scholarly journals Interaction of Serum Alkaline Phosphatase and Folic Acid Treatment on Chronic Kidney Disease Progression in Treated Hypertensive Adults

2022 ◽  
Vol 12 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Panpan He ◽  
Guobao Wang ◽  
Min Liang ◽  
Di Xie ◽  
...  

The relation of alkaline phosphatase (ALP) with chronic kidney disease (CKD) is still uncertain. We aimed to examine the prospective association between serum ALP and CKD progression, and the modifying effect of serum ALP on folic acid in preventing CKD progression in treated hypertensive patients. This is a post-hoc analysis of 12,734 hypertensive adults with relevant measurements and without liver disease at baseline from the renal sub-study of the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid, or 10 mg enalapril alone. The primary outcome was CKD progression, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of <60 ml/min/1.73 m2 if baseline eGFR was ≥60 ml/min/1.73 m2; or a decrease in eGFR of ≥50% if baseline eGFR was <60 ml/min/1.73 m2; or end-stage renal disease. Over a median of 4.4 years, in the enalapril only group, participants with baseline serum ALP≥110IU/L (quartile 4) had a significantly higher risk of CKD progression (3.4% vs 2.3%; adjusted OR,1.61; 95%CI:1.11, 2.32), compared with those with ALP<110IU/L. For those with enalapril and folic acid treatment, compared with the enalapril only treatment, the risk of CKD progression was reduced from 3.4 to 2.1% (adjusted OR, 0.53; 95%CI:0.34, 0.83) among participants with baseline ALP≥110IU/L, whereas there was no significant effect among those with ALP<110IU/L. In hypertensive patients, higher serum ALP was associated with increased risk of CKD progression, and this risk was reduced by 47% with folic acid treatment.

Author(s):  
Simon Correa ◽  
Xavier E. Guerra-Torres ◽  
Sushrut S. Waikar ◽  
Finnian R. Mc Causland

Magnesium is involved in the regulation of blood pressure (BP). Abnormalities in serum magnesium are common in chronic kidney disease (CKD), yet its association with the development of hypertension and CKD progression in patients with CKD is unclear. We analyzed data from 3866 participants from the CRIC Study (Chronic Renal Insufficiency Cohort). Linear regression assessed the association of serum magnesium with baseline systolic BP (SBP) and diastolic BP (DBP). Logistic regression explored the association of serum magnesium with various definitions of hypertension. Cox proportional hazards models explored assessed the risk of incident hypertension and CKD progression. Mean serum magnesium was 2.0 mEq/L (±0.3 mEq/L). Higher magnesium was associated with lower SBP (−3.4 mm Hg [95% CI, −5.8 to −1.0 per 1 mEq/L]) and lower DBP (−2.9 mm Hg [95% CI, −4.3 to −1.5 per 1 mEq/L]). Higher magnesium was associated with a lower risk of American Heart Association–defined hypertension (SBP≥130 mm Hg or DBP≥80 mm Hg) at baseline (adjusted hazard ratio, 0.65 [95% CI, 0.49–0.86 per 1 mEq/L]), a lower risk of suboptimally controlled BP (SBP≥120 mm Hg or DBP≥80 mm Hg; adjusted odds ratio, 0.58 [95% CI, 0.43–0.78 per 1 mEq/L]). In time-to-event analyses, higher baseline serum magnesium was associated with a nominally lower risk of incident CRIC-defined hypertension (adjusted hazard ratio, 0.77 [95% CI, 0.46–1.31 per 1 mEq/L]). Higher magnesium was associated with a significantly lower risk of CKD progression (adjusted hazard ratio, 0.68 [95% CI, 0.54–0.86 per 1 mEq/L]). In patients with CKD, higher serum magnesium is associated with lower SBP and DBP, and with a lower risk of hypertension and CKD progression. In patients with CKD, whether magnesium supplementation could optimize BP control and prevent disease progression deserves further investigation.


