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Gerjan Navis - One of the best experts on this subject based on the ideXlab platform.
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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
Nutrients, 2019Co-Authors: Heleen S Binnenmars, Arjan J Kwakernaak, Gozewijn D Laverman, Eva Corpeleijn, Daan J Touw, Ido P Kema, Stephan J L Bakker, Gerjan NavisAbstract: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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Sodium Restriction in heart failure where are the data
Nederlands Tijdschrift voor Geneeskunde, 2019Co-Authors: Gerjan NavisAbstract:Mahtani et al. review the evidence for Sodium Restriction in heart failure. The paucity of solid studies is striking, but deplorably in line with the paucity of high-quality studies on lifestyle management in general. One hard endpoint study (Sodium-HF) is underway. Promising results were obtained in the GOURMET study, which integrated Sodium Restriction into a broader nutritional approach that simultaneously targeted malnutrition, a major problem in heart failure. Targeting overall nutritional status - rather than single nutrients - matches current trends in nutrition guidelines, and deserves further exploration. Using fresh products and avoiding processed foods is the main step towards an overall healthier diet with less Sodium. Dietary improvement, with its clinical benefit, is feasible in most patients by means of adequate support and feedback. Hopefully, the emergence of 'lifestyle medicine' will, with clinical and scientific effort, allow for the health potential of nutrition to be translated into clinical benefit for patients.
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Sodium Restriction in patients with ckd a randomized controlled trial of self management support
American Journal of Kidney Diseases, 2017Co-Authors: Gerjan Navis, Liffert Vogt, Yvette Meuleman, Tiny Hoekstra, Friedo W Dekker, Paul J M Van Der Boog, Willem Jan W Bos, Gert A Van MontfransAbstract:Background To evaluate the effectiveness and sustainability of self-managed Sodium Restriction in patients with chronic kidney disease. Study Design Open randomized controlled trial. Setting & Participants Patients with moderately decreased kidney function from 4 hospitals in the Netherlands. Intervention Regular care was compared with regular care plus an intervention comprising education, motivational interviewing, coaching, and self-monitoring of blood pressure (BP) and Sodium. Outcomes Primary outcomes were Sodium excretion and BP after the 3-month intervention and at 6-month follow-up. Secondary outcomes were protein excretion, kidney function, antihypertensive medication, self-efficacy, and health-related quality of life (HRQoL). Results At baseline, mean Sodium excretion rate was 163.6±64.9 (SD) mmol/24 h; mean estimated glomerular filtration rate was 49.7±25.6mL/min/1.73m 2 ; median protein excretion rate was 0.8 (IQR, 0.4-1.7) g/24 h; and mean 24-hour ambulatory systolic and diastolic BPs were 129±15 and 76±9mmHg, respectively. Compared to regular care only (n=71), at 3 months, the intervention group (n=67) showed reduced Sodium excretion rate (mean change, −30.3 [95% CI, −54.7 to −5.9] mmol/24 h), daytime ambulatory diastolic BP (mean change, −3.4 [95% CI, −6.3 to −0.6] mmHg), diastolic office BP (mean change, −5.2 [95% CI, −8.4 to −2.1] mmHg), protein excretion (mean change, −0.4 [95% CI, −0.7 to −0.1] g/24h), and improved self-efficacy (mean change, 0.5 [95% CI, 0.1 to 0.9]). At 6 months, differences in Sodium excretion rates and ambulatory BPs between the groups were not significant, but differences were detected in systolic and diastolic office BPs (mean changes of −7.3 [95% CI, −12.7 to −1.9] and −3.8 [95% CI, −6.9 to −0.6] mmHg, respectively), protein excretion (mean changes, −0.3 [95% CI, −0.6 to −0.1] g/24h), and self-efficacy (mean change, 0.5 [95% CI, 0.0 to 0.9]). No differences in kidney function, medication, and HRQoL were observed. Limitations Nonblinding, relatively low response rate, and missing data. Conclusions Compared to regular care only, this self-management intervention modestly improved outcomes, although effects on Sodium excretion and ambulatory BP diminish over time.
