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Potassium citrate vs. hydrochlorothiazide to reduce urinary calcium excretion in calcium oxalate stone patients with hypercalciuria: a prospective randomized study.
Solak, V, Gökce, Mİ, Yaman, Ö
International urology and nephrology. 2021;(9):1791-1796
Abstract
PURPOSE Calcium oxalate (Ca-Ox) is the most common stone composition and one of the most common 24-h urine anomalies is hypercalciuria. The purpose of this study was to evaluate the efficacy of potassium citrate (K-CIT) for prevention of hypercalciuria in comparison with hydrochlorothiazide (HCT) in patients with calcium oxalate stones and hypercalciuria. MATERIALS AND METHODS In this prospective randomized study, patients were randomized to receive either HCT (50 mg/day) or K-CIT (40 mEq/day) following achieving stone-free status. Treatment was continued for 6 months. 24 h urine analysis was performed prior to treatment and repeated at third month and measured parameters were volume, calcium, oxalate, citrate, sodium, and uric acid. Stone recurrence was evaluated with KUB and ultrasonography at 6th and 12th months. RESULTS Data of 40 patients in each arm were evaluated. Mean 24 h urine calcium levels decreased to 205 ± 54.5 mg/day and 220.6 ± 96.3 mg/day in the K-CIT and HCT groups, respectively, and difference was not significant (p = 0.931). The reduction compared to pretreatment values was statistically significant in both groups. Urinary citrate levels also significantly increased in both groups and level of increase was significantly higher in K-CIT group. At 12th month, ultrasonography revealed stones in two patients in HCT group, and in one patient in the K-CIT group. CONCLUSIONS K-CIT provided significantly reduced calcium and increased citrate excretion in patients Ca-Ox stone patients with hypercalciuria. The efficacy in decreasing calcium excretion was comparable to HCT treatment. K-CIT can be used for medical prophylaxis of Ca-OX stone patients with hypercalciuria.
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The effect of amiloride in decreasing albuminuria in patients with diabetic kidney diseases: a prospective, crossover, open-label study.
Li, R, Xie, Z, Zhang, L, Huang, Y, Ma, J, Dong, W, Li, Z, Chen, Y, Liang, H, Wu, Y, et al
Renal failure. 2021;(1):452-459
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Abstract
BACKGROUND Diabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD. METHODS We conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial. RESULTS In this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group. CONCLUSION In summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR.
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Effects of hydrochlorothiazide on drainage volume and seroma formation in deep inferior epigastric perforator flap breast reconstruction: Randomized controlled trial.
Suh, YC, Oh, TM, Lee, YH, Kim, EK, Han, HH, Eom, JS
Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2020;(4):663-672
Abstract
BACKGROUND Seroma is a recognized complication encountered at the reconstructed breast and donor site after abdominal-based breast reconstruction. Seroma is caused by lymphatic channel disruption and the formation of a large space between the deep fascia during flap elevation. Surgical techniques to preserve the lymphatics and secure the closure of the donor site can reduce seroma formation. This study investigated the safety and effectiveness of the diuretic hydrochlorothiazide at reducing interstitial fluid accumulation and seroma formation during deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS Sixty patients with breast cancer who underwent skin- or nipple-sparing mastectomy and DIEP flap reconstruction were enrolled between August 2016 and June 2017. The patients were randomly assigned to receive either 25 mg per day of hydrochlorothiazide from the second to the twentieth day after surgery (treatment) or no diuretic (control). The clinicopathological characteristics, drainage time, and drainage volume were statistically compared between the two groups. RESULTS The average total drainage volume at the donor site was 291 mL in the treatment group and 434 mL in the control group (p = 0.003). The differences in body mass index and flap weight between the two groups were not statistically significant (p = 0.879 and p = 0.963, respectively). No hypotension or electrolyte imbalance was noted during the follow-up. CONCLUSIONS Intake of 25 mg per day of hydrochlorothiazide tablets effectively reduced the total abdominal drainage volume and removal time of indwelling drains. However, the adverse effects should be further investigated in a large population and multiracial cohort before using hydrochlorothiazide for seroma prevention.
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Pharmacokinetic Interaction Among Telmisartan, Amlodipine, and Hydrochlorothiazide After a Single Oral Administration in Healthy Male Subjects.
