Transcriptomic Profiling Identifies Neutrophil-Specific Upregulation of Cystatin F as a Marker of Acute Inflammation in Humans.

Cystatin F encoded by CST7 is a cysteine peptidase inhibitor known to be expressed in natural killer (NK) and CD8+ T cells during steady-state conditions. However, little is known about its expression during inflammatory disease states in humans. We have developed an analytic approach capable of not only identifying previously poorly characterized disease-associated genes but also defining regulatory mechanisms controlling their expression. By exploring multiple cohorts of public transcriptome data comprising 43 individual datasets, we showed that CST7 is upregulated in the blood during a diverse set of infectious and non-infectious inflammatory conditions. Interestingly, this upregulation of CST7 was neutrophil-specific, as its expression was unchanged in NK and CD8+ T cells during sepsis. Further analysis demonstrated that known microbial products or cytokines commonly associated with inflammation failed to increase CST7 expression, suggesting that its expression in neutrophils is induced by an endogenous serum factor commonly present in human inflammatory conditions. Overall, through the identification of CST7 upregulation as a marker of acute inflammation in humans, our study demonstrates the value of publicly available transcriptome data in knowledge generation and potential biomarker discovery.

Comment on: Evaluation of early biomarkers of renal dysfunction in diabetic patients.

[No Abstract Available].

Evaluation of Novel Biomarkers for Early Diagnosis of Acute Kidney Injury in Asphyxiated Full-Term Newborns: A Case-Control Study.

OBJECTIVES: To investigate the changes of serum cystatin C (Cys-C), beta 2-microglobulin (ß2-MG), urinary neutrophil gelatinase-associated lipocalin (NGAL), and alpha 1-microglobulin (α1-MG) in asphyxiated neonates, and to evaluate the value of combined detection of multiple biomarkers in the early diagnosis of acute kidney injury (AKI) in asphyxiated neonates. METHODS: A total of 110 full-term asphyxiated and 30 healthy neonates were included. The asphyxia neonates were divided into AKI and non-AKI groups. Serum Cys-C, ß2-MG, urine NGAL, and α1-MG were measured 24 h after birth. The diagnostic value of the biomarkers was determined using receiver operating characteristic (ROC) curves. RESULTS: There was no significant difference in serum creatinine and blood urea nitrogen among the control group, moderate asphyxia group, and severe asphyxia group at 24 h after birth. Significant differences were noticed in terms of serum Cys-C, ß2-MG, urinary NGAL, and α1-MG among the 3 groups. Moreover, with the aggravation of asphyxia, the above indicators gradually increased. There were significant differences in the 4 indicators between the AKI and non-AKI groups (p < 0.05). The area under the ROC curve of the above indicators was 0.670, 0.689, 0.865, and 0.617, respectively (p < 0.05). The sensitivity and specificity of the combined diagnosis of asphyxia neonatorum AKI with the 4 indicators were 0.974 and 0.506, respectively. CONCLUSIONS: Serum Cys-C, ß2-MG, urine NGAL, and α1-MG are early specific indicators for the diagnosis of renal injury after neonatal asphyxia. Combined detection of these parameters could aid clinical evaluation of renal injury in asphyxiated neonates.

An update on the use and discovery of prognostic biomarkers in acute decompensated heart failure.

Introduction: Acute decompensated heart failure (ADHF) remains a significant health care burden as evidenced by high readmission rates and mortality. Over the years, the care of patients with ADHF has been transformed by the use of biomarkers, specifically to aid in the diagnosis and prognosis. Patients with HF follow a variable course given the complex and heterogenous pathophysiological processes, thus it is imperative for clinicians to have tools to predict short and long-term outcomes in order to educate patients and optimize management. Areas Covered: The natriuretic peptides, including B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, are considered the gold standard biomarkers. Yet, other emerging biomarkers such as suppression of tumerogenicity-2, cardiac troponin, galectin-2, mid-regional pro-adrenomedullin, copeptin, cystatin, and neutrophil gelatinase-associated lipocalin have increasingly shown promise in evaluating prognosis in patients with ADHF. This article reviews the pathophysiology and utility of both established and emerging biomarkers for the prognostication of patients with ADHF. Expert Opinion: As of 2019, the most validated biomarkers for use in decompensated heart failure include natriuretic peptides, high sensitivity troponin, and sST2. These biomarkers are involved in the underlying pathophysiology of disease and as such provide added information to that of exam, x-ray, and echocardiography.