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vitamin d receptor activator and dietary Sodium Restriction to reduce residual urinary albumin excretion in chronic kidney disease virtue study rationale and study protocol
Nephrology Dialysis Transplantation, 2016Co-Authors: Charlotte A Keyzer, Gerjan Navis, Marc H Hemmelder, Gozewijn D Laverman, Hiddo J L Heerspink, Marc G Vervloet, Maarten A De Jong, Fenna G Van Breda, Wilbert M T Janssen, Martin H De BorstAbstract:Optimal albuminuria reduction is considered essential to halting chronic kidney disease (CKD) progression. Both vitamin D receptor activator (VDRA) treatment and dietary Sodium Restriction potentiate the efficacy of renin-angiotensin-aldosterone- system (RAAS) blockade to reduce albuminuria. The ViRTUE study addresses whether a VDRA in combination with dietary Sodium Restriction provides further albuminuria reduction in non-diabetic CKD patients on top of RAAS blockade. The ViRTUE study is an investigator-initiated, prospective, multi-centre, randomized, double-blind (paricalcitol versus placebo), placebo-controlled trial targeting stage 1-3 CKD patients with residual albuminuria of > 300 mg/day due to nondiabetic glomerular disease, despite angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. During run-in, all subjects switched to standardized RAAS blockade (ramipril 10 mg/day) and blood pressure titrated to <140/90 mmHg according to a standardized protocol. Eligible patients are subsequently enrolled and undergo four consecutive study periods in random order of 8 weeks each: (i) paricalcitol (2 mu g/day) combined with a liberal Sodium diet (similar to 200 mmol Na+/day, i.e. mean Sodium intake in the general population), (ii) paricalcitol (2 mu g/day) combined with dietary Sodium Restriction (target: 50 mmol Na+/day), (iii) placebo combined with a liberal Sodium diet and (iv) placebo combined with dietary Sodium Restriction. Data are collected at the end of each study period. The primary outcome is 24-h urinary albumin excretion. Secondary study outcomes are blood pressure, renal function (estimated glomerular filtration rate), plasma renin activity and, in a sub-population (N = 9), renal haemodynamics (measured glomerular filtration rate and effective renal plasma flow). A sample size of 50 patients provides 90% power to detect a 23% reduction in albuminuria, assuming a 25% dropout rate. Further reduction of residual albuminuria by combination of VDRA treatment and Sodium Restriction during single-agent RAAS-blockade will justify long-term studies on cardiorenal outcomes and safety.
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effects of dietary Sodium Restriction in kidney transplant recipients treated with renin angiotensin aldosterone system blockade a randomized clinical trial
American Journal of Kidney Diseases, 2016Co-Authors: Laura V De Vries, Stephan J L Bakker, Linn C Dobrowolski, Jacqueline J O N Van Den Bosch, Ineke J Riphagen, C Paul T Krediet, Frederike J Bemelman, Gerjan NavisAbstract:Background In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary Sodium Restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary Sodium Restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. Study Design Two-center randomized crossover trial. Setting & Participants Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP ≥120/80mmHg, receiving stable RAAS blockade therapy. Intervention 6-week regular-Sodium diet (target, 150mmol/24 h) and a 6-week low-Sodium diet (target, 50mmol/24 h). Outcomes & Measurements Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary Sodium excretion. Results We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58±8 [SD] years; 50% men; mean eGFR, 51±21mL/min/1.73m 2 ) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-Sodium diet. Sodium excretion decreased from 164±50mmol/24 h during the regular-Sodium diet to 87±55mmol/24 h during the low-Sodium diet (mean difference, −77 [95% CI, −110 to −44] mmol/24 h; P P P P =0.9) or eGFR. Limitations No hard end points; small study; small proportion of patients willing to test the intervention; adherence to Sodium diet was achieved in 86% of patients. Conclusions In stable kidney transplant recipients receiving RAAS blockade, dietary Sodium Restriction effectively reduces BP without affecting eGFR. Dietary Sodium Restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade.
Douglas R Seals - One of the best experts on this subject based on the ideXlab platform.
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dietary Sodium Restriction decreases urinary ngal in older adults with moderately elevated systolic blood pressure free from chronic kidney disease
Journal of Investigative Medicine, 2020Co-Authors: Wei Wang, Douglas R Seals, Michel Chonchol, Kristen L NowakAbstract:Increased aortic stiffness may contribute to kidney damage by transferring excessive flow pulsatility to susceptible renal microvasculature, leading to constriction or vessel loss. We previously demonstrated that 5 weeks of dietary Sodium Restriction (DSR) reduces large-elastic artery stiffness as well as blood pressure in healthy middle-aged/older adults with moderately elevated systolic blood pressure (SBP) who are free from chronic kidney disease (CKD). We hypothesized that DSR in this cohort would also reduce urinary concentrations of renal tubular injury biomarkers, which predict incident CKD in the general population. We performed a post hoc analysis using stored 24 hours urine samples collected in 13 participants as part of a randomized, double-blind, crossover clinical trial of DSR (low Sodium (LS) target: 50 mmol/day; normal Sodium (NS) target: 150 mmol/day). Participants were 61±2 (mean±SEM) years (8 M/5 F) with a baseline blood pressure of 139±2/82±2 mm Hg and an estimated glomerular filtration rate of 79±3 mL/min/1.73 m2 Twenty-four hour urinary Sodium excretion was reduced from 149±7 to 66±8 mmol/day during week 5. Despite having preserved kidney function, participants had a 31% reduction in urinary neutrophil gelatinase-associated lipocalin concentrations with just 5 weeks of DSR (LS: 2.8±0.6 vs NS: 4.2±0.8 ng/mL, p<0.05). Results were similar when normalized to urinary creatinine (urinary creatinine did not change between conditions). Concentrations of another kidney tubular injury biomarker, kidney injury molecule-1, were below the detectable limit in all but one sample. In conclusion, DSR reduces an established clinical biomarker of kidney tubular damage in adults with moderately elevated SBP who are free from prevalent kidney disease.
