Plasma Cystatin Research Articles

Inhibition of microbiota-dependent TMAO production attenuates chronic kidney disease in mice

Patients with chronic kidney disease (CKD) have elevated circulating levels of trimethylamine N-oxide (TMAO), a metabolite derived from gut microbes and associated with cardiovascular diseases. High circulating levels of TMAO and its dietary precursor, choline, predict increased risk for development of CKD in apparently healthy subjects, and studies in mice fed TMAO or choline suggest that TMAO can contribute to kidney impairment and renal fibrosis. Here we examined the interactions between TMAO, kidney disease, and cardiovascular disease in mouse models. We observed that while female hyperlipidemic apoE KO mice fed a 0.2% adenine diet for 14 weeks developed CKD with elevated plasma levels of TMAO, provision of a non-lethal inhibitor of gut microbial trimethylamine (TMA) production, iodomethylcholine (IMC), significantly reduced multiple markers of renal injury (plasma creatinine, cystatin C, FGF23, and TMAO), reduced histopathologic evidence of fibrosis, and markedly attenuated development of microalbuminuria. In addition, while the adenine-induced CKD model significantly increased heart weight, a surrogate marker for myocardial hypertrophy, this was largely prevented by IMC supplementation. Surprisingly, adenine feeding did not increase atherosclerosis and significantly decreased the expression of inflammatory genes in the aorta compared to the control groups, effects unrelated to TMAO levels. Our data demonstrate that inhibition of TMAO production attenuated CKD development and cardiac hypertrophy in mice, suggesting that TMAO reduction may be a novel strategy in treating CKD and its cardiovascular disease complications.

Plasma Cystatin C Level is a Prognostic Marker of Morbidity and Mortality in Hospitalized Decompensated Cirrhotic Patients.

Introduction : Cystatin C (CysC) is biomarker for early detection of acute kidney injury (AKI). However, there is limited evidence in decompensated cirrhotic patients without AKI at admission. This study aimed to assess CysC as a predictor of 90-day mortality. Methods : Decompensated cirrhotic patients without AKI were prospectively enrolled. CysC and creatinine were measured within 24 hours of admission and compared between patients with in-hospital complications (AKI, hepatorenal syndrome (HRS), acute-on-chronic liver failure (ACLF)) vs. those without, and survivors vs. non-survivors. The AUROC and cut-off point of CysC in predicting 90-day mortality were determined. Results : Of 137 decompensated cirrhotic patients, 46 without AKI at admission were included (58.7% male, age 60.8 ± 11.2years, MELD 13.1 ± 5.1, ChildA / B / C 43.5% / 39.1% / 17.4%). The mean CysC level tended to be higher in patients with ACLF (1.52 ± 0.60 vs. 1.11 ± 0.28, p = 0.05), and significantly higher in non-survivors than survivors (1.61 ± 0.53 vs. 1.08 ± 0.28, p = 0.013). The 90-day mortality rate was 21.7%. After adjusting with age and bacterial infection on admission, CysC level ≥ 1.25 mg / L was significantly associated with 90-day mortality. The CysC cut-off level ≥ 1.25 mg / L provided 80% sensitivity and 75% specificity for predicting 90-day mortality. Conclusion : Plasma CysC within 24 hours could be used as a predictor for 90-day mortality and development of ACLF in decompensated cirrhotic patients. J. Med. Invest. 68 : 302-308, August, 2021.

Reduced Cleavage of Von Willebrand Factor By ADAMTS13 Exacerbates Acute Kidney Injury Secondary to Traumatic Injury

