Abstract:
BACKGROUND:Determinants of inter-individual variation in blood pressure (BP) response to antihypertensive therapy remain largely unknown. Although differences in race, age and measures of the renin-angiotensin-aldosterone system (RAAS) have been associated with variation in blood pressure response to hydrochlorothiazide, whether these characteristics make additive contributions to predicting response has not been established. We conducted a comprehensive search for predictors of BP response to a standard dose of hydrochlorothiazide in a biracial sample to estimate how much inter-individual variation in BP response could be explained by all of the identified predictors. METHODS:After withdrawal of antihypertensive medications for at least four weeks (baseline) and stabilization on a diet approximating 150 mmol sodium per day, 225 African American and 280 Caucasian subjects with diagnosed essential hypertension were treated for four weeks with hydrochlorothiazide 25 mg per day. At baseline and the end of treatment, subjects were admitted to the General Clinical Research Center for measurement of activity of the RAAS and other regulators of BP. Characteristics measured at study enrollment, at baseline, and in response to drug treatment were incorporated stepwise into linear regression models in order to quantify their additive contributions to predicting BP responses to hydrochlorothiazide. RESULTS:Black race and female gender were both associated with significantly greater systolic (SBP) and diastolic (DBP) blood pressure responses to hydrochlorothiazide. Together the combined effects of race and gender accounted for 11% inter-individual variation in SBP response (P < 0.0001) and 4% of inter-individual variation in DBP response (P < 0.0001). Additional statistically significant predictors of greater systolic and diastolic responses to hydrochlorothiazide included, shorter duration of diagnosed or treated hypertension (P < 0.001), higher baseline BP level (P < 0.0001), lower baseline plasma renin activity (P < 0.05), lower baseline urinary aldosterone excretion (P < 0.002), and greater decrease in urinary sodium excretion (P < or = 0.004). Greater decrease in weight was an additional statistically significant predictor of SBP but not DBP response, and older age was a predictor of diastolic but not SBP response. The combined effects of all identified predictors accounted for 38% of inter-individual variation in SBP response (P < 0.0001) and 20% of inter-individual variation in DBP response (P < 0.0001). CONCLUSIONS:A systematic search reveals numerous predictors of BP response to a standard antihypertensive dose of hydrochlorothiazide. However, because the majority of inter-individual variation in SBP and DBP responses remains unexplained, there is considerable opportunity for future investigations to improve the ability to predict individual BP responses to antihypertensive drug therapy.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Chapman AB,Schwartz GL,Boerwinkle E,Turner STdoi
10.1046/j.1523-1755.2002.00200.xsubject
Has Abstractpub_date
2002-03-01 00:00:00pages
1047-55issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(15)48314-0journal_volume
61pub_type
杂志文章abstract::Experimental unilateral ureteral obstruction (UUO) is widely used to study renal fibrosis; however, renal injury can only be scored semiobjectively by histology. We sought to improve the UUO model by reimplanting the obstructed ureter followed by removal of the contralateral kidney, thus allowing longitudinal measurem...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002797
更新日期:2008-04-01 00:00:00
abstract::The inner medullary collecting duct (IMCD) is a major target site of atrial natriuretic peptide (ANP) for diuresis and natriuresis, and it is in a hypertonic condition made by the renal countercurrent multiplication system. We investigated the effects of hyperosmolality on ANP-stimulated cGMP generation in IMCD and gl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.178
更新日期:1994-05-01 00:00:00
abstract::Healthy male rats were exposed to a chronic ingesta of an isotonic NaCl solution during a period of four months. Two different preparations were utilized to study the effect of this treatment on the active mechanisms of Na+ reabsorption of kidney proximal tubular cells: outermost kidney cortex slices (rich in proximal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.216
更新日期:1986-10-01 00:00:00
abstract::We have previously established that interferon (IFN)-gamma stimulated, antigen-pulsed tubular epithelial cells (TEC) stimulate antigen (Ag) specific activation of T cell hybridomas to express IL-2. In contrast, these Ag pulsed TEC do not stimulate T helper 1 (Th1) clones to proliferate, but rather render them unrespon...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.147
更新日期:1994-04-01 00:00:00
abstract::As new components of the renin-angiotensin system (RAS) are elucidated, our understanding of the complexities of their interactions also advances. Previous studies have determined that podocytes possess a local RAS that can generate angiotensin II. Podocytes have also been shown to express angiotensin-converting enzym...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2012.127
更新日期:2012-08-01 00:00:00
abstract::The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.40
更新日期:1997-01-01 00:00:00
abstract::Normal urine contains thousands of proteins, largely due to the presence of 'exosomes,' tiny vesicles secreted into the urine by renal epithelial cells. These exosomes, demonstrated by Keller and colleagues to be also retrievable from amniotic fluid, offer great promise for future disease biomarker discovery studies. ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002510
更新日期:2007-11-01 00:00:00
abstract::Nitric oxide is generated from L-arginine by nitric oxide synthase (NOS), an enzyme that exists in several isoforms. Some studies found that a polymorphism (G894T) in the endothelial NOS gene was associated with decreased nitric oxide bioactivity and vascular complications. However, it is not known whether the enzyme ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.574
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:The superiority of renin-angiotensin system (RAS) blockade in providing renoprotection has been attributed to class-specific blood pressure "(BP)-independent" mechanisms. However, the conventional BP measurement methodology on which such conclusions are based is inherently limited for an accurate assessment ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00009.x
更新日期:2000-04-01 00:00:00
