Serum CysC Concentrations Research Articles

Associations of serum cystatin C concentrations with total mortality and mortality of 12 site-specific cancers.

Cystatin C (CysC), beyond its biomarker role of renal function, has been implicated in various physical and pathological activities. However, the impact of serum CysC on cancer mortality in a general population remains unknown. We aimed to examine the associations of serum CysC concentrations with total mortality and mortality of 12 site-specific cancers. We included 241,008 participants of the UK Biobank cohort with CysC measurements who had normal creatinine-based estimated glomerular filtration rates and were free of cancer and renal diseases at baseline (2006-2010). Death information was obtained from the National Health Service death records through 28 February 2021. Multivariable Cox proportional hazards models were used to compute hazard ratios (HR) per one standard deviation increase in log-transformed CysC concentrations and 95% confidence intervals (95% CI) for mortality. Over a median follow-up of 12.1 (interquartile range, 11.3-12.8) years, 5,744 cancer deaths occurred. We observed a positive association between serum CysC concentrations and total cancer mortality (HR = 1.16, 95% CI: 1.12-1.20). Specifically, participants with higher serum CysC concentrations had increased mortality due to lung cancer (HR = 1.12, 95% CI: 1.05-1.20), blood cancer (HR = 1.29, 95% CI: 1.16-1.44), brain cancer (HR = 1.19, 95% CI: 1.04-1.36), esophageal cancer (HR = 1.20, 95% CI: 1.05-1.37), breast cancer (HR = 1.18, 95% CI: 1.03-1.36), and liver cancer (HR = 1.49, 95% CI: 1.31-1.69). Our findings indicate that higher CysC concentrations are associated with increased mortality due to lung, blood, brain, esophageal, breast, and liver cancers. Future studies are necessary to clarify underlying mechanisms.

Prognostic Value of Cystatin C as a Predictor of Adverse Outcome in Severe Pneumonia Associated with COVID-19

Objective. To assess the cystatin C (CysC) prognostic value for probability of death in patients with severe and extremely severe pneumonia associated with COVID-19.Material and methods. A single-center prospective study included 72 patients with severe and extremely severe pneumonia associated with COVID-19 undergoing treatment in the ICU of multifunctional medical center from September 2020 to October 2021. Recovered survivors (N=55) were analyzed as a Group 1, nonsurvivors (N=17) were considered as a Group 2.Results. The serum (s-CysC) and urine (u-CysC) CysC concentrations were significantly lower in Group 1 patients vs Group 2, averaging 1.31 mg/l vs 1.695 mg/l (P=0.013550), and 0.25 mg/l vs 0.94 mg/l (P=0.026308), respectively. Significant differences were also revealed in the subgroups differed by age (P=0.0094), platelet count (P=0.001), serum fibrinogen concentration (P=0.016), as well as CURB (P=0.02334), CRB-65 (P=0.032564), and SOFA (P=0.042042) scores. Therefore, s-CysC and u-CysC were statistically significant predictors of death in patients with pneumonia associated with severe and extremely severe COVID-19: 16.273 (95% CI: 2.503–105,814), P=0.003 and 1.281 (95% CI: 1.011–1.622), P=0.040, respectively. Urine and serum CysC were established as predictors of death in pneumonia associated with severe and extremely severe COVID-19, where u-CysC was defined as highly informative (ROC AUC 0.938 (95% CI: 0.867–1.000; P=0.000), with 90% sensitivity and specificity), and s-CysC — as informative (ROC AUC 0.863 (95%CI: 0.738–0.988; P=0.000) with 80% sensitivity and 72% specificity) predictive markers.Conclusion. Levels of S-CysC and u-CysC are of high prognostic significance and may contribute to identifying patients at a high risk of unfavorable outcome (death) due to pneumonia associated with severe and extremely severe COVID-19. Both S-CysC and u-CysC concentrations increasing up to 1.44 mg/l and 0.86 mg/l, respectively, were associated with high probability of death.