Introduction: Increases in plasma von Willebrand Factor (vWF) antigen levels, accompanied by decreases in its respective metalloprotease, ADAMTS13, have been demonstrated following severe injury. We hypothesized that following traumatic injury, endothelial damage and activation would result in the release of high molecular weight multimeric (HMWM) vWF forms into circulation with a concominant decrease in ADAMTS13. We further hypothesized that the alterations in circulating levels and functions of these factors, following traumatic injury, promote an increased thrombogenic and inflammatory response, which exacerbates the risk of developing post traumatic acute kidney injury (AKI). Methods: Plasma samples from a cohort of patients with trauma induced AKI, collected at 0-, 24-, and 72-hours after admission, were evaluated against plasma samples from trauma patients that were matched for injury characteristics, but were without AKI. VWF and ADAMTS13 activity and antigen levels were evaluated. Circulating vWF multimeric composition was determined by vertical agarose gel electrophoresis. We further evaluated the effects of traumatic injury on ADAMTS13 and vWF by means of a pre-clinical model of trauma and hemorrhage, which is comprised of a liver laceration, cardiac puncture, and soft tissue injury. Following this polytrauma model, hepatic ADAMTS13 RNA expression was evaluated by qRT-PCR of total liver RNA; analyzed liver samples were taken immediately before, 24-, and 72-hours after injury. The impact of the polytrauma model on renal function was evaluated via changes in plasma cystatin C, while the effect on the renal microvasculature was evaluated by means of immunofluorescent staining of vWF and fibrinogen in kidney sections. Results: VWF antigen was increased in trauma patients when compared to healthy controls upon admission (11.0 ± 3.72 ug/mL vs. 4.64 ± 0.91 ug/mL), persisting through 72-hours (13.11 ± 3.16 ug/mL). The percentage of HMWM vWF forms in trauma patient samples was elevated at all time points compared to pooled normal plasma (PNP) (27.9 ± 4.5% and 15.9 ± 0.8). Trauma patient ADAMTS13 activity was decreased at all time points (0.48 ± 0.14 IU/mL vs. 1.27 ± 0.26 IU/mL). AKI patients showed a 1.54 ± 0.48-fold increase in vWF antigen levels over the 72-hour period (p=0.016), while there was no change in the control trauma group. Those who developed AKI demonstrated a larger proportion of HMWM vWF at 72-hours than their non-AKI counterparts (32.9 ± 2.4% vs 28.8 ± 3.2%). qRT-PCR of murine total liver RNA, following the polytrauma model, exhibited ADAMTS13 RNA expression levels that were 35% of normal at 24-hours and 60% of normal at 72 hours post-injury. A matched analysis of murine plasma cystatin C levels demonstrated a marked elevation 24-hours post polytrauma model (sham: 510ng/mL (435-561) vs trauma: 550 (479-701)). H&E staining of kidney sections, which were harvested following the polytrauma model, demonstrated generalized renal tubule dilation and denudation, suggestive of post-traumatic acute tubular necrosis. Immunofluorescent studies of kidney sections from the same mice exhibited 8-15µm microvascular plugs that were positive for fibrinogen with a vWF core; renal immunofluorescent studies of control mice demonstrated no microvascular depositions. Conclusions: These data indicate that traumatic injury alters the circulating composition of ADAMTS13 and its target, vWF, shifting their equilibrium to one that promotes inflammation and thrombosis. In the immediate moments following injury, these mechanisms support life-saving hemostasis; however, as these changes extend into the following days, the early hemostatic benefit quickly shifts to a burden that may produce microvascular clot deposition, exacerbating pathologic states such as acute kidney injury. Disclosures No relevant conflicts of interest to declare.

Aggressive therapy to prevent contrast-induced kidney damage during percutaneous coronary interventions

Abstract Introduction In the era of the development of medical technology percutaneous coronary intervention (PCI) has become the most common method of surgical treatment of coronary arteries in patients with coronary heart disease (CHD). Contrast-induced nephropathy (CIN) is a harbinger of chronic renal failure. The recommendations for myocardial revascularization for the prevention of CIN recommend the use of statin treatment. The choice of the optimal statin, the duration of its administration and the effectiveness of loading doses of statins in preventing CIN still remain unresolved topical issues. The purpose of research work: 1) to evaluate the effectiveness of the prevention of contrast-induced kidney damage when using a loading dose of statins; 2) to study the possibility of early diagnosis of renal damage by examining serum creatinine levels, calculating the glomerular filtration rate (GFR) and the index of a new biomarker of cystatin C. Material and methods All patients with CHD, hemodynamically significant stenosis of the coronary arteries were sent to elective endovascular myocardial revascularization. All patients underwent: general clinical examination, a serial study of biochemical blood analysis parameters: creatinine, c-reactive protein (CRP), cystatin C level, GFR. Using the envelope method, the patients were divided into two groups. Patients of the first group were prescribed atorvastatin at a dose of 80 mg for 7 days: 3 days before PCI and 4 days after it. The second group included patients who were treated with rosuvastatin at a dose of 40 mg for 7 days: 3 days before PCI and 4 days after PCI. Conclusion The incidence of CI AKI in patients with planned PCI during the administration of high doses of rosuvastatin was less frequent compared with loading therapy with atorvastatin, respectively 3.33% and 12.12%. On average, an increase in the concentration of serum creatinine to the maximum level in patients receiving atorvastatin was higher than in the second group with loading therapy of rosuvastatin (14.3% versus 8.1%, p=0.024). The decrease in GFR calculated by the formula CKD-Epi was detected 48 and 72 hours after PCI. At the same time, a study of plasma cystatin C showed a decrease in renal function 12 and 24 hours after surgery with the introduction of a contrast agent. This biomarker is an effective marker for early detection of renal failure, even with normal creatinine levels. The anti-inflammatory effect was evaluated by a highly sensitive CRP. In patients with CHD after PCI during therapy with rosuvastatin it was significantly stronger compared with the group of patients using atorvastatin. Thus, the use of rosuvastatin in order to prevent CI of AKI during CPI in patients with CHD seems to be preferable in comparison with atorvastatin due to a more pronounced nephroprotective and anti-inflammatory effect. Aggressive statin therapy Funding Acknowledgement Type of funding source: None

