Oral Bicarbonate Supplementation Research Articles

#2725 Chronic kidney disease is a risk factor for hyperchloremic metabolic acidosis after plasma exchange

Abstract Background and Aims Observational studies have demonstrated that metabolic acidosis due to hyperchloremia is an often encountered metabolic disorder following plasma exchange (PE) with an albumin-saline solution. Because of the reduced capacity for acid and chloride excretion, we hypothesized that patients with chronic kidney disease have the highest risk for hyperchloremic metabolic acidosis, in particular when multiple PE sessions are performed in a limited period. Method We prospectively collected data from all patients who received PE at Amsterdam UMC, between February 2023, and January 2024. We collected data on demographics, exchanged plasma volume, replacement fluids, and collected blood for analysis of sodium, chloride and bicarbonate before and after plasma exchange. We selected patients who received ≥5 plasma exchanges in an intensive cycle (≥4.2 sessions/week). We excluded patients who received Omniplasma, intravenous sodium bicarbonate or dialysis during the PE period. We assessed the effect of PE and kidney function on plasma bicarbonate and chloride concentration throughout the PE period with repeated measures mixed ANOVA, corrected for baseline plasma bicarbonate concentration, volume of exchanged plasma and PE intensity. Results Data from 26 patients, corresponding to 130 plasma exchanges, were included in the analysis. The mean age was 56 ± 14 years and 46% was female. Mean eGFR was 45 ± 14 ml/min/1.73 m2. Patients with an eGFR ≤59 ml/min/1.73 m2 (n = 17) had a significantly lower baseline plasma bicarbonate concentration (19.0 ± 2.8 versus 24.0 ± 1.9 mmol/L; p < 0.001) and used oral bicarbonate supplements (29% versus 0%; p = 0.02) more often than patients with an eGFR ≥60 ml/min/1.73 m2 (n = 9). Despite the lower baseline plasma bicarbonate and more frequent use of oral bicarbonate supplements, the plasma bicarbonate levels decreased the most in subjects with an eGFR ≤59 ml/min/1.73 m2 (mean difference −4.2; 95% CI −7.1 to −1.3; p = 0.006; Fig. 1A) during a cycle of 5 PE sessions. Baseline plasma chloride concentration was similar in both groups (103 ± 7 vs 103 ± 4 mmol/L) and increased the most in patients with an eGFR ≤59 ml/min/1.73 m2 (mean difference −1.4; 95% CI −2.2 to 5.0; p = 0.426; Fig. 1B). Conclusion Repeated plasma exchange with albumin-saline as a replacement fluid is associated with a significant decrease in plasma bicarbonate concentration in patients with impaired kidney function. Future studies should determine whether this hyperchloremic metabolic acidosis has impact on the patients’ symptoms or long-term outcome.

#2418 Effects of correction of acidosis on body composition and biochemical parameters in CKD patients on maintenance hemodialysis

Abstract Background and Aims Metabolic acidosis is a common problem in patients of chronic kidney disease and patients on maintenance hemodialysis. In resource poor countries, due to financial constraints frequency of dialysis and compliance to medication is adversely affected. This leads to worsening of clinical condition of patient and requirement of in hospital care, many times intensive care, further increasing cost of treatment. Metabolic acidosis has implications on bone and muscle health. Aim of our study was to assess the changes in body composition (fat percentage and lean body mass), changes in third space fluid, biochemical parameters, number of admissions and requirement of blood transfusions before and after correction of metabolic acidosis. Method This was a prospective, observational study. 25 patients on maintenance hemodialysis at our center were included in the study. Bio-impedance analysis (BIA), biochemical parameters (Complete blood counts, renal function tests, serum calcium and phosphorous, liver function tests, Blood gas analysis) were done at baseline before starting bicarbonate supplementation. Number of admissions and blood transfusions in 3 months prior to initiation of bicarbonate supplementation were noted. The oral bicarbonate supplementation was increased from baseline, based on the baseline blood gas analysis. The same parameters were assessed after 3 months and analyzed. Results At the end of 3 months we observed that there was significant reduction (p < 0.05) in total leucocyte counts (mean 8100/cumm to 6800/cumm), urea (mean 113.7 mg/dL to 83.72 ng/dL), creatinine (mean 7.87 mg/dL to 6.68 mg/dL), phosphorous (mean 5.18 mg/dL to 4.43 mg/dL), SGOT (mean 56.52 IU to 25.2 IU) and SGPT (mean 46.48 IU to 22.88 IU) with a trend of decrease (p ≤ 0.1) in percentage of extra cellular water (27.31% to 25.03%), lean body mass (44.27 kg to 43.0 kg) and trend of increase (p ≤ 0.1) in body fat composition (15.62 kg to 18.82 kg) and body fat percentage (26.924% to 31.90). There was a reduction in third space fluid (0.88 lit to 0.43 lit). The number of hospitalizations reduced (15 three months prior to initiation of therapy to 7 after initiation of therapy) and number of blood transfusions required also reduced (21 before initiation to 10 after initiation of therapy). Conclusion We concluded that correction of acidosis probably reduces the inflammation in patients of CKD on maintenance hemodialysis. This could be seen from the reduced total leucocyte counts, liver enzymes, urea and creatinine values. Changes in body composition with increased total fat mass, fat percentage and decreased lean mass was also noted. There was also a significant reduction in hospitalizations and number of blood transfusions.

