Acute Kidney Injury in CKD: Role of Metabolic Acidosis.
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ABSTRACT:
SUBMITTER: Kaufman JS
PROVIDER: S-EPMC9727512 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
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Acute Kidney Injury in CKD<b>:</b> Role of Metabolic Acidosis.
Kidney international reports 20221020 12
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Project description:IntroductionMetabolic acidosis in patients with chronic kidney disease (CKD) results from a loss of kidney function. It has been associated with CKD progression, all-cause mortality, and other adverse outcomes. We aimed to determine whether metabolic acidosis is associated with a higher risk of acute kidney injury (AKI).MethodsThis was a retrospective cohort study. Using electronic health records and administrative data, we enrolled 2 North American cohorts of patients with CKD Stages G3-G5 as follows: (i) 136,067 patients in the US electronic medical record (EMR) based cohort; and (ii) 34,957 patients in the Manitoba claims-based cohort. The primary exposure was metabolic acidosis (serum bicarbonate between 12 mEq/l and <22 mEq/l). The primary outcome was the development of AKI (defined using ICD-9 and 10 codes at hospital admission or a laboratory-based definition based on Kidney Disease: Improving Global Outcomes guidelines). We applied Cox proportional hazards regression models adjusting for relevant demographic and clinical characteristics.ResultsIn both cohorts, metabolic acidosis was associated with AKI: hazard ratio (HR) 1.57 (95% confidence interval [CI] 1.52-1.61) in the US EMR cohort, and HR 1.65 (95% CI 1.58-1.73) in the Manitoba claims cohort. The association was consistent when serum bicarbonate was treated as a continuous variable, and in multiple subgroups, and sensitivity analyses including those adjusting for albuminuria.ConclusionMetabolic acidosis is associated with a higher risk of AKI in patients with CKD. AKI should be considered as an outcome in studies of treatments for patients with metabolic acidosis.
| S-EPMC9546743 | biostudies-literature
Project description:Metabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical practice guidelines recommend maintaining serum total CO2 at ?22 mEq/L to help prevent these complications. Although a definitive trial testing whether correcting metabolic acidosis improves clinical outcomes has not been conducted, results from small, single-center studies support this notion. Furthermore, biologic plausibility supports the notion that a subset of patients with CKD have acid-mediated organ injury despite having a normal serum total CO2 and might benefit from oral alkali before overt acidosis develops. Identifying these individuals with subclinical metabolic acidosis is challenging, but recent results suggest that urinary acid excretion measurements may be helpful. The dose of alkali to provide in this setting is unknown as well. The review discusses these topics and the prevalence and risk factors of metabolic acidosis, mechanisms of acid-mediated organ injury, results from interventional studies, and potential harms of alkali therapy in CKD.
| S-EPMC5791070 | biostudies-other
Project description:BackgroundIn severe falciparum malaria metabolic acidosis and acute kidney injury (AKI) are independent predictors of a fatal outcome in all age groups. The relationship between plasma acids, urine acids and renal function was investigated in adult patients with acute falciparum malaria.MethodsPlasma and urinary acids which previously showed increased concentrations in proportion to disease severity in patients with severe falciparum malaria were quantified. Patients with uncomplicated malaria, sepsis and healthy volunteers served as comparator groups. Multiple regression and multivariate analysis were used to assess the relationship between organic acid concentrations and clinical syndromes, in particular AKI.ResultsPatients with severe malaria (n = 90), uncomplicated malaria (n = 94), non-malaria sepsis (n = 19), and healthy volunteers (n = 61) were included. Univariate analysis showed that both plasma and creatinine-adjusted urine concentrations of p-hydroxyphenyllactic acid (pHPLA) were higher in severe malaria patients with AKI (p < 0.001). Multiple regression analysis, including plasma or creatinine-adjusted urinary acids, and PfHRP2 as parasite biomass marker as independent variables, showed that pHPLA was independently associated with plasma creatinine (β = 0.827) and urine creatinine (β = 0.226). Principal component analysis, including four plasma acids and seven urinary acids separated a group of patients with AKI, which was mainly driven by pHPLA concentrations.ConclusionsBoth plasma and urine concentrations of pHPLA closely correlate with AKI in patients with severe falciparum malaria. Further studies will need to assess the potential nephrotoxic properties of pHPLA.
