+1 Recommend
1 collections
      Call for Papers in Kidney and Blood Pressure ResearchKidney Function and Omics Science

      Submission Deadline: December 20, 2023

      Submit now

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Causes and Consequences of Metabolic Acidosis in Patients after Kidney Transplantation


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Background: Metabolic acidosis (MA) is a common complication in kidney transplantation (KTx). It is more prevalent in KTx than in CKD, and it occurs at higher glomerular filtration rates. The pathophysiologic understanding of MA in KTx and its clinical impact has been highlighted by few recent studies. However, no guidelines exist yet for the treatment of MA after KTx. Summary: MA in KTx seems to share pathophysiologic mechanisms with CKD, such as impaired ammoniagenesis. Additional kidney transplant-specific factors seem to alter not only the prevalence but also the phenotype of MA, which typically shows features of renal tubular acidosis. There is evidence that calcineurin inhibitors, immunological factors, process of donation, donor characteristics, and diet may contribute to MA occurrence. According to several mainly observational studies, MA seems to play a role in disturbed bone metabolism, cardiovascular morbidity, declining graft function, and mortality. A better understanding of the pathophysiology and evidence from randomized controlled trials, in particular, are needed to clarify the role of MA and the potential benefit of alkali treatment in KTx. Alkali therapy might not only be beneficial but also cost effective and safe. Key Messages: MA seems to be associated with several negative outcomes in KTx. A deeper understanding of the pathophysiology and clinical consequences of MA in KTx is crucial. Clinical trials will have to determine the potential benefits of alkali therapy.

          Related collections

          Most cited references64

          • Record: found
          • Abstract: found
          • Article: not found

          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.
            • Record: found
            • Abstract: found
            • Article: not found

            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.
              • Record: found
              • Abstract: found
              • Article: not found

              Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD.

              Metabolic acidosis, usually manifested by low serum bicarbonate level, is common in chronic kidney disease (CKD) and appears to be associated with higher mortality in dialysis patients. It is not known whether a similar association is present in patients with non-dialysis-dependent CKD (NDD-CKD). We used multivariable-adjusted Cox models to examine the association between baseline and time-variable serum bicarbonate (measured as total CO2) with the outcomes of all-cause mortality and the composite of pre-dialysis mortality or end-stage renal disease in 1240 male patients with moderate and advanced NDD-CKD. Serum bicarbonate showed a significant U-shaped association with all-cause mortality, with the highest mortality rate observed in patients with baseline serum bicarbonate levels or =22 mmol/L: 1.33 (1.05-1.69), P = 0.02] and the lowest mortality observed in patients with baseline serum bicarbonate of 26-29 mmol/L. The associations between lower serum bicarbonate level and mortality were more accentuated in subgroups of patients with better nutritional status and lower inflammation. Both lower and higher serum bicarbonates are associated with increased all-cause mortality in patients with moderate and advanced NDD-CKD. Clinical trials are needed to determine if therapeutic interventions aimed at optimizing serum bicarbonate can result in improved outcomes in this population.

                Author and article information

                Kidney Blood Press Res
                Kidney and Blood Pressure Research
                S. Karger AG
                December 2020
                09 October 2020
                : 45
                : 6
                : 792-801
                [_a] aDivision of Nephrology, University Hospital of Zurich, Zurich, Switzerland
                [_b] bPraxis und Dialysezentrum Zürich-City, Zurich, Switzerland
                Author notes
                *Nilufar Mohebbi, Division of Nephrology, University Hospital Zurich, Rämistrasse 100, CH – 8091 Zurich (Switzerland), nilufar.mohebbi@usz.ch
                510158 Kidney Blood Press Res 2020;45:792–801
                © 2020 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.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.

                : 21 May 2020
                : 01 July 2020
                Page count
                Tables: 1, Pages: 10
                Review Article

                Cardiovascular Medicine,Nephrology
                Bone metabolism,Graft failure,Bicarbonate,Renal tubular acidosis,Mortality


                Comment on this article