Effects of Oral Bicarbonate Supplementation on the Cardiovascular Risk Factors and Serum Nutritional Markers in Non-Dialysed Chronic Kidney Disease Patients.

Background and Objectives: Kidneys play a key role in maintaining the acid–base balance. The aim of this study was to evaluate the effect of a 3-month oral sodium bicarbonate administration on arterial wall stiffness, arterial pressure and serum nutritional markers in non-dialysed patients with chronic kidney disease (CKD) stages 3–5 and metabolic acidosis. Methods: Eighteen CKD patients with eGFR < 45 mL/min/1.73 m2 and capillary blood bicarbonate (HCO3) < 22 mmol/L were enrolled in this single-centre, prospective study. Anthropometric parameters, pulse wave velocity, 24-h ambulatory blood pressure measurements, blood and urine parameters were assessed at the beginning and at the end of the study. The patients received supplementation with 2 g of sodium bicarbonate daily for three months. Results: A significant increase of pH: 7.32 ± 0.06 to 7.36 ± 0.06; p = 0.025, HCO3 from 18.7 mmol/L (17.7–21.3) to 22.2 mmol/L (20.2–23.9); p < 0.001 and a decrease in base excess from −6.0 ± 2.4 to −1.9 ± 3.1 mmol/L; p < 0.001 were found. An increase in serum total protein from 62.7 ± 6.9 to 65.8 ± 6.2; p < 0.013 and albumin from 37.3 ± 5.4 to 39.4 ± 4.8; p < 0.037 but, also, NT-pro-BNP (N-Terminal Pro-B-Type Natriuretic Peptide) from 794.7 (291.2–1819.0) to 1247.10 (384.7–4545.0); p < 0.006, CRP(C Reactive Protein) from 1.3 (0.7–2.9) to 2.8 (1.1–3.1); p < 0.025 and PTH (parathyroid hormone) from 21.5 ± 13.7 to 27.01 ± 16.3; p < 0.006 were observed, as well as an increase in erythrocyte count from 3.4 ± 0.6 to 3.6 ± 0.6; p < 0.004, haemoglobin from 10.2 ± 2.0 to 11.00 ± 1.7; p < 0.006 and haematocrit from 31.6 ± 6.00 to 33.6 ± 4.8; p < 0.009. The mean eGFR during sodium bicarbonate administration did not change significantly: There were no significant differences in pulse wave velocity or in the systolic and diastolic BP values. Conclusion: The administration of sodium bicarbonate in non-dialysed CKD patients in stages 3–5 improves the parameters of metabolic acidosis and serum nutritional markers; however, it does not affect the blood pressure and vascular stiffness.

Metabolic Acidosis in Chronic Kidney Disease: Pathogenesis, Clinical Consequences, and Treatment.

