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      Oral Bicarbonate Slows Decline of Residual Renal Function in Peritoneal Dialysis Patients

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          Abstract

          Background/Aims: Metabolic acidosis is a common consequence of end-stage renal disease (ESRD) which may result in a substantial adverse outcome. The effect of oral bicarbonate on the preservation of residual renal function (RRF) in peritoneal dialysis (PD) patients has been rarely reported. Methods: We randomly assigned 40 continuous ambulatory peritoneal dialysis (CAPD) patients to the oral bicarbonate group or placebo group at a 1: 1 ratio. All enrollments were followed for a duration of 104 weeks. We took residual creatinine clearance (CCr), a measure of residual renal function (RRF), as the primary outcome. Residual CCr was calculated as the average of urea and creatinine clearance from a 24-hour urine collection. Results: Thirteen patients in the placebo group and 15 patients in the treatment group completed the 104 weeks of follow-up with a comparable dropout rate (placebo group: 35% vs treatment group: 25%). Compared with the placebo group, serum bicarbonate in treatment group was significantly increased at each time point, and oral bicarbonate resulted in a slower declining rate of residual CCr (F=5.113, p=0.031). Baseline residual CCr at enrollment also had a significant effect on residual CCr (F=168.779, P<0.001). Charlson Comorbidity Index which was adopted to calculate a comorbidity score had no significant effect on residual CCr loss (F=0.168, P=0.685). Conclusion: Oral bicarbonate may have a RRF preserving effect in CAPD patients, and a normal to high level of serum bicarbonate (≥24mmol/L) may be appropriate for RRF preservation.

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          Bicarbonate supplementation slows progression of CKD and improves nutritional status.

          Bicarbonate supplementation preserves renal function in experimental chronic kidney disease (CKD), but whether the same benefit occurs in humans is unknown. Here, we randomly assigned 134 adult patients with CKD (creatinine clearance [CrCl] 15 to 30 ml/min per 1.73 m(2)) and serum bicarbonate 16 to 20 mmol/L to either supplementation with oral sodium bicarbonate or standard care for 2 yr. The primary end points were rate of CrCl decline, the proportion of patients with rapid decline of CrCl (>3 ml/min per 1.73 m(2)/yr), and ESRD (CrCl <10 ml/min). Secondary end points were dietary protein intake, normalized protein nitrogen appearance, serum albumin, and mid-arm muscle circumference. Compared with the control group, decline in CrCl was slower with bicarbonate supplementation (5.93 versus 1.88 ml/min 1.73 m(2); P < 0.0001). Patients supplemented with bicarbonate were significantly less likely to experience rapid progression (9 versus 45%; relative risk 0.15; 95% confidence interval 0.06 to 0.40; P < 0.0001). Similarly, fewer patients supplemented with bicarbonate developed ESRD (6.5 versus 33%; relative risk 0.13; 95% confidence interval 0.04 to 0.40; P < 0.001). Nutritional parameters improved significantly with bicarbonate supplementation, which was well tolerated. This study demonstrates that bicarbonate supplementation slows the rate of progression of renal failure to ESRD and improves nutritional status among patients with CKD.
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            The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials.

            To comprehend the results of a randomized, controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Con solidated S tandards o f R eporting T rials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this paper incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Discussion. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from four stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, for each intervention group, that are included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
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              Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy.

              In most patients with hypertensive nephropathy and low glomerular filtration rate (GFR), the kidney function progressively declines despite the adequate control of the hypertension with angiotensin-converting enzyme inhibition. Previously we found that 2 years of oral sodium citrate slowed GFR decline in patients whose estimated GFR (eGFR) was very low (mean 33 ml/min). This treatment also slowed GFR decline in an animal model of surgically reduced nephron mass. Here, we tested if daily oral sodium bicarbonate slowed GFR decline in patients with hypertensive nephropathy with reduced but relatively preserved eGFR (mean 75 ml/min) in a 5-year, prospective, randomized, placebo-controlled, and blinded interventional study. Patients matched for age, ethnicity, albuminuria, and eGFR received daily placebo or equimolar sodium chloride or bicarbonate while maintaining antihypertensive regimens (including angiotensin-converting enzyme inhibition) aiming for their recommended blood pressure targets. After 5 years, the rate of eGFR decline, estimated using plasma cystatin C, was slower and eGFR was higher in patients given sodium bicarbonate than in those given placebo or sodium chloride. Thus, our study shows that in hypertensive nephropathy, daily sodium bicarbonate is an effective kidney protective adjunct to blood pressure control along with angiotensin-converting enzyme inhibition.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2017
                October 2017
                18 September 2017
                : 42
                : 3
                : 565-574
                Affiliations
                [_a] aDepartment of Diabetic Nephropathy Hemodialysis, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
                [_b] bDepartment of Nephrology, Chinese PLA No. 254 Hospital, Tianjin, China
                [_c] cDepartment of Endocrinology, Chinese PLA No. 254 Hospital, Tianjin, China
                [_d] dDepartment of Endocrinology, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical Universtiy, Tianjin, China
                Author notes
                *Pei Yu, Department of Diabetic Nephropathy Hemodialysis, Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology,, Tianjin Medical University, NO. 66, Tongan Street, Heping District, Tianjin 300070 (China), E-Mails Yupei@tijmu.edu.cn
                Article
                479641 Kidney Blood Press Res 2017;42:565–574
                10.1159/000479641
                29032379
                f2f85b6e-4db3-4c2c-b827-b9c3d2321174
                © 2017 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 06 October 2016
                : 07 February 2017
                Page count
                Figures: 2, Tables: 3, Pages: 10
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                End-stage renal disease,Peritoneal dialysis,Continuous ambulatory peritoneal dialysis,Metabolic acidosis,Residual renal function

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