Abstract WP253: Cystatin C and the Risk of Cardioembolic Stroke in Patients Without Chronic Kidney Disease

Introduction: Serum lipocalin 2 serve as a marker for kidney function. Lipocalin 2 is found in both CKD and kidney injury and it rises in acute kidney injury (AKI) and in patients have faster decline in kidney function. Aims And Objectives: To nd out correlation and assess of serum Neutrophil gelatinase-associated lipocalin 2 (NGAL 2) in patients with stages 2 to 4 of Chronic Kidney disease. The aim of the study was NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD. Material And Methods: Study involved 120 patients divided in Case group (60 patients) attended medical/ urology OPD or admitted in medical/urology ward of CKD2 – CKD4 while control group – age and sex matched healthy individuals/ stage I CKD patients was taken as control. The plasma/ serum were used for serum urea, creatinine, Cystatin C and lipocalin 2 under all aseptic precaution on receiving consent. Result:The patients of CKD included in study were having glomerulonephritis (46.7%), pyelonephritis (21.7%), diabetic kidney disease (13.3%), polycystic kidney disease (1.7%) and other causes (16.7%). CKD patients demonstrated elevated serum NGAL 159.14 ± 48.73 ng/ml, together with a rise in urea 59.9 ± 17.6 mg/dL, serum creatinine 1.56 ± 0.97 mg/dL and Cystatin C 199 ± 113 ng/ml as compared to control have serum NGAL 76.31 ± 26.34 ng/ml, urea 22.3 ± 5.7 mg/dL, serum creatinine 0.75 ± 0.14 mg/dL and Cystatin C 76 ± 17 ng/ml (P value <0.05). Conclusion: Serum NGAL closely correlates with serum Cystatin C, creatinine, and eGFR, and serve as a potential early and sensitive marker of impaired kidney function/ kidney injury.

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Abstract MP08: Whole Exome Sequencing Study Identified A Novel Variant For Kidney Function And Progression Of Chronic Kidney Disease

Circulation ◽

10.1161/circ.143.suppl_1.mp08 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Changwei Li ◽

Michael Francis ◽

Adrianna Westbrook ◽

Ruiyuan Zhang ◽

Ye Shen ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Kidney Function ◽

Cystatin C ◽

Smoking Status ◽

Missense Variant ◽

Ckd Progression ◽

Whole Exome

Introduction: Most genetic variants for chronic kidney disease (CKD) have been identified in non-coding regions, with functional roles that are difficult to interpret. Hypothesis: A whole exome sequencing study focusing on coding variants will reveal novel mechanisms of kidney function and CKD. Methods: We performed whole exome sequencing analyses of cystatin C among 29,789 UK Biobank (UKB) participants with further confirmation among 4,297 white and 607 African American participants of the Health and Retirement Study (HRS). Conditional analyses for loci achieving exome-wide significance ( P <3.5х10 -7 ) were conducted in UKB using both the exome (n=29,789) and imputed GWAS data (n=295,122). Genomic findings were tested for relevance to baseline estimated glomerular filtration rate (eGFR) and stringently adjudicated CKD progression events among participants of the Chronic Renal Insufficiency Cohort (CRIC) by race and smoking status, using a base model and a full model ( Table ). Results: We identified a common missense variant, CST9 rs2983640, in a previously reported locus ( CST3 intron rs13038305), of which the minor G allele was associated with lower serum cystatin C level (UKB: beta=-0.03 mg/L, P =7.64х10 -92 ; HRS whites: beta=-0.05 mg/L, P =4.71х10 -6 ; HRS African Americans: beta=-0.03 mg/L, P =0.64; and multi-ethnic meta-analysis beta=-0.03 mg/L, P =2.46х10 -91 ). After controlling for the CST3 variant, the G allele was associated with higher cystatin C level (UKB exome: beta=0.003 mg/L, P =0.04; UKB GWAS: beta=0.003 mg/L, P =1.47х10 -10 ). Similar associations were identified in white CRIC participants (direct effect: beta=-0.05 mg/L, P =0.005; conditional effect: beta=0.004 mg/L, P =0.86). The CST9 rs2983640 G allele was associated with lower baseline eGFR (base model beta=-0.33 ml/min/1.73 m 2 , P =1.98х10 -6 ) and higher hazard of developing CKD progression independent of the reported CST3 variant ( Table ). Conclusions: We identified a novel missense variant influencing cystatin C level and CKD progression.