Prognostic value of serum cystatin C concentration in dogs with myxomatous mitral valve disease.

Impaired renal function is 1 of the poor prognostic factors in dogs with myxomatous mitral valve disease (MMVD). However, the value of cystatin C (Cys-C), a marker of renal function, as a prognostic marker for MMVD in dogs has not yet been explored. This study aims to investigate the prognostic value of Cys-C in dogs with MMVD. Fifty client-owned small-breed dogs with MMVD were included in this study. This is a retrospective, cross-sectional study. The prognostic value of serum Cys-C concentration was assessed using univariable and multivariable Cox hazard regression analyses. Kaplan-Meier survival curves for MMVD-specific survival in dogs stratified into high and low Cys-C groups were generated and analyzed using the log-rank test. Serum Cys-C concentrations were significantly associated with MMVD-related death (P < .01) in both univariable (hazard ratio [HR], 5.086; 95% confidence interval [CI], 1.950-13.270) and multivariable Cox hazard regression analysis (HR, 4.657; 95% CI, 1.767-12.270). The high Cys-C group (n=14) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n=36; P < .01). In dogs with normal blood creatinine concentrations, the high Cys-C group (n=10) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n=36; P < .01). High serum Cys-C concentrations were associated with a worse prognosis of MMVD. Furthermore, serum Cys-C could be a predictor of MMVD prognosis even in dogs with normal blood creatinineconcentration.

Acute Kidney Injury Is Associated with Higher Serum Cys-C and NGAL Concentrations, and Risk of Mortality in Premature Calves with Respiratory Distress Syndrome.

The purpose of the present study was to establish the development of acute kidney injury (AKI) and evaluate the usefulness of kidney-specific biomarkers in diagnosing AKI in premature calves with respiratory distress syndrome (RDS). Ten-term healthy and 70 premature calves with RDS were enrolled. Clinical examination, blood gases, and chemical analysis were performed at admission and 72 h. Serum concentrations of blood urea nitrogen (BUN), creatinine (Cre), phosphorus (P), cystatin-C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin (UMOD), and liver-type fatty acid-binding protein (L-FABP) were measured to evaluate kidney injury. Our findings showed that 38.5% of the premature calves with RDS developed AKI. The RDS-AKI group had a 4-fold higher mortality risk than the RDS-non-AKI group. Cys-C, with 90% and 89% specificity, and NGAL, with 100% sensitivity and 85% specificity, were the most reliable biomarkers to determine AKI in premature calves. The usefulness of any biomarker to predict mortality was not found to be convincing. In conclusion, AKI can develop as a consequence of hypoxia in premature calves and may increase the risk of mortality. In addition, serum Cys-C and NGAL concentrations may be useful in the diagnosis of AKI in premature calves with RDS.

Effect of age, sex, and breed on serum cystatin C and creatinine concentrations in dogs.

This study investigated the effects of age, sex and breed on serum cystatin C (Cys-C) and creatinine in small breed dogs. This retrospective study included 250 dogs weighing less than 15kg without azotemia. Serum Cys-C and creatinine concentrations were analyzed, along with their correlation with age, and the difference between sexes or dog breeds. Serum Cys-C concentration correlated with age (P < 0.001), and did not differ between sexes or dog breeds. By contrast, serum creatinine concentration did not correlate with age. Serum creatinine concentration was higher in males than females (P < 0.05), and was lower in Miniature Dachshunds and Chihuahuas, and was higher in Shiba Inus compared to the general study population (P < 0.001). Serum Cys-C concentration correlates with age, and might be more sensitive to aging-associated subclinical renal dysfunction than serum creatinine concentration in dogs. Unlike serum creatinine concentration, serum Cys-C concentration is not affected by sex or dog breed.

Predictive Value of Cystatin C for Stroke Recurrence in Patients With Acute Ischemic Stroke.

