Cystatin C as a biomarker of chronic kidney disease: latest developments.
Ontology highlight
ABSTRACT: Introduction
Chronic kidney disease (CKD) is common, occurring in over 10% of individuals globally, and is increasing in prevalence. The limitations of traditional biomarkers of renal dysfunction, such as serum creatinine, have been well demonstrated in the literature. Therefore, augmenting clinical assessment with newer biomarkers, such as serum cystatin C, has the potential to improve disease monitoring and patient care.Areas covered
The present paper assesses the utility and limitations of serum cystatin C as a biomarker for CKD in light of the current literature.Expert opinion
Serum cystatin C has been well established as an early and accurate biomarker of CKD that is particularly helpful in patients for whom creatinine is an inadequate marker or for whom more cumbersome methods of glomerular filtration rate (GFR) measurement are impractical. Current research questions are no longer focused on if, but rather when and how often cystatin C should be used in the evaluation of CKD patients. However, transition of all reagents and estimated GFR equations to the newly established International Standard is critical for developing generalizable data.
SUBMITTER: Benoit SW
PROVIDER: S-EPMC7657956 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Cystatin C is a cysteine protease inhibitor that is produced by nearly all human cells. The serum level of cystatin C is a stronger predictor of the renal outcome and the risk of cardiovascular events than the creatinine level. The resistive index (RI) on renal Doppler ultrasonography is a good indicator of vascular resistance as well as the renal outcomes in patients with chronic kidney disease (CKD). However, it is unclear whether serum cystatin C is associated with signs of vascular dysfunction, such as the renal RI. We measured the serum cystatin C levels in 101 CKD patients and investigated the relationships between cystatin C and markers of vascular dysfunction, including the renal RI, ankle-brachial pulse wave velocity (baPWV), intima-media thickness (IMT), and cardiac function. The renal RI was significantly correlated with the serum cystatin C level (p < 0.0001, r = 0.6920). The serum cystatin C level was found to be a significant determinant of the renal RI (p < 0.0001), but not the baPWV, in a multivariate regression analysis. The multivariate odds ratio of the serum cystatin C level for a renal RI of more than 0.66 was statistically significant (2.92, p = 0.0106). The area under the receiver-operating characteristic curve comparing the sensitivity and specificity of cystatin C for predicting an RI of more than 0.66 was 0.882 (cutoff value: 2.04 mg/L). In conclusion, the serum cystatin C level is an independent biomarker associated with the renal RI in patients with CKD.
| S-EPMC5841772 | biostudies-literature
Project description:Chronic kidney disease (CKD) has shown an increasing prevalence in the last century. CKD encompasses a poor prognosis related to a remarkable number of comorbidities, and many patients suffer from this disease progression. Once the factors linked with CKD evolution are distinguished, it will be possible to provide and enhance a more intensive treatment to high-risk patients. In this review, we focus on the emerging markers that might be predictive or related to CKD progression physiopathology as well as those related to a different pattern of response to treatment, such as inhibitors of the renin-angiotensin system (including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers; the vitamin D receptor agonist; salt sensitivity hypertension; and progressive kidney-disease markers with identified genetic polymorphisms). Candidate-gene association studies and genome-wide association studies have analyzed the genetic basis for common renal diseases, including CKD and related factors such as diabetes and hypertension. This review will, in brief, consider genotype-based pharmacotherapy, risk prediction, drug target recognition, and personalized treatments, and will mainly focus on findings in CKD patients. An improved understanding will smooth the progress of switching from classical clinical medicine to gene-based medicine.
| S-EPMC4157401 | biostudies-literature
Project description:Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved. However, this does not appear to have quelled the interest in MUC1 as a therapeutic target, as shown by the increase in the number of MUC1-based clinical trials initiated in 2017 ( Figure 1). As with all translational studies, incorporating new relevant research findings into therapeutic strategy is difficult. Decisions are made to commit to a specific strategy based on the information and data available when the trial is initiated. However, the time required for preclinical studies and early trials can render the founding concept not always appropriate for proceeding to a larger definitive trial. Here, we summarize the attempts made, to date, to bring MUC1 into the world of cancer immunotherapy and discuss how research findings regarding MUC1 structure and function together with expanded knowledge of its interactions with the tumour environment and immune effector cells could lead to improved therapeutic approaches. ppbiost;46/3/659/BST20170400CF1F1BST-2017-0400CF1Figure 1.Number of MUC1-targeted trials initiated each year.