The kidneys play an important role in regulating the acid-base balance. Metabolic acidosis is common in chronic kidney disease (CKD) patients and can lead to poor outcomes, such as bone demineralization, muscle mass loss, and worsening of renal function. Metabolic acidosis is usually approached with evaluating the serum bicarbonate levels but should be assessed by counting blood pH. Current guidelines recommend oral bicarbonate supplementation to maintain the serum bicarbonate levels within the normal range. However, a slow decline in the glomerular filtration rate might occur, even though the serum bicarbonate levels were in the normal range. Because the serum bicarbonate levels decrease when metabolic acidosis advances, other biomarkers are necessary to indicate acid retention for early diagnosis of metabolic acidosis. For this, urine citrate and ammonium excretion may be used to follow the course of CKD patients. Metabolic acidosis can be treated with an increased fruit and vegetable intake and oral alkali supplementation. Previous studies have suggested that administration of oral sodium bicarbonate may preserve kidney function without significant increases in blood pressure and body weight. Veverimer, a non-absorbed, counterion-free, polymeric drug, is emerging to treat metabolic acidosis, but further researches are awaited. Further studies are also needed to clarify the target therapeutic range of serum bicarbonate and the drugs used for metabolic acidosis.

The Prevalence of Metabolic Acidosis in Patients with Different Stages of Chronic Kidney Disease: Single-Centre Study

Background: Metabolic acidosis (MA) is one of the most common consequences of CKD. MA is also a risk factor of CKD progression and increased mortality in these patients. Aim: The aim of this retrospective, cross-sectional study was to assess the prevalence of MA in different stages of CKD and renal replacement therapy (RRT) modalities – haemodialysis (HD) and peritoneal dialysis (PD). Additionally, the relationship between the prevalence of MA and aetiology of kidney disease was analysed. Methods: One thousand five patients in different stages of CKD, or modalities of RRT were enrolled into this single-centre cross-sectional study. Forty-one patients were ruled out because of oral bicarbonate supplementation. In the remaining 964 patients (698 CKD stages 1–5, 226 HD, 40 PD), venous blood HCO₃⁻ concentration, as well as serum Cr and urea concentrations were assessed. MA was diagnosed when blood HCO₃⁻ concentration was below 22 mmol/L. Results: The prevalence of MA increased among all stages of CKD. Patients on HD had lower prevalence of MA in comparison with CKD 5 patients with no RRT (38.5 vs. 56.0%; p = 0.02) In PD patients, the prevalence of MA was significantly lower than in HD patients (2.5 vs. 38.5%; p < 0.001). In the whole study group, there were no significant differences in the prevalence of MA between different aetiologies of CKD (glomerulonephritis 24%, hypertension 23%, diabetes 25%, and tubule-interstitial diseases 24%). Also, when only patients in stages CKD 3–5 were compared, no significant differences in the prevalence of acidosis were found (glomerulonephritis 28%, hypertension 22%, diabetes 24%, and tubule-interstitial 21%). Conclusions: (1) MA is more frequent in patients with more advanced stages of CKD. (2) RRT reduces the prevalence of MA. (3) In PD patients, MA is rare. (4) Aetiology of CKD seems not to have a significant impact on MA prevalence.

Safety and Feasibility of Oral Bicarbonate Supplementation as an Intervention to Prevent Mobility Disability

Safety and Feasibility of Oral Bicarbonate Supplementation as an Intervention to Prevent Mobility Disability

Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Metabolic acidosis is a common complication in chronic kidney disease (CKD) patients, and is associated with an accelerated decline in renal function. Oral bicarbonate therapy has been used to counteract metabolic acidosis in CKD for decades. However, until recently, there have been very few intervention studies testing the effectiveness of bicarbonate therapy at improving metabolic acidosis or its consequences in patients with CKD. In this systematic review and meta-analysis, we aimed to examine the outcomes of all published randomised controlled trials (RCTs) that investigated the effect of oral bicarbonate therapy in adults with CKD. Ovid MEDLINE®, EMBASE® and Cochrane Library were searched in mid-October 2018 for English literature, with no restrictions applied to the publication status or date. Seven RCTs that recruited 815 participants met our inclusion criteria after full text review. Oral bicarbonate supplementation resulted in a slightly higher estimated glomerular filtration rate (eGFR) (mean difference 3.1 mL/min per 1.73 m2; 95% CI 1.3–4.9) and serum bicarbonate levels (mean difference 3.4 mmol/L; 95% CI 1.9–4.9) at the end of follow-up (three months to five years) compared to those given placebo or conventional CKD treatment. When limited to studies reporting outcomes at one year, the positive effect of oral bicarbonate therapy on eGFR was attenuated. There were no significant treatment effects in other parameters such as systolic blood pressure (BP) and weight. These findings should be interpreted with caution and further trial evidence is needed to establish the net overall benefit or harm of oral bicarbonate therapy in CKD.

