Dataset Information

Serum Cystatin C as an Indicator of Renal Function and Mortality in Liver Transplant Recipients.

ABSTRACT:

Background/aims

Chronic kidney disease (CKD) is an important comorbidity after liver transplantation (LT); however, reliable tools with which to evaluate these patients are limited. In this work, we examine the extent to which the addition of serum cystatin C improves glomerular filtration rate (GFR) estimation and mortality prediction, in comparison to various GFR-estimating equations.

Methods

The GFR was measured in LT recipients by iothalamate clearance. Concurrent serum cystatin C was assayed in banked serum samples. Performance of GFR-estimating equations with and without cystatin C, including the modification of diet in renal disease and CKD-epidemiology collaboration formulas was assessed. The proportional hazards regression analysis was performed to determine the association between serum cystatin C and mortality.

Results

A total of 586 iothalamate results were obtained in 401 patients after a mean of 4 years after LT. When compared to measured GFR, the formula with both creatinine and cystatin C, namely, CKD-epidemiology cr-cys, outperformed those with either marker alone. Performance of creatinine-based models was similar to one another. Serum cystatin C, by itself or as a part of an estimated GFR, was a significant predictor of mortality.

Conclusions

Serum cystatin C has an important role in enhancing accuracy of GFR estimation and predicting mortality in LT recipients.

SUBMITTER: Allen AM

PROVIDER: S-EPMC4551433 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

Serum Cystatin C as an Indicator of Renal Function and Mortality in Liver Transplant Recipients.

Allen Alina M AM Kim W Ray WR Larson Joseph J JJ Colby Colin C Therneau Terry M TM Rule Andrew D AD

Transplantation 20150701 7

<h4>Background/aims</h4>Chronic kidney disease (CKD) is an important comorbidity after liver transplantation (LT); however, reliable tools with which to evaluate these patients are limited. In this work, we examine the extent to which the addition of serum cystatin C improves glomerular filtration rate (GFR) estimation and mortality prediction, in comparison to various GFR-estimating equations.<h4>Methods</h4>The GFR was measured in LT recipients by iothalamate clearance. Concurrent serum cystat ...[more]

PMID: 25654627

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Project description:Serum cystatin C is a well-established marker of renal function and a valuable predictor of health risks and mortality. DNA methylation-predicted cystatin C (DNAmCystatinC), an advanced epigenetic biomarker, serves as a proxy for serum cystatin C levels. However, the relationships between serum cystatin C, DNAmCystatinC, renal function, and mortality outcomes have not been previously examined. This study aimed to examine the associations between serum cystatin C, DNAmCystatinC, renal function, and their joint and independent relationships with mortality in U.S. adults. We analyzed data from 1642 participants aged 50 and older from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, linked to mortality information from the National Center for Health Statistics (NCHS), with follow-up through 2019. Our analysis demonstrated a positive association between ln-DNAmCystatinC and ln-serum cystatin C (Adjusted β (SE) = 0.773 (0.267), p = 0.007), while ln-DNAmCystatinC was negatively correlated with ln-Estimated glomerular filtration rate, calculated using both creatinine and cystatin C (eGFRcr-cys) (Adjusted β (SE) = -1.123 (0.449), p = 0.018). In a weighted Cox regression model, a one-unit increase in ln-serum cystatin C was linked to an increased hazard ratio (HR) of 2.87 (95% CI: 1.938-4.26, p < 0.001) for all-cause mortality and 3.04 (95% CI: 1.34-6.88, p = 0.010) for cardiovascular mortality. Additionally, a one-unit increase in ln-DNAmCystatinC was associated with an HR of 135.86 (95% CI: 5.51-3349.69, p = 0.004) for all-cause mortality. This association was particularly pronounced in participants without chronic kidney disease (CKD), with a p-value for the interaction between DNAmCystatinC and CKD on all-cause mortality of 0.002. Furthermore, individuals with serum cystatin C and DNAmCystatinC levels above the 50th percentile showed the highest all-cause mortality risk when compared to other subgroups. In conclusion, our findings demonstrate that DNAmCystatinC is a stronger predictor of all-cause mortality than serum cystatin C, with potential additive effects when both biomarkers are considered together. These results suggest their utility as valuable clinical indicators for risk stratification and early intervention. Future research should validate these findings and further explore the clinical and public health implications of epigenetic biomarkers.

Project description:BackgroundChronic renal insufficiency, diagnosed using creatinine based estimated glomerular filtration rate (GFR) or microalbumiuria, has been associated with the presence of cerebral microbleeds (CMBs). Cystatin C has been shown to be a more sensitive renal indicator than conventional renal markers. Under the assumption that similar pathologic mechanisms of the small vessel exist in the brain and kidney, we hypothesized that the levels of cystatin C may delineate the relationship between CMBs and renal insufficiency by detecting subclinical kidney dysfunction, which may be underestimated by other indicators, and thus reflect the severity of CMBs more accurately.MethodsData was prospectively collected for 683 patients with ischemic stroke. The severity of CMBs was categorized by the number of lesions. Patients were divided into quartiles of cystatin C, estimated GFR and microalbumin/creatinine ratios. Ordinal logistic regression analysis was used to examine the association of each renal indicator with CMBs.ResultsIn models including both quartiles of cystatin C and estimated GFR, only cystatin C quartiles were significant (the highest vs. the lowest, adjusted OR, 1.88; 95% CI 1.05-3.38; p = 0.03) in contrast to estimated GFR (the highest vs. the lowest, adjusted OR, 1.28; 95% CI 0.38-4.36; p = 0.70). A model including both quartiles of cystatin C and microalbumin/creatinine ratio also showed that only cystatin C quartiles was associated with CMBs (the highest vs. the lowest, adjusted OR, 2.06; 95% CI 1.07-3.94; p = 0.03). These associations were also observed in the logistic models using log transformed-cystatin C, albumin/creatinine ratio and estimated GFR as continuous variables. Cystatin C was a significant indicator of deep or infratenorial CMBs, but not strictly lobar CMBs. In addition, cystatin C showed the greatest significance in c-statistics for the presence of CMBs (AUC = 0.73 ± 0.03; 95% CI 0.66-0.76; p = 0.02).ConclusionCystatin C may be the most sensitive indicator of CMB severity among the renal disease markers.

Dataset Information

Serum Cystatin C as an Indicator of Renal Function and Mortality in Liver Transplant Recipients.

Background/aims

Methods

Results

Conclusions

Publications

Serum Cystatin C as an Indicator of Renal Function and Mortality in Liver Transplant Recipients.

Similar Datasets

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