Arlene B Chapman's scientific contributionswhile working at Emory University and other institutions

Publications (227)

Publications citing this author (7497)

    • In addition, many patients, carriers of the Trp/Trp-genotype, were classified as carriers of a " low-renin " form of HT (66.7 %) compared with other patients (23.8%) [29,30]. In contrast to the well-designed study on the ADD1 Gly460Trp polymorphism, some other studies in other populations have shown insufficient results to confirm the same correlation between ADD1 polymorphism and sodium sensitivity [29,31] or a response to diuretic therapy [32], which causes great interest in continuing the investigations. A multiple choice of antihypertensive drugs is widely available.
    [Show abstract] [Hide abstract] ABSTRACT: The purpose of the present study was to evaluate pharmacogenetic aspects of the antihypertensive, cardioprotective and vasoprotective efficacy of Indapamide in association with the ADD1 Gly460Trp polymorphism in Uzbek hypertensive patients. Materials and Methods: The study included 37 ethnic Uzbek patients (mean age of 47.14±9.54) with untreated hypertension (HT) of Grade 1 and 2 (ESH/ESC, 2013) and average HT duration of 5.7±4.33 years. All patients underwent clinical examination, echocardiography, Doppler sonography study, assessment of flow-mediated dilation (FMD) of the brachial artery and microalbuminuria (MAU) in daily urine. Genomic DNA was extracted from peripheral blood using the DiatomTM DNA Prep 200 Kit according to the manufacturer's protocol. The PCR-RFLP technique with visualization was performed to determine the ADD1 Gly460Trp polymorphism. Indapamide was prescribed as monotherapy for 12 weeks with an initial dose of 2.5 mg. Results: A 12-week monotherapy with Indapamide in a daily dose of 2.5mg showed the high antihypertensive efficacy of this drug expressing a reliable decrease in absolute values of SBP and DBP independently as carrying of the ADD1 Gly460Trp polymorphism allele. Positive changes in LVM during therapy in patients of both allele groups were accompanied by an improvement in LV diastolic function with significant positive dynamics of IRP. The target normalization of FMD was achieved only in the presence of Gly-allele, as well as a significant decrease in IMT and MAU during treatment. Conclusion: The results of our study showed high antihypertensive and cardioprotective efficacy of Indapamide treatment independently on carrying of the ADD1 Gly460Trp polymorphism. At the same time, we revealed certain advantages in the vasoprotective efficacy of Indapamide treatment in Uzbek hypertensive patients who are carriers of Gly-allele of the ADD1 Gly460Trp polymorphism.
    Article · Sep 2015
    • However, previous studies failed to demonstrate the relationship between biomarker and underlying renal pathophysiology. ADPKD patients develop hypertension earlier than the essential hypertensive patients and it is also well known that early-onset hypertension is the major predictor of renal outcome in ADPKD [11] . Intrarenal reninangiotensin system (RAS) has been suggested as the main mechanism in the development of hypertension in ADPKD since cyst development and growth activate and accelerate intrarenal RAS far earlier than renal fibrosis and renal dysfunction.
    [Show abstract] [Hide abstract] ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney diseases that frequently result in renal failure. In this cross-sectional observational cohort study, we evaluated urinary angiotensinogen (AGT) as a potential biomarker to assess renal function in ADPKD. Urinary AGT was measured in 233 ADPKD patients and its association with estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV) were evaluated. The localization of AGT and other renin-angiotensin system (RAS)-related molecules were identified using immunohistochemistry in human ADPKD tissues. Baseline urinary AGT/Cr was negatively correlated with CKD-EPI eGFR (r (2) = 0.162, P < 0.001) and positively correlated with htTKV (r (2) = 0.107, P < 0.001). Both urinary AGT/Cr and plasma renin activity levels were significantly elevated in hypertensive ADPKD patients. Among hypertensive subjects, urinary AGT/Cr was significantly increased in the advanced CKD stages (III-V) compared to early CKD stages (I-II) (28.6 ± 60.3 vs. 93.2 ± 139.3 μg/g, P < 0.001). Immunohistochemical study showed strong expression of AGT along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. Our results suggested that urinary AGT/Cr may be a valuable biomarker for renal damage in ADPKD since intrarenal ischemic insults induced by cyst growth and subsequent intrarenal RAS activation may play a potential role in the development of hypertension and renal dysfunction in ADPKD.