This study explored the value of cystatin C (CysC) in predicting stroke recurrence in patients with acute ischemic stroke. This was a post hoc analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) on 3,474 acute ischemic stroke patients with documented serum CysC and high-sensitivity C-reactive protein (hsCRP) concentrations. Study outcomes included stroke recurrence and combined vascular events within 2 years after stroke. In stroke patients with higher (i.e., ≥4.8ng/mL), but not lower, hsCRP concentrations, a higher CysC concentration (i.e., ≥0.78 mg/L) was associated with a 2.48-fold increase in the risk of recurrent stroke (95% confidence interval [CI] 1.37-4.51; P=0.003) and a 2.04-fold increase in the risk of vascular events (95% CI 1.27-3.28; P=0.003). Serum hsCRP concentrations significantly modified the association of serum CysC with recurrent stroke (Pinteraction=0.001) and vascular events (Pinteraction=0.007). Moreover, CysC may improve reclassification of stroke recurrence (net reclassification improvement [NRI] 42.9%, P=0.001; integrated discrimination improvement [IDI] 1.2%, P=0.001) and vascular events (NRI 35.8%, P=0.001; IDI 1.1%, P=0.004). In ischemic stroke patients with high hsCRP concentrations, higher CysC concentrations increased the risk of stroke recurrence and vascular events. This indicates that the predictive value of CysC on stroke recurrence may depend on the inflammation status of patients.

Serum Cystatin C Concentrations in Patients with Graves' Ophthalmopathy.

PurposeTo evaluate the concentration of serum cystatin C (CysC) in patients with Graves’ ophthalmopathy (GO) and the usability of the serum CysC concentrations in the follow-up of the disease.MethodsThirty patients with GO and 30 healthy age-matched volunteers were included in this cross-sectional study. GO was diagnosed based on the European Group on Graves’ Orbitopathy consensus. Serum thyroid-stimulating hormone, free triiodothyronine, free thyroxine, and CysC concentrations were measured in the participants. The serum CysC concentrations were compared between patients with GO and controls. Patients with GO were subdivided into hyperthyroid and euthyroid patients, and their serum CysC concentrations were compared. In addition, the CysC concentrations in hyperthyroid and euthyroid patients with GO were compared separately with those of healthy subjects. Kruskal-Wallis test and Student’s t-test were used for statistical evaluation.ResultsThe mean serum CysC concentrations in GO patients and controls were 1.04 ± 0.36 and 0.74 ± 0.09 mg/L, respectively. There was a statistically significant difference in the serum CysC concentrations between patients with GO and control subjects (p < 0.001). Fifteen patients had hyperthyroid status, and 15 patients had euthyroid status. The mean serum CysC concentrations in hyperthyroid and euthyroid patients with GO were 1.35 ± 0.22 and 0.72 ± 0.13 mg/L, respectively. Serum CysC concentrations were significantly higher in hyperthyroid patients than in euthyroid patients (p = 0.001). In addition, hyperthyroid patients had significantly higher serum CysC concentrations than healthy subjects. Among patients with GO, 21 and nine had mild and moderate-to-severe GO, respectively. Active and inactive GO were observed in eight and 22 patients, respectively.ConclusionsThe serum CysC concentrations in hyperthyroid patients were higher than those in healthy subjects. Moreover, hyperthyroid patients had higher serum CysC concentrations than euthyroid patients. Further studies with a larger sample size are needed to confirm these results.

The effect of increased frequency of hemodialysis on serum cystatin C and β2-microglobulin concentrations: A secondary analysis of the frequent hemodialysis network (FHN) trial.

