scholarly journals Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease

2020 ◽  
Vol 9 (7) ◽  
pp. 2289 ◽  
Author(s):  
Andrea Baragetti ◽  
Alice Ossoli ◽  
Arianna Strazzella ◽  
Sara Simonelli ◽  
Ivano Baragetti ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Lecithin Cholesterol Acyltransferase ◽  
Low Hdl ◽  
Moderate Chronic Kidney Disease ◽  
Disease Stages

Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. In the present study, we test the hypothesis that reduced LCAT concentration in CKD contributes to the progression of renal damage. The study includes two cohorts of subjects selected from the PLIC study: a cohort of 164 patients with CKD (NefroPLIC cohort) and a cohort of 164 subjects selected from the PLIC participants with a basal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 (PLIC cohort). When the NefroPLIC patients were categorized according to the LCAT concentration, patients in the 1st tertile showed the highest event rate at follow-up with an event hazard ratio significantly higher compared to the 3rd LCAT tertile. Moreover, in the PLIC cohort, subjects in the 1st LCAT tertile showed a significantly faster impairment of kidney function compared to subjects in the 3rd LCAT tertile. Serum from subjects in the 1st LCAT tertile promoted a higher reactive oxygen species (ROS) production in renal cells compared to serum from subjects in the third LCAT tertile, and this effect was contrasted by pre-incubation with recombinant human LCAT (rhLCAT). The present study shows that reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population.

scholarly journals SO081LITHIUM EXPOSURE AND OCCURENCE OF CHRONIC KIDNEY DISEASE IN THE IRISH HEALTH SYSTEM: A COHORT STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mark Behan ◽  
Leonard Browne ◽  
Stack Austin
Keyword(s):  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Linear Regression ◽  
Health System ◽  
Multiple Linear Regression ◽  
Kidney Function ◽  
Ckd Progression ◽  
Duration Of Treatment

Abstract Background and Aims Lithium is implicated as a causative factor in the development and progression of chronic kidney disease (CKD). Few studies have assessed the independent impact of plasma levels and duration of lithium therapy on CKD progression. We examined the influence of lithium on CKD progression in the Irish health system. Method We utilised data from the Irish Kidney Disease Surveillance System (IKDSS) to explore associations of lithium levels and duration of exposure with kidney function in a regional cohort. A retrospective cohort study was conducted between 1999 to 2014 from the Midwest Region. All adult patients with lithium levels were identified and followed longitudinally. Kidney function was assessed at baseline and longitudinally using serum creatinine and estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI. Patients with < 2 lithium values, missing data on creatinine were excluded. The index date was the date of the first lithium blood test. Toxicity from lithium was defined as levels >1.2mmol/L as per NICE guidelines while duration of treatment was calculated based on patient –years of exposure as determined by positive blood lithium levels. Relationships between baseline kidney function, lithium levels, duration of exposure and each patients most recent eGFR value on follow up were assessed using multiple linear regression Results We identified 1,978 patients exposed to lithium from 1999-2014, mean age was 47.4 (15.6), 45.1% were men, eGFR [median (IQR)] at baseline was 84.4 (32.1) ml/min1.73m and the median duration of exposure was 3.0 years (IQR=4 years). Frequency of lithium testing increased from 1.77 in 1999 to 2.66 in 2014. In multiple linear regression, the final eGFR on follow-up was significantly lower in older patients (-0.48 ml/min/1.73m per year increase in age), P<0.001; in patients with elevated baseline lithium levels (-2.18 ml/min1.73m lower per unit increase), P<0.05, with long duration of exposure (-1.42 ml/min/1.73m lower for each year on lithium), P<0.001, and for patients with low GFR at baseline (P<0.001). Together these variables explained 58% of the variation in the final model. Conclusion Both the magnitude of and the duration of lithium exposure are both independently associated with CKD progression among lithium users in the Irish health system. Higher baseline lithium values had a more deleterious impact on kidney function. Continued efforts should be expended in minimising the risks of lithium induced nephrotoxicity through switching to alternatives and dose reduction when over possible. Funding This study is funded by the Health Research Board and the Midwest Research and Education Foundation (MKid).

scholarly journals Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hardik Ghelani ◽  
Valentina Razmovski-Naumovski ◽  
Dennis Chang ◽  
Srinivas Nammi
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acids ◽  
Kidney Disease ◽  
Free Fatty Acids ◽  
Kidney Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherogenic Index ◽  
Low Density ◽  
Cardiovascular Morbidity And Mortality