Clinical evaluation of presepsin considering renal function.

Presepsin, a glycoprotein produced during bacterial phagocytosis, is used as a sepsis marker for bacterial infections. However, presepsin levels are affected by renal function, and the evaluation criteria according to kidney function or in chronic kidney diseases remain controversial. Furthermore, presepsin may be increased by sample stirring, but no studies have evaluated this effect.In this study, we excluded the effect of stirring by standardizing the blood collection conditions, analyzed the influence of kidney function on presepsin concentrations, and recalculated the reference range based on the findings. EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected to measure presepsin by PATHFAST. Presepsin was found to be significantly correlated with the levels of creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845), and eGFRcys (r = 0.879). Furthermore, in patients with CKD, presepsin levels stratified by eGFRcys showed a significant increase in the CKD G2 patient group and with advancing glomerular filtration rate stage. The following values were obtained: Normal: 97.6 ± 27.4 pg/mL, CKD G1: 100.2 ± 27.6 pg/mL, CKD G2: 129.7 ± 40.7 pg/mL, CKD G3: 208.1 ± 70.2 pg/mL, CKD G4: 320.2 ± 170.1 pg/mL, CKD G5: 712.8 ± 336.3 pg/mL. The reference range, calculated by a nonparametric method using 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59-153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with a few biomarkers of renal function, indicating the necessity to consider the effect of renal function in patients with renal impairment. Using the recalculated reference range considering kidney function may improve the accuracy of evaluating presepsin for diagnosis of sepsis compared to the standard reference currently in use.

Colour Doppler and Biomarkers Utility for Renal Damage due to Congenital Hydronephrosis.

OBJECTIVE: To determine colour doppler and serum biomarkers spectrum in children with congenital hydronephrosis. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Pediatric Nephrology, West China 2nd University Hospital of Sichuan University and Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), China, from January to December 2017. METHODOLOGY: A total of 95 children with hydronephrosis were selected as case group. According to the degree of hydronephrosis, the patients were divided into mild hydronephrosis group, moderate hydronephrosis group, and severe hydronephrosis group. Forty children with normal renal function were selected as normal comparison group. Peak systolic velocity (Vmax), end diastolic velocity (Vmin), resistance index (RI), pulsatility index (PI), and serum cystatin C (CysC), ß2-microglobulin (ß2-MG), and 1-microglobulin (ß1-MG) of all subjects in both groups were recorded and compared. RESULTS: The Vmax, Vmax of main renal artery (MRA) and interlobar renal artery (IRA) in case group were lower than those of normal group (all p<0.001). RI of MRA and IRA in case group were higher than those of normal control group (both p<0.001). There were no significant differences in the PI of MRA and IRA between the two groups (p=0.700, and 0.250 respectively). The levels of serum CysC, ß2-MG and α1-MG in normal control group, mild hydronephrosis group, moderate hydronephrosis group, and severe hydronephrosis group were significantly different (all p<0.001), and the levels of serum CysC, ß2-MG, α1-MG were also different in children with different degrees of hydronephrosis. CONCLUSION: Combined detection of colour doppler and serum biomarkers CysC, ß2-MG and α1-MG in the diagnosis of renal damage in congenital hydronephrosis is feasible and reliable.

Combination of Cystatins 9 and C Modulates Serum Biomarkers Associated with Inflammation and Provides Prophylactic as Well as Long-Term Protection against Multidrug-Resistant Klebsiella pneumoniae.

We have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-ß-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 K. pneumoniae pneumonia. Results showed that rCST9/rCSTC treatment modulated endogenous serum biomarkers, cystatins 9 and C and amyloid A, associated with poor patient outcomes and provided prophylactic and long-term protection in a murine model of pneumonia.

Selective abdominal venous congestion to investigate cardiorenal interactions in a rat model.

