-
1.
Current Management of Hyperkalemia in Non-Dialysis CKD: Longitudinal Study of Patients Receiving Stable Nephrology Care.
Borrelli, S, De Nicola, L, Minutolo, R, Conte, G, Chiodini, P, Cupisti, A, Santoro, D, Calabrese, V, Giannese, D, Garofalo, C, et al
Nutrients. 2021;(3)
Abstract
BACKGROUND No study has explored the limitations of current long-term management of hyperkalemia (HK) in outpatient CKD clinics. METHODS We evaluated the association between current therapeutic options and control of serum K (sK) during 12-month follow up in ND-CKD patients stratified in four groups by HK (sK ≥ 5.0 mEq/L) at baseline and month 12: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). RESULTS We studied 562 patients (age 66.2 ± 14.5 y; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m2, RAASI 76.2%). HK was "absent" in 50.7%, "resolving" in 15.6%, "new onset" in 16.6%, and "persistent" in 17.1%. Twenty-four hour urinary measurements testified adherence to nutritional recommendations in the four groups at either visit. We detected increased prescription from baseline to month 12 of bicarbonate supplements (from 5.0 to 14.1%, p < 0.0001), K-binders (from 2.0 to 7.7%, p < 0.0001), and non-K sparing diuretics (from 34.3 to 41.5%, p < 0.001); these changes were consistent across groups. Similar results were obtained when using higher sK level (≥5.5 mEq/L) to stratify patients. Mixed-effects regression analysis showed that higher sK over time was associated with eGFR < 60, diabetes, lower serum bicarbonate, lower use of non-K sparing diuretics, bicarbonate supplementation, and K-binder use. Treatment-by-time interaction showed that sK decreased in HK patients given bicarbonate (p = 0.003) and K-binders (p = 0.005). CONCLUSIONS This observational study discloses that one-third of ND-CKD patients under nephrology care remain with or develop HK during a 12-month period despite low K intake and increased use of sK-lowering drugs.
-
2.
Modulation of the Association of Hypobicarbonatemia and Incident Kidney Failure With Replacement Therapy by Venous pH: A Cohort Study.
Kajimoto, S, Sakaguchi, Y, Asahina, Y, Kaimori, JY, Isaka, Y
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(1):35-43
Abstract
RATIONALE & OBJECTIVE Studies showing an association between lower bicarbonate levels and worse kidney disease prognosis have not accounted for the influence of pH. It remains unknown whether this association is consistent across a wide range of blood pH values. This study sought to assess how pH modifies the relationship between hypobicarbonatemia and incident kidney failure requiring kidney replacement therapy (KFRT). STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 1,058 Japanese patients with estimated glomerular filtration rates<60mL/min/1.73m2. EXPOSURE Baseline venous bicarbonate levels and venous pH. OUTCOME KFRT defined as initiation of kidney replacement therapy (hemodialysis, peritoneal dialysis, and kidney transplantation). ANALYTICAL APPROACH Cox proportional hazards model assessing the interaction between baseline bicarbonate levels and venous pH on incident KFRT. RESULTS In the lowest bicarbonate quartile (≤21.5 mEq/L), 59% of patients had acidemia (pH<7.32), whereas 38% had venous pH within the normal range and 3% had alkalemia (pH>7.42). During a median follow-up of 3.0 years, 374 patients developed KFRT. Venous pH modified the association between bicarbonate level and rate of KFRT (P for interaction=0.04). After adjustment for potential confounders, including capacity for respiratory compensation, the lowest (vs the highest) bicarbonate quartile was associated with a 2.29-fold (95% CI, 1.10-4.77; P=0.03) higher rate of KFRT among patients with acidemia (pH<7.32). In contrast, among patients without acidemia (pH≥7.32), no significant association was found between bicarbonate level and KFRT. In an exploratory analysis, patients with higher respiratory compensation capacity had a lower rate of KFRT (HR per 0.1 increase in respiratory compensation capacity, 0.90; 95% CI, 0.87-0.94; P<0.001). LIMITATIONS Observational study design; blood gas measurements were performed in a select patient population. CONCLUSIONS Venous pH modified the association of hypobicarbonatemia with progression of chronic kidney disease to KFRT. Measurement of venous pH may be valuable for identifying patients with chronic kidney disease and hypobicarbonatemia and may inform treatment.
-
3.
Metabolic acidosis is associated with increased risk of adverse kidney outcomes and mortality in patients with non-dialysis dependent chronic kidney disease: an observational cohort study.