| S-EPMC5865348 | biostudies-literature
Project description:Rationale & objectiveMetabolic acidosis related to chronic kidney disease (CKD) is associated with an accelerated decline in glomerular filtration rate (GFR) and the development of end-stage kidney disease. Whether metabolic acidosis is associated with cardiovascular (CV) events in patients with CKD is unclear.Study designRetrospective cohort study.Setting & participantsThe Optum De-identified Electronic Health Records Dataset, 2007-2017, was used to generate a cohort of patients with non-dialysis-dependent CKD who had at least 3 estimated GFR < 60 mL/min/1.73 m2. Patients with metabolic acidosis (serum bicarbonate 12 to <22 mEq/L) or normal serum bicarbonate (22‒29 mEq/L) at baseline were identified by 2 consecutive measurements 28‒365 days apart.PredictorSerum bicarbonate as a continuous variable.OutcomePrimary outcome was a composite of major adverse cardiovascular events (MACE+). Secondary outcomes included individual components of the composite outcome.Analytical approachCox proportional hazards models to evaluate the association between 1-mEq/L increments in serum bicarbonate and MACE+.ResultsA total of 51,558 patients were evaluated, 34% had metabolic acidosis. The median follow-up period was 3.9-4.5 years, depending on the outcome assessed. The adjusted hazard ratio (HR) for MACE+ was 0.964 (95% CI, 0.961-0.968). For the individual components of incident heart failure (HF), stroke, myocardial infarction (MI), and CV death, HRs were 0.98 (95% CI, 0.97-0.98), 0.98 (95% CI, 0.97-0.99), 0.96 (95% CI, 0.96-0.97), and 0.94 (95% CI, 0.93-0.94), respectively, for every 1-mEq/L increase in serum bicarbonate.LimitationsPossible residual confounding.ConclusionsMetabolic acidosis in CKD is associated with an increased risk of MACE+ as well as the individual components of incident HF, stroke, MI, and CV death. Randomized controlled trials evaluating treatments for the correction of metabolic acidosis in CKD to prevent CV events are needed.
| S-EPMC8551483 | biostudies-literature
Project description:Fibrosis is the pathophysiological hallmark of progressive chronic kidney disease (CKD). The kidney is a highly metabolically active organ, and it has been suggested that disruption in its metabolism leads to renal fibrosis. We developed a longitudinal mouse model of acute kidney injury leading to CKD and an in vitro model of epithelial to mesenchymal transition to study changes in metabolism, inflammation, and fibrosis. Using transcriptomics, metabolic modeling, and serum metabolomics, we observed sustained fatty acid metabolic dysfunction in the mouse model from early to late stages of CKD. Increased fatty acid biosynthesis and downregulation of catabolic pathways for triglycerides and diacylglycerides were associated with a marked increase in these lipids in the serum. We therefore suggest that the kidney may be the source of the abnormal lipid profile seen in patients with CKD, which may provide insights into the association between CKD and cardiovascular disease.
| S-EPMC7843454 | biostudies-literature
Project description:Metabolic acidosis, a common complication in patients with chronic kidney disease (CKD), results in a multitude of deleterious effects. Though the restoration of kidney function following transplantation is generally accompanied by a correction of metabolic acidosis, a subset of transplant recipients remains afflicted by this ailment and its subsequent morbidities. The vulnerability of kidney allografts to metabolic acidosis can be attributed to reasons similar to pathogenesis of acidosis in non-transplant CKD, and to transplant specific causes, including donor related, recipient related, immune mediated factors, and immunosuppressive medications. Correction of metabolic acidosis in kidney transplantation either with alkali therapy or through dietary manipulations may have potential benefits and the results of such clinical trials are eagerly awaited. This review summarizes the published evidence on the pathogenesis and clinical consequences of chronic metabolic acidosis in kidney transplant recipients.