Small molecular weight toxin clearance is the main method of assessment of hemodialysis efficiency. Middle molecules including cystatin C (CysC) and Beta-2 microglobulin (β2-M) are understudied. We hypothesized that lowering of predialysis CysC and β2-M serum concentrations would be affected by switching to more frequent hemodialysis. Predialysis CysC and β2-M serum concentrations were measured from serum samples of the Frequent Hemodialysis Network (FHN) Daily and Nocturnal Trials. The differences between predialysis concentrations at baseline (while on conventional thrice weekly dialysis) and those after 12-months of study (on more frequent dialysis) were compared separately by trial (Nocturnal, Daily). We tested the associations between predialysis serum CysC and β2-M concentrations and outcomes. Forty-nine percent and 52% of the patients from the FHN Daily and Nocturnal Trials respectively were included in this ancillary study. Predialysis serum CysC concentrations remained unchanged after intensifying hemodialysis dose by either modality. There was significant lowering of the serum β2-M concentrations in the frequent Daily Trial hemodialysis group at 12 months in all patients and in patients without residual renal function at baseline (-3.8 ± 12.62 μg/mL, P = 0.004; -5.9 ± 12.99 μg/mL, P = 0.02, respectively). There were no significant differences between the baseline and the 12-months predialysis β2-M serum concentrations in the two control groups (Daily 3× and Nocturnal 3× groups). No association between the changes in the two biomarkers between baseline and 12-months and in changes in left ventricular mass, physical-health composite scores, hospitalization rate, and death were found. The numbers of hospitalizations and deaths were small. β2-M may be a better biomarker of dialysis dose than CysC. Reduction in the concentration of potentially toxic long-lived proteins of the size of β-2M is one potential long-term benefit of more intensive dialysis that may be explored.

Serum cystatin C concentration measured routinely is a prognostic marker for renal disease in dogs

This study examined the predictive value of serum cystatin C (Cys-C) concentration, measured during routine periodic health examinations, in the renal prognosis of dogs. A cohort of 140 dogs weighing <15 kg whose serum Cys-C concentrations were measured during periodic health examinations from December 2013 to March 2016 were prospectively studied, with renal disease-related death the predicted end point. Of the 140 dogs, nine died from renal diseases during the follow-up period (539 ± 249 days). Serum Cys-C concentrations were higher in the dogs that subsequently died of renal disease than in the censored group (0.8 ± 0.25 vs. 0.3 ± 0.1 mg/dl, respectively; P < .01). Dogs with high serum Cys-C concentrations (>0.55 mg/dl) had a shorter (P < .01) renal disease-specific survival period than those with low serum Cys-C concentrations (≤0.55 mg/dl). In conclusion, high serum Cys-C concentrations in periodic health examinations in dogs <15 kg predicted poorer prognosis for renal function.

Evaluation of serum cystatin-C and symmetric dimethylarginine concentrations in dogs with heart failure from chronic mitral valvular insufficiency.

Reduction in glomerular filtration rate (GFR) is a common complication in advanced stages of heart failure (HF). The convenient and precise assessment for GFR would be useful for early detection of renal impairment in HF dogs. Our hypothesis of this study was the GFR would be reduced in advanced stages of HF from chronic mitral valvular insufficiency (CMVI), as indicated by renal markers including serum cystatin-C (Cys-C) and symmetric dimethylarginine (SDMA) concentrations. Forty-three client-owned dogs consisting of 33 dogs with different stages of HF from CMVI and 10 age-matched healthy dogs were enrolled in this study. Serum Cys-C and SDMA concentrations along with other renal (i.e., urea nitrogen and creatinine) and echocardiographic markers were evaluated in healthy and CMVI dogs. Serum Cys-C concentrations were 1.4 ± 0.4 mg/l in control, 2.1 ± 0.9 mg/l in ISACHC I, 2.9 ± 0.8 mg/l in ISACHC II and 3.6 ± 0.6 mg/l in ISACHC III dogs, whereas serum SDMA concentrations were 8 ± 2 µg/dl in control, 14 ± 3 µg/dl in ISACHC I, 18 ± 6 µg/dl in ISACHC II and 22 ± 7 µg/dl in ISACHC III dogs. There was close correlation of serum Cys-C and SDMA concentrations to serum creatinine, urea nitrogen and the severity of HF. Our study demonstrated that the GFR was decreased in dogs with CMVI having earlier stages of HF.

