scholarly journals Serum Carnosinase-1 and Albuminuria Rather than the CNDP1 Genotype Correlate with Urinary Carnosinase-1 in Diabetic and Nondiabetic Patients with Chronic Kidney Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Angelica Rodriguez-Niño ◽  
Sibylle J. Hauske ◽  
Anna Herold ◽  
Jiedong Qiu ◽  
Jacob van den Born ◽  
...  

Background. Carnosinase-1 (CN-1) can be detected in 24 h urine of healthy individuals and patients with type 2 diabetes (T2DM). We aimed to assess whether urinary CN-1 is also reliably measured in spot urine and investigated its association with renal function and the albumin/creatinine ratio (ACR). We also assessed associations between the CNDP1 (CTG)n genotype and CN-1 concentrations in serum and urine. Methods. Patients with T2DM (n=85) and nondiabetic patients with chronic kidney disease (CKD) (n=26) stratified by albuminuria (ACR≤300 mg/g or ACR>300 mg/g) recruited from the nephrology clinic and healthy subjects (n=24) were studied. Results. Urinary CN-1 was more frequently detected and displayed higher concentrations in patients with ACR>300 mg/g as compared to those with ACR≤300 mg/g irrespective of the baseline disease (T2DM: 554 ng/ml [IQR 212-934 ng/ml] vs. 31 ng/ml [IQR 31-63 ng/ml] (p<0.0001) and nondiabetic CKD: 197 ng/ml [IQR 112-739] vs. 31 ng/ml [IQR 31-226 ng/ml] (p=0.015)). A positive correlation between urinary CN-1 and ACR was found (r=0.68, p<0.0001). Multivariate linear regression analysis revealed that ACR and serum CN-1 concentrations but not eGFR or the CNDP1 genotype are independent predictors of urinary CN-1, explaining 47% of variation of urinary CN-1 concentrations (R2=0.47, p<0.0001). Conclusion. These results confirm and extend previous findings on urinary CN-1 concentrations, suggesting that assessment of CN-1 in spot urine is as reliable as in 24 h urine and may indicate that urinary CN-1 in macroalbuminuric patients is primarily serum-derived and not locally produced.

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Hiraku Kameda ◽  
Kumiko Yamashita ◽  
Yoshio Kurihara

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018


Author(s):  
Augustine Onovuakpo Eguvbe ◽  
Marcellinus Uchechukwu Nwagu ◽  
Eshiotseme Sylvester Idogun ◽  
Adeyinka Abdulrasaq Akande

<p><strong>BACKGROUND</strong></p><p>Chronic kidney disease (CKD) is an increasing burden on individuals and on the healthcare system. The need to identify more sensitive and specific markers of CKD cannot be overemphasized to facilitate detection and appropriate intervention. β2 microglobulin is one of such markers of CKD. The aim of this study was to investigate the sensitivities and specificities of serum β2 microglobulin and major biochemical markers of CKD, namely creatinine and urine albumin.</p><p><strong> </strong></p><p><strong>METHODS</strong></p><p>This was a hospital-based cross-sectional study involving 124 subjects with CKD and 124 healthy controls. Participants were categorized in two groups : group 1 the CKD based on persistent reduction in GFR &lt;60 mL/min/1.73 m2 and group 2 healthy subjects as controls. Blood (serum) samples of participants were analyzed for serum creatinine and serum β2 microglobulin while their urine samples were analyzed for creatinine and albumin. Urine albumin creatinine ratio (UACR) was calculated from the results of the analyses.</p><p><strong> </strong></p><p><strong>RESULTS</strong></p><p>There was a very strong positive correlation of serum β2 microglobulin with serum creatinine (r=0.750; p=0.000) and UACR (r=0.775; p=0.000), respectively. Also, there was a very strong negative correlation between serum β2 microglobulin and eGFR (r=-0.866; p=0.000). UACR had the highest sensitivity and specificity as shown by receiver operating curve characteristics (ROC) analysis.</p><p><strong> </strong></p><p><strong>CONCLUSION</strong></p><p>In CKD, UACR and serum β2 microglobulin had the best diagnostic value. Periodic renal assessment of renal patients is mandatory as they may be affected by hidden renal dysfunction.</p>


2021 ◽  
Vol 12 ◽  
Author(s):  
QiFeng Liu ◽  
LiXia Yu ◽  
XiaoYa Yin ◽  
JianMing Ye ◽  
ShaSha Li