A New Perspective for Isolated Coronary Artery Ectasia: Cystatin C.

IntroductionThe pathophysiology of isolated coronary artery ectasia (iCAE) has not been clearly identified, although multiple abnormalities, including arteritis, endothelial dysfunction, and vascular destruction, have been reported. In this study, we aimed to analyze serum cystatin C concentrations in patients with iCAE and controls.MethodsForty-seven patients with iCAE (mean age: 55.9 ± 11.5) and 32 individuals with normal coronary angiography (mean age: 57.8.1 ± 9.6) were included in the study. Plasma cystatin C levels were measured by using the principle of particle-enhanced turbidimetric immunoassay (PETIA).ResultsSerum cystatin C concentrations were significantly lower in patients with iCAE compared with the control group (0.98 ± 0.17 mg/L versus 1.17 ± 2.6 mg/L, p-value = 0.001). A significantly positive relationship was found between serum cystatin C levels and creatinine and high-sensitivity C-reactive protein (hs-CRP) levels in both groups (r-value = 0.288, p-value = 0.005, r-value = 0.143, p-value = 0.007, respectively). In multivariate logistic regression analysis, serum cystatin C level found to be a significant predictor for the presence of iCAE (OR: 0.837, CI: 95% (0.341 - 1.637), p-value = 0.013). Receiver operating characteristic (ROC) analysis determined that a cystatin C value < 1.02 mg/L had a sensitivity of 56% and a specificity of 78% for the prediction of ectasia.ConclusionWe conclude that cystatin C independently can be a useful predictor for the presence of iCAE.

Plasma cystatin C is a marker of renal glomerular injury in children treated with cisplatin or ifosfamide.

Plasma cystatin C is a potential marker of the glomerular filtration rate (GFR), and urinary cystatin C has been proposed as a marker of tubular dysfunction. A prospective study (NCT02822404) was conducted to assess the benefit of considering cystatin C plasma and urinary levels to better evaluate cisplatin and/or ifosfamide renal toxicity in children with cancer. Plasma 51 Cr-EDTA clearance as a marker of GFR and urinary markers of tubular toxicity were monitored in 40 children treated by cisplatin and/or ifosfamide. Several equations previously proposed to estimate GFR, with or without inclusion of plasma cystatin C level, were compared. A population pharmacokinetic approach was also used to analyze plasma 51 Cr-EDTA data, and evaluate the relationship between patient covariates (including plasma cystatin C level) and GFR during the course of chemotherapy treatment. Equations including plasma cystatin C described GFR changes during chemotherapy better than those without this variable. An equation based on plasma cystatin C, serum creatinine, and body weight enabled us to accurately describe the evolution of GFR during chemotherapy. The urinary cystatin C/creatinine ratio was compared between children with or without tubular toxicity, according to a standard assessment of tubular dysfunction. However, although the urinary cystatin C/creatinine ratio was increased in children with tubular toxicity, this marker does not provide additional information to the well-known markers of tubulopathy. Monitoring of plasma cystatin C may be substituted to radionucleide glomerular exploration in children treated by cisplatin and/or ifosfamide.

Estimation of piperacillin clearance with different glomerular filtration rate formulas in critically ill children.

