scholarly journals Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results

2021 ◽  
Vol 8 ◽  
Author(s):  
Hyo Jin Kim ◽  
Hyunjin Ryu ◽  
Eunjeong Kang ◽  
Minjung Kang ◽  
Miyeun Han ◽  
...  

Background: We aimed to evaluate serum bicarbonate as a risk factor for renal progression, cardiovascular events, and mortality in Korean CKD patients.Methods: We analyzed 1,808 participants from a Korean CKD cohort whose serum bicarbonate levels were measured at enrollment. Serum bicarbonate levels were categorized as low, lower normal, higher normal, and high (total carbon dioxide <22, 22–26, 26.1–29.9, and ≥30 mmol/L, respectively) groups. Metabolic acidosis was defined as a serum bicarbonate level <22 mmol/L. The primary outcome was renal events defined as doubling of serum creatinine, 50% reduction of eGFR from the baseline values, or development of end-stage kidney disease. The secondary outcome consisted of cardiovascular events and death. In addition, patients whose eGFR values were measured more than three times during the follow-up period were analyzed for eGFR decline. The rapid decline in eGFR was defined as lower than the median value of the eGFR slope.Results: The mean serum bicarbonate level was 25.7 ± 3.7 mmol/L and 240 (13.2%) patients had metabolic acidosis. During the follow-up period of 55.2 ± 24.1 months, 545 (30.9%) patients developed renal events and 187 (10.6%) patients developed a composite of cardiovascular events and death. After adjustment, the low serum bicarbonate group experienced 1.27 times more renal events than the lower normal bicarbonate group [hazard ratio (HR): 1.27; 95% CI: 1.01–1.60, P = 0.043]. There was no significant association between the bicarbonate groups and the composite outcome of cardiovascular events and death. The low bicarbonate group showed a significantly rapid decline in eGFR [odds ratio (OR): 2.12; 95% CI: 1.39–3.22, P < 0.001] compared to the lower normal bicarbonate group.Conclusions: Metabolic acidosis was significantly associated with increased renal events and a rapid decline in renal function in Korean predialysis CKD patients.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mirela Dobre ◽  
Neil Patel ◽  
Hima Sapa ◽  
Edward Horwitz ◽  
Michal Melamed ◽  
...  

Abstract Background and Aims Circulating cardiac biomarkers implicated in the pathogenesis of heart disease are a non-invasive platform to assess the cardiovascular disease (CVD) burden in individuals with chronic kidney disease (CKD). Galectin 3 is a 26 kDa β-galactoside-binding lectin that has a graded and positive association with CKD stages. In animal models, inhibition of galectin-3 prevents myocardial fibrosis. These pre-clinical findings have not been replicated in randomized controlled studies in humans. Metabolic acidosis of CKD has been shown to be associated with adverse CVD outcomes. We sought to examine whether correction of metabolic acidosis of CKD leads to lower circulating levels of Galectin 3, as an expression of myocardial fibrosis. Method A total of 95 participants with stages 3 and 4 CKD and a serum bicarbonate level between 21-25 mEq/L, were randomized to receive sodium bicarbonate at a dose of 0.4 mEq/kg/day once a day or placebo for two years at two clinical sites in US. Galectin 3, was measured at study baseline and after one year. Results Fifty participants were randomized to sodium bicarbonate and 45 to placebo. Mean age (SD) was 61.4 (10.2) years, 48% were women, 57% were non-Hispanic black, and 40% were non-Hispanic white, 61% had diabetes mellitus and 90% had hypertension at baseline. Mean baseline serum bicarbonate level was 23.5 (SD 1.7), mean (SD) baseline eGFR was 38.8 (11.2) ml/min/1.7m2 and mean (SD) baseline systolic BP was 130 (17) mmHg. There were no differences in baseline characteristics between treatment groups. Compared to the placebo group, participants randomized to sodium bicarbonate had statistically significant change in the levels of Galectin 3 after one year of treatment (-7.12% vs 7.76% and -1.25 vs 1.54 ng/ml, p=0.03 in the sodium bicarbonate vs. placebo group, respectively, Figure). In subgroup analyses by CKD stages, participants with stage 3A randomized to sodium bicarbonate observed the highest decrement in Galectin 3 levels (-19.2% vs 14.7%, p=0.01; -3.3% vs -4.8%, p=0.49; and -7.4% vs 29.1%, p=0.09; for CKD 3B, 3B and 4, respectively). Conclusion The level of Galectin 3 was reduced in patients with CKD 3 and 4 treated with sodium bicarbonate. This provides a framework for future therapeutic interventions aimed at reduction of myocardial fibrosis in patients with CKD and metabolic acidosis.


