scholarly journals Metabolic acidosis augments exercise pressor responses in chronic kidney disease

2019 ◽  
Vol 317 (2) ◽  
pp. R312-R318
Author(s):  
Justin D. Sprick ◽  
Doree Lynn Morison ◽  
Ida T. Fonkoue ◽  
Yunxiao Li ◽  
Dana DaCosta ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Near Infrared ◽  
Voluntary Contraction ◽  
Normal Serum ◽  
Serum Bicarbonate ◽  
Pressor Responses ◽  
Increased Risk ◽  
Muscle Mechanoreflex

Chronic kidney disease (CKD) patients experience augmented blood pressure (BP) reactivity during exercise that is associated with an increased risk of cardiovascular mortality. Exaggerated exercise pressor responses in CKD are in part mediated by augmented sympathetic nerve activation due to heightened muscle mechanoreflex. One mechanism that may lead to sensitization of the muscle mechanoreflex in CKD is metabolic acidosis. We hypothesized that CKD patients with low serum [bicarbonate] would exhibit exaggerated increases in arterial BP, greater reductions in muscle interstitial pH, and fatigue earlier during exercise compared with CKD patients with normal serum bicarbonate concentration ([bicarbonate]). Eighteen CKD participants with normal serum [bicarbonate] (≥24 mmol/l, normal-bicarb) and 9 CKD participants with mild metabolic acidosis ([bicarbonate] range 20–22 mmol/l, low-bicarb) performed rhythmic handgrip (RHG) exercise to volitional fatigue at 40% of maximal voluntary contraction. BP, heart rate, and muscle interstitial pH using near infrared spectroscopy were measured continuously. While mean arterial pressure (MAP) increased with exercise in both groups ( P ≤ 0.002), CKD with low-bicarb had an exaggerated MAP response compared with CKD with normal-bicarb (+5.9 ± 1.3 mmHg/30 s vs. +2.6 ± 0.5 mmHg/30 s, P = 0.01). The low-bicarb group reached exhaustion earlier than the normal-bicarb group (179 ± 21 vs. 279 ± 19 s, P = 0.003). There were no differences in the change in muscle interstitial pH during exercise between groups ( P = 0.31). CKD patients with metabolic acidosis have augmented exercise-induced increases in BP and poorer exercise tolerance. There was no difference in change in muscle interstitial pH between groups, however, suggesting that augmented exercise BP responses in metabolic acidosis are not due to impaired muscle-buffering capacity.

scholarly journals Metabolic acidosis is associated with pulse wave velocity in chronic kidney disease: Results from the KNOW-CKD Study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyo Jin Kim ◽  
Eunjeong Kang ◽  
Hyunjin Ryu ◽  
Miyeun Han ◽  
Kyu-Beck Lee ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Pulse Wave ◽  
Serum Bicarbonate ◽  
Data Set ◽  
Baseline Serum

Abstract 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.

P0001EFFECTS OF VEVERIMER ON SERUM BICARBONATE AND PHYSICAL FUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND METABOLIC ACIDOSIS ARE INDEPENDENT OF ALBUMINURIA: SUBGROUP ANALYSES FROM A RANDOMIZED TRIAL

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Donald E Wesson ◽  
Vandana Mathur ◽  
Navdeep Tangri ◽  
Yuri Stasiv ◽  
Dawn Parsell ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Placebo Group ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Physical Function ◽  
Dose Titration ◽  
Serum Bicarbonate ◽  
Chair Stand ◽  
Stand Test ◽  
Chair Stand Test