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effect of dietary Sodium Restriction on human urinary metabolomic profiles
Clinical Journal of The American Society of Nephrology, 2015Co-Authors: Kristen L Jablonski, Matthew L Racine, Michel Chonchol, Jelena Klawitter, Candace J Bassett, Douglas R SealsAbstract:Background and objectives Metabolomics is a relatively new field of “-omics” research, focusing on high-throughput identification of small molecular weight metabolites. Diet has both acute and chronic effects on metabolic profiles; however, alterations in response to dietary Sodium Restriction (DSR) are completely unknown. The goal of this study was to explore changes in urine metabolites in response to DSR, as well as their association with previously reported improvements in vascular function with DSR. Design, setting, participants, & measurements Using stored urine samples from a 10-week randomized placebo-controlled crossover study of DSR in 17 middle-aged/older adults (six men and 11 women; mean age 62±8 years) who had moderately elevated systolic BP (130–159 mmHg) and were otherwise healthy, a liquid chromatography/mass spectrometry–based analysis of 289 metabolites was performed. This study identified metabolites that were significantly altered between the typical (153±29 mmol/d) and low (70±29 mmol/d) Sodium conditions, as well as their baseline (typical Sodium) association with responsiveness to previously reported improvements in vascular endothelial function (brachial artery flow-mediated dilation) and large elastic artery stiffness (aortic pulse wave velocity). Results Of the 289 metabolites surveyed, 10 were significantly altered (nine were upregulated and one was downregulated) during the low Sodium condition, and eight of these exceeded our prespecified clinically significant threshold of a >40% change. These metabolites were involved in biologic pathways broadly related to cardiovascular risk, nitric oxide production, oxidative stress, osmotic regulation, and metabolism. One metabolite, serine, was independently (positively) associated with previously reported improvements in the primary vascular outcome of brachial artery flow-mediated dilation. Conclusions This proof-of-concept study provides the first evidence that DSR is a stimulus that induces significant changes in urinary metabolomic profiles. Moreover, serine was independently associated with corresponding changes in vascular endothelial function after DSR. Larger follow-up studies will be required to confirm and further elucidate the metabolic pathways that are altered in response to DSR.
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dietary Sodium Restriction and association with urinary marinobufagenin blood pressure and aortic stiffness
Clinical Journal of The American Society of Nephrology, 2013Co-Authors: Kristen L Jablonski, Phillip E Gates, Olga V Fedorova, Matthew L Racine, Candace J Geolfos, Michel Chonchol, Bradley S Fleenor, Edward G Lakatta, Alexei Y Bagrov, Douglas R SealsAbstract:Summary Background and objectives Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary Sodium Restriction. Production of the natriuretic hormone marinobufagenin, an endogenous α1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during Sodium loading. Design, setting, participants, & measurements The hypothesis was that dietary Sodium Restriction performed in middle-aged/older adults (eight men and three women; 60±2 years) with moderately elevated systolic BP (139±2/83±2 mmHg) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity (randomized, placebo-controlled, and crossover design). This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-Sodium (77±9 mmol/d) and 5 weeks of a normal-Sodium (144±7 mmol/d) diet. Results Urinary marinobufagenin excretion (weekly measurements; 25.4±1.8 versus 30.7±2.1 pmol/kg per day), systolic BP (127±3 versus 138±5 mmHg), and aortic pulse-wave velocity (700±40 versus 843±36 cm/s) were lower during the low- versus normal-Sodium condition (all P P P P P =0.02) and endothelial cell expression of NAD(P)H oxidase-p47phox (slope=0.64, P =0.006). Conclusions These results show, for the first time in humans, that dietary Sodium Restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP, aortic stiffness (aortic pulse-wave velocity), and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase. Importantly, marinobufagenin excretion is positively related to systolic BP over ranges of Sodium intake typical of an American diet, extending previous observations in rodents and humans fed experimentally high-Sodium diets.
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dietary Sodium Restriction reverses vascular endothelial dysfunction in middle aged older adults with moderately elevated systolic blood pressure
Journal of the American College of Cardiology, 2013Co-Authors: Kristen L Jablonski, Phillip E Gates, Matthew L Racine, Candace J Geolfos, Michel Chonchol, Matthew B Mcqueen, Douglas R SealsAbstract:Objectives This study sought to determine the efficacy of dietary Sodium Restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP) (130–159 mm Hg) and the associated physiological mechanisms. Background Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown. Methods Seventeen subjects (11 men and 6 women; mean age, 62 ± 7 years) completed a, randomized crossover study of 4 weeks of both low (DSR) and normal Sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability, and oxidative stress-associated mechanisms were assessed following each condition. Results Urinary Sodium excretion was reduced by ∼50% (to 70 ± 30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following DSR (p Conclusions DSR largely reversed both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces “vascular protection” beyond that attributable to its BP-lowering effects.