2020 ◽  
Author(s):  
Luciana Saraiva da Silva ◽  
Tiago Ricardo Moreira ◽  
Rodrigo Gomes da Silva ◽  
Rosângela Minardi Mitre Cotta

Abstract Background Recent studies suggest that the progression of chronic kidney disease (CKD) is not linear, but we do not have clear evidence on this issue, especially in hypertensive patients. We sought to evaluate the progression of CKD and associated factors over four years in a cohort of hypertensive patients. Methods We conducted a prospective cohort study during the years 2012 and 2016, with hypertensive patients diagnosed with CKD (n = 113). The progression of CKD was assessed through the evolution of the glomerular filtration rate (GFR) and the change in the stage of CKD between 2012 and 2016. Sociodemographic, economic, lifestyle, clinical, anthropometric, and biochemical variables were evaluated. The strength of the association between CKD progression and explanatory variables was assessed by odds ratio (OR) and their respective 95% confidence intervals using univariate and multivariate logistic regression. Results Regarding progression, 78.1% of the CKD patients did not progress over four years. When assessing the CKD trajectory (2012–2016) through the evolution of GFR, there was a mean reduction of 1.3 mL/min/1.73m² in four years. In the group that progressed, there was a reduction of 13 mL/min/1.73m², while in the group that did not progress, there was an increase of 2 mL/min/1.73m². In the multivariate analyses, age (p = 0.047), diabetes mellitus (DM) (p = 0.042), and urea (p = 0.050) were independently associated with CKD progression. Conclusions The findings of the present study showed a non-linear progression of CKD over the four years, contrary to what is traditionally expected. Age, DM and urea were independently associated with CKD progression.


Author(s):  
Sahir Kalim ◽  
Anders Berg ◽  
S Ananth Karumanchi ◽  
Ravi Thadhani ◽  
Andrew S Allegretti ◽  
...  

Abstract Background Protein carbamylation is a posttranslational protein modification caused, in part, by exposure to urea’s dissociation product cyanate. Carbamylation is linked to cardiovascular outcomes and mortality in dialysis dependent end stage kidney disease (ESKD), but its effects in earlier pre-dialysis stages of chronic kidney disease (CKD) are not established. Methods We conducted two nested case-control studies within the CRIC Study. First, we matched 75 cases demonstrating CKD progression (50% eGFR reduction or reaching ESKD) to 75 controls (matched on baseline eGFR, 24-hour proteinuria, age, sex, and race). In the second study, we similarly matched 75 subjects who died during follow up (cases) to 75 surviving controls. Baseline carbamylated albumin levels (C-Alb, a validated carbamylation assay) were compared between cases and controls in each study. Results At baseline, in the CKD progression study, other than blood urea nitrogen (BUN) and smoking status, there were no significant differences in any matched or other parameter. In the mortality group, the only baseline difference was smoking status. Adjusting for baseline differences, the top tertile of C-Alb was associated with an increased risk of CKD progression (odds ratio [OR], 7.9; 95% CI, 1.9-32.8; P = 0.004) and mortality (OR 3.4; 95% CI, 1.0-11.4; P = 0.05) when compared to the bottom tertile. C-Alb correlated with eGFR but was more strongly correlated with BUN. Conclusions Our data suggest protein carbamylation is a predictor of CKD progression, beyond traditional risks including eGFR and proteinuria. Carbamylation’s association with mortality was smaller in this limited sample size.


2016 ◽  
Vol 64 (4) ◽  
pp. 861-866 ◽  
Author(s):  
Nuri Fidan ◽  
Ayca Inci ◽  
Melahat Coban ◽  
Cevval Ulman ◽  
Seyhun Kursat

The aim of the study was to evaluate the usefulness of serum bone turnover markers (BTM) and bone mineral density (BMD) determined by dual-energy X-ray absorptiometry (DEXA) in predialysis patients with chronic kidney disease (CKD). We enrolled 83 patients with CKD, 41 (49.4%) males, 42 (50.6%) females, with mean estimated glomerular filtration rate (eGFR) 23.90±12 (range=6.0–56.0). BMD of the lumbar spine (LS) (anteroposterior, L2 through L4), femoral neck (FN) and femoral trochanter (FT) were measured by DEXA. Biochemical BTM, including calcium (Ca), phosphorus (P), intact parathyroid hormone (PTH), serum specific alkaline phosphatase (serum AP), bone-specific AP (BSAP), plasma bicarbonate and 25-hydroxy-vitamin D (25hD) were used for the prediction of BMD loss. T score results of LS and FN were worse than FT. BMD levels were lower in females than in males (all p<0.05). According to different BMD T score levels, patients with age ≥65 years and patients in menopause were significantly more osteopenic (p=0.026) and there was no relation between different BMD T scores and presence of diabetes (p=0.654). A positive correlation was identified between the BMD of FN T-Z scores (r=0.270, p=0.029, r=0.306, p=0.012), FT T-Z scores (r=0.220, p=0.076, r:0.250, p=0.043) and serum HCO3, while the correlation with serum alkaline phosphatase (AP) and BSAP was considered to be negative. No statistically significant association was found between BMD of all the measured skeletal sites and eGFR. Loss of BMD was identified mostly in females over ≥65 years of age and after menopause. Higher serum levels of BSAP and AP can be determined in the advanced stages of renal failure and they reflect fracture risk of the femur, but not spine. Measurements of BMD by DEXA are useful to demonstrate bone loss, but not technical enough to distinguish the quantity of bone loss between different stages of CKD.