    Full-text · Article · Jun 2015
    • Dilations in the tubules from an early staged ADPKD patient show thickened and deformed basement membrane having single layer of lined epithelial cells with abnormal proliferation, protein sorting defects and altered planar cell polarity434445. Many factors associated with the variability of the disease such as hypertension, early onset, male gender, increase in kidney size and growth rate of cysts in multiple organs, and microalbuminuria are said to contribute towards progression of the disease46474849. Patients experience pangs of abdominal pain, hypertension, renal insufficiency, hematuria and/or proteinuria [50].
    [Show abstract] [Hide abstract] ABSTRACT: The normal architecture of the kidney is crucial for maintaining biological function and its homeostasis. Its proper development depends on highly dynamic processes which modulate the integrity of its associated cellular functions, interactive events and regulatory cascades altogether providing proper turnover in adult life. Any alteration in regulatory processes and normal utility holds crucial consequences for proper functioning of the kidney. These variations accompany renal injury, various etiologic events, deviation from genetic-wild type processes and metabolic disturbances leading to major lesion of end-stage renal disease (ESRD). Major renal disorders developing today affecting millions globally include diabetes, hypertension, glomerulonephritis and Polycystic Kidney Disease (PKD). Among these diseases, PKD is becoming relatively common, and has emerged as one of the largest causes of renal transplantation and dialysis. Therefore, understanding the development, function and progression of normal kidneys to cystic renal kidneys serves an important way in understanding pathophysiology of PKD and cystogenesis.
    Article · Jan 2015 · Oncotarget
    • The decrease in GFR is inversely proportional to kidney size and cyst volume as assessed by the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP).181920 Because ultrasound measurements cannot discern changes in kidney size over short time intervals, magnetic resonance imaging (MRI) with or without gadolinium has become the gold standard for assessing changes in kidney volume and thereby prognosis.[21,22] As there is no specific or targeted clinically approved therapy, current practice focuses on strict blood pressure control with ACE inhibition and the use of statins to reduce the associated cardiac mortality that coincides with chronic kidney disease.[23]
    [Show abstract] [Hide abstract] ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent, inherited condition for which there is currently no effective specific clinical therapy. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells which gradually compress the parenchyma and compromise renal function. Current interests in the field focus on understanding and exploiting signaling mechanisms underlying disease pathogenesis as well as delineating the role of the primary cilium in cystogenesis. This review highlights the pathogenetic pathways underlying renal cyst formation as well as novel therapeutic targets for the treatment of PKD. This article is part of a Special Issue entitled: Polycystic Kidney Disease.
    Full-text · Article · Dec 2010
    • As the kidneys undergo the gestational process, a corresponding physiological compensation, such as glomerular hypertrophy and hyper-filtration, would occur to meet the excessive requirements of pregnancy, which is a consequence of increased renal blood flow [7, 8]. In healthy women, the changes in the kidneys as a result of pregnancy would stabilize naturally without any sequel after the delivery of a child [7][8][9]. However, patients with chronic kidney disease (CKD) would probably fail to overcome these problems during pregnancy.