Glomerular filtration rate (GFR) is difficult to assess in critically ill children using gold standard method and alternatives are needed. This study aimed to determine the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children, using a published piperacillin pharmacokinetics (PK) population model. All children hospitalized in the paediatric intensive care unit of a single institution who were receiving piperacillin were included. PK were described using the nonlinear mixed effect modelling software MONOLIX. In the initial PK model, GFR was estimated according to the Schwartz 1976 formula. We evaluated a set of 12 additional validated formulas, developed using plasma creatinine and/or cystatin C concentrations, in the building model to assess the lowest between-subject variability for piperacillin clearance. We included 20 children with a median (range) postnatal age of 1.9 (0.1-19) years, body weight of 12.5 (3.5-69) kg. Estimated GFR according to the Schwartz 1976 formula was 160.5 (38-315) mL min-1 1.73 m-2 . Piperacillin clearance was best predicted by the Bouvet combined formula. The combined Bouvet formula was the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children.

Higher plasma cystatin C is associated with mortality after acute respiratory distress syndrome: findings from a Fluid and Catheter Treatment Trial (FACTT) substudy

BackgroundCystatin C is a well-validated marker of glomerular filtration rate in chronic kidney disease. Higher plasma concentrations of cystatin C are associated with worse clinical outcomes in heterogenous populations of critically ill patients and may be superior to creatinine in identifying kidney injury in critically ill patients. We hypothesized that elevated levels of plasma cystatin C in patients with acute respiratory distress syndrome (ARDS) would be associated with mortality risk.MethodsIn a retrospective study, cystatin C was measured by nephelometry on plasma obtained at enrollment from 919 patients in the Fluid and Catheter Treatment Trial. Multivariable logistic regression was performed testing the association between quartiles of cystatin C and 60-day mortality. Analyses were stratified by acute kidney injury (AKI) status identified in the first 7 days after enrollment by Kidney Disease: Improving Global Outcomes (KDIGO) criteria.ResultsCystatin C was significantly higher among those patients who died compared to those who survived to 60 days [1.2 (0.9–1.9) mg/L vs. 0.8 (0.6–1.2) mg/L, p < 0.001]. Compared to the lower three quartiles, subjects in the highest quartile of cystatin C had a significantly higher odds of death at 60 days [OR 1.8 (1.2–2.6), p = 0.003 in adjusted analyses]; the odds of death incrementally rose in higher cystatin C quartiles compared to the lowest quartile (OR 1.1, 1.8, and 2.5). In adjusted analyses stratified by AKI status, compared to subjects in the lower three quartiles, subjects in the highest quartile of cystatin C with AKI had a significantly higher odds of death at 60 days both in participants with AKI [OR 1.6 (1.0–2.4), p = 0.048] and those without AKI [OR 2.4 (1.2–5.0), p = 0.017]. In adjusted analyses, there was no significant association between sex-stratified baseline creatinine quartiles and mortality.ConclusionsHigher plasma levels of cystatin C on enrollment were strongly associated with mortality at 60 days in patients with ARDS with and without AKI identified by creatinine-based definitions. Compared to creatinine, cystatin C may be a better biomarker of kidney function in patients with ARDS and therefore identify patients with multiple organ failure at higher risk of death.

Western Diet Promotes Renal Injury, Inflammation, and Fibrosis in a Murine Model of Alström Syndrome

Introduction: Alström syndrome is a rare recessive genetic disease caused by mutations in ALMS1, which encodes a protein that is related to cilia function and intracellular endosome trafficking. The syndrome has been linked to impaired glucose metabolism and CKD. Polymorphisms in Alms1 have likewise been linked to CKD, but little is known about the modification of the phenotype by environmental factors. Methods: To gain further insights, the fat aussie (foz) mouse strain, a genetic murine model of Alström syndrome, was exposed to a normal chow (NC) or to a Western diet (WD, 20% fat, 34% sucrose by weight, and 0.2% cholesterol) and renal outcomes were measured. Results: Body weight and albuminuria were higher in foz than in wild-type (WT) mice on both diets but WD significantly increased the difference. Measurement of plasma creatinine and cystatin C indicated that glomerular filtration rate was preserved in foz versus WT independent of diet. Renal markers of injury, inflammation, and fibrosis were similar in both genotypes on NC but significantly greater in foz than in WT mice on WD. A glucose tolerance test performed in foz and WT mice on WD revealed similar basal blood glucose levels and subsequent blood glucose profiles. Conclusions: WD sensitizes a murine model of Alström syndrome to kidney injury, inflammation, and fibrosis, an effect that may not be solely due to effects on glucose metabolism. Polymorphisms in Alms1 may induce CKD in part by modulating the deleterious effects of high dietary fat and sucrose on kidney outcome.