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dietary Sodium Restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension
Hypertension, 2004Co-Authors: Phillip E Gates, Douglas R Seals, Hirofumi Tanaka, William R HiattAbstract:We determined the temporal effects of dietary Sodium Restriction on large elastic artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64+/-2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal Sodium intake (randomized, crossover design). Urinary Sodium excretion was reduced by 60% by the end of week 1 of Sodium Restriction (54+/-11 mmol/d, P 5 mm Hg by week 1 of Sodium Restriction, attaining peak reductions by week 2 (-12 mm Hg, P<0.01 versus baseline). The 24-hour ambulatory SBP was approximately 3 mm Hg lower at week 1 of Sodium Restriction and approximately 6 mm Hg lower by week 2 (P<0.01 versus baseline). The reductions in resting SBP from baseline to week 2 of Sodium Restriction were strongly related to the corresponding increases in carotid compliance (r=0.80, P<0.01). Urinary Sodium excretion, carotid artery compliance, and SBP were not different during normal Sodium intake versus baseline. Other subject characteristics were not different across conditions. Sodium Restriction rapidly improves large elastic artery compliance in older adults with stage 1 systolic hypertension. These improvements in central arterial compliance appear to be a key mechanism in the rapid normalization of SBP by Sodium Restriction in these patients.
Femke Waanders - One of the best experts on this subject based on the ideXlab platform.
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fibroblast growth factor 23 and the antiproteinuric response to dietary Sodium Restriction during renin angiotensin aldosterone system blockade
American Journal of Kidney Diseases, 2015Co-Authors: Jelmer K Humalda, Arjan J Kwakernaak, Hiddo J L Heerspink, Maartje C J Slagman, Femke Waanders, Marc G Vervloet, Pieter M Ter Wee, Gerarda Navis, Martin H De BorstAbstract:Background Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary Sodium Restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patients. Previous studies linked high fibroblast growth factor 23 (FGF-23) levels with volume overload; others linked higher serum phosphate levels with impaired RAAS-blockade efficacy. We hypothesized that FGF-23 reduces the capacity of dietary Sodium Restriction to potentiate RAAS blockade, impairing the antiproteinuric effect. Study Design Post hoc analysis of cohort data from a randomized crossover trial with two 6-week study periods comparing proteinuria after a regular-Sodium diet with proteinuria after a low-Sodium diet, both during background angiotensin-converting enzyme inhibition. Setting & Participants 47 nondiabetic patients with CKD with residual proteinuria (median protein excretion, 1.9 [IQR, 0.8-3.1] g/d; mean age, 50±13 [SD] years; creatinine clearance, 69 [IQR, 50-110] mL/min). Predictor Plasma carboxy-terminal FGF-23 levels. Outcomes Difference in residual proteinuria at the end of the regular-Sodium versus low-Sodium study period. Residual proteinuria during the low-Sodium diet period adjusted for proteinuria during the regular-Sodium diet period. Results Higher baseline FGF-23 level was associated with reduced antiproteinuric response to dietary Sodium Restriction (standardized β=−0.46; P =0.001; model R 2 =0.71). For every 100-RU/mL increase in FGF-23 level, the antiproteinuric response to dietary Sodium Restriction was reduced by 10.6%. Higher baseline FGF-23 level was a determinant of more residual proteinuria during the low-Sodium diet (standardized β=0.27; P =0.003) in linear regression analysis adjusted for baseline proteinuria (model R 2 =0.71). There was no interaction with creatinine clearance ( P interaction=0.5). Baseline FGF-23 level did not predict changes in systolic or diastolic blood pressure upon intensified antiproteinuric treatment. Limitations Observational study, limited sample size. Conclusions FGF-23 levels are associated independently with impaired antiproteinuric response to Sodium Restriction in addition to RAAS blockade. Future studies should address whether FGF-23−lowering strategies may further optimize proteinuria reduction by RAAS blockade combined with dietary Sodium Restriction.