Abstract P263: Acid-Base Status as a Modifier of Loss of Lean Mass During Intentional Weight Loss in Older Adults

Weight loss interventions present a unique challenge in older adults: relative loss of lean mass during weight loss, if superimposed on age-related sarcopenia may increase the risk for mobility disability. Relative loss of lean mass (25-30%) during weight loss depends on the severity/duration of caloric restriction, initial body mass, and concomitant exercise training. We hypothesized that subclinical imbalances of acid-base status (reflected in lower serum bicarbonate) may also affect relative loss of lean mass during weight loss. The rationale: even subtle imbalances of acid-base status (e.g. bicarbonate &lt;23 mmol) impact clinical outcomes in older adults such as gait speed or incidence of functional limitation, while bicarbonate supplementation reduces urinary nitrogen wasting and may improve physical function. However, data on acid-base balance and serum bicarbonate during moderate caloric restriction are lacking. We, therefore, analyzed 2 randomized, controlled weight loss trials (including moderate caloric restriction and exercise): The Diet, Exercise, and Metabolism for Older Women [DEMO; (58±5.2 y)] and Cooperative Lifestyle Program; [CLIP; (67±4.7 y)]. Serum bicarbonate was assessed as total CO 2 (in mmol) and whole body lean mass measured by dual-energy X-ray absorptiometry. The analysis showed that 48% of participants had bicarbonate &lt;23. DEMO participants with lower serum bicarbonate at baseline lost more lean mass during the intervention (unadjusted β(SE)=0.32(0.16); p=0.04; n=92). Adjustments for age, BMI, eGFR, % weight loss, baseline, intervention group, had little effect, but adjusting for protein intake during weight loss attenuated the association (β(SE)=0.17(0.15); p=0.28.). Similarly, a change in serum bicarbonate during the trial was associated with % lean mass change, but attenuated after controlling for protein intake. This is not unexpected: protein is acid-producing and one of two major determinants of net dietary acid load; higher dietary acid load correlates with lower serum bicarbonate, in older adults. Results from the CLIP trial were remarkably similar, and consistently, baseline serum bicarbonate level was marginally predictive of baseline daily protein intake, with highest baseline serum bicarbonate having the lowest protein intake [bicarbonate: &gt;24 (n=58); &gt;21-24 (n=121); &lt;21 (N=93); protein in g/kg body weight 0.7(0.4); 0.9(0.4); 0.8(0.4) respectively, p=0.057). In conclusion, our analysis suggests that higher serum bicarbonate before and during weight loss may ameliorate loss of lean mass, however, to obtain definitive answer such analysis needs to be conducted under conditions of controlled or randomized protein intake. Importantly, our findings suggest that oral bicarbonate supplementation, a simple and relatively safe intervention, may ameliorate loss of lean mass during weight loss interventions in older adults.

The Relationship between Metabolic Acidosis and Nutritional Parameters in Patients on Hemodialysis.

The progressive loss of kidney function is accompanied by metabolic acidosis. The relationship between metabolic acidosis, nutritional status, and oral bicarbonate supplementation has not been assessed in the Indian chronic kidney disease (CKD) population who are on maintenance hemodialysis (MHD). This is a single-center prospective study conducted in the Western part of India. Thirty-five patients, who were receiving MHD were assessed for metabolic acidosis along with various nutritional parameters at the baseline and at the follow-up after 3 months, postcorrection of acidosis with oral sodium bicarbonate supplements. The relationship between the correction of metabolic acidosis with oral bicarbonate supplements and changes in dietary and various nutritional parameters were evaluated. Metabolic acidosis at the baseline evaluation was found in 62.86% cases of the cohort with a mean serum bicarbonate value of 20.18 ± 4.93 mmol/L. The correction of acidosis with increment in the mean dosage of oral sodium bicarbonate supplements from 0.69 ± 0.410 mmol/kg/day at baseline to 1.04 ± 0.612 mmol/kg/day, significantly reduced the prevalence of metabolic acidosis to 23.33% cases at the follow-up. Improvement in serum bicarbonate level showed significant dietary, anthropometric, and nutritional improvements in these patients. Hence, we conclude that correction of metabolic acidosis with optimal oral bicarbonate supplementation plays a pivotal role in the treatment of malnourished CKD patients on MHD.