    [Show abstract] [Hide abstract] ABSTRACT: Background Data on long-term maternal outcomes in patients with systemic lupus erythematosus (SLE) are lacking. The study aimed to explore the relationships among SLE, pregnancy, outcomes of end-stage renal disease (ESRD), and overall mortality. Methods We established a retrospective cohort study consisting of four cohorts: pregnant (case cohort) and nonpregnant SLE patients, as well as pregnant and nonpregnant non-SLE patients. One case cohort and three comparison cohorts were matched by age at first pregnancy and index date of pregnancy by using the Taiwan National Health Insurance Research Dataset. All study subjects were selected based on the index date to the occurrence of ESRD or overall death. Cox proportional hazard regression models and Kaplan–Meier curves were used in the analysis. Results SLE pregnant patients exhibited significantly increased risk of ESRD after adjusting for other important confounders, including immunosuppressant and parity (HR = 3.19, 95% CI: 1.35–7.52 for pregnant non-SLE; and HR = 2.77, 95% CI: 1.24–6.15 for nonpregnant non-SLE patients). No significant differences in ESRD incidence were observed in pregnant and nonpregnant SLE patients. Pregnant SLE patients exhibited better clinical condition at the baseline and a significantly lower risk of overall mortality than nonpregnant SLE patients. Conclusions Our data support current recommendations for SLE patients to avoid pregnancy until disease activity is quiescent. Multicenter recruitment and clinical information can be used to further examine the association of SLE and ESRD (or mortality) after pregnancy.
    Full-text · Article · Dec 2016
    • It has been suggested that an elevated ARR should be considered only when the SAC exceeds a minimum concentration. The motivation for this recommendation is that even in low aldosterone states, if renin is undetectable, the ARR may still be high, depending on the lower reportable limit of the renin assay, leading to false positives[104,105]. While Young recommended a minimum SAC of 415 pmol/L (15 ng/dL) before a high ARR be considered a positive screen for PA[106,107], it has been observed that in bona fide cases of PA, the ambulatory aldosterone level may be as low as 250 pmol/L[108]and that about one-third of PA patients have ambulatory aldosterone levels b415 pmol/L[109].
    [Show abstract] [Hide abstract] ABSTRACT: The laboratory has a critical role to play in the screening and diagnosis of primary aldosteronism. This review highlights some of the important analytical considerations and the new developments in the determination of aldosterone and renin. The review considered the published literature and clinical practice guidelines in the area of primary aldosteronism. A brief introduction to primary aldosteronism is provided. A detailed description of the pre-analytical, analytical and post- analytical considerations for the laboratory determination of aldosterone, renin and the aldosterone to renin ratio follows. The lack of internationally accepted standardized methodologies and standard reference material has impeded screening and diagnosis of primary aldosteronism. The development of more accurate and sensitive methods by LC-MS/MS has improved the reliability of aldosterone and renin testing and the availability of commercial chemiluminescent assays may improve the standardization of reporting. Laboratorians need to understand the strengths and weaknesses of their analytical approach and ensure that their interpretative reports are appropriate to their assays. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jan 2015
    • However, our study was not specifically designed to address this question, and further randomized prospective studies will be needed to address this point also considering that available information in the literature is very limited. Specifically, a few studies showed that drugs acting on RAA system and, in particular, ARBs could improve metabolic status in patients with metabolic syndrome [32], decreasing visceral fat accumulation [33] and improving insulin sensitivity and lipid profile [34] , whereas visceral adiposity increases the risk of developing adverse metabolic effects upon treatment with β-blockers or thiazide diuretics [35]. Moreover, an important limitation of these studies was the short duration of drug exposure ranging around several weeks.
    [Show abstract] [Hide abstract] ABSTRACT: Background Although the pathophysiological mechanisms of arterial hypertension are different in obese and lean patients, hypertension guidelines do not include specific recommendations for obesity-related hypertension and, therefore, there is a considerable uncertainty on which antihypertensive drugs should be used in this condition. Moreover, studies performed in general population suggested that some antihypertensive drugs may increase body weight, glycemia and LDL-cholesterol but it is unclear how this impact on drug choice in clinical practice in the treatment of obese hypertensive patients. Therefore, in order to identify current preferences of practitioners for obesity-related hypertension, in the present work we evaluated antihypertensive drug therapy in a cohort of 129 pharmacologically treated obese hypertensive patients (46 males and 83 females, aged 51.95 ± 10.1 years) that came to our observation for a nutritional consultation. Methods Study design was retrospective observational. Differences in the prevalence of use of the different antihypertensive drug classes among groups were evaluated with χ2 square analysis. Threshold for statistical significance was set at p < 0.05. Results 41.1 % of the study sample was treated with one, 36.4 % with two and the remaining 22.5 % with three or more antihypertensive drugs. In patients under single drug therapy, β-blockers, ACEIs and ARBs accounted each for about 25 % of prescriptions. The prevalence of use of β-blockers was about sixfold higher in females than males. Diuretics were virtually never used in monotherapy regimens but were used in more than 60 % of patients on dual antihypertensive therapy and in all patients assuming three or more drugs. There was no significant difference in the prevalence of use of any of the aforementioned drugs among patients with obesity of type I, II and III or between patients with or without metabolic syndrome. Conclusions Our data show that no first choice protocol seems to be adopted in clinical practice for the treatment of obesity-related hypertension. Importantly, physicians do not seem to differentiate drug use according to the severity of obesity or to the presence of metabolic syndrome or to avoid drugs known to detrimentally affect body weight and metabolic profile in general population.