2019 ◽  
Vol 51 (1) ◽  
pp. 24-34 ◽  
Author(s):  
Piyawan Kittiskulnam ◽  
Somrath Srijaruneruang ◽  
Adhisabandh Chulakadabba ◽  
Nintita Sripaiboonkij Thokanit ◽  
Kearkiat Praditpornsilpa ◽  
...  

Background: Treatment of metabolic acidosis to target the higher serum bicarbonate level than guideline recommendation may downregulate muscle protein degradation and improve renal function among chronic kidney disease (CKD) patients. We conducted a study to test the effects of increased serum bicarbonate level on muscle parameters, nutrition, and renal function in pre-dialysis CKD patients. Methods: This was a randomized, controlled study. CKD stage 3–4 patients with serum HCO3– <22 mEq/L were randomized to either receive oral sodium bicarbonate with high target bicarbonate level of 25 ± 1 or standard level of 22 ± 1 mEq/L as control group using protocol-based titration of dosage adjustment. The changes of muscle mass measured by bioelectrical impedance analysis (BIA), muscle strength by hand grip dynamometer, estimated glomerular filtration rate (eGFR) using CKD-Epidemiology Collaboration equation, nutritional markers, and muscle-related biomarkers were determined. Data at baseline and after 4 months of sodium bicarbonate supplementation were compared between groups using Student t test or chi-square test as appropriate. Results: Forty-two patients completed the study (n = 21 per group). The mean age and eGFR were 61.2 ± 9.8 years and 32.4 ± 14.1 mL/min respectively. Serum bicarbonate levels at baseline were 21.0 ± 2.1 mEq/L. Baseline data including sex, diabetes, serum bicarbonate level, creatinine, and blood pressure were similar. After 4 months of treatment, the average serum bicarbonate levels in both groups were 24.0 ± 1.4 and 20.7 ± 2.3 mEq/L (p < 0.001). Both BIA-derived total-body muscle mass and appendicular lean balance were increased at 4 months in the higher bicarbonate group (26.0 ± 5.3 to 26.7 ± 5.5 kg, p = 0.04 and 19.8 ± 4.1 to 20.7 ± 4.4 kg, p = 0.06, respectively) despite comparable body weight and protein intake. Patients in the high bicarbonate group had a significant reduction of plasma myostatin levels, a surrogate of muscle degradation, at the study exit after adjusting for baseline values (–3,137.8; 95% CI –6,235.3 to –40.4 pg/mL, p= 0.04), but unaltered insulin-like growth factor-1 level, as the mediator of muscle cell growth, (141 [106–156] to 110 [87–144] ng/mL, p = 0.13) compared to the control group. Muscle strength, eGFR as well as serum prealbumin were not significantly different between 2 groups (p > 0.05). Neither worsening hypertension nor congestive heart failure was found throughout the study. Conclusion: Bicarbonate supplementation to achieve the serum level ∼24 mEq/L demonstrates better muscle mass preservation in patients with pre-dialysis CKD. The impact of alkaline therapy on renal function may require a longer period of study.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Ilter Bozaci ◽  
Ali Nazmi Can Doğan ◽  
Merve Aktar ◽  
Alev Mahşer ◽  
Gizem Yıldırım ◽  
...  

AbstractObjectivesMetabolic acidosis is a common disorder seen in course of chronic kidney disease (CKD). In this study, we aimed to investigate the association of Base excess (BE), Anion gap (AG) and Delta Ratio with progression of CKD, renal replacement therapy (RRT) requirement and mortality in patients with stage 3–5 CKD.MethodsA total of 212 patients with stage 3–5 CKD were included in this study. Patients were divided into two groups according to the baseline BE level. Patients were also grouped according to the delta ratio such as non- AG, High AG and mixed type.ResultsMean BE level was significantly lower (−4.7 ± 4.0 vs. −3.3 ± 4.3; p=0.02) in patients with CKD progression. The patients in group 1 (n: 130) (Be<−2.5) revealed more CKD progression (%53 vs. %32; p=0.002), and RRT requirement (%35 vs. %15; p=0.001). Baseline BE <−2.5 (odds ratio, 0.38; 95% CI, 0.16 to 0.91; p<0.05) and baseline GFR (odds ratio, 0.94; 95% CI, 0.90 to 0.97; p<0.001) were independently related to RRT requirement. Delta BE was independently associated with mortality (odds ratio, 0.90; 95% CI, 0.85–0.96; p<0.01).ConclusionsLow BE levels were associated with CKD progression and RRT requirement. BE change is associated with mortality during the follow-up of those patients.