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Sodium Restriction on top of renin angiotensin aldosterone system blockade increases circulating levels of n acetyl seryl aspartyl lysyl proline in chronic kidney disease patients
Journal of Hypertension, 2013Co-Authors: Arjan J Kwakernaak, Gozewijn D Laverman, Maartje C J Slagman, Femke Waanders, Martin M Dokter, Rudolf A De Boer, Gerjan NavisAbstract:Objective: Sodium Restriction potentiates the efficacy of the rennin–angiotensin–aldosterone system (RAAS)blockade and improves long-term cardiovascular and renal protection, even independent of the better blood pressure control. The mechanisms underlying the potentiation of cardiorenal protection by Sodium Restriction are incompletely understood. RAAS-blockade with angiotensinconverting enzyme (ACE) inhibitors increases circulating levels of the anti-inflammatory and antifibrotic peptide Nacetyl-seryl-aspartyl-lysyl-proline (AcSDKP), which is assumed to contribute to its therapeutic effects. We hypothesized that Sodium Restriction on top of RAASblockade further increases AcSDKP, as a possible explanation for the enhanced effects of RAAS-blockade during Sodium Restriction. Methods: To test this hypothesis, we performed a secondary analysis of a randomized clinical trial investigating 46 nondiabetic chronic kidney disease (CKD) patients (age 50 � 13 years, 80% men) with overt
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moderate dietary Sodium Restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure randomised controlled trial
BMJ, 2011Co-Authors: Maartje C J Slagman, Gerjan Navis, Marc H Hemmelder, Arendjan Woittiez, Hiddo J L Heerspink, Femke Waanders, Wilbert M T Janssen, Gozewijn D LavermanAbstract:Objective To compare the effects on proteinuria and blood pressure of addition of dietary Sodium Restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose. Design Multicentre crossover randomised controlled trial. Setting Outpatient clinics in the Netherlands. Participants 52 patients with non-diabetic nephropathy. Interventions All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low Sodium diet (target 50 mmol Na+/day) and a regular Sodium diet (target 200 mmol Na+/day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label. Main outcome measures The primary outcome measure was proteinuria; the secondary outcome measure was blood pressure. Results Mean urinary Sodium excretion, a measure of dietary Sodium intake, was 106 (SE 5) mmol Na+/day during a low Sodium diet and 184 (6) mmol Na+/day during a regular Sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular Sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low Sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low Sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low Sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the reduction of proteinuria by the addition of both angiotensin receptor blockade and a low Sodium diet to ACE inhibition (62%, 53% to 70%). Mean systolic blood pressure was 134 (3) mm Hg during ACE inhibition plus a regular Sodium diet. Mean systolic blood pressure was not significantly altered by the addition of angiotensin receptor blockade (131 (3) mm Hg; P=0.12) but was reduced by the addition of a low Sodium diet (123 (2) mm Hg; P<0.001) and angiotensin receptor blockade plus a low Sodium diet (121 (3) mm Hg; P<0.001) to ACE inhibition. The reduction of systolic blood pressure by the addition of a low Sodium diet (7% (SE 1%)) was significantly larger (P=0.003) than the reduction of systolic blood pressure by the addition of angiotensin receptor blockade (2% (1)) and was similar (P=0.14) to the reduction of systolic blood pressure by the addition of both angiotensin receptor blockade and low Sodium diet (9% (1)), to ACE inhibition. Conclusions Dietary Sodium Restriction to a level recommended in guidelines was more effective than dual blockade for reduction of proteinuria and blood pressure in non-diabetic nephropathy. The findings support the combined endeavours of patients and health professionals to reduce Sodium intake. Trial registration Netherlands Trial Register NTR675.
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effect of renin angiotensin aldosterone system inhibition dietary Sodium Restriction and or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease a post hoc analysis of a randomized controlled trial
American Journal of Kidney Diseases, 2009Co-Authors: Femke Waanders, Vishal S Vaidya, Harry Van Goor, Henri G D Leuvenink, Kevin Damman, Inge Hamming, Joseph V Bonventre, Liffert Vogt, Gerjan NavisAbstract:Background Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. Study Design Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. Setting & Participants 34 proteinuric patients without diabetes from our outpatient renal clinic. Intervention Stepwise 6-week interventions of losartan, Sodium Restriction (low-Sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. Outcomes & Measurements Urinary excretion of KIM-1, total protein, and N -acetyl-β-d-glucosaminidase (NAG) as a positive control for tubular injury. Results Mean baseline urine protein level was 3.8 ± 0.4 (SE) g/d, and KIM-1 level was 1,706 ± 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 ± 388 ng/d; P = 0.04), losartan/high Sodium (1,184 ± 296 ng/d; P = 0.09), losartan/LS (921 ± 176 ng/d; P = 0.008), losartan/high Sodium plus HCT (862 ± 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 ± 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria ( R = 0.523; P Limitations Post hoc analysis. Conclusions Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, Sodium Restriction, their combination, losartan plus HCT, and the latter plus Sodium Restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.