CD-1db/db mice: A novel type 2 diabetic mouse model with progressive kidney fibrosis.

Aims/IntroductionTo establish novel therapies to combat diabetic kidney disease, a human disease‐relevant animal model is essential. However, a type 2 diabetic mouse model presenting progressive kidney fibrosis has not yet been established. Kidneys of streptozotocin‐induced diabetic CD‐1 mice showed severe fibrosis compared with other backgrounds of mice associated with the suppression of antifibrotic peptide N‐acetyl‐seryl‐aspartyl‐lysyl‐proline. The BKS background (BKSdb / db) is often utilized for diabetic kidney disease research; the kidney fibrosis in the BKSdb / db phenotype is minimal.Materials and MethodsWe generated CD‐1db / db mice by backcrossing the db gene into the CD‐1 background, and analyzed phenotypic differences compared with BKSdb / db and CD‐1db / m mice.ResultsMale CD‐1db / db mice appeared to have elevated blood glucose levels compared with those of BKSdb / db mice. Fasting insulin levels declined in CD‐1db / db mice. Plasma cystatin C levels tended to be elevated in CD‐1db / db mice from 16 to 24 weeks‐of‐age. Male CD‐1db / db mice showed significantly progressive kidney and heart fibrosis from 16 to 24 weeks‐of‐age when compared with that of age‐matched BKSdb / db mice. The gene expression profile showed fibrogenic program‐associated genes in male CD‐1db / db mice. Male CD‐1db / db mice displayed significantly lower urine antifibrotic peptide N‐acetyl‐seryl‐aspartyl‐lysyl‐proline when compared to that of BKSdb / db at 24 weeks‐of‐age. The gene expression of prolyl oligopeptidase, the enzyme essential for antifibrotic peptide N‐acetyl‐seryl‐aspartyl‐lysyl‐proline production from thymosin β4, was significantly lower in the CD‐1 mice. Thymosin β4 levels were also lower in CD‐1 mice.ConclusionsThese results suggest that CD‐1db / db mice are a novel type 2 diabetic mouse model with progressive kidney and heart fibrosis.

Prognostic value of dynamic plasma endostatin for the prediction of mortality in acute kidney injury: A prospective cohort study.

ObjectiveThe aim of the current study was to evaluate the value of plasma endostatin for predicting 30-day mortality of patients with acute kidney injury (AKI).MethodsPatients who underwent non-cardiac major surgery and developed AKI in the first 48 hours after admission to the intensive care unit were consecutively included. Concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys C), and endostatin were measured at three time points: 0, 24, and 48 hours after the AKI diagnosis. Clinical patient characteristics were recorded after AKI was diagnosed.ResultsA total of 256 new-onset AKI patients were enrolled. Of these, 48 (18.7%) patients died within 30 days. The difference in plasma endostatin values between 0 and 24 hours (ΔEndostatin-24h) yielded the best area under the curve (AUC) of 0.747 for predicting 30-day mortality in AKI patients; NGAL and Cys C achieved AUC of 0.672 and 0.647, respectively. The predictive AUC increased to 0.833 when ΔEndostatin-24h was combined with sequential organ failure assessment score and AKI classification.ConclusionDynamic plasma endostatin is useful for predicting 30-day mortality in AKI patients. The predictive power of dynamic plasma endostatin can be significantly improved when it is combined with clinical patient data.

New renal haemodynamic indices can predict worsening of renal function in acute decompensated heart failure.

AimsWorsening of renal function (WRF) is a common complication in patients with acute decompensated heart failure (ADHF). We aimed to evaluate the role of intrarenal Doppler ultrasound (IRD) in the early prediction of WRF in this patient group.Methods and resultsAmong 90 patients (age: 57.5 ± 11.1 years; 62% male) hospitalized with ADHF, resistivity index (RI), acceleration time (AT), and pulsatility index (PI) were measured on admission and at 24 and 72 h. WRF was defined as increased serum creatinine ≥0.3 mg/dL from baseline. Adverse clinical outcomes were defined as the composite of death, use of vasopressors, and need for ultrafiltration for refractory oedema. WRF developed in 40% of patients. Mean values of renal AT, RI, and PI on admission were 59.7 ± 15, 0.717 ± 0.08, and 1.5 ± 0.48 ms, respectively. At 24 h, there was significant decrease in AT (to 56.7 ± 10 ms, P = 0.02) and renal RI (to 0.732 ± 0.07; P < 0.001); these changes were maintained up to 72 h. Renal PI showed no significant changes. Independent predictors of WRF were renal AT at 24 h and admission values of renal RI, left ventricular ejection fraction, and plasma cystatin C. Renal AT at 24 h ≥ 57.8 ms had 89% sensitivity and 70% specificity for the prediction of WRF. Independent predictors for adverse clinical outcomes were left ventricular end systolic dimension and WRF.ConclusionsAmong ADHF patients receiving diuretic therapy, measurement of renal AT and RI by IRD can help identify patients at increased risk for WRF.