Tangri, N, Reaven, NL, Funk, SE, Ferguson, TW, Collister, D, Mathur, V
BMC nephrology. 2021;(1):185
Abstract
BACKGROUND Management of chronic kidney disease (CKD) requires the management of risk factors, such as hypertension and albuminuria, that affect CKD progression. Identification of additional modifiable risk factors is necessary to develop new treatment strategies for CKD. We sought to quantify the association of metabolic acidosis with CKD progression and mortality in a large U.S. community-based cohort. METHODS In this longitudinal, retrospective cohort study we identified non-dialysis-dependent patients with stage 3‒5 CKD from Optum's de-identified integrated electronic health records. We selected cohorts of patients with confirmed metabolic acidosis or normal serum bicarbonate levels based on 2 consecutive serum bicarbonate values: 12 to < 22 mEq/L or 22-29 mEq/L, respectively, 28‒365 days apart. The primary composite outcome was ≥ 40 % decline in estimated glomerular filtration rate (eGFR), renal replacement therapy (chronic dialysis or kidney transplant), or all-cause mortality (DD40). Secondary outcomes included each component of the composite outcome. Cox proportional hazards models were used for the DD40 outcome and secondary outcomes, while logistic regression models were used for the DD40 outcome at 2 years. RESULTS A total of 51,558 patients qualified for the study. The unadjusted 2-year incidence of adverse renal and fatal outcomes was significantly worse among patients in the metabolic acidosis group vs. those who had normal serum bicarbonate levels: 48 % vs. 17 % for DD40, 10 % vs. 4 % for ≥ 40 % decline in eGFR, 20 % vs. 6 % for renal replacement therapy, and 31 % vs. 10 % for all-cause mortality (all P < 0.001). Over a ≤ 10-year period, for each 1-mEq/L increase in serum bicarbonate, the adjusted hazard ratio for DD40 was 0.926 (95 % confidence interval [CI], 0.922-0.930; P < 0.001); over a ≤ 2-year period, the adjusted odds ratio for DD40 was 0.873 (95 % CI, 0.866-0.879; P < 0.001). CONCLUSIONS In this large community cohort of patients with stage 3‒5 CKD, the presence of metabolic acidosis was a significant, independent risk factor for the composite adverse outcome of CKD progression, renal replacement therapy, and all-cause mortality (DD40).
-
4.
Impact of the dialysate acid component on haemodialysis mortality rates.
Couchoud, C, Hannedouche, T, Bauwens, M, Ecochard, R, Lassalle, M, Frimat, L, Choukroun, G, Lobbedez, T
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(7):1244-1249
Abstract
BACKGROUND No prospective study has evaluated the long-term effect on mortality of the new acid concentrates added to bicarbonate dialysate. The aim of this pharmacoepidemiological study was to evaluate the association between hydrochloric or citric acid-based dialysate and mortality on haemodialysis (HD). METHODS This study included 117 796 patients with 3 723 887 months on HD recorded in the national French Renal Epidemiology and Information Network registry. Dialysate acid components were retrospectively reconstructed for each facility. All patients on HD were associated each month with an exposure based on that at their facility of treatment. We took each patient's time-varying exposure into account to calculate the monthly mortality rates for each exposure. Incidence rate ratios (IRRs) for mortality were calculated with a Poisson regression, with acetic acid as the reference. Regressions were adjusted for initial clinical characteristics (age, gender, previous cardiovascular events, active malignancy, diabetes, pulmonary disease, mobility), dialysis technique and location (in-centre, outpatient centre, self-care unit) and ESRD vintage, updated monthly. RESULTS The crude mortality rate per 1000 patient-months with citric acid {11.5 [95% confidence interval (CI) 11.1-12.0]} was lower than with either acetic acid [12.9 (95% CI 12.8-13.1)] or hydrochloric acid [12.8 (95% CI 12.2-13.5)]. For the 2014-17 period, the IRR for mortality with citric acid [adjusted IRR 0.94 (95% CI 0.90-0.99)] and with hydrochloric acid [adjusted IRR 0.86 (95% CI 0.79-0.94)] were significantly lower than with acetic acid. CONCLUSION This post-marketing study of long-term exposure to dialysate acidifiers at the patient level found the use of citric and hydrochloric acid-based dialysates, compared with acetic acid, was associated with lower mortality.
-
5.
Long-term effects of citric acid-based bicarbonate haemodialysis on patient outcomes: a survival propensity score-matched study in western France.