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Abstract MP30: Chronic Kidney Disease Progression and Risk of End-Stage Renal Disease: The Use of Change in Novel Kidney Filtration Markers

Circulation ◽

10.1161/circ.129.suppl_1.mp30 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Casey M Rebholz ◽

Kunihiro Matsushita ◽

Elizabeth Selvin ◽

Morgan E Grams ◽

Josef Coresh

Keyword(s):

Chronic Kidney Disease ◽

Clinical Trials ◽

Kidney Disease ◽

Cystatin C ◽

End Stage Renal Disease ◽

Ckd Progression ◽

Percent Change ◽

Stage Renal Disease ◽

End Stage

Introduction: Chronic kidney disease (CKD) progression assessed by estimated GFR from creatinine (eGFR-Cr) is a risk factor for cardiovascular disease and end-stage renal disease (ESRD) and has been proposed as a surrogate endpoint for clinical trials. It is unclear if CKD progression assessed by change in different filtration markers has similar risk associations with ESRD. Hypothesis: We hypothesized that percent change in novel kidney filtration markers (β 2 -microglobulin and cystatin C) over a 6-year period would be independently associated with increased risk of ESRD during 15 years of follow-up, similar to the risk seen with change in eGFR-Cr. Methods: We conducted prospective analyses of the ARIC study (N=9,703). β 2 -microglobulin, cystatin C, and creatinine were measured at study visits 1 (1990-92) and 2 (1996-98). Incident ESRD (kidney dialysis or transplant) was defined as entry into the U.S. Renal Data System registry between study visit 2 and September 30, 2011. Cox proportional hazards regression was used to estimate the association between percent change in filtration marker and incident ESRD, adjusting for demographics, kidney disease risk factors, and 1 st measurement of the filtration marker. Results: During a median follow-up of 13.1 years, there were 142 incident ESRD cases. Median eGFR-Cr was 97.3 mL/min/1.73 m 2 at 1 st measurement and 89.0 mL/min/1.73 m 2 at 2 nd measurement. Percent change in eGFR-Cr was moderately correlated with percent change in the inverse of β 2 -microglobulin (r = 0.34) and the inverse of cystatin C (r = 0.36). Progression of CKD (10-25% and >25% decline in filtration function) was associated with increased ESRD risk, with novel markers (β 2 -microglobulin, cystatin C) showing an association at least as strong as the creatinine and eGFR-Cr estimates (Table). Conclusions: CKD progression assessed using novel filtration markers is independently associated with ESRD risk, suggesting the potential utility of measuring change in β 2 -microglobulin and cystatin C in clinical trials.

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P0737THE ASSOCIATION BETWEEN CYSTATIN C AND ARTERIAL STIFFNESS IN NON-CKD PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0737 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Nejc Piko ◽

Tadej Petreski ◽

Robert Ekart ◽

Radovan Hojs ◽

Sebastjan Bevc

Keyword(s):

Diabetes Mellitus ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Myocardial Perfusion ◽