Identification and validation of biomarkers of persistent acute kidney injury: the RUBY study

PurposeThe aim of the RUBY study was to evaluate novel candidate biomarkers to enable prediction of persistence of renal dysfunction as well as further understand potential mechanisms of kidney tissue damage and repair in acute kidney injury (AKI).MethodsThe RUBY study was a multi-center international prospective observational study to identify biomarkers of the persistence of stage 3 AKI as defined by the KDIGO criteria. Patients in the intensive care unit (ICU) with moderate or severe AKI (KDIGO stage 2 or 3) were enrolled. Patients were to be enrolled within 36 h of meeting KDIGO stage 2 criteria. The primary study endpoint was the development of persistent severe AKI (KDIGO stage 3) lasting for 72 h or more (NCT01868724).Results364 patients were enrolled of whom 331 (91%) were available for the primary analysis. One hundred ten (33%) of the analysis cohort met the primary endpoint of persistent stage 3 AKI. Of the biomarkers tested in this study, urinary C–C motif chemokine ligand 14 (CCL14) was the most predictive of persistent stage 3 AKI with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.83 (0.78–0.87). This AUC was significantly greater than values for other biomarkers associated with AKI including urinary KIM-1, plasma cystatin C, and urinary NGAL, none of which achieved an AUC > 0.75.ConclusionElevated urinary CCL14 predicts persistent AKI in a large heterogeneous cohort of critically ill patients with severe AKI. The discovery of CCL14 as a predictor of persistent AKI and thus, renal non-recovery, is novel and could help identify new therapeutic approaches to AKI.

Endurance Exercise Intervention Is Beneficial to Kidney Function in a Rat Model of Isolated Abdominal Venous Congestion: a Pilot Study.

In this study, the effects of moderate intense endurance exercise on heart and kidney function and morphology were studied in a thoracic inferior vena cava constricted (IVCc) rat model of abdominal venous congestion. After IVC surgical constriction, eight sedentary male Sprague-Dawley IVCc rats (IVCc-SED) were compared to eight IVCc rats subjected to moderate intense endurance exercise (IVCc-MOD). Heart and kidney function was examined and renal functional reserve (RFR) was investigated by administering a high protein diet (HPD). After 12weeks of exercise training, abdominal venous pressure, indices of body fat content, plasma cystatin C levels, and post-HPD urinary KIM-1 levels were all significantly lower in IVCc-MOD versus IVCc-SED rats (P < 0.05). RFR did not differ between both groups. The implementation of moderate intense endurance exercise in the IVCc model reduces abdominal venous pressure and is beneficial to kidney function.

Glomerular Filtration Rate Calculation Based on Serum Creatinin and Cystatin C in Type 2 Diabetic Patients

Glomerular Filtration Rate Calculation Based on Serum Creatinin and Cystatin C in Type 2 Diabetic Patients

Measurements of echocardiographic indices and biomarkers of kidney injury in dogs with chronic kidney disease

Pathophysiological cardiac and renal interactions are termed cardiovascular-renal disorder (CvRD). Cardiovascular disease/dysfunction secondary to kidney disease (CvRDK), is a leading cause of death in human chronic kidney disease (CKD) patients. The presence and clinical impact of CvRDK in dogs with CKD is unknown. We hypothesized that echocardiographic measurements, and cardiac and renal biomarkers, will be altered in dogs with CKD and associated with survival. Eleven dogs with CKD (n = 6 IRIS stage 2, n = 5 IRIS stage 3) and without primary cardiac disease, plus 12 healthy age-matched control dogs, were recruited to this prospective observational study. Dogs underwent standard echocardiography, glomerular filtration rate (GFR) estimation by iohexol clearance, and measurement of plasma cardiac troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP), plasma and urinary cystatin B, and urinary clusterin and neutrophil gelatinase-associated lipocalin (NGAL). Values were compared between groups, and their association with all-cause mortality explored.Dogs with CKD had significantly lower GFR and higher NT-proBNP, urinary cystatin B, clusterin, and NGAL, compared to controls (P < 0.05). Echocardiographic measurements were similar between dogs with CKD and controls. Median follow-up time was 666 days, during which six dogs with CKD died. Risk of death was associated with increasing age, serum total protein, and normalized left ventricular posterior wall thickness (LVPWDN) and decreasing bodyweight and packed cell volume. Although baseline differences in echocardiographic measurements were not evident between dogs with moderate CKD and controls, the presence of CvRDK was suggested by the association between LVPWDN and survival.