2019 ◽  
Vol 65 (11) ◽  
pp. 1448-1457 ◽  
Author(s):  
Nisha Bansal ◽  
Leila Zelnick ◽  
Michael G Shlipak ◽  
Amanda Anderson ◽  
Robert Christenson ◽  
...  

Abstract BACKGROUND Increases in cardiac and stress biomarkers may be associated with loss of kidney function through shared mechanisms involving cardiac and kidney injury. We evaluated the associations of cardiac and stress biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), soluble ST-2 (sST-2)] with progression of chronic kidney disease (CKD). METHODS We included 3664 participants with CKD from the Chronic Renal Insufficiency Cohort study. All biomarkers were measured at entry. The primary outcome was CKD progression, defined as progression to end-stage renal disease (ESRD) or 50% decline in estimated glomerular filtration rate (eGFR). Cox models tested the association of each biomarker with CKD progression, adjusting for demographics, site, diabetes, cardiovascular disease, eGFR, urine proteinuria, blood pressure, body mass index, cholesterol, medication use, and mineral metabolism. RESULTS There were 1221 participants who had CKD progression over a median (interquartile range) follow-up of 5.8 (2.4–8.6) years. GDF-15, but not sST2, was significantly associated with an increased risk of CKD progression [hazard ratios (HRs) are per SD increase in log-transformed biomarker]: GDF-15 (HR, 1.50; 95% CI, 1.35–1.67) and sST2 (HR, 1.07; 95% CI, 0.99–1.14). NT-proBNP and hsTnT were also associated with increased risk of CKD progression, but weaker than GDF-15: NT-proBNP (HR, 1.24; 95% CI, 1.13–1.36) and hsTnT (HR, 1.11; 95% CI, 1.01–1.22). CONCLUSIONS Increases in GDF-15, NT-proBNP, and hsTnT are associated with greater risk for CKD progression. These biomarkers may inform mechanisms underlying kidney injury.


2021 ◽  
Vol 22 ◽  
Author(s):  
Andressa Keiko Matsumoto ◽  
Ana Paula Michelin ◽  
Laura de Oliveira Semeão ◽  
Walter Sepúlveda-Loyolaa ◽  
João Victor de Lima Pedrão ◽  
...  

Background: Increased generation of reactive oxygen and nitrogen species in chronic kidney disease (CKD) patients leads to increased oxidative stress. The antioxidant capacity of folic acid has been shown to scavenge radicals efficiently. Objective: The current study was carried out to examine the effects of folic acid treatment on biochemical and oxidative stress biomarkers in patients in different stages of CKD. Methods: This was a randomized, non-blinded, clinical trial that assessed the effects of 3 months of treatment with 5 mg of folic acid daily or no treatment in 113 outpatients within CKD stages 3a and 3b. At the end of the intervention, we analyzed the data of 66 patients treated with folic acid and 47 in the control group. Serum homocysteine levels and biochemical and oxidative/nitrosative stress biomarkers were analyzed in all patients. Results: In most patients, folic acid treatment normalized homocysteine levels and increased antioxidant enzyme activity (paraoxonase 1) and decreased sulfhydryl (SH) groups. In addition, oxidative biomarkers (products of nitric oxide and lipid hydroperoxide) were significantly lower post-treatment compared to baseline in the active intervention group. In the no active intervention group, no statistically significant effects were found on the oxidative and biochemical biomarkers. Conclusion: Folic acid treatment in stages 3a-4 CKD patients effectively ameliorated their hyperhomocysteinemia and increased the activity of antioxidant enzymes, as well as decreased the levels of pro-oxidant biomarkers in stage G3a and G3b CKD patients. Folic acid treatment attenuated oxidative/nitrosative stress and may be considered as a possible strategy to improve redox status and diminish the damages associated with oxidative/nitrosative stress in CKD patients. Further studies are needed to confirm these findings.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Daisuke Mori ◽  
Shinjiro Tamai ◽  
Maho Tokuchi ◽  
Natsumi Inoue ◽  
Hideaki Kawai ◽  
...  