abstract::Progressive glomerulonephritis and attendant end-stage renal disease (ESRD) result from antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The optimum time of kidney transplantation in patients with ESRD due to ANCA-associated vasculitis (AAV) and the risk of renal or nonrenal recurrence of vasculitis a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002244
更新日期:2007-06-01 00:00:00
abstract::Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outc...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2015.12.001
更新日期:2016-03-01 00:00:00
abstract::The cardiorenal safety database from the Celecoxib Long-term Arthritis Safety Study (CLASS) was analyzed to examine whether supratherapeutic doses of celecoxib are associated with decreased renal function and blood pressure (BP) effects compared with standard doses of diclofenac and ibuprofen in osteoarthritis (OA) an...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001766
更新日期:2006-10-01 00:00:00
abstract::In Australia, Canada, New Zealand, and the United States indigenous people have high rates of chronic kidney disease but poor access to effective therapies. To more fully define these issues, we compared the demographics of renal transplantation of indigenous patients in these 4 countries. Data encompassing 312,507 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.236
更新日期:2009-09-01 00:00:00
abstract::We present a new hypothesis to explain the development of salt-dependent hypertension in humans. We propose that hypertension has two phases: an early phase in which elevations in blood pressure (BP) are mainly episodic and are mediated by a hyperactive sympathetic nervous or renin-angiotensin system, and a second pha...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1997.442
更新日期:1997-11-01 00:00:00
abstract:BACKGROUND:Susceptibility to skin cancer after transplantation is multifactorial, and risk factors include skin type, sun exposure, and level of immunosuppression. A major mechanism of carcinogenesis is ultraviolet radiation-induced free radical damage, and genetically determined ability to metabolize free radicals may...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00392.x
更新日期:2000-11-01 00:00:00
abstract::The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs) of the target genes. We have shown that the interaction of VDRs with VDREs is inhibited by uremic toxins. We hypothesize that uremic toxins form Schiff bases with the lysine re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.469
更新日期:1996-11-01 00:00:00
abstract::Autophagy is a dynamic and highly regulated process of self-digestion responsible for cell survival and reaction to oxidative stress. As oxidative stress is increased in uremia and is associated with vascular calcification, we studied the role of autophagy in vascular calcification induced by phosphate. In an in vitro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.482
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:The objectives of this study were to compare the effects of the angiotensin II receptor blocker, losartan, to those of the angiotensin-converting enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic subjec...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2000.00224.x
更新日期:2000-08-01 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::Continuous antigen stimulation during chronic infection or malignancy can promote functional T cell silencing, a phenomenon called T cell exhaustion. The prevalence and impact of T cell exhaustion following organ transplantation, another immune stimulus with persistently high antigen load, are unknown. Here, we charac...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.01.040
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Wegener's granulomatosis (WG) is characterized by systemic vasculitis with crescentic glomerulonephritis (CGN) and circulating autoantibodies directed against neutrophil cytoplasmic antigens (ANCA). Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00100.x
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND:A family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown. METHODS:We evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0600031141.x
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS:To gain insights into this issue, we evaluated the renal response to a maximal vasodilating s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590031052.x
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:We evaluated the effects of different concentrations of iron dextran administered through the intraperitoneal route, in iron-deficient rats, on hematocrit (Hct in percentage), serum iron (mg/dL), total iron binding capacity (TIBC in mg/dL), and the function and histology of the peritoneal membrane. METHODS:...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059002764.x
更新日期:2001-02-01 00:00:00
abstract::The transition between the glomerulus and the proximal tubule was studied by light and electron microscopy in perfusion-fixed rabbit kidneys. In most nephrons a transitional segment of tubule occurred between the Bowman's capsule and the proximal tubule proper. This initial part of the tubule was lined by flattened ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.22
更新日期:1975-03-01 00:00:00
abstract::It is known that in rodents recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor (rhIGF-1) increase renal mass. It is uncertain, however, whether renal mass increases in proportion to body growth, or whether renal growth is stimulated selectively. In 120 to 150 g female Sprague-Dawl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.376
更新日期:1993-12-01 00:00:00
abstract::Apoptosis mediated by verotoxins (VTs) has been identified in a renal carcinoma cell line, ACHN cells, which are an in vitro model of renal tubular epithelial cells. ACHN cells express the renal tubular marker CD24 as well as globotriaosyl ceramide/CD77, the receptor for VTs. VT binding to the ACHN cell surface was co...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00939.x
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:This multicenter, open-label, dose-titration study assessed the safety and efficacy of RenaGel(R), a nonabsorbed calcium- and aluminum-free phosphate binder, in lowering serum phosphorus. Secondary outcomes were its effects on serum intact parathyroid hormone (iPTH) and serum lipids. METHODS:Phosphate binde...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1046/j.1523-1755.1999.00240.x
更新日期:1999-01-01 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::For reasons that are not well understood, Aboriginal people with end-stage renal disease (ESRD) have lower rates of kidney transplantation. We hypothesized that distance between residence location and the closest transplant center was greater in Aboriginal dialysis patients and would partially explain the lower rate o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001607
更新日期:2006-09-01 00:00:00