2021 ◽  
Vol 6 (14) ◽  
pp. 80-88
Author(s):  
Huseyin Duru ◽  
Ekrem KARA

Objective: To evaluate the effect of 24 hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) variability (BPV) on renal progression in hypertensive patients with chronic kidney disease (CKD) Methods: A total 59 hypertensive patients (mean age: 54.2±14.6 years, 50.8% male) with CKD who underwent 24 hours ambulatory blood pressure measurement (ABPM) were included. Data on SBP, DBP, BPV coefficients (VC) for SBP (SBP-CV) and DBP (DBP-CV) were recorded. A decrease in e-GFR of <5 ml/min/year was considered as normal renal progression and a decrease in ≥5 ml/min/year was considered as rapid renal progression. Results: Overall, 40.6% of the patients had uncontrolled HT, while 45.8% had non-dipper pattern. Mean±SD daytime and night-time SBP and SBP-VC values were 135.3±17.9 mmHg, 128.6±23.0 mmHg, 11.7±2.8 and 9.5±3.6, respectively. Mean±SD daytime and nigh-time DBP and DBP-VC values were 84.5±13.4 mmHg, 77.2±16.1 mmHg, 13.8±3.8 and 12.0±3.7, respectively. Rapid renal progression was detected in 25.4% of patients with no significant difference in daytime, night-time and total SBP, SBP-VC, DBP and DBP-VC values between patients with rapid vs. natural renal progression. The regression analysis adjusted for age, gender, presence of DM, baseline e-GFR and dipping status revealed no significant impact of SBP-VC and DBP-VC in predicting rapid progression (p> 0.05). Conclusion: In conclusion, our finding revealed no significant association between BPV and renal progression in hypertensive patients with CKD. Larger scale prospective, randomized controlled trials with longer follow-up are needed to clarify this issue.


2016 ◽  
Vol 43 (5) ◽  
pp. 383-388 ◽  
Author(s):  
Lucie Bauer ◽  
Insa E. Emrich ◽  
John W. Pickering ◽  
Kathrin Untersteller ◽  
Franziska Sandermann ◽  
...  

Background: Kidney Disease Improving Global Outcomes (KDIGO) guidelines encourage clinicians to estimate 24-hour albuminuria as albumin to creatinine ratio (ACR) from spot urine samples. However, ACR underestimates 24-hour albumin excretion in muscular individuals. Equations that adjust ACR for surrogates of muscle mass to yield an estimated albumin excretion rate (eAER) were developed. We hypothesised that eAER is a better predictor of cardiovascular and renal outcomes than ACR. Methods: We determined ACR and eAER among 443 patients with chronic kidney disease G2-G4 recruited into the CARE FOR HOMe study. Patients were classified into KDIGO albuminuria categories, and followed for cardiovascular and renal events. The primary analysis was the net reclassification improvement (NRI) for those with and without events within 3 years of follow-up. Results: Eighty five patients experienced cardiovascular events during 3 years of follow-up, 13 of whom were reclassified to a more advanced albuminuria category, and 1 patient to a less advanced category by eAER compared to ACR (NRIevent: 14.1% (95% CI 5.8-22.4)). Among 358 patients without a cardiovascular event, 17 patients were reclassified to a more advanced albuminuria category, and 2 patients to a less advanced category by eAER (NRIno event: -4.2%, 95% CI -8.5 to -1.8). Sixty patients went through renal events, and 383 patients had event-free 3-year follow-up. NRIevent was 6.7% (95% CI -1.2 to 14.5), and NRIno event was -6.0% (95% CI -10.6 to 3.4) for renal events. Conclusion: Compared to ACR albuminuria categories, eAER categories are better associated with future cardiovascular events, but not with renal events.


Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 686-686
Author(s):  
Santosh L. Saraf ◽  
Maya Viner ◽  
Ariel Rischall ◽  
Binal Shah ◽  
Xu Zhang ◽  
...  