Alkaline Water–An Alternative to Oral Bicarbonate Supplementation in CKD?

Alkaline Water–An Alternative to Oral Bicarbonate Supplementation in CKD?

Alkaline Salts to Counteract Bone Resorption and Protein Wasting Induced by High Salt Intake: Results of a Randomized Controlled Trial

High sodium chloride (NaCl) intake can induce low-grade metabolic acidosis (LGMA) and may thus influence bone and protein metabolism. We hypothesized that oral potassium bicarbonate (KHCO(3)) supplementation may compensate for NaCl-induced, LGMA-associated bone resorption and protein losses. Eight healthy male subjects participated in a randomized trial with a crossover design. Each of two study campaigns consisted of 5 d of dietary and environmental adaptation followed by 10 d of intervention and 1.5 d of recovery. In one study campaign, 90 mmol KHCO(3)/d were supplemented to counteract NaCl-induced LGMA, whereas the other campaign served as a control with only high NaCl intake. When KHCO(3) was ingested during high NaCl intake, postprandial buffer capacity ([HCO(3)(-)]) increased (P = 0.002). Concomitantly, urinary excretion of free potentially bioactive glucocorticoids [urinary free cortisol (UFF) and urinary free cortisone (UFE)] was reduced by 14% [∑(UFF,UFE); P = 0.024]. Urinary excretion of calcium and bone resorption marker N-terminal telopeptide of type I collagen was reduced by 12 and 8%, respectively (calcium, P = 0.047; N-terminal bone collagen telopeptide, P = 0.044). There was a trend of declining net protein catabolism when high NaCl was combined with KHCO(3) (P = 0.052). We conclude that during high salt intake, the KHCO(3)-induced postprandial shift to a more alkaline state reduces metabolic stress. This leads to decreased bone resorption and protein degradation, which in turn might initiate an anticatabolic state for the musculoskeletal system in the long run.

Green urine, but no infection

In September, 2007, an unconscious 88-year-old woman was brought to the emergency room. She had undergone a hysterectomy and radiotherapy because of carcinoma of the cervix 30 years previously; 10 years later she had developed neurogenic bladder dysfunction, requiring intermittent self-catheterisation. She had had mild renal insuffi ciency (creatinine 100 μmol/L) and mild hydronephrosis unilaterally, because of ureteric obstruction following the irradiation. Her medical history also included bilateral femoral artery angioplasty, a transient ischaemic attack, and group B streptococcal endocarditis with remaining mild mitral valve insuffi ciency. Medications included an ACE-inhibitor, aspirin, and dipyridamole for the past 4 years. On presentation she was unresponsive and hyperventilating (20 breaths per min) with a body temperature of 33·0°C, an irregular pulse (110 beats per min), and a blood pressure of 110/60 mm Hg. Auscultation showed no new cardiac abnormalities, and neurological evaluation was unremarkable. The electrocardiogram showed atrial fi brillation (110 beats per min). Blood gas analysis on supplemental oxygen, corrected for hypothermia, showed a pH of 7·08, pCO2 1·85 kPa, bicarbonate 3·6 mmol/L, and pO2 18·5 kPa, indicative of metabolic acidosis with incomplete respiratory compensation. 1300 mL of green purulent urine was emptied from the bladder on catheterisation. Urosepsis was suspected, blood samples were taken, and she was rehydrated with saline and treated with ceftriaxone and 8·4% NaHCO3. 1 h later laboratory test results showed a normal anion gap hyperchloraemic acidosis (anion gap 16, sodium 147 mmol/L, and chloride 127 mmol/L). Lactate (1 mmol/L), potassium (4·3 mmol/L), albumin (34 g/L), and glucose (7·9 mmol/L) were normal. Until this point she had received 1250 mL 0·9% NaCl (saline) and 200 mL of 8·4% NaHCO3. Repeat analysis showed sodium 159 mmol/L, chloride 131 mmol/L, potassium 3·4 mmol/L, and bicarbonate 7·0 mmol/L. Although the saline was replaced by 5% glucose solution, 1·5 L/day, with 4 mmol potassium added, plasma sodium and chloride concentrations inceased to 170 mmol/L and 143 mmol/L, respectively, over the next 2 days. Urine cultures were negative. Hyperchloraemia and hypernatraemia because of endogenous reuptake of urinary chloride in the bowel was suspected. Cystoscopy showed a large bladder wall defect with a vesicojejunal fi stula on CT (fi gure). Our patient refused additional procedures and was discharged to a nursing home with oral bicarbonate supplementation. She passed away 2 months later. Our patient had a hyperchloraemic metabolic acidosis because of a fi stula between bladder and jejunum caused by previous radiotherapy; it is possible that the fi stula caused the group B streptococcal endocarditis 3 years before presentation. The ileal and colonic mucous membrane harbours a Cl/HCO3 transporter that exchanges intraluminal chloride (in our patient, a large amount via the communication to the bladder) for bicarbonate; sodium is actively reabsorbed, leading to potassium excretion. This explains the hyperchloraemic acidosis that can be seen in patients following ureter implantation into the sigmoid commonly presenting with hypokalaemia. However, in our patient, renal insuffi ciency and ACE-inhibitor use induced normokalaemia, and correction of the acid-base status provoked hypokalaemia. Saline infusion and bicarbonate supplementation during initial resuscitation resulted in additional sodium re-uptake and worsening of hyperchloraemia and hypernatraemia. Several other factors may have contributed to the observed acidosis, for example elevated bladder pressure between the selfcatheterisations promoting fl uid movement through the fi stula. In addition, the proximal localisation of the fi stula could have extended ileal and colonic transit time, augmenting intestinal chloride uptake. Enterovesical fi stula can occur years after pelvic radiotherapy; the importance of taking into account the patient’s history cannot be emphasised enough.

