Effect of Bicarbonate Supplement on Kidney Function

Effect of Bicarbonate Supplement on Kidney FunctionBicarbonate Supplementation Slows procession of CKD and Improves Nutritional StatusIone de Brito-Ashurst, Mira Varagunam, Martin J. Raftery, and Muhammad M. YaqoobLayAbstractChronic kidney unsoundness (CKD) is the coarse- name damage of the kidney. Symptoms precisely start presenting when the disease is progressing towards the advanced stages. It is a disease of the cured population, and with the UKs ageing population, cases be likely to increase in the near prospective. Metabolic acidosis (MA) is a common complication of CKD and plowing this has been thought to slow down the lessen in kidney function. Bicarbonate appurtenance has previously been used as an experimental interference on rat models to correct the MA except results have been inconclusive. at that place is also a lack of long- frontier ladders investigating the effect on humans. The results showed bicarbonate supplementation was beneficial to kidney functi on and dietal status of forbearings, while causing nominal side effects. More clinical trials need to be performed to consolidate these findings and to look at alternative treatment regimens before being implemented into clinical practice.Background Information and Rationale for Carrying Out the WorkChronic kidney disease (CKD) is the long-term decline in kidney function. It is defined as kidney damage resulting in a GFR 60 mL/min/1.73m2 for more than 3 months, or kidney damage for more than 3 months with evidence of structural or functional abnormalities, with GFR non ineluctably trim (1). In advanced stages it can lead to metabolic acidosis (MA) due to a decreased tubular bicarbonate secretion, which has been known to cause protein catabolism and change magnitude insulin resistance (2), and impaired ammonium excretion (3).The lesser stages of CKD are quite common in communities but ESRD is quite rare in populations. CKD is a disease of the elderly with around 30-40% of the population 75 years having CKD at stages 3-5 (1). It is usually asymptomatic until the later stages of the disease and during ESDR, the only possible life supporting treatments are transplantation or dialysis (4).Obesity is associated with an increased risk of CKD by over 2.5 times (5). With obesity, type 2 diabetes and hypertension all on the rise (6-8) , on that point is likely to be a boom in the number of CKD cases within the next couple of decades. There is clearly a need to address this future burden on the healthcare system.Correction of MA in dialysis patients has shown to slow down protein degradation in a small number of short term clinical trials (9, 10). Studies on rat models have shown inconsistent evidence where MA has been shown to slow down progression of nephritic failure (11). Due to the short term nature of these studies, there has been inadequate evidence on the impact of renal function.There have been very few studies investigating the correction of MA in CK D in humans and also the lack of long term studies of the effect on pre-dialysis patients, which were the main motives for carrying away this study.Approaches to the Question and Key ResultsThe research question elevated was whether bicarbonate supplementation to patients with MA in CKD could slow its progression and improve nutritional status. A single-centre, open-label, randomised, parallel-group study was carried out to investigate this question.The inclusion and ejection criteria were verbalize explicitly. 134 eligible patients were randomly assigned to either routine standard care or spontaneous sodium bicarbonate tablets 600mg TID which was increased as necessary to find bicarbonate 23mmol/L. The treatment assignment procedure was done by an external statistician and involved block stratification, then randomisation carried out within apiece stratum of men, women, diabetics and non-diabetics. This method helped to balance each of the patients covariates and ensured ad equate concealment. As a result, 67 patients were assigned to the control group and 67 patients to the treatment group. To reach a power of 90% which would accommodate an absolute difference of 30% to be detected, 63 patients in each group would have to be studied, but to allow for non-compliance, this was increased to 67. Calculation of statistical power ensured a large enough sample size. The 2 groups had similar baseline characteristics (Table 1) and apart from the bicarbonate supplementation, they were both treat equally.Patients were followed up every 2 months for 2 years for the primary outcome measurements while nutritional assessments were carried out at 0, 6, 12, 18 and 24 months by a single dietician. All patients were able to be analysed with none of the patients being lost to follow up or discontinuing the intervention, however 5 withdrew before receiving the treatment. Intention to treat analysis was performed. The investigators, statisticians and the single dietician were blinded to the initial group assignment as they were directly involved in assessing the outcomes, but since the trial was open-label, it suggests that patients and external clinicians were not.The outcomes were pore on the research question and were measured in a standard way. The primary outcomes were the decline in renal function, the number of patients with rapid progression of renal failure, and the development of ESRD that required dialysis.After 12 months, the rate in decline of CrCl was trim down in