Potier, J, Dolley-Hitze, T, Hamel, D, Landru, I, Cardineau, E, Queffeulou, G, Zagdoun, E, Renaudineau, E, Molinari, N, Gamon, L, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(7):1228-1236
Abstract
BACKGROUND Citric acid-based bicarbonate haemodialysis (CIT-HD) has gained more clinical acceptance over the last few years in France and is a substitute for other acidifiers [e.g. acetic acid (CH3COOH) and hydrochloric acid (HCl)]. This trend was justified by several clinical benefits compared with CH3COOH as well as the desire to avoid the consequences of the corrosive action of HCl, but a nationwide clinical report raised concerns about the long-term safety of CIT-HD. The aim of this study was to assess the long-term effects of CIT-HD exposure on patient outcomes in western France. METHODS This is a population-based retrospective multicentre observational study performed in 1132 incident end-stage kidney disease patients in five sanitary territories in western France who started their renal replacement therapy after 1 January 2008 and followed up through 15 October 2018. Relevant data, collected prospectively with the same medical software, were anonymously aggregated for the purposes of the study. The primary goal of this study was to investigate the effects of citrate exposure on all-cause mortality. To provide a control group to CIT-HD one, propensity score matching (PSM) at 2:1 was performed in two steps: the first analysis was intended to be exploratory, comparing patients who received citrate ≤80% of the time (CIT-HD ≤80) versus those who received citrate >80% of the time (CIT-HD >80), while the second analysis was intended to be explanatory in comparing patients with 0% (CIT-HD0) versus 100% citrate time exposure (CIT-HD100). RESULTS After PSM, in the exploratory part of the analysis, 432 CIT-HD ≤80 patients were compared with 216 CIT-HD >80 patients and no difference was found for all-cause mortality using the Kaplan-Meier model (log-rank 0.97), univariate Cox regression analysis {hazard ratio [HR] 1.01 [95% confidence interval (CI) 0.71-1.40]} and multivariate Cox regression analysis [HR 1.11 (95% CI 0.76-1.61)] when adjusted for nine variables with clinical pertinence and high statistical relevance in the univariate analysis. In the explanatory part of the analysis, 316 CIT-HD0 patients were then compared with 158 CIT-HD100 patients and no difference was found using the Kaplan-Meier model (log-rank 0.06), univariate Cox regression analysis [HR 0.69 (95% CI 0.47-1.03)] and multivariate Cox regression analysis [HR 0.87 (95% CI 0.57-1.33)] when adjusted for seven variables with clinical pertinence and high statistical relevance in the univariate analysis. CONCLUSIONS Findings of this study support the notion that CIT-HD exposure ≤6 years has no significant effect on all-cause mortality in HD patients. This finding remains true for patients receiving high-volume online haemodiafiltration, a modality most frequently prescribed in this cohort.
-
6.
Longer-Period Effects of Bicarbonate/Lactate-Buffered Neutral Peritoneal Dialysis Fluid in Patients Undergoing Peritoneal Dialysis.
Hoshino, T, Kaneko, S, Minato, S, Yanai, K, Mutsuyoshi, Y, Ishii, H, Kitano, T, Shindo, M, Miyazawa, H, Aomatsu, A, et al
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2018;(6):641-648
Abstract
High concentrations of lactate are considered to contribute to impairment of the peritoneal membrane. We investigated the longer-period effects of bicarbonate/lactate-buffered neutral peritoneal dialysis fluid (PDF) in patients undergoing PD for about 2 years. Patients undergoing PD were changed from a lactate-buffered neutral PDF to a bicarbonate/lactate-buffered neutral PDF. We then investigated the patients' clinical outcomes and peritoneal membrane functions as well as the surrogate markers in the drained dialysate. Fourteen patients undergoing PD were enrolled. Peritonitis was observed in one patient. No other adverse events were observed. Peritoneal function did not change as the ultrafiltration volume decreased. Fibrin degradation products and vascular endothelial growth factor in the drained dialysate decreased while the interleukin level increased. These results suggest that bicarbonate/lactate-buffered neutral PDF may have beneficial effects in terms of peritoneal preservation and can be safely used in patients undergoing PD.
-
7.
Are low levels of serum bicarbonate associated with risk of progressing to impaired fasting glucose/diabetes? A single-centre prospective cohort study in Beijing, China.
Li, S, Wang, YY, Cui, J, Chen, DN, Li, Y, Xin, Z, Xie, RR, Cao, X, Lu, J, Yang, FY, et al
BMJ open. 2018;(7):e019145
Abstract
AIMS: Bicarbonate is involved in many human essential metabolic processes, but little is known about the association between serum bicarbonate and glucose metabolism. This study aims to investigate the association between serum bicarbonate and the risk of progressing to impaired fasting glucose (IFG)/diabetes mellitus (DM). SETTING The data were obtained from a large-scale prospective cohort study in a single health centre in Beijing. PARTICIPANTS A total of 5318 participants aged 18-70 years who underwent health examinations annually with baseline fasting plasma glucose (FPG) ranging from 3.9 to 5.5 mmol/L, without a history of either diabetes or concomitant chronic diseases, were enrolled in this 6-year observational study. PRIMARY OUTCOME MEASURES A logistic regression analysis was used to calculate ORs for progressing to IFG/DM by the category of baseline serum bicarbonate. In addition, an analysis of the receiver operating characteristic (ROC) curve for predicting IFG was performed. RESULTS Of the 5318 participants, 210 developed IFG after a median 2.2 years of follow-up. After adjusting for sex, age, FPG, body mass index, systolic blood pressure, serum creatinine, serum alanine aminotransferase and low-density lipoprotein cholesterol at baseline, the participants in the first (OR 4.18, 95% CI 2.42 to 7.21; p<0.001), second (OR 3.02, 95% CI 1.71 to 5.33; p<0.001) and third (OR 2.12, 95% CI 1.15 to 3.89; p=0.015) quartiles of serum bicarbonate had higher odds for progressing to IFG/DM compared with those in the highest quartile. The area under the ROC curve for predicting IFG/DM was 0.69 (95% CI 0.65 to 0.72; p<0.001). CONCLUSIONS Lower serum bicarbonate is associated with higher risk of the development of IFG/DM.