Modified ureterosigmoidostomy for management of malignant and non-malignant conditions

To investigate the outcome of Mainz Pouch II urinary diversion for both malignant and non-malignant diseases. A retrospective analysis. Kilimanjaro Christian Medical Centre, Institute of Urology, Moshi, Tanzania from April 1995 to May 2007. Mainz Pouch II was created in 83 patients of which, 38 were females and 45 were males (M:F 1.2:1). Early complications were seen in 11 (13.2%) patients, as follows: one (1.2%) prolonged ileus, 1(1.2%) wound dehiscence, two (2.4%) perioperative deaths among the malignant group, seven (8.4%) superficial wound sepsis. Long term complications were seen in 14 (16.9%) patients, as follows: one (1.2%) patient developed an incision hernia, one (1.2%) patient developed unilateral pyelonephritis, one (1.2%) patient developed unilateral ureteral stenosis, two (2.4%) patients had deterioration of renal function, three (3.6%) patients developed mild to moderate unilateral hydronephrosis, three (3.6%) patients developed mucoceles. Among the 83 patients in this series, three (3.6%) patients developed metabolic acidosis, two (2.4%) of which, required oral bicarbonate supplementation. All (100%) patients had daytime continence while three (3.6%) patients had occasional night time incontinence. Overall total continence was achieved in 80 (96.4%) of the patients. The Mainz Pouch II is a safe and reproducible method of urinary diversion and serves as a satisfying method of continent urinary diversion in all age groups. This reconstructive surgery enabled the afflicted to achieve personal goals, hopes and aspirations, positively influencing their quality of life. The follow up show low complication rate with good results in terms of continence and quality of life, however, long term results remain to be evaluated.

Correction of chronic metabolic acidosis for chronic kidney disease patients

Metabolic acidosis is a feature of chronic kidney disease (CKD) due to the reduced capacity of the kidney to synthesise ammonia and excrete hydrogen ions. It has adverse consequences on protein and muscle metabolism, bone turnover and the development of renal osteodystrophy. Metabolic acidosis may be corrected by oral bicarbonate supplementation or in dialysis patients by increasing the bicarbonate concentration in dialysate fluid. To examine the benefits and harms of treating metabolic acidosis in patients with CKD, both prior to reaching end-stage renal disease (ESRD) or whilst on renal replacement therapy (RRT), with sodium bicarbonate or increasing the bicarbonate concentration of dialysate. We searched CENTRAL (The Cochrane Library, issue 4 2005), Cochrane Renal Group's specialised register (October 2005), MEDLINE (1966 - October 2005) and EMBASE (1980 - October 2005). Randomised controlled trials (RCTs), crossover RCTs and quasi-RCTs investigating the correction of chronic metabolic acidosis in adults or children with CKD. Outcomes were analysed using relative risk (RR) and weighted mean difference (MD) for continuous measures. We identified three trials in adult dialysis patients (n = 117). There were insufficient data for most outcomes for meta-analysis. In all three trials acidosis improved in the intervention group though there was variation in achieved bicarbonate level. There was no evidence of effect on blood pressure or sodium levels. Some measures of nutritional status/protein metabolism (e.g. SGA, NP NA) were significantly improved by correction in the one trial that looked in these in detail. There was heterogeneity of the effect on serum albumin in two trials. Serum PTH fell significantly in the two trials that estimated this, there was no significant effect on calcium or phosphate though both fell after correction. Complex bone markers were assessed in one study, with some evidence for a reduction in bone turnover in those with initial high bone turnover and an increase in low turnover patients. The studies were underpowered to assess clinical outcomes, in the one study that did there was some evidence for a reduction in hospitalisation after correction. The evidence for the benefits and risks of correcting metabolic acidosis is very limited with no RCTs in pre-ESRD patients, none in children, and only three small trials in dialysis patients. These trials suggest there may be some beneficial effects on both protein and bone metabolism but the trials were underpowered to provide robust evidence.