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effect of renin angiotensin aldosterone system inhibition dietary Sodium Restriction and or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease a post hoc analysis of a randomized controlled trial
American Journal of Kidney Diseases, 2009Co-Authors: Femke Waanders, Harry Van Goor, Vishal S Vaidya, Henri G D Leuvenink, Kevin Damman, Inge Hamming, Joseph V Bonventre, Liffert Vogt, Gerjan NavisAbstract:Background Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. Study Design Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. Setting & Participants 34 proteinuric patients without diabetes from our outpatient renal clinic. Intervention Stepwise 6-week interventions of losartan, Sodium Restriction (low-Sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. Outcomes & Measurements Urinary excretion of KIM-1, total protein, and N -acetyl-β-d-glucosaminidase (NAG) as a positive control for tubular injury. Results Mean baseline urine protein level was 3.8 ± 0.4 (SE) g/d, and KIM-1 level was 1,706 ± 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 ± 388 ng/d; P = 0.04), losartan/high Sodium (1,184 ± 296 ng/d; P = 0.09), losartan/LS (921 ± 176 ng/d; P = 0.008), losartan/high Sodium plus HCT (862 ± 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 ± 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria ( R = 0.523; P Limitations Post hoc analysis. Conclusions Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, Sodium Restriction, their combination, losartan plus HCT, and the latter plus Sodium Restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.
Phillip E Gates - One of the best experts on this subject based on the ideXlab platform.
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dietary Sodium Restriction and association with urinary marinobufagenin blood pressure and aortic stiffness
Clinical Journal of The American Society of Nephrology, 2013Co-Authors: Kristen L Jablonski, Phillip E Gates, Olga V Fedorova, Matthew L Racine, Candace J Geolfos, Michel Chonchol, Bradley S Fleenor, Edward G Lakatta, Alexei Y Bagrov, Douglas R SealsAbstract:Summary Background and objectives Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary Sodium Restriction. Production of the natriuretic hormone marinobufagenin, an endogenous α1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during Sodium loading. Design, setting, participants, & measurements The hypothesis was that dietary Sodium Restriction performed in middle-aged/older adults (eight men and three women; 60±2 years) with moderately elevated systolic BP (139±2/83±2 mmHg) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity (randomized, placebo-controlled, and crossover design). This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-Sodium (77±9 mmol/d) and 5 weeks of a normal-Sodium (144±7 mmol/d) diet. Results Urinary marinobufagenin excretion (weekly measurements; 25.4±1.8 versus 30.7±2.1 pmol/kg per day), systolic BP (127±3 versus 138±5 mmHg), and aortic pulse-wave velocity (700±40 versus 843±36 cm/s) were lower during the low- versus normal-Sodium condition (all P P P P P =0.02) and endothelial cell expression of NAD(P)H oxidase-p47phox (slope=0.64, P =0.006). Conclusions These results show, for the first time in humans, that dietary Sodium Restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP, aortic stiffness (aortic pulse-wave velocity), and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase. Importantly, marinobufagenin excretion is positively related to systolic BP over ranges of Sodium intake typical of an American diet, extending previous observations in rodents and humans fed experimentally high-Sodium diets.
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dietary Sodium Restriction reverses vascular endothelial dysfunction in middle aged older adults with moderately elevated systolic blood pressure
Journal of the American College of Cardiology, 2013Co-Authors: Kristen L Jablonski, Phillip E Gates, Matthew L Racine, Candace J Geolfos, Michel Chonchol, Matthew B Mcqueen, Douglas R SealsAbstract:Objectives This study sought to determine the efficacy of dietary Sodium Restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP) (130–159 mm Hg) and the associated physiological mechanisms. Background Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown. Methods Seventeen subjects (11 men and 6 women; mean age, 62 ± 7 years) completed a, randomized crossover study of 4 weeks of both low (DSR) and normal Sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability, and oxidative stress-associated mechanisms were assessed following each condition. Results Urinary Sodium excretion was reduced by ∼50% (to 70 ± 30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following DSR (p Conclusions DSR largely reversed both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces “vascular protection” beyond that attributable to its BP-lowering effects.
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dietary Sodium Restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension
Hypertension, 2004Co-Authors: Phillip E Gates, Douglas R Seals, Hirofumi Tanaka, William R HiattAbstract:We determined the temporal effects of dietary Sodium Restriction on large elastic artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64+/-2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal Sodium intake (randomized, crossover design). Urinary Sodium excretion was reduced by 60% by the end of week 1 of Sodium Restriction (54+/-11 mmol/d, P 5 mm Hg by week 1 of Sodium Restriction, attaining peak reductions by week 2 (-12 mm Hg, P<0.01 versus baseline). The 24-hour ambulatory SBP was approximately 3 mm Hg lower at week 1 of Sodium Restriction and approximately 6 mm Hg lower by week 2 (P<0.01 versus baseline). The reductions in resting SBP from baseline to week 2 of Sodium Restriction were strongly related to the corresponding increases in carotid compliance (r=0.80, P<0.01). Urinary Sodium excretion, carotid artery compliance, and SBP were not different during normal Sodium intake versus baseline. Other subject characteristics were not different across conditions. Sodium Restriction rapidly improves large elastic artery compliance in older adults with stage 1 systolic hypertension. These improvements in central arterial compliance appear to be a key mechanism in the rapid normalization of SBP by Sodium Restriction in these patients.