Cystatin C provides a better estimate of the effect of glomerular filtration rate on serum human epididymis protein 4 concentrations.

We evaluated the effect of kidney glomerular function on serum concentrations of human epididymis protein 4 (HE4) using creatinine (Cr), cystatin C (CysC) and related chronic kidney disease epidemiology collaboration (CKD-EPI) equations. We enrolled 101 women aged ≤56 years with a glomerular filtration rate (GFR) (estimated by CKD-EPI eGFRCr) ranging from 60 to 120 mL/min/1.73 m2, free of any disease and biological and life-style factors known to influence serum HE4 concentrations, and we measured serum Cr, CysC and HE4 concentrations. Cr and CysC values were included in the three CKD-EPI equations to obtain GFR estimates. A statistically significant increase in HE4 median concentrations was detected in subjects with an eGFRCr between 60 and 74 mL/min/1.73 m2 when compared with those with an eGFR >90 mL/min/1.73 m2 (54.2 vs. 42.2 pmol/L, p=0.003). Regression models showed that CysC measurement per se and eGFRCysC were the most sensitive markers to catch HE4 increases due to a mild decrease in renal function [adjusted r2, 0.38 (p=0.00003) and 0.37 (p=0.0004), respectively]. By assuming baseline CysC and eGFRCysC at 0.80 mg/L and 101.5 mL/min/1.73 m2, an increase of 0.10 mg/L in CysC concentrations and a decrease of 10 mL/min of eGFRCysC implied an average (±SE) increase in serum HE4 concentrations of 9.2 (±1.2) and 8.8 (±1.1) pmol/L, respectively. Our study shows that a better estimate of the effect of GFR on serum HE4 is obtained by measuring CysC in serum or using CKD-EPI eGFRCysC equation.

Serum Cystatin C in Patients with Delayed Graft Function

Summary Despite recent studies showing that serum Cystatin C (CysC) is a better marker for glomerular filtration rate (GFR) than the ubiquitously used creatinine, the clinical utility of these findings remains to be evaluated. This marker is very sensitive for allograft function after renal transplantation. The concentration of CysC was compared with that of the creatinine. Decreased renal function was followed in 64 transplanted patients. Serum CysC significantly correlated with creatinine in healthy controls (r = 0.625, p &lt; 0.0001), whereas in the transplanted patients the mean serum creatinine and CysC concentrations were: 81 ± 13 mmol/L and 0.90 ± 0.22 mg/L, respectively. Serum CysC and creatinine significantly correlated throughout the post transplantation period (r = 0.686, p &lt; 0.001), but we confirmed differences between kinetics of these parameters. In the first four days after transplantation the CysC concentration was normalized faster than the creatinine concentration. Development of acute rejection episode (between 5 and 7 days) showed high sensitivity and specificity of the changes of CysC compared with those of creatinine.

Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus.

AimsSerum cystatin C (CysC) has recently been shown to be associated with the incidence of type 2 diabetes mellitus (T2DM) and progression to the pre-diabetic state. The aim of this study was to explore the relationship between serum CysC and the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women.MethodsThis cross-sectional study consisted of 400 pregnant women including111 with GDM and 289 with normal glucose tolerance at 24–28 weeks of gestation. The subjects were further divided into four groups according to the CysC quartiles, and their clinical characteristics were compared. The serum CysC concentration was measured using immunoturbidimetry and the degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR).ResultsSerum CysC levels were significantly higher in pregnant women with GDM than in the healthy pregnant women[1.0(0.8–1.8) vs 0.7(0.6–1.0), P<0.01). The Spearman’s correlation analysis showed that serum CysC was positively associated with HOMA-IR(r = 0.118, P<0.05) and the occurrence of GDM(r = 0.348, P<0.01). The pregnant women were divided into quartiles according to their serum CysC concentrations. Compared to the first quartile, pregnant women in Q2 (OR, 2.441; P = 0.025), Q3 (OR, 3.383; P = 0.001) and Q4 (OR, 5.516; P<0.001) had higher risk of GDM after adjusted for age, BMI, HbA1c and HOMA-IR. Further, with a rise in the serum CysC, there was an increasing trend in the HOMA-IR levels (P<0.05). A binary logistic regression analysis after adjusting for other confounding variables revealed a significant and independent association between serum CysC and GDM [OR = 14.269; 95% confidence interval, 4.977–40.908, P<0.01].The receiver operating characteristic curve analysis revealed that the optimal cutoff point for serum CysC to indicate GDM was 0.95mg/L.ConclusionsSerum CysC is significantly and independently associated with insulin resistance and GDM. It may be a helpful biomarker to identify the risk of GDM in Chinese pregnant women.