Abdominal congestion may play an important role in the cardiorenal syndrome and has been demonstrated to drive disease progression. An animal model for abdominal congestion, without other culprit mechanisms that are often present in patients such as low cardiac output or chronic kidney disease, might be interesting to allow a better study of the pathophysiology of the cardiorenal syndrome. The objective of this study was to develop a clinically relevant and valid rat model with abdominal venous congestion and without pre-existing heart and/or kidney dysfunction. To do so, a permanent surgical constriction (20 Gauge) of the thoracic inferior vena cava (IVC) was applied in male Sprague Dawley rats (IVCc, n = 7), which were compared to sham-operated rats (SHAM, n = 6). Twelve weeks after surgery, abdominal venous pressure (mean: 13.8 vs 4.9 mmHg, p < 0.01), plasma creatinine (p < 0.05), plasma cystatin c (p < 0.01), urinary albumin (p < 0.05), glomerular surface area (p < 0.01) and width of Bowman's space (p < 0.05) of the IVCc group were significantly increased compared to the SHAM group for a comparable absolute body weight between groups (559 vs 530g, respectively, p = 0.73). Conventional cardiac echocardiographic and hemodynamic parameters did not differ significantly between both groups, indicating that cardiac function was not compromised by the surgery. In conclusion, we demonstrate that constriction of the thoracic IVC in adult rats is feasible and significantly increases the abdominal venous pressure to a clinically relevant level, thereby inducing abdominal venous congestion.

The Association between Glomerular Filtration Rate Estimated Using Different Equations and Mortality in the Japanese Community-Based Population: The Yamagata (Takahata) Study.

BACKGROUND: To evaluate renal function, the indices of estimated glomerular filtration rate (eGFR) obtained using several equations, including the Japanese versions of the serum creatinine-based MDRD equation (eGFRcreat), Chronic Kidney Disease Epidemiology Collaboration equation (eGFR-EPI), and serum cystatin C-based equation (eGFRcys), are utilized. This study prospectively examined the association between these eGFR values and all-cause mortality during a 12-year observational period in a community-based population. METHODS AND RESULTS: The subjects of this study were 1312 participants undergoing a health checkup, aged ≥40 years. In the total population, the mean eGFR values (mL·min-1·1.73 m-2) were 81.5 for eGFRcreat, 78.1 for eGFR-EPI, and 76.6 for eGFRcys. There were 141 deaths during the observation period, and the area under the receiver operating characteristic curve for predicting mortality was 0.59 for eGFRcreat, 0.67 for eGFR-EPI, and 0.70 for eGFRcys (all P < 0.01). In the Cox proportional analysis adjusted for age and sex, eGFRcys, but not eGFRcreat and eGFR-EPI, showed a significant association with all-cause mortality (per 15 mL·min-1·1.73 m-2 decrease: hazard ratio 1.40, 95% confidence interval 1.18-1.67). CONCLUSIONS: This study revealed that eGFRcys showed lower values than eGFRcreat and eGFR-EPI and was significantly associated with all-cause mortality in the Japanese community-based population.

Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury.

Traumatic brain injury (TBI) is set to become the leading cause of neurological disability across all age groups. Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries. Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions. Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins. Using the Proseek Multiplex Inflammation assay, we measured in patients that had suffered mild TBI (n = 10) or severe TBI (n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92 inflammation-associated proteins in serum obtained: <1 hr (within 1-hour), 4-12 hr and 48-72 hr post injury. Changes were compared to healthy volunteers (HV). Our results identified CST5, AXIN1 and TRAIL as novel early biomarkers of TBI. CST5 identified patients with severe TBI from all other cohorts and importantly was able to do so within the first hour of injury. AXIN1 and TRAIL were able to discriminate between TBI and HV at <1 hr. We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.

Comparison of creatinine and cystatin formulae with 51 Chromium-ethylenediaminetetraacetic acid glomerular filtration rate in patients with decompensated cirrhosis.