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dietary Sodium Restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension
Hypertension, 2004Co-Authors: Phillip E Gates, Douglas R Seals, Hirofumi Tanaka, William R HiattAbstract:We determined the temporal effects of dietary Sodium Restriction on large elastic artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64±2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal Sodium intake (randomized, crossover design). Urinary Sodium excretion was reduced by 60% by the end of week 1 of Sodium Restriction (54±11 mmol/d, P P P 5 mm Hg by week 1 of Sodium Restriction, attaining peak reductions by week 2 (−12 mm Hg, P P r =0.80, P
Gozewijn D Laverman - One of the best experts on this subject based on the ideXlab platform.
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a self management approach for dietary Sodium Restriction in patients with ckd a randomized controlled trial
American Journal of Kidney Diseases, 2020Co-Authors: Jelmer K Humalda, Gozewijn D Laverman, Yvette Meuleman, Willem Jan W Bos, Gerald Klaassen, Hanne De Vries, Lara C Verschuur, Elisabeth J M Straathof, Paul J M Van Der BoogAbstract:Rationale & objective: Patients with chronic kidney disease (CKD) are particularly sensitive to dietary Sodium. We evaluated a self-management approach for dietary Sodium Restriction in patients with CKD. Study design: Randomized controlled trial. Setting & participants: Nephrology outpatient clinics in 4 Dutch hospitals. 99 adults with CKD stages 1 to 4 or a functioning (estimated glomerular filtration rate≥25mL/min/1.73m2) kidney transplant, hypertension, and Sodium intake>130mmol/d. Intervention: Routine care was compared with routine care plus a web-based self-management intervention including individual e-coaching and group meetings implemented over a 3-month intervention period, followed by e-coaching over a 6-month maintenance period. Outcomes: Primary outcomes were Sodium excretion after the 3-month intervention and after the 6-month maintenance period. Secondary outcomes were blood pressure, proteinuria, costs, quality of life, self-management skills, and barriers and facilitators for implementation. Results: Baseline estimated glomerular filtration rate was 55.0±22.0mL/min/1.73m2. During the intervention period, Sodium excretion decreased in the intervention group from 188±8 (SE) to 148±8mmol/d (P<0.001), but did not change significantly in the control group. At 3 months, mean Sodium excretion was 24.8 (95% CI, 0.1-49.6) mmol/d lower in the intervention group (P=0.049). At 3 months, systolic blood pressure (SBP) decreased in the intervention group from 140±3 to 132±3mm Hg (P<0.001), but was unchanged in the control group. Mean difference in SBP across groups was-4.7 (95% CI, -10.7 to 1.3) mm Hg (P=0.1). During the maintenance phase, Sodium excretion increased in the intervention group, but remained lower than at baseline at 160±8mmol/d (P=0.01), while it decreased in the control group from 174±9 at the end of the intervention period to 154±9mmol/d (P=0.001). Consequently, no difference in Sodium excretion between groups was observed after the maintenance phase. There was no difference in SBP between groups after the maintenance phase. Limitations: Limited power, postrandomization loss to follow-up, Hawthorne effect, lack of dietary data, short-term follow-up. Conclusions: A coaching intervention reduced Sodium intake at 3 months. Efficacy during the maintenance phase was diminished, possibly due to inadvertent adoption of the intervention by the control group. Funding: Grant funding from the Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation. Trial registration: Registered at ClinicalTrials.gov with study number NCT02132013.
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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
Nutrients, 2019Co-Authors: Heleen S Binnenmars, Arjan J Kwakernaak, Gozewijn D Laverman, Eva Corpeleijn, Daan J Touw, Ido P Kema, Stephan J L Bakker, Gerjan NavisAbstract: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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effects of vitamin d receptor activation and dietary Sodium Restriction on residual albuminuria in ckd the virtue ckd trial
Journal of The American Society of Nephrology, 2017Co-Authors: Charlotte A Keyzer, Arjan J Kwakernaak, Marc H Hemmelder, Gozewijn D Laverman, Hiddo J L Heerspink, Marc G Vervloet, Maarten A De Jong, Fenna G Van Breda, Wilbert M T Janssen, Stephan J L BakkerAbstract:Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary Sodium Restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 μg/d) or PLAC, each combined with a low-Sodium (LS) or regular Sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (P=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (P<0.001 versus RS + PLAC), and LS + PARI reduced albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h (P<0.001 versus RS + PLAC). The reduction by PARI beyond the effect of LS was nonsignificant (P=0.60). In the per-protocol analysis restricted to participants with ≥95% compliance with study medication, PARI did provide further albuminuria reduction (P=0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na+ per day in the combined RS groups and 108±61 mmol Na+ per day in the LS groups (P<0.001). In conclusion, moderate dietary Sodium Restriction substantially reduced residual albuminuria during fixed dose angiotensin-converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.