the treatment group at 1.88 ml/min per 1.73 m2 (95% CI 0.39 to 4.15 ml/min per 1.73 m2) than the control group at 5.93 ml/min per 1.73 m2 (95% confidence musical interval CI 4.19 to 7.76 ml/min per 1.73 m2) (PSecondary outcomes were measurements of changes in normalized protein nitrogen appearance (nPNA), dietary protein intake (DPI), serum albumin and mid-arm muscle circumference (MAMC) to identify the nutritional status of patients. Results showed an increase in DPI (P L ikely Impact of Research OutcomeThe feature that there was both a slowdown of the decline in kidney function and a reduction in the number of patients progressing to ESRD is clinically beneficial. However, the confidence interval for the treatment group is quite large (0.39 to 4.15 ml/min per 1.73 m2) and the upper limit is close to overlapping with the confidence interval of the control group at the lower limit (4.19 to 7.76 ml/min per 1.73 m2) for the rate in decline of CrCl. Statistically, the treatment may only offer a marginal feeler over the control, but the bicarbonate supplementation clearly does offer some benefit to stage 4 CKD patients. There are also significant nutritional benefits to CKD patients. Poor nutrition leads to protein energy wasting (PEW) and a low serum albumin which increase morbidity and mortality in dialysis patients (12), but this can be easily reduced with bicarbonate supplementation.The patients studied in this trial are not 100% representative of t he population. This trial had to exclude 30 out of 184 potential subjects due to eligibility criteria. The exclusion criteria included morbid obesity, congestive heart failure, chronic sepsis, malignant diseases, cognitive impairment or uncontrolled hypertension so findings will not gain to patients that fall into these categories, however the findings will be important for the majority of patients with CKD. The trial was only a single centre study on patients at the kinglike capital of the United Kingdom Hospital in the East End of London. The demographic in this area of London is likely to vary from demographics in other parts of London and the UK.I think all the outcomes of interest to the patient were considered before the trial. Side effects of worsening hypertension and oedema that required an increase in therapy and grommet diuretics respectively were minimal (Table 3). Blood pressures rose and oedema worsened more in the treatment group but these were not statistically si gnificant (P=0.17 and P=0.5). The single main issue was that 6.5% of subjects experienced a bad taste taking the tablet of the sodium bicarbonate, which was then switched to a powder form.In the long term I think this trial will form the basis of a future change in clinical practice. The change will not be immediate as this is the first RCT on pre-ESRD patients with MA and more clinical trials need to be carried out in this area, with a subsequent imperious review and meta-analysis. Overall, the bicarbonate supplementation does offer an advantage over standard treatment, and the fact that bicarbonate itself is simple and very cheap to source and produce with minimal side effects also works in its favour.Future Work and ConclusionThere are some changes I would make to the trial. The confidence interval for the treatment group is quite large (0.39 to 4.15 ml/min per 1.73 m2) and the upper limit is close to overlapping with the confidence interval of the control group at the lower lim it (4.19 to 7.76 ml/min per 1.73 m2) for the rate in decline of CrCl. So statistically, the treatment may only offer a marginal improvement over the control. In order to achieve a more precise CI, a larger sample size could be used, and a multi-centre trial could be conducted so that the findings can be applied to a wider population. I think the accuracy of the outcomes would also benefit from the use of a placebo and double-blinding.This study focused only on patients in stage 4 CKD. While these patients are likely to experience MA, it may also be beneficial to study the effect on patients in stage 3 CKD. Patients especially in stage 3b CKD (GFR 30-44 mL/min) are at risk of slipping into the stage 4 category and bicarbonate supplementation has potential to act as a preventative treatment.The serum bicarbonate level in the treatment group was maintained at 23 mmol/L or greater. There was no upper limit for the bicarbonate level and considering that the normal range of serum bicarbon ate is 22-28 mmol/L, we can see that the trial looked at the lower end of the reference range. I think a future clinical trial should look at the effect of bicarbonate supplementation on stage 4 CKD patients when serum bicarbonate is controlled within a middle range of 24-26 mmol/L and at the upper end range of 26-28 mmol/L.It is further to see that there have been more RCTs investigating the positive outcomes of bicarbonate supplementation on CKD (13-15), however further investigations still need to be carried out to reach an optimal and definitive treatment plan.References1.Barratt J, Topham PD, Harris KPG. Nephrology. Oxford Oxford University Press 2009.2.Kopple JD, Kalantar-Zadeh K, Mehrotra R. Risks of chronic metabolic acidosis in patients with chronic kidney disease. Kidney Int Suppl. 2005(95)S21-7.3.Bailey JL. Metabolic acidosis an unrecognized cause of morbidity in the patient with chronic kidney disease. Kidney Int Suppl. 2005(96)S15-23.4.Smart NA, Dieberg G, Ladhani M, T itus T. 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