Abstract Background Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders due to the dysregulation of lipoprotein metabolism which progresses kidney disease. The objective of this study is to evaluate the protective effects of curcumin on dyslipidaemia associated with adenine-induced chronic kidney disease in rats. Methods Male SD rats (n = 29) were divided into 5 groups for 24 days: normal control (n = 5, normal diet), CKD control (n = 6, 0.75% w/w adenine-supplemented diet), CUR 50 (n = 6, 50 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), CUR 100 (n = 6, 100 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), and CUR 150 (n = 6, 150 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet). The serum and tissue lipid profile, as well as the kidney function test, were measured using commercial diagnostic kits. Results The marked rise in total cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids in serum, as well as hepatic cholesterol, triglyceride and free fatty acids of CKD control rats were significantly protected by curcumin co-treatment (at the dose of 50, 100 and 150 mg/kg). Furthermore, curcumin significantly increased the serum high-density lipoprotein (HDL) cholesterol compared to the CKD control rats but did not attenuate the CKD-induced weight retardation. Mathematical computational analysis revealed that curcumin significantly reduced indicators for the risk of atherosclerotic lesions (atherogenic index) and coronary atherogenesis (coronary risk index). In addition, curcumin improved kidney function as shown by the reduction in proteinuria and improvement in creatinine clearance. Conclusion The results provide new scientific evidence for the use of curcumin in CKD-associated dyslipidaemia and substantiates the traditional use of curcumin in preventing kidney damage.

scholarly journals P0782PROGNOSTIC IMPACT OF NECK CIRCUMFERENCE ON CARDIVASCULAR OUTCOMES AND MORTALITY IN PATIENTS WITH MODERATE CHRONIC KIDNEY DISEASE: AN ANALYSIS FROM THE GERMAN CHRONIC KIDNEY DISEASE (GCKD) STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Vladimir Cejka ◽  
Stefan Störk ◽  
Jennifer Nadal ◽  
Ulla T Schultheiß ◽  
Anna Köttgen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Event ◽  
Univariate Analysis ◽  
Neck Circumference ◽  
Upper Body ◽  
Event Risk ◽  
Caucasian Origin ◽  
Moderate Chronic Kidney Disease

Abstract Background and Aims Neck circumference (NC) is an approximator of upper body subcutaneous fat tissue and a marker of obesity. It has been shown to be associated with cardiovascular risk factors and incident chronic kidney disease (CKD). In CKD patients, the impact on cardiovascular events and all cause death has not been fully elucidated yet. The prognostic impact on these outcomes in a representative cohort of adult patients with moderate CKD of Caucasian origin was investigated here. Method We used data from the GCKD study, a German multi-centric prospective observational cohort study of 5217 adults with moderate chronic kidney disease, defined as eGFR 30–60 mL/min/1.73 m2 or eGFR >60 mL/min/1.73 m2 and significant proteinuria (albuminuria >300 mg/g creatinine or proteinuria >500 mg/g creatinine). Exclusion criteria were active malignancy, heart failure NYHA class IV, organ transplantation, and non-Caucasian origin. NC was measured repeatedly (annually, except at first year of follow-up) during the study, therefore, the mean value was analyzed. We report data from the 4-year follow-up visit regarding 1) a combined endpoint of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, and peripheral artery disease event (amputation or revascularization) and 2) all-cause death as another endpoint. Cox proportional hazard regression was used to calculate hazard ratios (HR) with 95% CIs. In univariate analysis, ordinal regression with quintiles of NC was applied. Results NC was accrued in 4453 participants and analyzed. NC overall was 40±5 cm (43±4 cm in men and 37±4 cm in women, p<0.001), mean age 60±12 years, 41% were female, 96% had hypertension, 35% were diabetic, 58% had ever smoked, eGFR was 50±18 ml/min/1.73 m (CKD-EPI), BMI 28±6 kg/m, LDL-cholesterol 119±43 mg/dl. Higher quintiles of NC were associated increased risk of the cardiovascular outcome in univariate analysis: highest (44 cm) vs. lowest (36.5 cm), HR 2.34 (1.63–3.36; p<0.001). In multivariable analysis adjusted for age, sex, and BMI, this effect was reduced but still apparent: HR 1.04 (1.01–1.08, p=0.025). Age (HR per year 1.05, 1.04–1.07, p<0.001), and female sex (HR 0.69, 0.50–0.95, p=0.023), showed also significant effects, whereas BMI did not (p=0.831). The effect of higher quintiles of NC on the risk of all-cause death in univariate analysis was even stronger: highest vs. lowest, HR 3.2 (1.72–5.81, p=0.006). However, after adjustment this effect was abolished: HR 0.99 (0.95–1.04; p=0.85). Only age (HR 1.07, 1.04–1.09, p<0.001), and female sex (HR 0.45, 0.27-0.74, p=0.002), remained significant predictors of all-cause death in this model. Conclusion In patients with chronic kidney disease, we found higher NC to be associated with increased cardiovascular event risk, but not all-cause death, after adjustment for age, sex and BMI. The risk of cardiovascular outcomes and overall mortality was consistently lower in women. Our analysis supports evidence, that upper body subcutaneous adipose tissue might be an independent contributor to cardiovascular event risk.