Arterial Stiffness ◽

Arterial Hypertension ◽

Cystatin C ◽

Laboratory Data ◽

Applanation Tonometry ◽

Serum Cystatin C

Abstract Background and Aims Serum cystatin C (cysC) is produced by all nucleated cells at a constant rate, is filtered freely by the glomerulus and metabolized after tubular reabsorption. It is influenced less by age, gender and muscle mass compared to serum creatinine. These properties make it an important marker in detecting renal impairment. Arterial stiffness is a hallmark of atherosclerosis and is connected to cardiovascular events and mortality. In patients with chronic kidney disease (CKD), cysC correlates with increased arterial stiffness, but less is known about the association between cysC and arterial stiffness in non-CKD patients. Method The study was performed at the University Medical Centre Maribor between October 1st 2018 and January 1st 2020. Basic demographic and laboratory data were recorded. To estimate glomerular filtration rate (eGFR), Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used. Patients with previously diagnosed CKD and/or eGFR ≤ 60 ml/min/1.73m2 at the time of admission, known malignancy, thyroid disease and/or on steroid therapy were not enrolled in the study. Arterial stiffness was measured with applanation tonometry (Sphygmocor®, Australia), carotid-femoral pulse wave velocity (cfPWV) was used as the gold standard of central arterial stiffness and subendocardial viability ratio (SEVR) was used as the marker of myocardial perfusion. SPSS® version 22 was used for statistical analysis. Results 111 patients (65.8% male, average age 64.3±9.4 years) were included in our study. Most common comorbidities were arterial hypertension (n=86, 77.5%), hyperlipidaemia (n=64, 57.7%) and diabetes mellitus (n=22, 19.8%). Mean creatinine value was 77.7±13.8 μmol/L (range 49-108 μmol/L), mean eGFR was 81.3±9.4 ml/min/1.73m2 (range 62-90 ml/min/1.73m2) and mean value of cysC was 0.94±0.18 mg/L (range 0.67-1.63 mg/L). Mean SEVR value was 165.7±36.1% (range 92-299%) and mean cfPWV value was 10.1±2.4 m/s (range 6.2-16.8 m/s). Significant correlation was found between cysC and SEVR (r=-0.316, p<0.001) and between cysC and cfPWV (r=0.472, p<0.001). Multiple regression analysis of arterial stiffness indices and cysC, age, gender, diabetes mellitus, arterial hypertension, eGFR and hyperlipidemia, showed statistically significant association between cysC and cfPWV (ß=0.220, p=0.038) and cysC and SEVR (ß=-0.278, p=0.017). Conclusion Serum cysC is independently associated with increased arterial stiffness, reduced myocardial perfusion and increased cardiovascular risk in non-CKD patients.

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Chronic Kidney Disease in Adolescents after Surgery for Congenital Heart Disease

Cardiorenal Medicine ◽

10.1159/000508177 ◽

2020 ◽

Vol 10 (5) ◽

pp. 353-361

Author(s):

Mirela Bojan ◽

Laurence Pieroni ◽

Cristian Mirabile ◽

Marc Froissart ◽

Damien Bonnet

Keyword(s):

Chronic Kidney Disease ◽

Congenital Heart Disease ◽

Heart Disease ◽

Kidney Disease ◽

Cystatin C ◽

Congenital Heart ◽

Cross Sectional Study ◽

Cross Sectional ◽

Orthostatic Proteinuria ◽

Age Range

Background: The onset of chronic kidney disease (CKD) is an important prognostic factor in young adults with congenital heart disease (CHD). Although it is likely that CKD is manifest early in CHD patients, the prevalence among adolescents is still unknown. The National Kidney Foundation’s Kidney Disease Improving Global Outcomes guidelines 2012 recommend new equations for the estimated glomerular filtration rate (eGFR) and highlight the importance of albuminuria for CKD screening. The objective of the present study was to estimate the prevalence of CKD in CHD adolescents. Methods: This observational cross-sectional study included 115 patients aged 10–18 years attending the cardiologic outpatient clinic at our institution as a follow-up after cardiac surgery in infancy related to various CHDs. CKD assessment used the CKD criteria 2012, including eGFR equations based on serum creatinine and cystatin C, and measurement of albuminuria. Results: No patient had an eGFR <60 mL min–1 1.73 m–2. However, 28.7% of all patients (95% CI 20.7–37.9) had eGFRbetween 60 and 89 mL min–1 1.73 m–2 when estimated by the bedside Schwartz creatinine-based equation,and 17.4% (95% CI 11.2–24.1) had eGFRbetween 60 and 89 mL min–1 1.73 m–2 when estimated by the Zappitelli equation, combining creatinine and cystatin C. Of all patients, 20.0% (95% CI 12.1–26.7) had orthostatic proteinuria, and none had persistent albuminuria. Conclusions: There was no evidence of CKD in the present population aged 10–18 years. The significance of an eGFR between 60 and 90 mL min–1 1.73 m–2 is not concordant for this age range and requires further investigations.

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