Moon, SJ, Jeon, JY, Yu, KS, Kim, MG
Clinical therapeutics. 2019;(11):2273-2282
Abstract
PURPOSE Hypertension is a major risk factor for cardiovascular diseases, necessitating hypertension control. Antihypertensive drugs are more potent when administered in combinations of 2 or 3 different classes of drugs. One such therapy includes a combination of an angiotensin receptor blocker, a calcium channel blocker, and a diuretic. The objective of this study was to evaluate the pharmacokinetic interaction among telmisartan, amlodipine, and hydrochlorothiazide. METHODS A randomized, open-label, 3-period, 6-sequence, 3-treatment, single-dose crossover study was conducted in healthy male subjects. Subjects were randomly assigned to 1 of 6 sequences and one of the following treatments was administered in each period: treatment A, co-administration of one tablet of telmisartan 80 mg and one tablet of amlodipine 10 mg; treatment B, one tablet of hydrochlorothiazide 25 mg alone; and treatment C, co-administration of all 3 investigational products. Serial blood samples were collected up to 144 hours postdose. Plasma drug concentrations were measured by using LC/MS-MS. Pharmacokinetic parameters, including Cmax and AUC0-last, were determined by using noncompartmental analysis. The geometric least squares mean ratios and associated 90% CIs of log-transformed Cmax and AUC0-last for separate administration or co-administration were calculated to evaluate pharmacokinetic interactions. FINDINGS Twenty-seven subjects completed the study. The geometric least squares mean ratios and 90% CIs of Cmax and AUC0-last were 1.02 (0.85-1.21) and 1.04 (0.97-1.13) for telmisartan; 1.00 (0.95-1.04) and 0.95 (0.91-0.99) for amlodipine; and 0.88 (0.82-0.96) and 0.86 (0.82-0.90) for hydrochlorothiazide, respectively. No serious adverse events were recorded, and all reported adverse events were of mild intensity. IMPLICATIONS The pharmacokinetic parameters of telmisartan, amlodipine, and hydrochlorothiazide when administered separately or co-administered were compared, and all the parameters met the criteria for pharmacokinetic equivalence. Combination therapy of these 3 drugs had no significant impact on the pharmacokinetic parameters of each drug. (ClinicalTrials.gov Identifier: NCT03889145).
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The Effects of Dapagliflozin on Systemic and Renal Vascular Function Display an Epigenetic Signature.
Solini, A, Seghieri, M, Giannini, L, Biancalana, E, Parolini, F, Rossi, C, Dardano, A, Taddei, S, Ghiadoni, L, Bruno, RM
The Journal of clinical endocrinology and metabolism. 2019;(10):4253-4263
Abstract
CONTEXT Mechanisms mediating the cardiovascular and renal protection exerted by SGLT2 inhibitors are still partially unknown. We investigated whether dapagliflozin modulates systemic and renal vascular function and structure, and induces epigenetic modifications. SUBJECTS AND METHODS Forty hypertensive patients with type 2 diabetes were randomly assigned to 4-week treatment with dapagliflozin 10 mg or hydrochlorothiazide (HCT) 12.5 mg. Routine analyses; plasma renin activity; aldosterone, catecholamine, and 24-hour urinary electrolyte levels; flow-mediated dilation (FMD) of the brachial artery; carotid-femoral pulse-wave velocity (PWV); augmentation index; and resistive index and dynamic renal resistive index (DRIN) were measured at baseline and after treatment. Circulating miRNAs (miRs) related to heart failure (miR30e-5p, miR199a-3p), endothelial dysfunction (miR27b and miR200b), and renal function (miR130b-3p, miR21-5p) were assessed and related to the effects of treatments. RESULTS Dapagliflozin and HCT marginally lowered blood pressure. Fasting glucose was lowered, whereas 24-hour diuresis, glycosuria, and osmolar clearance were increased by dapagliflozin (P < 0.001 for all), without affecting sodium excretion and glomerular filtration rate. Magnesium levels significantly increased after dapagliflozin treatment (P = 0.02). Neither dapagliflozin nor HCT modified FMD or PWV. DRIN did not vary in the dapagliflozin group, whereas it increased in the HCT group (P = 0.047 for time by treatment interaction). Both treatments induced variations in the expression of some miRs; dapagliflozin, but not HCT, significantly up-regulated miR30e-5p and downregulated miR199a-3p. CONCLUSION A putative epigenetic regulation of the protecting cardiovascular effect exerted by SGLT2 inhibitors was found. Dapagliflozin might exert nephroprotection by preserving renal vasodilating capacity.
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Impact of Moderate Sodium Restriction and Hydrochlorothiazide on Iodine Excretion in Diabetic Kidney Disease: Data from a Randomized Cross-Over Trial.