    Full-text · Article · Dec 2016
    • Between the ovulatory phase of the cycle and gestation week 6, plasma estradiol, a molecule known to mobilize CACs (CD34+KDR+ cells) [14], rose tenfold. A rise in effective renal plasma flow consistent with primary renal vasodilation was also significant by gestation week 6 [30]. During these early pregnancy weeks, the uterine lining also transforms from cycling endometrium into decidua, a process that involves extensive neoangiogenesis .
    [Show abstract] [Hide abstract] ABSTRACT: Type 1 and 2 diabetes decrease the frequencies and functional capacities of circulating angiogenic cells (CAC). Diabetes also elevates gestational complications. These observations may be interrelated. We undertook pilot studies to address the hypothesis that preconception diabetes deviates known gestational increases in CACs. Cross-sectional study of type 1 diabetic, type 2 diabetic and normoglycemic pregnant women was conducted at 1st, 2nd, and 3rd trimester and compared to a 6mo postpartum surrogate baseline. Circulating progenitor cells (CPC; CD34+CD45dimSSlow) and CACs (CD34+CD45dimSSlow expressing CD133 without or with KDR) were quantified by flow cytometry and by colony assay (CFU-Hill). In pregnant normoglycemic women, CD34+CD45dimSSlow cell frequency was greater in 1st and 3rd trimester than postpartum but frequency of these cells was static over type 1 or 2 diabetic pregnancies. Type 1 and type 2 diabetic women showed CACs variance versus normal controls. Type 1 diabetic women had more total CD34+KDR+ CACs in 1st trimester and a higher ratio of CD133+KDR+ to total CD133+ cells in 1st and 2nd trimesters than control women, demonstrating an unbalance in CD133+KDR+ CACs. Type 2 diabetic women had more CD133+KDR+ CACs in 1st trimester and fewer CD133+KDR- CACs at mid-late pregnancy than normal pregnant women. Thus, pregnancy stage-specific physiological fluctuation in CPCs (CD34+) and CACs (CD133+KDR+ and CD133+KDR-) did not occur in type 1 and type 2 diabetic women. Early outgrowth colonies were stable across normal and diabetic pregnancies. Therefore, preconception diabetes blocks the normal dynamic pattern of CAC frequencies across gestation but does not alter colony growth. The differences between diabetic and typical women were seen at specific gestational stages that may be critical for initiation of the uterine vascular pathologies characterizing diabetic gestations.
    Full-text · Article · Mar 2017
    • We decided a priori to use it as the response phenotype in PEAR because home blood pressure is a more accurate phenotype, as home blood pressure predicts cardiovascular risk better than office blood pressure[25,26]. In addition, we previously found ambulatory blood pressure measurement, another potentially better predictor of cardiovascular risk, correlated with home blood pressure more than with office blood pressure in a subset of PEAR participants[27]. PEAR home blood pressure entries were averages of multiple measurements spanning at least five days, thus they likely give a better estimate of participants' actual blood pressures.