Effect of isoflurane preconditioning on cell apoptosis during renal ischemia-reperfusion in rats

Objective To evaluate the effect of isoflurane preconditioning on cell apoptosis during renal ischemia-reperfusion (I/R) in rats. Methods Thirty male Sprague-Dawley rats, aged 12-14 weeks, weighing 300-320 g, were randomly divided into 3 groups (n = 10 each) using a random number table: sham operation group (group S); I/R group; isoflurane preconditioning plus I/R group (group Iso+ I/R). The rats were anesthetized with intraperitoneal pentobarbital sodium 30 mg/kg.To establish the model of renal I/R injury, the right kidney was removed, and the left renal pedicle was occluded for 30 min with atraumatic mini-clamp for 30 min, followed by 2 h reperfusion.In Iso+ I/R group, 1.5% isoflurane was inhaled for 1 h, followed by 30 min of washout before I/R.In S and I/R groups only oxygen 2 L/min was inhaled for 1 h. Arterial blood samples were taken at 2 h of reperfusion to determine the concentrations of serum creatinine (Cr), blood urea nitrogen (BUN) and cystatin C (CysC). The animals were then sacrificed, and left kidneys were sampled for determination of the cell apoptosis (by TUNEL), expression of p53, Bax and Bcl-2 mRNA (using real-time fluorescent quantitative PCR), and expression of Bax, Bcl-2, and caspase-3 (by Western blot analysis). The Bcl-2/Bax ratio was calculated. Results Compared with group S, the serum Cr, BUN, and CysC concentrations were significantly increased, the Bcl-2/Bax ratio was decreased, Bcl-2 mRNA, Bax mRNA, Bcl-2, Bax and caspase-3 expression was up-regulated, and AI was increased in group I/R.Compared with group I/R, the serum Cr, BUN, and CysC concentrations were significantly decreased, the Bcl-2/Bax ratio was increased, Bcl-2 mRNA, Bax mRNA, Bax and caspase-3 expression was down-regulated, and AI was decreased in group Iso+ I/R.There was no significant difference in p53 mRNA expression among the three groups. Conclusion Regulating the balance between Bcl-2 and Bax and inhibiting apoptosis in kidney cells are involved in the mechanism by which isoflurane preconditioning reduces renal I/R injury in rats. Key words: Isoflurane; Ischemic preconditioning; Apoptosis; Kidney; Reperfusion injury

Assessment Of Renal Function Using Canine Cystatin-C Levels In Canine Babesiosis And Ehrlichiosis