Determinants of metabolic acidosis among hemodialysis patients

Metabolic acidosis is frequently present, poorly controlled, and associated with adverse effects among hemodialysis patients. Potential determinants of metabolic acidosis include endogenous acid production, administration of alkali, neutralization of acid by buffers, dilution of serum bicarbonate by interdialytic fluid gain, and loss of bicarbonate in stool. Understanding the relative importance of these determinants may help guide efforts to manage metabolic acidosis. We used chart abstraction, patient interviews, and laboratory testing to assess variables related to acid production (protein breakdown), alkali administration (dialysis dose, missed treatments, dialysate bicarbonate concentration, oral bicarbonate supplements), acid buffering (phosphorus binders), dilution of bicarbonate (interdialytic weight gain), and loss of bicarbonate in stool (diarrhea) for 190 randomly selected patients from 44 hemodialysis facilities. We used multivariate analyses to determine which potential determinants were independently associated with predialysis serum bicarbonate levels. Of all patients, 30% had metabolic acidosis (serum bicarbonate level <22 mEq/L). On multivariate analysis, metabolic acidosis was more likely with increased protein nitrogen appearance (odds ratio [OR] 1.60 per 0.2 g/kg/day, p=0.001) and less likely with increased Kt/V (OR 0.61 per 0.20 increase in Kt/V, p<0.001) and with increased calcium carbonate use (OR 0.38 per 2 g/day, p=0.003). Key determinants of metabolic acidosis among hemodialysis patients are protein breakdown, dialysis dose, and specific phosphorus binders. Further work is needed to develop interventions to address these determinants.

Lactic acidosis in an HIV-infected patient receiving highly active antiretroviral therapy

A 51-year-old man with HIV infection on highly active antiretroviral therapy presented with abdominal pain and exertional dyspnea. Physical examination revealed increased respiration and cachexia. Laboratory tests showed a lactic acid concentration elevated to 6.4 mM. Physical examination, blood chemistry, arterial blood gas, urine analysis, chest X-ray, and ultrasound of liver. Nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis, hepatitis and chemical pancreatitis. Proximal renal tubular acidosis with Fanconi's syndrome, secondary to treatment with tenofovir. The patient was supported on intravenous and oral bicarbonate, riboflavin and phosphorus supplementation. Highly active antiretroviral therapy was discontinued. The patient's lactate level decreased about 2 weeks after discharge.

Effect of Oral Sodium Bicarbonate Supplementation on Interdialytic Weight Gain, Plasma Sodium Concentrations and Predialysis Blood Pressure in Hemodialysis Patients

