K+-ATPase and/or Na+/H+ exchanger. Defects in this dopaminergic system are proposed to be a pathogenic factor of genetic hypertension. However, microperfusion studies have not consistently confirmed direct tubular...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00873.x
更新日期:2000-02-01 00:00:00
abstract::We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized t...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2010.352
更新日期:2011-01-01 00:00:00
abstract::Current characterization of the immune risk in renal transplant patients is only focused on the assessment of preformed circulating alloantibodies; however, alloreactive memory T cells are key players in mediating allograft rejection. Immune monitoring of antidonor alloreactive memory/effector T cells using an IFN-γ E...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.236
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Macrophage-mesangial cell interaction plays a crucial role in the pathogenesis of glomerulonephritis. We established a novel system for continuous, real-time monitoring of cross-talk between macrophages and mesangial cells in vitro and ex vivo. METHODS:Rat mesangial cells were genetically engineered to prod...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00471.x
更新日期:2005-08-01 00:00:00
abstract::The impact of early-diagnosed new-onset post-transplantation diabetes mellitus (PTDM) on cardiovascular (CV) disease is not well described. The objectives of the present prospective single-center observational study were to assess the long-term effects of early-diagnosed new-onset PTDM on major cardiac events (MCE; ca...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000116
更新日期:2006-02-01 00:00:00
abstract::The pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.71
更新日期:1984-04-01 00:00:00
abstract:BACKGROUND:Phenylalanine is converted to para- and ortho-tyrosine by hydroxyl free radical, or to para-tyrosine by the phenylalanine hydroxylase enzyme. The aim of this study was to measure para- and ortho-tyrosine in the urine and plasma of patients with chronic renal disease and/or diabetes, to obtain information on ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00687.x
更新日期:2005-11-01 00:00:00
abstract::The addition of spironolactone or hydrochlorothiazide enhances the antialbuminuric effect of renin-angiotensin blockers. However, comparative studies on the effect of different diuretics are lacking. We conducted a prospective randomized crossover study to compare the effects of spironolactone (25 mg/day), hydrochloro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.249
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Non-(1-84) parathyroid hormone (PTH) fragments are large circulating carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. hPTH (7-84), a synthetic surrogate, has been demonstrated to exert biologic effects in vivo and in vitro which are opposite to those of hPTH (1-34) on ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00493.x
更新日期:2005-09-01 00:00:00
abstract::Tubulointerstitial fibrosis is one of the most important histologic features that predicts progression in kidney disease. Thrombospondin 1 is an extracellular matrix protein that can activate latent TGF-beta, a cytokine implicated in the pathogenesis of tubulointerstitial fibrosis. We examined the expression of thromb...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00774.x
更新日期:1998-02-01 00:00:00
abstract::How much dialysis is required for optimal well-being and long-term survival? The Frequent Hemodialysis Network completed two prospective trials examining the effect of more frequent, short hours and, now, of nocturnal hemodialysis compared with standard thrice-weekly treatments. Whereas the short-hours trial reported ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2011.267
更新日期:2011-11-01 00:00:00
abstract::In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.373
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND:Cellular and molecular mechanisms responsible for cisplatin-induced nephrotoxicity to renal tubular epithelial cells are not well understood. Although caspases play a critical role in the execution of the cell death pathway, their specific role in toxic injury to renal tubular epithelial cells has not been e...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00026.x
更新日期:2001-11-01 00:00:00
abstract::The distribution of precursor nitrogen between urea and glutamine was studied in control and acidotic rats. Acidosis, either acutely induced with hydrochloric acid or chronically induced with ammonium chloride, resulted in a rise in ammonia and a fall in urinary urea excretion; the percent of urinary nitrogen excreted...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.182
更新日期:1981-11-01 00:00:00
abstract::We previously demonstrated that urinary endothelin excretion is increased in rats with extensive renal mass reduction, a model of progressive renal disease. Here we explored whether the increased urinary endothelin in this model were due to induction of renal pre-pro-endothelin-1 gene and whether changes in endothelin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.53
更新日期:1993-02-01 00:00:00