BACKGROUND AND AIM: Evaluation of renal function, that is, glomerular filtration rate (GFR), has become very important, but conventional mathematical formulae for GFR assessment are inaccurate in patients with cirrhosis. The aim of the present study was to compare serum creatinine (sCr)-based and serum cystatin C (cysC)-based estimated GFR (eGFR) formulae with 51 Chromium-ethylenediaminetetraacetic acid GFR (51 Chr-GFR) in patients with stable decompensated cirrhosis. METHODS: In 129 Caucasian patients with decompensated cirrhosis, we assessed sCr-based GFRs [Modification of Diet in Renal Disease and chronic kidney disease-epidemiology (CKD-EPI)-sCr formulae], cysC-based GFRs [Hoek, Larsson, and CKD-EPI-cysC equations], and the mathematical formulae, which combined both sCr and cysC [i.e. CKD-EPI-sCr-cysC and the specific for cirrhotics formula recently proposed by Mindikoglu et al. (Mindikoglu-eGFR)]. Multivariate linear regression analysis was used for GFR predictors in our cohort. RESULTS: The correlations between 51 Chr-GFR and all mathematical formulae were good (Spearman r2 > 0.68, P < 0.001). Modification of Diet in Renal Disease and CKD-EPI-sCr had lower bias (6.6 and -4.8, respectively), compared with the other eGFRs, while Mindikoglu-eGFR and CKD-EPI-sCr-cysC formulae had greater precision (17.1 and 17.3, respectively), compared with the other eGFRs. CKD-EPI-sCr and Mindikoglu-eGFR had higher accuracy (39% and 41%, respectively), compared with the other eGFRs. The factors independently associated with the 51 Chr-GFR were age, cysC, and sCr, and the new derived formula had lower bias (0.89) and similar precision (17.2) and accuracy (41%) with Mindikoglu-eGFR formula. CONCLUSION: The specific mathematical formulae derived from patients with cirrhosis seem to provide superior assessment of renal function, compared with the conventional used sCr-based and cysC-based formulae.

Estimated glomerular filtration rate calculated using different creatinine and cystatin based formulas in prediction of trough plasma Dabigtran concentration.

BACKGROUND: In this paper we evaluated the relationship between trough DAB concentration with eGFR calculated using CRE and CYS based formulas. MATERIALS AND METHODS: We considered 100 patients. eGFR was calculated using CKD-EPIcreat, CG, MDRD, CKD-EPIcys and CKD-EPIcombined equations. DAB dosage was selected on the basis of CKD-EPIcreat and relationship between trough DAB concentration and eGFRs was evaluated. RESULTS: Trough DAB concentration roughly correlates with eGFR calculated using various formulas. CKD-EPIcreat eGFR was higher than CKD-EPIcys. In patients receiving a DAB dosage considered adequate using CKD-EPIcreat eGFR but considered excessive using CKD-EPIcys, we observed higher DAB trough concentration and an increased prevalence of subjects with drug concentration >200ng/mL. CONCLUSION: These results suggest that eGFR alone was unable to fully explain trough DAB plasma concentration. Therefore a drug's prescription schedule based on eGFR only should be inadequate. We observed a better correlation between trough DAB concentration and CKD-EPIcys rather than CKD-EPIcreat eGFR. Thus, in patients chronically treated with DAB for thromboprophylaxis in nonvalvular atrial fibrillation evaluation of eGFR using a cystatin base formula should be considered.

Diagnostic Biomarkers in Women With Suspected Preeclampsia in a Prospective Multicenter Study.

OBJECTIVE: To evaluate 47 biomarkers (selected from the current medical literature), in isolation or in combination with placental growth factor (PlGF), to determine the need for delivery within 14 days, in women presenting with suspected preterm preeclampsia. METHODS: In a prospective, multicenter observational study, 47 biomarkers were measured in 423 women presenting with suspected preterm preeclampsia (in two prespecified groups: group 1 at less than 35 weeks of gestation and group 2 presenting between 35 0/7 and 36 6/7 weeks of gestation) to evaluate their ability to determine the primary endpoint: preeclampsia requiring delivery within 14 days. Using factor analysis and stepwise logistic regression, we sought one or more additional biomarkers for optimal determination of the primary endpoint. RESULTS: In women presenting at less than 35 weeks of gestation (n=286), the best performing combination of PlGF, podocalyxin, endoglin, procalcitonin (receiver operating curve [ROC] area 0.90, 95% confidence interval [CI] 0.86-0.93) was not statistically better than PlGF alone (ROC 0.87, 95% CI 0.83-0.92; P=.43) for preeclampsia requiring delivery within 14 days. Two other single markers had test performance that was not significantly different to PlGF (soluble fms-like tyrosine kinase-1 [sFlt-1] ROC 0.83, 95% CI 0.78-0.88; endoglin ROC 0.83, 95% CI 0.79-0.88). Similar findings were found in women presenting between 35 0/7 and 36 6/7 weeks of gestation (n=137): ROC for PlGF alone 0.75 (95% CI 0.67-0.83); ROC for PlGF, cystatin, pregnancy-associated plasma protein A in combination 0.81 (95% CI 0.74-0.88; P=.40). CONCLUSION: This study supports the growing body of evidence that a single angiogenesis-related biomarker (PlGF, sFlt-1, or endoglin) alone represents a useful diagnostic test for women presenting with suspected preterm preeclampsia.