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vitamin d receptor activator and dietary Sodium Restriction to reduce residual urinary albumin excretion in chronic kidney disease virtue study rationale and study protocol
Nephrology Dialysis Transplantation, 2016Co-Authors: Charlotte A Keyzer, Gerjan Navis, Marc H Hemmelder, Gozewijn D Laverman, Hiddo J L Heerspink, Marc G Vervloet, Maarten A De Jong, Fenna G Van Breda, Wilbert M T Janssen, Martin H De BorstAbstract:Optimal albuminuria reduction is considered essential to halting chronic kidney disease (CKD) progression. Both vitamin D receptor activator (VDRA) treatment and dietary Sodium Restriction potentiate the efficacy of renin-angiotensin-aldosterone- system (RAAS) blockade to reduce albuminuria. The ViRTUE study addresses whether a VDRA in combination with dietary Sodium Restriction provides further albuminuria reduction in non-diabetic CKD patients on top of RAAS blockade. The ViRTUE study is an investigator-initiated, prospective, multi-centre, randomized, double-blind (paricalcitol versus placebo), placebo-controlled trial targeting stage 1-3 CKD patients with residual albuminuria of > 300 mg/day due to nondiabetic glomerular disease, despite angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. During run-in, all subjects switched to standardized RAAS blockade (ramipril 10 mg/day) and blood pressure titrated to <140/90 mmHg according to a standardized protocol. Eligible patients are subsequently enrolled and undergo four consecutive study periods in random order of 8 weeks each: (i) paricalcitol (2 mu g/day) combined with a liberal Sodium diet (similar to 200 mmol Na+/day, i.e. mean Sodium intake in the general population), (ii) paricalcitol (2 mu g/day) combined with dietary Sodium Restriction (target: 50 mmol Na+/day), (iii) placebo combined with a liberal Sodium diet and (iv) placebo combined with dietary Sodium Restriction. Data are collected at the end of each study period. The primary outcome is 24-h urinary albumin excretion. Secondary study outcomes are blood pressure, renal function (estimated glomerular filtration rate), plasma renin activity and, in a sub-population (N = 9), renal haemodynamics (measured glomerular filtration rate and effective renal plasma flow). A sample size of 50 patients provides 90% power to detect a 23% reduction in albuminuria, assuming a 25% dropout rate. Further reduction of residual albuminuria by combination of VDRA treatment and Sodium Restriction during single-agent RAAS-blockade will justify long-term studies on cardiorenal outcomes and safety.
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effects of Sodium Restriction and hydrochlorothiazide on raas blockade efficacy in diabetic nephropathy a randomised clinical trial
The Lancet Diabetes & Endocrinology, 2014Co-Authors: Arjan J Kwakernaak, Jan A Krikken, Heleen S Binnenmars, Folkert W Visser, Marc H Hemmelder, Arendjan Woittiez, Henk Groen, Gozewijn D Laverman, Gerjan NavisAbstract:Summary Background Reduction of dietary Sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system (RAAS) blockade efficacy in non-diabetic nephropathy. We aimed to investigate the effect of Sodium Restriction and the diuretic hydrochlorothiazide, separately and in combination, added to RAAS blockade on residual albuminuria in patients with type 2 diabetic nephropathy. Methods In this multicentre, double-blind, placebo-controlled, crossover randomised trial, we included patients with type 2 diabetic nephropathy. Main entry criteria were microalbuminaria or macroalbuminuria, and creatinine clearance of 30 mL/min or higher with less than 6 mL/min decline in the previous year. We tested the separate and combined effects of Sodium Restriction (dietary counselling in the outpatient setting) and hydrochlorothiazide (50 mg daily), added to standardised maximal angiotensin-converting enzyme (ACE) inhibition (lisinopril 40 mg daily), on albuminuria (primary endpoint). Patients were given hydrochlorothiazide (50 mg per day) or placebo during four treatment periods of 6 weeks. Both treatments were combined with regular Sodium diet or Sodium Restriction (target Sodium intake 50 mmol Na + per day). The 6-week treatment periods were done consecutively in a random order. Patients were randomised in blocks of two patients. The trial was analysed by intention to treat. The trial is registered with TrialRegister.nl, number 2366. Findings Of 89 eligible patients, 45 were included in the study. Both Sodium Restriction and hydrochlorothiazide significantly reduced albuminuria, irrespective of treatment sequence. Residual geometric mean albuminuria with baseline treatment was 711 mg per day (95% CI 485–1043); it was significantly reduced by Sodium Restriction (393 mg per day [258–599], p=0·0002), by hydrochlorothiazide (434 mg per day [306–618], p=0·0003), and to the greatest extent by their combination (306 mg per day [203–461], p Interpretation We conclude that Sodium Restriction is an effective non-pharmacological intervention to increase RAAS blockade efficacy in type 2 diabetic nephropathy. Funding None.