abstract::Thrombomodulin (TM), an endothelial receptor for thrombin, endowed with a powerful anticoagulant activity, plays an important role in the antithrombogenicity of the vascular endothelium. Its presence within the human renal glomerulus is already known but was thought to be only endothelial. We looked for TM expression ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.99
更新日期:1997-03-01 00:00:00
abstract::Antibodies against purified rat-kidney-cortex pyruvate carboxylase were raised in rabbits. These polyspecific antibodies recognize pyruvate carboxylase enzymes alone without cross reactivity with other carboxylases as detected by immunoblotting. The abundance of pyruvate carboxylase in the various renal fractions was ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.147
更新日期:1991-06-01 00:00:00
abstract::We have previously suggested that albumin in tubule fluid at concentrations found in the nephrotic syndrome (NS) binds furosemide, thereby diminishing diuretic effect. This mechanism may contribute to diuretic resistance in NS. If this hypothesis is correct, displacement of albumin from furosemide should restore diure...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.228
更新日期:1991-09-01 00:00:00
abstract::Long-term treatment (8 and 13 weeks) of rats with FGF-2 led to albuminuria and to increase in serum creatinine indicating the development of chronic renal failure. Histologically, the classic picture of focal segmental glomerulosclerosis (FSGS) was found; males were more severely affected than females. Among the early...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.433
更新日期:1995-11-01 00:00:00
abstract::Spontaneous polycystic kidney and liver disease in an inbred herd of Springbok (Antidorcas marsupialis) was studied by light microscopy, transmission electron microscopy, and microdissection. Springbok are a small species of gazelle of the family Bovidae native to South Africa. Since 1976, 18% of all live calves born ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.146
更新日期:1982-08-01 00:00:00
abstract:BACKGROUND:Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the purom...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060003957.x
更新日期:2001-09-01 00:00:00
abstract::The presence of CR1 mRNA in podocytes was investigated using a 35S-labeled CR1 cDNA probe and in situ hybridization in sections from fetal and adult human kidneys. CR1 mRNA was only detected in immature podocytes at early stages of glomerular differentiation in the fetal kidney. In contrast, CR1 antigen was abundantly...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.198
更新日期:1990-08-01 00:00:00
abstract::Ischemia-reperfusion occurs in a great many clinical settings and contributes to organ failure or dysfunction. CD154-CD40 signaling in leukocyte-endothelial cell interactions or T-cell activation facilitates tissue inflammation and injury. Here we tested a siRNA anti-CD40 in rodent warm and cold ischemia models to che...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.146
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:Both high glucose (HG) and angiotensin II (Ang II) causes glomerular mesangial cell (GMC) growth and increased synthesis of matrix proteins like collagen IV contributing to diabetic nephropathy. We have recently found that exposure of vascular smooth muscle cells to HG augments the Ang II activation of the g...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00311.x
更新日期:2002-05-01 00:00:00
abstract::Adynamic bone disease (ABD) is increasingly recognized, especially in dialysis patients treated with oral calcium carbonate, vitamin D supplements, or supraphysiological dialysate calcium. We undertook this study to assess the effect of lowering dialysate calcium on episodes of hypercalcemia, serum parathyroid hormone...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001666
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Recent clinical trials of mycophenolate mofetil (MMF) in chronic allograft nephropathy (CAN) demonstrated that the dose of cyclosporine A (CsA) is one of the critical factors in determining graft function in CAN, but the effect of MMF on chronic CsA nephropathy is undetermined. We undertook this study to eva...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00400.x
更新日期:2002-07-01 00:00:00
abstract::Serum calcitriol and the free calcitriol index together with factors considered to regulate calcitriol production were measured in eleven patients with moderate chronic renal failure (MCRF) and eleven age- and sex-matched normal subjects. Although the serum dialysable calcium levels were similar in the two groups, the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.58
更新日期:1988-03-01 00:00:00
abstract::Mineralocorticoid hormones stimulate Na+ absorption and K+ secretion by the cortical collecting tubule. There is good evidence that this stimulation involves increasing luminal membrane Na+ permeability and the turnover rate (or number) of the Na+-K+ pumps. These experiments were designed to examine whether mineraloco...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.177
更新日期:1985-10-01 00:00:00
abstract::Inflammatory responses in the kidney lead to tubulointerstitial fibrosis, a common feature of chronic kidney diseases. Here we examined the role of prostaglandin E(2) (PGE(2)) in the development of tubulointerstitial fibrosis. In the kidneys of wild-type mice, unilateral ureteral obstruction leads to progressive tubul...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.115
更新日期:2012-07-01 00:00:00