| S-EPMC6008591 | biostudies-literature
Project description:BackgroundRenal dysfunction after acute kidney injury (AKI) is common, potentially modifiable, but poorly understood. Acute kidney disease (AKD) describes renal dysfunction 7 to 90 days after AKI and is determined by percentage change in creatinine from baseline. Chronic kidney disease (CKD) is defined as the estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 persisting for more than 90 days. We compared CKD incidence using both creatinine- and cystatin C-based GFR with AKD incidence at 90 days in AKI survivors.MethodsA prospective cohort study was conducted in a Swedish intensive care unit (ICU) between 2008 and 2010. We included AKI patients alive at 90 days. We excluded patients <18 and >100 years, death before follow-up, CKD prior to admission, and follow-up before 60 days or beyond 270 days. Creatinine and cystatin C were measured at 90 days and converted to eGFR (mL/min/1.73 m2).ResultsWe included 274 patients. At 90-day follow-up, the median creatinine eGFR (MDRD) was 81.6 (IQR 58.6-106.8) and median cystatin C eGFR was 51.5 (IQR 35.8-70.7). The incidence of CKD (eGFR < 60) was 25.8% based on creatinine but 63.7% using cystatin C estimates. AKD was present in 47 patients (18.9%). Age, discharge cystatin C, creatinine at discharge, and female gender predicted creatinine-defined CKD at follow-up. Age, discharge cystatin C, CRRT on ICU, and diabetes were associated with cystatin C-based CKD.ConclusionsIn AKI survivors followed up at 3 months, CKD criteria were met in a quarter of patients using creatinine and in two-thirds using cystatin C eGFR. Less than one-fifth of patients fulfilled AKD criteria. The application of AKD criteria may underestimate renal dysfunction in AKI survivors.
| S-EPMC6180984 | biostudies-literature
Project description:BackgroundSerum cystatin C (sCysC) and urinary cystatin C (uCysC) are potential biomarkers for early detection of chronic kidney disease (CKD) in cats. An in-depth clinical validation is required.ObjectivesTo evaluate CysC as a marker for CKD in cats and to compare assay performance of the turbidimetric assay (PETIA) with the previously validated nephelometric assay (PENIA).AnimalsNinety cats were included: 49 CKD and 41 healthy cats.MethodsSerum CysC and uCysC concentrations were prospectively evaluated in cats with CKD and healthy cats. Based on plasma exo-iohexol clearance test (PexICT), sCysC was evaluated to distinguish normal, borderline, and low GFR. Sensitivity and specificity to detect PexICT < 1.7 mL/min/kg were calculated. Serum CysC results of PENIA and PETIA were correlated with GFR. Statistical analysis was performed using general linear modeling.ResultsCats with CKD had significantly higher mean ± SD sCysC (1.4 ± 0.5 mg/L) (P < .001) and uCysC/urinary creatinine (uCr) (291 ± 411 mg/mol) (P < .001) compared to healthy cats (sCysC 1.0 ± 0.3 and uCysC/uCr 0.32 ± 0.97). UCysC was detected in 35/49 CKD cats. R(2) values between GFR and sCysC or sCr were 0.39 and 0.71, respectively (sCysC or sCr = μ + GFR + ε). Sensitivity and specificity were 22 and 100% for sCysC and 83 and 93% for sCr. Serum CysC could not distinguish healthy from CKD cats, nor normal from borderline or low GFR, in contrast with sCr.ConclusionSerum CysC is not a reliable marker of reduced GFR in cats and uCysC could not be detected in all CKD cats.