scholarly journals Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study

2020 ◽  
Author(s):  
Ulla T Schultheiss ◽  
Inga Steinbrenner ◽  
Matthias Nauck ◽  
Markus P Schneider ◽  
Fruzsina Kotsis ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Thyroid Function ◽  
Positive Association ◽  
Inverse Association ◽  
All Cause Mortality ◽  
Disease Study ◽  
Reduced Kidney Function

Abstract Background Hypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function. Methods Thyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04 years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status. Results Cross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (Nevents = 297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65–0.82; Nevents = 615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint. Conclusions Patients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.

scholarly journals Associations between urinary cysteine-rich protein 61 excretion and kidney function decline in outpatients with chronic kidney disease: a prospective cohort study in Taiwan

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e051165
Author(s):  
Chun-Fu Lai ◽  
Jian-Jhong Wang ◽  
Ya-Chun Tu ◽  
Chia-Yu Hsu ◽  
Hon-Yen Wu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Kidney Function ◽  
Creatinine Ratio ◽  
Discriminative Performance ◽  
Cysteine Rich Protein ◽  
Kidney Function Decline ◽  
Egfr Decline

ObjectivesTo examine whether urinary excretion of cysteine-rich protein 61 (Cyr61), an acknowledged proinflammatory factor in kidney pathologies, increases in chronic kidney disease (CKD) and is associated with subsequent rapid kidney function decline.DesignAn observational cohort study.SettingIn the nephrology outpatient clinics of a tertiary hospital in Taiwan.ParticipantsWe enrolled 138 adult CKD outpatients (n=12, 32, 18, 18, 29 and 29 in stages 1, 2, 3a, 3b, 4 and 5 CKD, respectively) between February and October 2014 and followed them for 1 year. Their mean age was 60.46±13.16 years, and 51 (37%) of them were women.Primary outcome measuresUrinary Cyr61 levels were measured by ELISA. Rapid kidney function decline was defined as an estimated glomerular filtration rate (eGFR) decline rate ≥ 4 mL/min/1.73 m2/year or developing end-stage renal disease during subsequent 3-month or 1-year follow-up period. Models were adjusted for demographic and clinical variables.ResultsThe urine Cyr61-to-creatinine ratio (UCyr61CR) increased significantly in patients with stage 4 or 5 CKD. Multivariable linear regression analysis showed that log(UCyr61CR) was positively correlated with log(urine protein-to-creatinine ratio) (p<0.001) but negatively correlated with baseline eGFR (p<0.001) and hypertension (p=0.007). Complete serum creatinine data during the follow-up were available for 112 patients (81.2%). Among them, multivariable logistic regression identified log(UCyr61CR) was independently associated with rapid kidney function decline (adjusted OR 2.29, 95% CI 1.27 to 4.15) during the subsequent 3 months. UCyr61CR improved the discriminative performance of clinical models to predict 3-month rapid kidney function decline. In contrast, log(UCyr61CR) was not associated with rapid eGFR decline during the entire 1-year follow-up.ConclusionsElevated urinary Cyr61 excretion is associated with rapid short-term kidney function deterioration in patients with CKD. Measuring urinary Cyr61 excretion is clinically valuable for monitoring disease trajectory and may guide treatment planning.

scholarly journals Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database

2021 ◽  
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Kidney Function ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Glucose Lowering ◽  
Glucose Transporter 2 ◽  
Egfr Decline

<b>Objective: </b>Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. <p><b>Research Design and Methods: </b>Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. </p> <p><b>Results: </b>At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (p<sub>heterogeneity</sub> ≥0.35). </p> <p><b>Conclusions: </b>The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.</p>

scholarly journals Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database

2021 ◽  
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Kidney Function ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Glucose Lowering ◽  
Glucose Transporter 2 ◽  
Egfr Decline

<b>Objective: </b>Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. <p><b>Research Design and Methods: </b>Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. </p> <p><b>Results: </b>At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (p<sub>heterogeneity</sub> ≥0.35). </p> <p><b>Conclusions: </b>The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.</p>

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