    [Show abstract] [Hide abstract] ABSTRACT: Nearly one-third of the United States adult population suffers from hypertension. Hydrochlorothiazide (HCTZ), one of the most commonly used medications to treat hypertension, has variable efficacy. The renal epithelial sodium channel (ENaC) provides a mechanism for fine-tuning sodium excretion, and is a major regulator of blood pressure homeostasis. DOT1L, MLLT3, SIRT1, and SGK1 encode genes in a pathway that controls methylation of the histone H3 globular domain at lysine 79 (H3K79), thereby modulating expression of the ENaCα subunit. This study aimed to determine the role of variation in these regulatory genes on blood pressure response to HCTZ, and secondarily, untreated blood pressure. We investigated associations between genetic variations in this candidate pathway and HCTZ blood pressure response in two separate hypertensive cohorts (clinicaltrials.gov NCT00246519 and NCT00005520). In a secondary, exploratory analysis, we measured associations between these same genetic variations and untreated blood pressure. Associations were measured by linear regression, with only associations with P ≤ 0.01 in one cohort and replication by P ≤ 0.05 in the other cohort considered significant. In one cohort, a polymorphism in DOT1L (rs2269879) was strongly associated with greater systolic (P = 0.0002) and diastolic (P = 0.0016) blood pressure response to hydrochlorothiazide in Caucasians. However, this association was not replicated in the other cohort. When untreated blood pressure levels were analyzed, we found directionally similar associations between a polymorphism in MLLT3 (rs12350051) and greater untreated systolic (P < 0.01 in both cohorts) and diastolic (P < 0.05 in both cohorts) blood pressure levels in both cohorts. However, when further replication was attempted in a third hypertensive cohort and in smaller, normotensive samples, significant associations were not observed. Our data suggest polymorphisms in DOT1L, MLLT3, SIRT1, and SGK1 are not likely associated with blood pressure response to HCTZ. However, a possibility exists that rs2269879 in DOT1L could be associated with HCTZ response in Caucasians. Additionally, exploratory analyses suggest rs12350051 in MLLT3 may be associated with untreated blood pressure in African-Americans. Replication efforts are needed to verify roles for these polymorphisms in human blood pressure regulation.
    Full-text · Article · Mar 2012
    • In contrast, CT is useful in visualizing smaller renal cysts and to measure renal volume [18,19]. Similarly, MRI provides excellent visualization of simple and complex renal cysts and enables an accurate measurement of renal volume [3,20] . Radionuclide renal scintigraphy and positron emission tomography (PET) are used in the diagnosis and management of patients with a variety of suspected genitourinary tract problems and diseases but are not commonly used to evaluate ADPKD patients [21,22].
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Prognostic markers for progression of polycystic kidney disease (PKD) are limited. We evaluated the potential of early para-[18F]fluorohippurate ([18F]PFH) positron emission tomography (PET) renography to predict future progression of PKD in Han:SPRD rats with slowly progressive autosomal dominant PKD. Materials and methods: Male and female heterozygous (Cy/+) and normal littermate (+/+) Han:SPRD rats underwent [18F]PFH PET renography and blood sampling to measure serum creatinine (S-Cr) and serum urea nitrogen (SUN) concentrations at 6 and 26wk of age. T2 and T20 values, which represent the percent of the injected dose of [18F]PFH in kidneys at 2 and 20min after injection, were determined from imaging data. T20/T2 ratio was assessed as a prognostic marker. Rats were euthanized after renography at 26wk of age, and kidney weight/body weight ratios (KW/BW%) were determined as a measure of PKD progression. Results: Male and female Cy/+ rats are known to manifest PKD of different severity, male Cy/+ rats display much more severe PKD than female rats. S-Cr and SUN concentrations did not differ between +/+ and Cy/+ rats and between female and male Cy/+ rats at 6. wk of age, but they were higher at 26. wk of age and male rats displayed higher values than female rats, which indicates inability of S-Cr and SUN to measure disease severity at an early stage. T20/T2 ratios were higher for Cy/+ than +/+ rats at 6. wk of age. Importantly, male Cy/+ rats displayed higher T20/T2 ratios than female Cy/+ rats. T20/T2 ratios obtained at 6. wk of age correlated well with S-Cr, SUN, and KW/BW% values obtained at 26. wk of age. Conclusions: This study indicates that T20/T2 ratio derived from [18F]PFH PET renography at an early age could be useful as a novel prognostic marker to predict future disease severity in a rat model of ADPKD.