Abstract Acute kidney injury (AKI) is associated with tubulointerstitial fibrosis and nephron loss and may lead to an increased risk for subsequently developing chronic kidney disease (CKD). In adults with sickle cell anemia (SCA), high rates of CKD have been consistently observed, although the incidence and risk factors for AKI are less clear. We evaluated the incidence of AKI, defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a rise in serum creatinine by ≥0.3mg/dL within 48 hours or ≥1.5 times baseline within seven days, in 158 of 299 adult SCA patients enrolled in a longitudinal cohort from the University of Illinois at Chicago. These patients were selected based on the availability of genotyping for α-thalassemia, BCL11A rs1427407, APOL1 G1/G2, and the HMOX1 rs743811 and GT-repeat variants. Median values and interquartile range (IQR) are provided. With a median follow up time of 66 months (IQR, 51-74 months), 137 AKI events were observed in 63 (40%) SCA patients. AKI was most commonly observed in the following settings: acute chest syndrome (25%), an uncomplicated vaso-occlusive crisis (VOC)(24%), a VOC with pre-renal azotemia determined by a fractional excretion of sodium &lt;1% or BUN-to-creatinine ratio &gt;20:1 (14%), or a VOC with increased hemolysis, defined as an increase in serum LDH or indirect bilirubin level &gt;1.5 times over the baseline value at the time of enrollment (12%). Compared to individuals who did not develop AKI, SCA adults who developed an AKI event were older (AKI: median and IQR age of 35 (26-46) years, no AKI: 28 (23 - 26) years; P=0.01) and had a lower estimated glomerular filtration rate (eGFR) (AKI: median and IQR eGFR of 123 (88-150) mL/min/1.73m2, no AKI: 141 (118-154) mL/min/1.73m2; P=0.02) by the Kruskal-Wallis test at the time of enrollment. We evaluated the association of a panel of candidate gene variants with the risk of developing an AKI event. These included loci related to the degree of hemolysis (α-thalassemia, BCL11A rs1427407), to chronic kidney disease (APOL1 G1/G2 risk variants), and to heme metabolism (HMOX1) . Using a logistic regression model that adjusted for age and eGFR at the time of enrollment, the risk of an AKI event was associated with older age (10-year OR 2.6, 95%CI 1.4-4.8, P=0.002), HMOX1 rs743811 (OR 3.1, 95%CI 1.1-8.7, P=0.03), and long HMOX1 GT-repeats, defined as &gt;25 repeats (OR 2.5, 95%CI 1.01-6.1, P=0.04). Next, we assessed whether AKI is associated with a more rapid decline in eGFR and with CKD progression, defined as a 50% reduction in eGFR, on longitudinal follow up. Using a mixed effects model that adjusted for age and eGFR at the time of enrollment, the rate of eGFR decline was significantly greater in those with an AKI event (β = -0.51) vs. no AKI event (β = -0.16) (P=0.03). With a median follow up time of 66 months (IQR, 51-74 months), CKD progression was observed in 21% (13/61) of SCA patients with an AKI event versus 9% (8/88) without an AKI event. After adjusting for age and eGFR at the time of enrollment, the severity of an AKI event according to KDIGO guidelines (stage 1 if serum creatinine rises 1.5-1.9 times baseline, stage 2 if the rise is 2.0-2.9 times baseline, and stage 3 if the rise is ≥3 times baseline or ≥4.0 mg/dL or requires renal replacement therapy) was a risk factor for CKD progression (unadjusted HR 1.6, 95%CI 1.1-2.3, P=0.02; age- and eGFR-adjusted HR 1.6, 95%CI 1.1-2.5, P=0.03). In conclusion, AKI is commonly observed in adults with sickle cell anemia and is associated with increasing age and the HMOX1 GT-repeat and rs743811 polymorphisms. Furthermore, AKI may be associated with a steeper decline in kidney function and more severe AKI events may be a risk factor for subsequent CKD progression in SCA. Future studies understanding the mechanisms, consequences of AKI on long-term kidney function, and therapies to prevent AKI in SCA are warranted. Disclosures Gordeuk: Emmaus Life Sciences: Consultancy.


2017 ◽  
Vol 33 (11) ◽  
pp. e108-e113
Author(s):  
Naveen Poonai ◽  
David Mainprize ◽  
Carolyn Travers ◽  
Lilian Lee Yan Vivas ◽  
Peter Tryphonopoulos ◽  
...  

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