Background: The correlation between soluble Klotho (sKlotho) level and vascular calcification (VC) in patients with chronic kidney disease (CKD) remains controversial. Using meta-analysis, we aimed to address this controversy and assess the feasibility of applying sKlotho as a biomarker for VC.Methods: Medical electronic databases were thoroughly searched for eligible publications on the association between sKlotho level and VC in CKD patients. Effectors, including correlation coefficients (r), odds ratios (ORs), hazard ratio (HR) or β-values, and 95% confidence intervals (CIs) were extracted and combined according to study design or effector calculation method. Pooled effectors were generated using both random-effects models and fixed-effects models according to I2-value. Origin of heterogeneity was explored by sensitivity analysis and subgroup analysis.Results: Ten studies with 1,204 participants from a total of 1,199 publications were eligible and included in this meta-analysis. The combined correlation coefficient (r) was [−0.33 (−0.62, −0.04)] with significant heterogeneity (I2 = 89%, p &lt; 0.001) based on Spearman correlation analysis, and this significant association was also demonstrated in subgroups. There was no evidence of publication bias. The combined OR was [3.27 (1.70, 6.30)] with no evidence of heterogeneity (I2 = 0%, p = 0.48) when sKlotho was treated as a categorical variable or [1.05 (1.01, 1.09)] with moderate heterogeneity (I2 = 63%, p = 0.10) when sKlotho was treated as a continuous variable based on multivariate logistic regression. No significant association was observed and the pooled OR was [0.29 (0.01, 11.15)] with high heterogeneity (I2 = 96%, p &lt; 0.001) according to multivariate linear regression analysis. There was an inverse association between sKlotho and parathyroid hormone levels. The combined coefficient (r) was [−0.20 (−0.40, −0.01)] with significant heterogeneity (I2 = 86%, p &lt; 0.001), and without obvious publication bias. No significant association was found between sKlotho and calcium or phosphate levels.Conclusion: There exists a significant association between decreased sKlotho level and increased risk of VC in CKD patients. This raises the possibility of applying sKlotho as a biomarker for VC in CKD populations. Large, prospective, well-designed studies or interventional clinical trials are required to validate our findings.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Adheesh Agnihotri ◽  
Kalkidan Bishu ◽  
James Arnold ◽  
Gary Gustafson ◽  
Inder S Anand

Background : Chronic kidney disease (CKD) is a known risk factor for adverse events in patients with heart failure (HF). Whether albuminuria defined as urine albumin creatinine ratio ≥30 mg/g with or without CKD is also a risk factor for adverse events, is unclear. Methods : Data was abstracted from the electronic medical records of 442 patients admitted to the Minneapolis VA Medical Center with a primary diagnosis of HF, and an outpatient measurement of albumin creatinine ratio between September 2002 and March 2006. Multivariable Cox regression analysis was used to determine the impact of albuminuria on mortality and hospitalizations for HF at 1-year. Results : Albuminuria was seen in 54% (238/442) patients at baseline. Patients with albuminuria were more likely to have edema, higher systolic blood pressure, left ventricular hypertrophy, lower eGFR and use of beta-blockers (all p<0.05). Albuminuria correlated (p<0.05) with serum creatinine (rho=0.23), systolic blood pressure (0.37), and LVEF (0.13). The presence of albuminuria did not increase the risk of death (HR 0.65, 95% CI 0.38 –1.11), but was strongly associated with the risk of hospitalization for HF at 1-year (HR 1.77, 95% CI 1.11–2.82, p=0.017) independent of age, gender, h/o HTN, DM, CAD, PVD, COPD, CKD, atrial fibrillation, EF, use of ACE-I, spironolactone and beta-blocker. Conclusion : The presence of albuminuria is an independent prognostic marker for hospitalizations for heart failure.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Matthew Weir ◽  
George Bakris ◽  
Coleman Gross ◽  
Martha Mayo ◽  
Dahlia Garza ◽  
...  

Introduction: Elevated aldosterone (ALD) is associated with chronic kidney disease (CKD) and cardiovascular (CV) complications. Patiromer, a nonabsorbed potassium (K + )-binding polymer, decreases serum K + (sK + ) and may allow increased use of RAAS inhibitors (RAASi) in patients (pts) with CKD and hyperkalemia (HK). This analysis examined the effect of patiromer on ALD, urinary albumin/creatinine ratio (ACR), and blood pressure (BP) in pts with CKD on RAASi. Methods: OPAL-HK was a 2-part, phase 3 study in 243 CKD pts with sK + 5.1–<6.5 mEq/L on RAASi. Pts received patiromer for 4 wks (Part A); pts with moderate-severe HK at baseline (sK + ≥5.5 mEq/L) and sK + 3.8–<5.1 at Part A wk 4 continued on patiromer (n=55) or switched to placebo (n=52) in the 8-wk withdrawal phase (Part B). RAASi were stable prior to and during Part A. Changes in ALD, ACR, and systolic BP/diastolic BP (SBP/DBP) were analyzed. Results: After 4 wks of patiromer sK + , serum ALD and urine ALD/creatinine decreased, while plasma renin activity (PRA) was unchanged; SBP, DBP, and ACR also declined (Table). Mean±SE changes (ng/dL) in serum ALD from Part A wk 4 to Part B wk 4 and to Part B wk 8 were 4.6±1.6 (p<0.01) and 5.7±1.8 (p<0.01) in the placebo and 0.9±1.0 (p=NS) and 0.2±0.8 (p=NS) in the patiromer groups, respectively. Compared with Part A wk 4, SBP (mm Hg) was further reduced at Part B wk 4 (3.1±2.1, p=NS) and Part B wk 8 (5.4±1.9, p<0.01) with maintained improvement in ACR in patiromer pts. Conclusions: Patiromer reduced both sK + and ALD (independent of PRA) in CKD pts with HK on RAASi. ALD reductions correlated with lower BP and ACR. Reduction in sK + may have lowered ALD possibly improving BP and ACR.


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