    Full-text · Article · Oct 2015
    • A decrease in the availability of the junior faculty to participate may be an indication that there has been a significant workload increase in academic medical life, along with family responsibility trends for today's junior faculty compared to yesterday's junior faculty. Another possible explanation is that since mentoring is an emotional and personal experience (Chapman & Guay-Woodford 2008; Bickel & Rosenthal 2011), some individuals may be hesitant to discuss their views in a group. The terms mentorship and role model in the survey and interviews were not clearly defined for the participants so that in future studies the definitions should be clearly articulated for participants.
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: This study explored the views of junior faculty toward informing mentorship program development. Method: Mixed sampling methodologies including questionnaires (n = 175), focus groups (female, n = 4; male, n = 4), and individual interviews (female n = 10; male, n = 9) of junior faculty were conducted in clinical departments at one academic health sciences center. Results: Questionnaire results indicated that having role models increased commitment to an academic career; mentorship experience during residency training was a high incentive to pursue an academic career; and junior faculty did have identifiable mentorship experiences. Focus group results revealed that mentoring as well as the presence of role models a few years ahead of the junior faculty would promote career development. Females preferred similar age role models who spoke the same language, particularly in the area of promotion. Females identified several challenges and issues including a lack of researcher role models, a range of perceptions regarding the merits of formal versus informal mentoring, and the idea that mentors should provide advice on promotion and grants. Males valued advice on finances while females wanted advice on work-life balance. Conclusions: Mentorship emerged as an important factor in academic faculty recruitment and retention, with varying perceptions of how it should be institutionalized. Role models were viewed as important for retention, and a paucity of mid-career, female researcher role models suggests a gap to be filled in future programmatic efforts.
    Full-text · Article · Nov 2012
    • Cysts in ADPKD kidneys form in utero (2, 3) and clinical manifestations are increasingly being recognized in newborns, children, and adolescents. These include left ventricular hypertrophy with or without systemic hypertension, proteinuria, hematuria, nephrolithiasis, flank pain, and impaired renal function (3–5).
    [Show abstract] [Hide abstract] ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are significant causes of morbidity and mortality in children and young adults. ADPKD, with an incidence of 1:400 to 1:1,000, affects more than 13 million individuals worldwide and is a major cause of end-stage renal disease in adults. However, symptomatic disease is increasingly recognized in children. ARPKD is a dual-organ hepatorenal disease with an incidence of 1:20,000 to 1:40,000 and a heterozygote carrier rate of 1 in 70. Currently, no clinically significant disease-specific therapy exists for ADPKD or ARPKD. The genetic basis of both ADPKD and ARPKD have been identified, and delineation of the basic molecular and cellular pathophysiology has led to the discovery that abnormal ADPKD and ARPKD gene products interact to create "polycystin complexes" located at multiple sites within affected cells. The extracellular matrix and vessels produce a variety of soluble factors that affect the biology of adjacent cells in many dynamic ways. This review will focus on the molecular and cellular bases of the abnormal cystic phenotype and discuss the clinical translation of such basic data into new therapies that promise to alter the natural history of disease for children with genetic PKDs.Pediatric Research (2013); doi:10.1038/pr.2013.191.
    Article · Oct 2013
    • Hypertension, smoking and alcohol consumption are major determinants of IA risk56 showing a strong interaction with each other but also with non-modifiable IA risk factors such as ethnicity, gender, age, IA localization and size, and genetic background. Genetic contribution to IA is supported by studies on monozygotic twins, familial occurrence, and also by its co-morbidity with other genetic diseases such as adult polycystic kidney disease78. Nevertheless, progress in finding IA genes and the disease-associated alleles has proven difficult and to date no single gene has been unequivocally identified as responsible for IA formation or rupture. Genome-wide association studies (GWAS) represent the gold-standard approach for uncovering novel genetic risk variants and have brought novel insights into the biological and genetic underpinnings of many complex traits.