| S-EPMC5108422 | biostudies-literature
Project description: Not available
| S-EPMC4421875 | biostudies-literature
Project description:Donor nephrectomy in living-donor kidney transplantation may result in hyperfiltration injury in remnant kidney; however, its clinical implication in partial recovery of kidney function (PRKF) in remnant kidney and chronic kidney disease (CKD) progression remains unclear. Thus, we investigated the effect of PRKF on CKD development in the residual kidney and the utility of cystatin-C (Cys-C) in evaluating renal function in living-donor kidney transplantation donors.The electronic medical records and laboratory results of 1648 kidney transplant (KT) donors and 13,834 healthy nondonors between January 2006 and November 2014 were reviewed. The predictors of PRKF and CKD diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria were evaluated by multivariate analysis. CKD risk was compared between KT donors and healthy nondonors using Cox proportional hazard regression analysis following propensity score matching (PSM).The incidence of PRKF for KT donors was 49.3% (813). CKD incidence was 24.8% (408) in KT donors and 2.0% (277) in healthy nondonors. The predictors of PRKF were, male sex (odds ratio [OR], 17.32; 95% confidence interval [CI] 9.16-32.77), age (OR, 1.02; 95% CI, 1.00-1.04; P < 0.001), Cys-C concentration (OR, 1.02; 95% CI, 1.00-1.04; P = 0.02), and preoperative albumin level (OR, 0.49; 95% CI, 0.27-0.89; P = 0.02). The predictors of CKD were age (hazards ratio [HR], 1.04; 95% CI, 1.02-1.05; P < 0.001), Cys-C concentration (HR, 1.024; 95% CI, 1.012-1.037; P < 0.001), and PRKF (HR, 1.41; 95% CI, 1.04-1.92; P = 0.03). After PSM, the risk of progression to CKD was higher in KT donors than in healthy nondonors (HR, 58.4; 95% CI, 34.2-99.8; P < 0.001).Donor nephrectomy is associated with PRKF and progression to CKD. Cys-C is a useful early marker for detecting PRKF and CKD.
| S-EPMC5293475 | biostudies-literature
Project description:Although kidney disease has been a recognized complication of HIV infection since the beginning of the HIV epidemic, its epidemiology, underlying causes and treatment have evolved in developed countries where HAART has been widely available. HIV-associated nephropathy and HIV immune complex-mediated kidney disease were the prominent renal diagnoses in the earlier period of the HIV epidemic. While HIV immune complex-mediated kidney disease remains a common finding among HIV-infected individuals with kidney disease, the incidence of HIV-associated nephropathy has been diminishing in developed countries. The role of the metabolic effects of long-term HAART exposure and nephrotoxicity of certain antiretroviral medications on the development and progression of chronic kidney disease is now of increasing concern. The long-term clinical implications of acute kidney injury among HIV-infected persons are increasingly recognized. Kidney disease in HIV-infected persons continues to be a major risk factor for morbidity and mortality in this patient population; therefore, early recognition and treatment of kidney disease are imperative in lessening the impact of kidney disease on the health of HIV-infected individuals. This review focuses on recent developments and ongoing challenges in the understanding, diagnosis and management of HIV-related kidney disease.
| S-EPMC3038636 | biostudies-literature
Project description:Patients with chronic kidney disease (CKD) of all stages experience extremely high mortality, with cardiovascular causes accounting for about half of all their deaths. Traditional risk factors such as hypertension, hypercholesterolemia and diabetes mellitus cannot explain the excessively high cardiovascular mortality in CKD. Chronic inflammation is one of the novel risk factors that appear to contribute to the increased mortality seen in patients with CKD. Therapeutic interventions targeting chronic inflammation in CKD may lead to improved outcomes.To describe the role of inflammation in CKD and to review anti-inflammatory pharmacologic therapies that could have a role in its therapy.A review of the literature was carried out and expert opinion expressed.Inflammation is a common and significant problem in CKD. There are currently no approved pharmacologic anti-inflammatory therapies in CKD but several agents are being studied in early clinical trials, while others could become viable alternatives in the future.
| S-EPMC5500838 | biostudies-other
Project description:Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system leading to demyelination and neurodegeneration. While the initial presentation is mostly characterized by a relapsing-remitting disease, patients often progress naturally after 10-15 years to a secondary-progressive disease course. Another 10-15% present with an initial, primary-progressive MS course. Pathogenic mechanisms possibly driving progression include continued compartmentalized inflammation by T- and B-lymphocytes and cells of innate immunity, oxidative stress, iron accumulation, and consecutive mitochondrial damage, altogether leading to neurodegeneration with accumulation of disability. Increasing knowledge about pathogenic mechanisms involved in progressive MS helps to design more specific and precise therapeutic approaches. Successful examples are the B-cell targeting monoclonal antibody ocrelizumab, effective in primary progressive MS, and the sphingosine-1-receptor modulator siponimod, effective in active forms of secondary-progressive MS. Apart from that, other medications such as the B-cell targeted antibody ofatumumab, cladribine due to T- and B-cell depletion, and other sphingosine-1-receptor modulators such as ozanimod and ponesimod are under development. Moreover, some therapeutic approaches in preclinical stages are under development. In this review, we will summarize the newest therapeutic development in the field of progressive MS of the last 3 years, and shed light on auspicious substances with similar mechanisms and new developments in the therapeutic pipeline, presumably supporting a bright future for progressive MS treatment.
| S-EPMC6764045 | biostudies-literature