Background: Correction of metabolic acidosis in dialysis patients should be considered of paramount importance. However, consuming sodium bicarbonate tablets during the interdialytic interval to reach predialysis bicarbonate levels of 23–24 mmol/l is not widespread due to the fear of greater interdialytic weight gain and fluid overload. For this reason we investigated in a cross-sectional and in an interventional study the effect of oral sodium bicarbonate supplementation on body weight gain, plasma sodium concentrations and predialysis blood pressure in a group of stable uremic patients on regular hemodialysis (HD) treatment. Study Design: 110 patients (67 men, 43 women), mean age 67 ± 15 (range 22–89) years, on regular chronic HD treatment for 6–372 (median 48) months were studied. 70 patients were on regular oral bicarbonate supplementation for at least 4 weeks (group A), 40 patients were not on oral bicarbonate supplementation (group B). The following parameters were recorded: dry body weight (DBW), interdialytic weight gain (IWG), body mass index (BMI), plasma sodium (Na), serum pH, serum bicarbonate (sBic), K_t/V, normalized protein catabolic rate (PCRn), predialysis systolic (SBP) and diastolic (DBP) blood pressure, and bicarbonate therapy (g/day). 18 patients not on oral bicarbonate supplementation with sBic levels ≤20 mmol/l were started on oral bicarbonate therapy and were prospectively followed in the context of an interventional study of correction of chronic metabolic acidosis. The same parameters were recorded before (pre) and after (post) 4 months of oral bicarbonate supplementation. Results:Serum pH and sBic concentrations were significantly higher in patients in group A compared to patients in group B (pH 7.37 ± 0.02 group A vs. 7.33 ± 0.02 group B: p <0.001: sBic 23.8 ± 1.4 group A vs. 20.9 ± 1.4 group B: p < 0.0001). Age, DBW, BMI, IWG, SBP, DBP, Na, K_t/V and PCRn did not differ between groups. The mean daily dose of oral sodium bicarbonate administered to patients in group A was 1.9 ± 0.9 (range 1–5, median 2) g/day. Also in the 18 patients who started bicarbonate treatment, a significant increase in serum pH and sBic concentrations and a significant reduction in PCRn were observed. No significant change in DBW, IWG, SBP, DBP and Na concentrations after 4 months of treatment was found. Conclusions: Our data show that in stable uremic patients on regular HD treatment, oral daily administration of sodium bicarbonate is effective in correcting mild-moderate chronic metabolic acidosis, and does not cause increased interdialytic body weight gain, different plasma sodium concentrations and different systolic-diastolic blood pressure levels compared to patients not on oral sodium bicarbonate supplementation.

Nutritional effects of delivered bicarbonate dose in maintenance hemodialysis patients

Objective: Metabolic acidosis is common in patients with end-stage renal disease (ESRD). Studies suggest that correction of acidosis may improve nutritional status and patient outcomes. The purpose of this study was to examine the effects of increasing delivered bicarbonate dose from 35 mmol/L to 39 mmol/L with respect to nutrition-related outcomes in maintenance hemodialysis patients (MHD). Design and Setting: This was a longitudinal, observational study conducted at 4 dialysis centers in western Massachusetts. Patients were followed for 6 months after change in bicarbonate dose protocol. Patients: The study sample consisted of 248 patients who had been on MHD for at least 1 year on the standard bicarbonate dialysate of 35 mmol/L without oral bicarbonate supplements. Main Outcome Measures: Measures of interest included predialysis serum bicarbonate, albumin, hemoglobin, potassium, phosphorus, calcium, and parathyroid hormone (iPTH), as well as protein catabolic rate (nPCR). A subset of patients (n = 35) was examined for changes via Subjective Global Assessment (SGA). Results: Serum bicarbonate improved significantly from baseline (21.7 ± 2.8 mmol/L; mean ± SD) at 3 months (23.3 ± 3.3) and 6 months (23.1 ± 3.3) ( P < .0001). Phosphorus decreased from 6.0 ± 2.0 mmol/L at baseline to 5.7 ± 1.7 mmol/L ( P = .02) at 6 months, although calcium, iPTH, and potassium remained relatively stable. Serum bicarbonate was inversely and significantly correlated with nPCR at baseline ( r = −0.23; P < .05) and 3 months ( r = −0.22; P < .05). The nPCR decreased significantly ( P = .001) from baseline (0.99 ± 0.26) at 6 months (0.93 ± 0.23), whereas the serum albumin and SGA scores did not differ. Conclusion: Increasing delivered bicarbonate dose improves serum bicarbonate and may decrease catabolism. Further study is needed to confirm the potential nutritional benefits.

Bones benefit from better biochemical control in type 1 glycogen storage disease

Bones benefit from better biochemical control in type 1 glycogen storage disease

Oral bicarbonate supplementation improves amino acid-induced gluconeogenesis and ureagenesis in hepatocytes isolated from uremic rats

Oral bicarbonate supplementation improves amino acid-induced gluconeogenesis and ureagenesis in hepatocytes isolated from uremic rats