Abstract Background and Aims Veverimer, an investigational, novel, orally-administered, non-absorbed polymer that binds gastrointestinal hydrochloric acid and results in an increase in serum bicarbonate, is being developed as a treatment for metabolic acidosis in patients with chronic kidney disease (CKD). Metabolic acidosis is a complication of CKD that has deleterious effects on kidney function, bone (demineralization), and muscle (protein catabolism).1 Albuminuria and metabolic acidosis are independently associated with CKD progression and treatment of each may reduce the risk of kidney failure.2,3 We sought to assess (post-hoc) if albuminuria impacts the ability of veverimer to increase serum bicarbonate level and improve physical functioning. Method TRCA-301E is a multicenter, Phase 3, randomized, blinded, placebo-controlled trial in 196 patients with CKD (eGFR 20 - 40 ml/min/1.73 m2) and metabolic acidosis (serum bicarbonate 12 - 20 mEq/L) who were treated for up to 1 year with veverimer (previously TRC101) or placebo, with dose titration targeted to achieve a normal serum bicarbonate. 4 The randomization was performed in a ratio of 4:3 (veverimer:placebo). Results We previously reported4 that, compared with placebo, veverimer significantly increased serum bicarbonate and significantly improved physical function as reported on the Kidney Disease and Quality of Life-Physical Function Domain (KDQOL-PFD) (e.g., walking several blocks, climbing stairs) and as measured objectively using the 5-times repeated chair stand test with a safety profile that was similar to placebo. Baseline characteristics of the subgroups of patients by baseline urine albumin to creatinine ratio (UACR) ≤ 300 vs. &gt;300 mg/g are shown in the Table. Neither albuminuria (log UACR) as a continuous covariate nor the presence of UACR &gt; 300 mg/g had an effect on the efficacy of veverimer treatment in correction of acidosis or improvement of physical function (interaction p-values &gt;0.4). In patients with UACR &gt; 300 mg/g, at Week 52, serum bicarbonate increased by 4.1 (0.5) mEq/L on veverimer (p = 0.047 vs. placebo) and a significantly higher percentage (vs. placebo) had a ≥ 4 mEq/L increase or normalization of serum bicarbonate (59% vs. 30%, p = 0.014). Patient-reported limitations of physical function (KDQOL-PFD) improved in the veverimer vs. placebo group (+10.4 vs. +1.2 seconds, respectively, p = 0.034). Objective physical performance on the chair stand test at Week 52 also improved in the veverimer group vs. placebo (p &lt; 0.001). In patients with UACR ≤ 300 mg/g, at Week 52, serum bicarbonate increased by 5.2 (0.5) mEq/L on veverimer (p = 0.003 vs. placebo) and a numerically higher percentage (vs. placebo) had a ≥ 4 mEq/L increase or normalization of serum bicarbonate (65% vs. 45%, p = 0.063). KDQOL-PFD improved in the veverimer vs. placebo group (+12.5 vs. -2.8 seconds, respectively, p = 0.001). The chair stand test at Week 52 also improved in the veverimer group vs. placebo (p = 0.002). Conclusion The drug candidate veverimer effectively treated metabolic acidosis and improved the ability to repeatedly stand from a seated position and physical function related to daily activities independent of albuminuria, and therefore independent of the kidney injury reflected by albuminuria.

scholarly journals The very elderly followed at a nephrology center: metabolic acidosis as a predictor of progressive chronic kidney disease

2021 ◽  
Vol 35 (2) ◽  
Author(s):  
Marina Reis ◽  
◽  
Catarina Almeida ◽  
Catarina Ribeiro ◽  
Daniela Alferes ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Elderly Patients ◽  
Glomerular Filtration ◽  
Progressive Disease ◽  
Very Elderly ◽  
Increased Risk ◽  
Common Diagnosis

Chronic kidney disease is an increasingly common diagnosis in the very elderly and identifying the patients who benefit from a nephrologist’s intervention and the ones who would not might avoid wasteful or harmful interventions. The aim of this study is to identify the risk factors for progressive versus non -progressive chronic kidney disease in a population aged over 80 years old. We performed a cohort single -center retrospective study including 101 patients over 80 years old with chronic kidney disease diagnosed for at least five years and followed regularly by a nephrologist. Progressive disease was defined as glomerular filtration rate declines greater than 5 mL/min/1.73 m2/year. Of the 101 patients, 33.7% had progressive chronic kidney disease. The median glomerular filtration progression rate was 3.0 [2.1 -6.0] mL/ min/1.73m2/year. Hypertension and diabetes mellitus prevalence was similar between groups. Nephrology follow -up time was longer in the progressive group (5.0 vs 2.0 years, p=0.01). Regarding chronic kidney disease complications, 37.6% had anemia and half of these needed erythropoiesis -stimulating agents. None of the patients had hyperphosphatemia. About 18.8% presented metabolic acidosis. In multivariable analysis, after adjusting for covariables such as age, hypertension, and diabetes mellitus only the presence of metabolic acidosis (OR 0.4, CI: 0.1 -0.8) was associated with the development of progressive chronic kidney disease. Progressive chronic kidney disease group presented higher mortality (log rank 4.5, p=0.03). Ischemic cardiomyopathy (OR: 0.5, CI: 0.2 -0.9) and progressive chronic kidney disease (OR: 0.6, CI:0.3 -0.8) were associated with all -cause mortality. Our results showed that most elderly patients have non -progressive chronic kidney disease. Patients with metabolic acidosis seem to be at an increased risk for developing progressive disease. Most elderly patients die before reaching end -stage kidney disease, so it is important to look at progressive kidney disease in those patients as an important marker of comorbidity and privilege cardioprotective measures.