Abstract The purpose of the present study was to evaluate serum canine Cystatin-C (Cys-C) concentration for the prediction of renal function (RF) in dogs naturally infected with Babesia canis vogeli and Ehrlichia canis. A total of 46 dogs were enrolled into three groups. Group B included 16 dogs naturally infected with B. c. vogeli, group E 10 dogs naturally infected with E. canis [dogs diagnosed as canine monocytic ehrlichiosis (CME)], and group H involved 20 healthy controls (negative for B. c. vogeli and E. canis). Solely dogs presenting uncomplicated babesiosis caused by B. c. vogeli were enrolled. Serum urea and serum creatinine (Cre) levels with serum Urea:Cre ratios were analyzed. Canine serum Cys-C was determined with a species-specific commercially available and validated ELISA assay as a reference. Mean serum Cys-C levels were 5.28 mg/L, 3.02 mg/L, and 2.30 mg/L for groups B, E and H, respectively. RF in uncomplicated CB caused by B. c. vogeli seems to be affected based on serum Cys-C concentrations. To the author's knowledge, this is the first study reporting that mean serum canine Cys-C levels in dogs with CME demonstrated no elevation. Serum canine Cys-C as a novel RF marker could be used for early detection of renal injury in both babesiosis and CME.

Serum Interleukin-18 at Commencement of Renal Replacement Therapy Predicts Short-Term Prognosis in Critically Ill Patients with Acute Kidney Injury

BackgroundAcute kidney injury (AKI) requiring renal replacement therapy (RRT) in critically ill patients results in a high hospital mortality. Outcome prediction in this selected high-risk collective is challenging due to the lack of appropriate biomarkers. The aim of this study was to identify outcome-specific biomarkers in this patient population.Methodology/Principal FindingsSerum samples were collected from 101 critically ill patients with AKI at the initiation of RRT in intensive care units (ICUs) of a tertiary care university hospital between August 2008 and March 2011. Measurements of serum levels of cystatin C (CysC), neutrophil gelatinase-associated lipocalin, and interleukin-18 (IL-18) were performed. The primary outcome measure was hospital mortality. The observed overall mortality rate was 56.4% (57/101). Multiple logistic regression analysis indicated that the serum IL-18 and CysC concentrations and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of RRT were independent predictors of hospital mortality. The APACHE III score had the best discriminatory power (0.872±0.041, p<0.001), whereas serum IL-18 had the best Youden index (0.65) and the highest correctness of prediction (83%). Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for serum IL-18 <1786 pg/ml vs. ≥1786 pg/ml in these critically ill patients.ConclusionsIn this study, we confirmed the grave prognosis for critically ill patients at the commencement of RRT and found a strong correlation between serum IL-18 and the hospital mortality of ICU patients with dialysis-dependent AKI. In addition, we demonstrated that the APACHE III score has the best discriminative power for predicting hospital mortality in these critically ill patients.

Impact of Thyroid Function on Serum Cystatin C and Estimated Glomerular Filtration Rate: A Cross-Sectional Study

To determine the relationship between thyroid-stimulating hormone (TSH) and cystatin C (CysC) and estimated glomerular filtration rate calculated by Cys C (eGFR(CysC)). We conducted a cross-sectional study including 8,126 male participants. Serum creatinine (Cr), CysC, eGFR calculated by Cr (eGFR(Cr)), and eGFR(CysC) were determined and compared in euthyroid and subclinical thyroid dysfunction patients. Relationships between TSH and Cr, cystatin C, eGFR(Cr), and eGFR(CysC) were assessed by linear and quadratic trend analyses. Odds ratios (ORs) of chronic kidney disease (CKD; eGFR<60 mL/min/1.73 m2) were calculated according to categories of thyroid function using TSH values of 2.01-3.00 mIU/L as a reference. Serum CysC level was significantly elevated, and eGFR(CysC) was significantly reduced in both subclinical hypothyroidism and subclinical hyperthyroidism. TSH was negatively and linearly associated with Cr and eGFR(Cr) (P<.001). Quadratic trends were found between TSH and cystatin C or eGFR(CysC) (P<.001). Compared with individuals with TSH of 2.01-3.00 mIU/L, the prevalence of CKD(CysC) was significantly higher in subjects with TSH<0.40 mIU/L, 3.01-4.00 mIU/L, and 4.01-7.00 mIU/L, while the prevalence of CKD(Cr) was only significantly higher in subjects with TSH>7.0 mIU/L. Despite only studying male subjects and using eGFR rather than standard GFR, we conclude that thyroid function differentially affects serum CysC and Cr concentrations. Subclinical hypothyroidism and subclinical hyperthyroidism are both associated with elevated CysC, reduced eGFR(CysC), and higher prevalence of CKDCysC. Assessment of renal function with CysC should be avoided in patients with thyroid dysfunction.