    [Show abstract] [Hide abstract] ABSTRACT: Subarachnoid hemorrhage (SAH) is a life-threatening event that most frequently leads to severe disability and death. Its most frequent cause is the rupture of a saccular intracranial aneurysm (IA), which is a blood vessel dilation caused by disease or weakening of the vessel wall. Although the genetic contribution to IA is well established, to date no single gene has been unequivocally identified as responsible for IA formation or rupture. We aimed to identify IA susceptibility genes in the Portuguese population through a pool-based multistage genome-wide association study. Replicate pools were allelotyped in triplicate in a discovery dataset (100 IA cases and 92 gender-matched controls) using the Affymetrix Human SNP Array 6.0. Top SNPs (absolute value of the relative allele score difference between cases and controls |RASdiff|≥13.0%) were selected for technical validation by individual genotyping in the discovery dataset. From the 101 SNPs successfully genotyped, 99 SNPs were nominally associated with IA. Replication of technically validated SNPs was conducted in an independent replication dataset (100 Portuguese IA cases and 407 controls). rs4667622 (between UBR3 and MYO3B), rs6599001 (between SCN11A and WDR48), rs3932338 (214 kilobases downstream of PRDM9), and rs10943471 (96 kilobases upstream of HTR1B) were associated with IA (unadjusted allelic chi-square tests) in the datasets tested (discovery: 6.84E-04≤P≤1.92E-02, replication: 2.66E-04≤P≤2.28E-02, and combined datasets: 6.05E-05≤P≤5.50E-04). Additionally, we confirmed the known association with IA of rs1333040 at the 9p21.3 genomic region, thus validating our dataset. These novel findings in the Portuguese population warrant further replication in additional independent studies, and provide additional candidates to more comprehensively understand IA etiopathogenesis.
    Full-text · Article · Jul 2015
    • Ten RCTs with 1,386 participants were included after assessment of 45 full-text articles and 197 records12345678101112131415. Electronic searching process was shown in the flowchart (Figure 1).
    [Show abstract] [Hide abstract] ABSTRACT: Background: Blood pressure (BP) control is one of the most important treatments of Autosomal dominant polycystic kidney disease (ADPKD). The comparative efficacy of antihypertensive treatments in ADPKD patients is inconclusive. Methods: Network meta-analysis was used to evaluate randomized controlled trials (RCT) which investigated antihypertensive treatments in ADPKD. PubMed, Embase, Ovid, and Cochrane Collaboration were searched. The primary outcome was estimated glomerular filtration rate (eGFR). Secondary outcomes were serum creatinine (Scr), urinary albumin excretion (UAE), systolic BP (SBP), diastolic BP (DBP), mean artery pressure (MAP) and left ventricular mass index (LVMI). Results: We included 10 RCTs with 1386 patients and six interventions: angiotensin-converting enzyme inhibitors (ACEI), Angiotensin II receptor blocker (ARB), combination of ACEI and ARB, calcium channel blockers (CCB), β-blockers and dilazep. There was no difference of eGFR in all the treatments in both network and direct comparisons. No significant differences of Scr, SBP, DBP, MAP, and LVMI were found in network comparisons. However, ACEI significantly reduced SBP, DBP, MAP and LVMI when compared to CCB. Significantly increased UAE was observed in CCB compared with ACEI or ARB. Bayesian probability analysis found ARB ranked first in the surrogate measures of eGFR, UAE and SBP. Conclusions: There is little evidence to detect differences of antihypertensive treatments on kidney disease progression in ADPKD patients. More RCTs will be needed in the future. Use of ARB may be an optimal choice in clinical practice.
    Full-text · Article · Dec 2015

Institutions

    • Emory University
    • University of Alabama at Birmingham
      • Department of Medicine
    • Utrecht University
      • Division of Pharmacoepidemiology and Pharmacotherapy
      Utrecht, Utrecht, Netherlands
    • Mayo Foundation for Medical Education and Research
      • Department of Internal Medicine
      Rochester, MI, United States

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