Plasma cystatin C versus renal resistive index as early predictors of acute kidney injury in critically ill neonates

Acute kidney injury (AKI) independently predicts morbidity and mortality of critically ill neonates. Serum cystatin C is a promising early biomarker for AKI. Evaluating the renal resistive index (RRI) by Doppler ultrasound demonstrates abnormal intrarenal vascular impendence. The objective of this study was to compare the ability of plasma cystatin C and the RRIto predict AKI early in critically ill neonates. Sixty critically ill neonates in neonatal intensive care units were assigned to three groups: group 1 (cases) of thirty participants fulfilling the AKI diagnostic criteria of neonatal Kidney Disease Improving Global Outcome, group 2 of thirty participants not fulfilling the criteria, as well as the 3rd group of thirty age- and sex-matching healthy participants. Group 1 demonstrated a significantly high mean cystatin C level during the 1st day of incubation compared with the other two groups [group 1 (3.18±1.25), group 2 (1.68±0.66), and group 3 (0.80±0.26)]. Serum creatinine and RRI were insignificantly different among all groups. At a cutoff value of 2.68 (mg/l), cystatin C level had significantly higher area under the curve (AUC) (0.804) than both serum creatinine (0.453) and RRI (0.551) and had 53.3% sensitivity and 100% specificity in the early prediction of neonates with AKI. The RRI had a lower non-significant AUC(0.551) at a cutoff value of 0.53 and had 100% sensitivity and 40% specificity, while serum creatinine had a low non-significant AUC(0.453) at a cutoff value of 0.49 (mg/dl) and had 33.3%sensitivity and 86.7%specificity. Applying regression analysis to predict AKI in critically ill neonates as early as possible, higher plasma cystatin C and lower estimated glomerular filtration rate cystatin were the only independent risk factors within critically ill neonates. The level of plasma cystatin C increased 48h before both RRI and serum creatinine did in critically ill neonates who developed AKI, soit is more reliable in predicting AKI in critically ill neonates than serum creatinine and RRI.

One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study.

The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge. Ancillary investigation of a prospective observational study. Twenty-one ICUs with 1-year follow-up. Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included. Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors. The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease). Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

Role of biomarkers as predictors of acute kidney injury and mortality in decompensated cirrhosis

Evidence suggests that novel biomarkers predict acute kidney injury (AKI) development and outcome earlier than serum creatinine. The aim of this study was to determine the incidence and prognosis of AKI in decompensated cirrhotic patients, and also assess the usefulness of plasma cystatin C, urine neutrophil gelatinase associated lipocalin (NGAL), tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) in early prediction of AKI and mortality. Single-center, prospective observational study enrolling decompensated cirrhotic patients without AKI at the time of admission. Of 111 patients with decompensated cirrhosis, 45 (40.5%) developed AKI while hospitalized. Even with 53.3% being transient (stage 1), mortality was significantly higher in AKI than non-AKI patients (46.5% vs. 25%, p = 0.02). Plasma cystatin C and urine NGAL, but not urine [TIMP-2]·[IGFBP7] at the time of admission were found to be independent early predictors of AKI. Substitution of cystatin C for creatinine significantly improved the model for end-stage liver disease (MELD) score accuracy for mortality prediction. The incidence of AKI is high and is associated with high mortality in decompensated cirrhotic patients. Plasma cystatin C and urine NGAL are useful for early detection of AKI. MELD-cystatin C, rather than original MELD, improves predictive accuracy of mortality.

A study of plasma Cystatin C as a marker of nephropathy in diabetes mellitus in a Tertiary Care Hospital

A study of plasma Cystatin C as a marker of nephropathy in diabetes mellitus in a Tertiary Care Hospital