-
8.
The impact of high serum bicarbonate levels on mortality in hemodialysis patients.
Chang, KY, Kim, HW, Kim, WJ, Kim, YK, Kim, SH, Song, HC, Kim, YO, Jin, DC, Choi, EJ, Yang, CW, et al
The Korean journal of internal medicine. 2017;(1):109-116
Abstract
BACKGROUND/AIMS: The optimal serum bicarbonate level is controversial for patients who are undergoing hemodialysis (HD). In this study, we analyzed the impact of serum bicarbonate levels on mortality among HD patients. METHODS Prevalent HD patients were selected from the Clinical Research Center registry for End Stage Renal Disease cohort in Korea. Patients were categorized into quartiles according to their total carbon dioxide (tCO2) levels: quartile 1, a tCO2 of < 19.4 mEq/L; quartile 2, a tCO2 of 19.4 to 21.5 mEq/L; quartile 3, a tCO2 of 21.6 to 23.9 mEq/L; and quartile 4, a tCO2 of ≥ 24 mEq/L. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) and confidence interval (CI) for mortality. RESULTS We included 1,159 prevalent HD patients, with a median follow-up period of 37 months. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher in patients from quartile 4, compared to those from the other quartiles (p = 0.009, log-rank test). The multivariate Cox proportional hazard model revealed that patients from quartile 4 had significantly higher risk of mortality than those from quartile 1, 2 and 3, after adjusting for the clinical variables in model 1 (HR, 1.99; 95% CI, 1.15 to 3.45; p = 0.01) and model 2 (HR, 1.82; 95% CI, 1.03 to 3.22; p = 0.04). CONCLUSIONS Our data indicate that high serum bicarbonate levels (a tCO2 of ≥ 24 mEq/L) were associated with increased mortality among prevalent HD patients. Further effort might be necessary in finding the cause and correcting metabolic alkalosis in the chronic HD patients with high serum bicarbonate levels.
-
9.
Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.
Jung, SY, Park, JT, Kwon, YE, Kim, HW, Ryu, GW, Lee, SA, Park, S, Jhee, JH, Oh, HJ, Han, SH, et al
Medicine. 2016;(13):e3216
-
-
Free full text
-
Abstract
Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.
-
10.
Serum bicarbonate concentration and the risk of cardiovascular disease and death in type 2 diabetes: the Fremantle Diabetes Study.
Paul Chubb, SA, Davis, WA, Peters, KE, Davis, TM
Cardiovascular diabetology. 2016;(1):143
Abstract
BACKGROUND Serum bicarbonate is associated with mortality, heart failure (HF) and progression of renal failure in studies of healthy people and patients with chronic kidney disease, but the significance of these observations in unselected patients with diabetes in the general population is unknown. The aim of this study was to determine whether serum bicarbonate was associated with mortality and cardiovascular disease risk in type 2 diabetes. METHODS Baseline serum bicarbonate was available for 1283 well-characterized community-based patients (mean ± SD age 64.1 ± 11.3 years, 48.7 % males) from the longitudinal observational Fremantle Diabetes Study followed for a mean of 12 years. Associations between serum bicarbonate and mortality, coronary heart disease (CHD) and incident HF were analysed using Cox proportional hazards regression. RESULTS Serum bicarbonate was independently and negatively associated with incident CHD. For each 1 mmol/L increase in bicarbonate, the hazard ratio for CHD was 0.95 (95 % confidence interval 0.92-0.99) after adjustment for age as time scale, age at baseline, sex, English fluency, diabetes duration, loge(serum triglycerides), loge(urinary albumin: creatinine ratio), peripheral sensory neuropathy and peripheral arterial disease. There were no independent associations between serum bicarbonate and all-cause mortality [0.98 (0.95-1.004)] or incident HF [0.99 (0.95-1.03)]. CONCLUSIONS Serum bicarbonate was a significant independent predictor of incident CHD but not death or HF in community-based patients with type 2 diabetes. This supports intervention trials of bicarbonate replacement in type 2 patients at risk of CHD and who have a low serum bicarbonate concentration.