Abstract Background and Aims Plasma potassium levels are impacted by decreased kidney function and are known to be associated with increased mortality, adverse cardiovascular events and adverse kidney events. However, the prognostic implication of urinary potassium is unclear. Method We conducted an observational study of 1102 patients with chronic kidney disease (CKD) who were hospitalized between 2010 and 2018. The expected primary outcomes were all-cause mortality, adverse cardiovascular events and CKD progression. CKD progression was defined as a 30% increase in serum creatinine, the initiation of maintenance dialysis or the need for kidney transplantation. The Cox proportional hazards model was used to analyse the association between urinary potassium excretion and adverse clinical outcomes after adjustment for potential confounders. Results At baseline, 66% of the patients were men, with a median age of 72 years (interquartile range or IQR, 64–79 years); 61% of the patients were diabetic, and 54% of them were hypertensive. The median values for estimated glomerular filtration rate (eGFR) was 12 mL/min/1.73m2 (IQR, 8–18), serum potassium 4.5 mmol/L (IQR, 4.1–5.1) and urinary potassium/creatinine ratio (UK/Cr) 27 mmol/gCr (IQR, 20–38). Over a median follow-up period of 2.6 years (IQR 0.2–4.5), the number of all-cause deaths was 87. There were 171 cases of cardiovascular events and 860 cases of CKD progression. After adjusting for the eGFR, serum potassium level, proteinuria, renin–angiotensin system inhibitors, diuretics and other potential confounders, UK/Cr was found to be neither significantly associated with all-cause mortality nor with adverse cardiovascular events. However, a low UK/Cr was associated with an increased risk of CKD progression (adjusted hazard ratio [95% confidence interval] for the first, second and third quartiles, compared with the fourth quartile, were as follows: 2.09 [1.43-3.06], 1.33 [0.96-1.86] and 1.05 [0.75-1.46]) Conclusion A low UK/Cr might be an independent risk factor for poor renal outcome.


Author(s):  
Sangmi Lee ◽  
Shinchan Kang ◽  
Young Su Joo ◽  
Changhyun Lee ◽  
Ki Heon Nam ◽  
...  

Abstract Introduction In patients with chronic kidney disease (CKD), studies investigating the association between smoking and deterioration of kidney function are scarce. Aims and Methods We analyzed data for 1,951 patients with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. Patients were categorized by smoking load. Primary outcome was a composite of a ≥50% reduction in eGFR, initiation of dialysis, or kidney transplantation. Results There were 967 never-smokers and 369, 276, and 339 smokers who smoked &lt;15, 15 to 29, ≥30 pack-years, respectively. During a mean follow-up of 3.0 years, the incidence rates (95% confidence interval [CI]) of the primary outcome were 54.3 (46.4–63.5), 46.9 (35.9–61.4), 69.2 (52.9–90.6), and 76.3 (60.7–96.0) events per 1,000 person-yr in never-, &lt;15, 15 to 29, and ≥30 pack-year smokers. In cause-specific hazard model after adjustment of confounding factors, smokers were associated with 1.09 (0.73–1.63), 1.48 (1.00–2.18), and 1.94 (1.35–2.77) fold increased risk (95% CI) of primary outcome in &lt;15, 15–29, and ≥30 pack-year smokers compared with never-smokers. The association of longer smoking duration with higher risk of CKD progression was evident particularly in patients with eGFR &lt; 45 mL/min/1.73 m2 and proteinuria ≥ 1.0 g/g. In contrast, the risk of adverse kidney outcome decreased with longer smoking-free periods among former-smokers. Conclusions These findings suggest potentially harmful effects of the degree of exposure to smoking on the progression of CKD. Implications Among patients with CKD, there has been lack of studies on the association between smoking and CKD progression and studies to date have yielded conflicting results. In this prospective cohort study involving Korean CKD patients, smoking was associated with significantly higher risk of worsening kidney function. Furthermore, the risk of adverse kidney outcome was incrementally higher as smoking pack-years were higher. As the duration of smoking cessation increased, the hazard ratios for adverse kidney outcome were attenuated, suggesting that quitting smoking may be a modifiable factor to delay CKD progression.


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