scholarly journals Upper Normal Serum Creatinine Concentrations as a Predictor for Chronic Kidney Disease: Analysis of 14 Years’ Korean Genome and Epidemiology Study (KoGES)

2018 ◽  
Vol 7 (11) ◽  
pp. 463 ◽  
Author(s):  
Jong Jhee ◽  
Seun Hwang ◽  
Joon Song ◽  
Seoung Lee
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Normal Serum ◽  
Epidemiology Study ◽  
Normal Range ◽  
Increased Risk ◽  
Cox Analysis

Both serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) have been used to assess kidney function in public health check-ups. However, when the sCr is within the normal levels but the eGFR is <60 mL/min/1.73 m2, a dilemma arises, as the patients might progress to chronic kidney disease (CKD) after several years. We aimed to evaluate the association between normal sCr and the risk of incident CKD in the general population. For this, 9445 subjects from the Korean Genome and Epidemiology Study, with normal sCr and eGFR of >60 mL/min/1.73 m2 were analyzed. The subjects were classified into quartiles based on sCr levels. The primary outcome was the development of eGFR <60 mL/min/1.73 m2 on two consecutive measures. During a mean follow-up of 8.4 ± 4.3 years, 779 (8.2%) subjects developed eGFR <60 mL/min/1.73 m2. The incidence of the development of eGFR <60 mL/min/1.73 m2 was higher in the higher quartiles than in the lowest quartile. In multivariable Cox analysis, the highest quartile was associated with an increased risk for the development of eGFR <60 mL/min/1.73 m2 (hazard ratio (HR), 4.71; 95% confidence interval (CI), 3.29–6.74 in females; HR, 12.77; 95% CI, 7.69–21.23 in males). In the receiver operating characteristic curve analysis, adding sCr to the traditional risk factors for CKD improved the accuracy of predicting the development of eGFR <60 mL/min/1.73 m2 (area under the curve, 0.83 vs. 0.80 in females and 0.85 vs. 0.78 in males), and the cutoff value of sCr was 0.75 mg/dL and 0.78 mg/dL in females and males. Cautious interpretation is necessary when sCr is within the normal range, considering that the upper normal range of sCr has a higher risk of CKD development.

scholarly journals Oral Sodium Bicarbonate Supplementation Does Not Affect Serum Calcification Propensity in Patients with Chronic Kidney Disease and Chronic Metabolic Acidosis

2019 ◽  
Vol 44 (2) ◽  
pp. 188-199 ◽  
Author(s):  
Christof Aigner ◽  
Daniel Cejka ◽  
Christopher Sliber ◽  
Melanie Fraunschiel ◽  
Gere Sunder-Plassmann ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Sodium Bicarbonate ◽  
Intervention Group ◽  
Study Cohort ◽  
Serum Bicarbonate ◽  
Chronic Metabolic Acidosis ◽  
The Mean ◽  
Oral Sodium

Background: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and metabolic acidosis might accelerate vascular calcification. The T50 calcification inhibition test (T50-test) is a global functional test analyzing the overall propensity of calcification in serum, and low T50-time is associated with progressive aortic stiffening and with all-cause mortality in non-dialysis CKD, dialysis, and transplant patients. Low serum bicarbonate is associated with a short T50-time and alkali supplementation could be a simple modifier of calcification propensity. The aim of this study was to investigate the short-term effect of oral sodium bicarbonate supplementation on T50-time in CKD patients. Material and Methods: The SoBic-study is an ongoing randomized-controlled trial in CKD-G3 and G4 patients with chronic metabolic acidosis (serum HCO3– ≤21 mmol/L), in which patients are randomized to either achieve serum HCO3– levels of 24 ± 1 mmol/L (intervention group) or 20 ± 1 mmol/L (rescue group). The effect of bicarbonate treatment on T50-time was assessed. Results: The study cohort consisted of 35 (14 female) patients aged 57 (±15) years, and 18 were randomized to the intervention group. The mean T50-time was 275 (± 64) min. After 4 weeks, the mean change of T50-time was 4 (±69) min in the intervention group and 18 min (±56) in the rescue group (β = –25; 95% CI: –71 to 22; p = 0.298). Moreover, change of serum bicarbonate in individual patients was not associated with change in T50-time, analyzed by regression analysis. Change of serum phosphate had a significant impact on change of T50-time (β = –145; 95% CI: –237 to –52). Conclusion: Oral sodium bicarbonate supplementation showed no effect on T50-time in acidotic CKD patients.

Stroke in chronic renal failure

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Kidney Diseases ◽  
Cerebrovascular Diseases ◽  
Lipid Lowering ◽  
Increased Risk ◽  
Intracerebral Hemorrhages

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.

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