| S-EPMC9445136 | biostudies-literature
Project description:Metabolic acidosis is fairly common in patients with chronic kidney disease (CKD). The prevalence of metabolic acidosis increases with worsening kidney function and is observed in ∼40% of those with stage 4 CKD. For the past 2 decades, clinical practice guidelines have suggested treatment of metabolic acidosis to counterbalance adverse effects of metabolic acidosis on bone and muscle. Studies in animal models of CKD also demonstrated that metabolic acidosis causes kidney fibrosis. During the past decade, results from observational studies identified associations between metabolic acidosis and adverse kidney outcomes, and results from interventional studies support the hypothesis that treating metabolic acidosis with sodium bicarbonate preserves kidney function. However, convincing data from large-scale, double-blinded, placebo-controlled, randomized trials have been lacking. This review discusses findings from recent interventional trials of alkali therapy in CKD and new findings linking metabolic acidosis with cardiovascular disease in adults and CKD progression in children. Finally, a novel agent that treats metabolic acidosis in patients with CKD by binding hydrochloric acid in the gastrointestinal tract is discussed.
| S-EPMC8039421 | biostudies-literature
Project description:BackgroundThe kidney plays an important role in maintaining normal blood pH. Metabolic acidosis (MA) upregulates the pathway that mitochondria in the proximal tubule (PT) use to produce ammonia and bicarbonate from glutamine, and is associated with AKI. However, the extent to which MA causes AKI, and thus whether treating MA would be beneficial, is unclear.MethodsGavage with ammonium chloride induced acute MA. Multiphoton imaging of mitochondria (NADH/membrane potential) and transport function (dextran/albumin uptake), oxygen consumption rate (OCR) measurements in isolated tubules, histologic analysis, and electron microscopy in fixed tissue, and urinary biomarkers (KIM-1/clara cell 16) assessed tubular cell structure and function in mouse kidney cortex.ResultsMA induces an acute change in NAD redox state (toward oxidation) in PT mitochondria, without changing the mitochondrial energization state. This change is associated with a switch toward complex I activity and decreased maximal OCR, and a major alteration in normal lipid metabolism, resulting in marked lipid accumulation in PTs and the formation of large multilamellar bodies. These changes, in turn, lead to acute tubular damage and a severe defect in solute uptake. Increasing blood pH with intravenous bicarbonate substantially improves tubular function, whereas preinjection with the NAD precursor nicotinamide (NAM) is highly protective.ConclusionsMA induces AKI via changes in PT NAD and lipid metabolism, which can be reversed or prevented by treatment strategies that are viable in humans. These findings might also help to explain why MA accelerates decline in function in CKD.
| S-EPMC8054907 | biostudies-literature
Project description:Metabolic acidosis is common in chronic kidney disease (CKD) and may have various deleterious consequences. Arterial stiffness in CKD patients is associated with poor cardiovascular outcomes. The present study aimed to evaluate the association between serum bicarbonate and arterial stiffness using the baseline cross-sectional data set of a large-scale Korean CKD cohort. 2,238 CKD patients were enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. The present study was conducted on 1,659 patients included in this cohort with baseline serum bicarbonate and brachial-to-ankle pulse wave velocity (baPWV) data. Metabolic acidosis was defined as a serum bicarbonate level of <22 mmol/L, and baPWV was used as a surrogate of arterial stiffness. Mean serum bicarbonate was 25.8 ± 3.6 mmol/L. 210 (12.7%) patients had metabolic acidosis. baPWV was significantly higher in patients with metabolic acidosis (P < 0.001) and showed a significant inverse correlation with serum bicarbonate (Unstandardized β -16.0 cm/sec; 95% CI -20.5, -11.4; P < 0.001) in an unadjusted model, which was retained after adjustment (Unstandardized β -5.4 cm/sec; 95% CI -9.9, -1.0; P = 0.017). Metabolic acidosis was found to be associated with a high baPWV in pre-dialysis CKD patients.
| S-EPMC6834555 | biostudies-literature
Project description: Not available
| S-EPMC7547837 | biostudies-literature