Binnenmars, SH, Corpeleijn, E, Kwakernaak, AJ, Touw, DJ, Kema, IP, Laverman, GD, Bakker, SJL, Navis, G
Nutrients. 2019;(9)
Abstract
Sodium restriction may potentially reduce iodine intake. This study aimed to determine the effect of sodium restriction (dietary counseling) on 24-h urinary iodine excretion. Diuretics provide an alternative to sodium restriction and are frequently added to sodium restriction, so the effects of hydrochlorothiazide (50 mg daily) and combined therapy were also studied. We performed a post-hoc analysis of a Dutch multi-center, randomized cross-over trial in 45 patients with diabetic kidney disease with a mean age of 65 ± 9 years, mean eGFR of 65 ± 27 mL/min/1.73 m2, median albuminuria of 648 [230-2008] mg/24 h and 84% were male. During regular sodium intake with placebo, mean 24 h urinary sodium and iodine excretion were 224 ± 76 mmol/24 h and 252 ± 94 ug/24 h, respectively (r = 0.52, p < 0.001). Mean iodine excretion did not change significantly if sodium restriction and hydrochlorothiazide were applied separately; mean difference -8 ug/day (95% CI -38, 22; p = 0.6) and 14 ug/day (95% CI -24, 52; p = 0.5), respectively. Combined therapy induced a significant decrease in mean iodine excretion (-37 ug/day; 95% CI -67, -7; p = 0.02), yet this was not seen to a clinically meaningful level. The number of patients with an estimated intake below recommended daily allowances did not differ significantly between the four treatment periods (p = 0.3). These findings show that sodium restriction is not a risk factor for iodine deficiency.
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Circulating microparticles and central blood pressure according to antihypertensive strategy.
Massunaga, ND, França, CN, Bianco, HT, Ferreira, CES, Kato, JT, Póvoa, RMS, Figueiredo Neto, AM, Izar, MCO, Fonseca, FAH
Clinics (Sao Paulo, Brazil). 2019;:e1234
Abstract
OBJECTIVES This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.
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Efficacy of standard and low dose hydrochlorothiazide in the recurrence prevention of calcium nephrolithiasis (NOSTONE trial): protocol for a randomized double-blind placebo-controlled trial.
Dhayat, NA, Faller, N, Bonny, O, Mohebbi, N, Ritter, A, Pellegrini, L, Bedino, G, Schönholzer, C, Venzin, RM, Hüsler, C, et al
BMC nephrology. 2018;(1):349
Abstract
BACKGROUND Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known. METHODS The NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response. DISCUSSION The NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support. TRIAL REGISTRATION ClinicalTrials.gov, NCT03057431 . Registered on February 20 2017.
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Patient characteristics do not predict the individual response to antihypertensive medication: a cross-over trial.
van der Wel, MC, Biermans, M, Akkermans, R, Lenders, JWM, van Weel, C, Deinum, J
Family practice. 2018;(1):67-73
Abstract
BACKGROUND International guidelines on hypertension management do not agree on whether patient characteristics can be used for the first choice of treatment of uncomplicated essential hypertension. OBJECTIVE We wanted to identify predictive patient characteristics to the response of two different classes of antihypertensive drugs in patients with newly diagnosed hypertension in primary care. METHODS We conducted a prospective, open label, blinded endpoint cross-over trial in 120 patients with a new diagnosis of hypertension from 10 family practices. Patients received 4 weeks of 12.5 mgr hydrochlorothiazide once daily and 4 weeks of 80 mgr valsartan once daily, each followed by a 4-week washout. The sequence of drugs was randomized. Age, sex and menopausal state were recorded at run in and 24 h ambulatory blood pressure, office blood pressure, plasma renin concentration, NT-proBNP, potassium, estimated glomerular filtration rate, urinary albumin, body mass index and waist circumference at each regimen change. The difference in systolic blood pressure response between both study drugs, calculated from mean daytime ambulatory blood pressures, was the main outcome measure. RESULTS Ninety-eight patients (52% female; median age 53 years) were eligible for per-protocol-analysis. None of the studied variables were predictive for the difference in systolic blood pressure response. Individual systolic blood pressure responses ranged from an increase by 18 mmHg to a decrease of 39 mmHg. CONCLUSION In a relevant group of primary care patients with newly diagnosed hypertension, we were unable to detect predictors of treatment response. This study rather supports the United States and European guidelines than the United Kingdom and Dutch guidelines on hypertension.
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The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct.
Joseph, P, Pais, P, Dans, AL, Bosch, J, Xavier, D, Lopez-Jaramillo, P, Yusoff, K, Santoso, A, Talukder, S, Gamra, H, et al
American heart journal. 2018;:72-79
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BACKGROUND It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial. METHODS TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events. RESULTS The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk. CONCLUSION Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.