Is Cyctatin C Valuable Marker of Glomerular Filtration Rate in Living Kidney Donors After Uninephrectomy?

BackgroundThe determination of kidney function plays a pivotal role in living donors renal assessment because of the long-term hazards of life with one kidney. Guidelines recommend estimation of glomerular filtration rate (GFR) by the Modification of Renal Disease (MDRD) or Cockroft-Gault equations for people with normal or near-normal renal function. Cystatin C (CysC) has been introduced as an alternative endogenous marker of GFR. ObjectiveThe objective of the study was to evaluate residual renal function among living kidney donors by comparing serum CysC concentrations and estimated GFR according to the MDRD formula or the Cockroft-Gault equation. Patients and methodsForty living kidney donors showed a mean age of 46.14 years. Their GFR was estimated according to the abbreviated MDRD (aMDRD) and Cockroft-Gault formula adjusted for body surface area. Twenty-two donors underwent diethylenetriaminepentaacetic acid (DTPA) renal studies. Serum CysC concentrations were measured during the last follow-up visit. GFR values according to Cockroft-Gault formula and MDRD formula were correlated with CysC concentrations using Pearson's linear correlation. ResultsMean GFR according to the aMDRD formula and Cocroft-Gault formula decreased after nephrectomy. The Cockroft-Gault formula overestimated the DTPA GFR in our study. No significant differences were observed between DTPA GFR and GFR estimated using the aMDRD equation. The rate of GFR decrease was approximately 0.8 mL/min/1.73m2 per year. No significant correlation was observed between serum CysC concentration and GFR. Microalbuminuria was observed in one patient after nephrectomy. ConclusionsaMDRD equation to estimate GFR is more precise than Cockroft-Gault formula and cystatin C in living kidney donors after nephrectomy and should be preferred model in these patients.

Measurements of serum cystatin C concentrations underestimate renal dysfunction in pediatric patients with chronic kidney disease

In our clinical experience, cystatin C (CysC) concentrations are not as high as expected in patients with chronic kidney disease (CKD) and high-stage renal dysfunction. We therefore investigated whether measurements of serum CysC result in an underestimation of renal dysfunction in pediatric patients with CKD. Glomerular filtration rate (GFR) was estimated from serum creatinine (Cr) concentration, using the equation Cr-GFR (%)=[0.30×body length (m)/serum Cr]×100; and from serum CysC concentration, using the equation Cys-GFR (%)=(0.70/serum CysC)×100. We investigated the relationship between GFR estimated by these 2 equations. Patients aged 2-12years were assorted into 5 groups, based on GFR-Cr categories of <12.5, ≥12.5 to <25, ≥25 to <50, ≥50 to <75, and ≥75%, and GFR-CysC/GFR-Cr ratios were compared in these 5 groups. The median GFR-CysC/GFR-Cr ratio in groups of patients with GFR-Cr of <12.5, ≥12.5 to <25, ≥25 to <50, ≥50 to <75, and ≥75% were 2.28, 1.48, 1.22, 1.18 and 0.98, respectively, with statistically significant differences between any two groups (p<0.001). Measurements of serum CysC concentrations lead to underestimation of renal dysfunction in pediatric patients with CKD.

Vitamin B12 and folate deficiency and elevated plasma total homocysteine in workers with chronic exposure to chromate

ObjectivesChronic occupational exposure to chromium can result in a broad range of adverse effects including multiple organ damage, genotoxicity and carcinogenesis. However, the metabolic consequences of chromium exposure have not...