The Preinterventional Cystatin-Creatinine-Ratio: A Prognostic Marker for Contrast Medium-Induced Acute Kidney Injury and Long-Term All-Cause Mortality.

BACKGROUND/AIMS: Contrast medium-induced acute kidney injury (CI-AKI) is an important iatrogenic complication following the injection of iodinated contrast media. The level of serum creatinine (SCr) is the currently accepted 'gold standard' to diagnose CI-AKI. Cystatin C (CyC) has been detected as a more sensitive marker for renal dysfunction. Both have their limitations. METHODS: The role of the preinterventional CyC-SCr ratio for evaluating the risk for CI-AKI and long-term all-cause mortality was retrospectively analyzed in the prospective single-center 'Dialysis-versus-Diuresis trial'. CI-AKI was defined and staged according to the Acute Kidney Injury Network classification. RESULTS: Three hundred and seventy-three patients were included (average age 67.4 ± 10.2 years, 16.4% women, 29.2% with diabetes mellitus, mean baseline glomerular filtration rate 56.3 ± 20.2 ml/min/1.73 m(2) [as estimated by Chronic Kidney Disease Epidemiology Collaboration Serum Creatinine Cystatin C equation], 5.1% ejection fraction <35%). A total of 79 patients (21.2%) developed CI-AKI after elective heart catheterization, and 65 patients (17.4%) died during follow-up. Multivariate analyses by logistic regression confirmed that the preinterventional CyC-SCr ratio is independently associated with CI-AKI (OR 9.423, 95% CI 1.494-59.436, p = 0.017). Also, the Cox regression model found a high significant association between preinterventional CyC-SCr ratio and long-term all-cause mortality (mean follow-up 649 days, hazards ratio 4.096, 95% CI 1.625-10.329, p = 0.003). CONCLUSION: The preinterventional CyC-SCr ratio is independently associated with CI-AKI and highly significant associated with long-term mortality after heart catheterization.

Cost-effectiveness analysis of acute kidney injury biomarkers in pediatric cardiac surgery.

INTRODUCTION: Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnosis of AKI in children after cardiac surgery compared with current diagnostic method (monitoring of serum creatinine (sCr) level). MATERIALS AND METHODS: We developed a decision analytical model to estimate incremental cost-effectiveness of different biomarker-based diagnostic strategies compared to current diagnostic strategy. The Markov model was created to compare the lifetime cost associated with using of sCysC, uNGAL, uL-FABP with monitoring of sCr level for the diagnosis of AKI. The utility measurement included in the analysis was quality-adjusted life years (QALY). The results of the analysis are presented as the incremental cost-effectiveness ratio (ICER). RESULTS: Analysed biomarker-based diagnostic strategies for AKI were cost-effective compared to current diagnostic method. However, uNGAL and sCys C strategies yielded higher costs and lower effectiveness compared to uL-FABP strategy. uL-FABP added 1.43 QALY compared to current diagnostic method at an additional cost of $8521.87 per patient. Therefore, ICER for uL-FABP compared to sCr was $5959.35/QALY. CONCLUSIONS: Our results suggest that the use of uL-FABP would represent cost effective strategy for early diagnosis of AKI in children after cardiac surgery.

Variations in glomerular filtration rate are associated with subclinical atherosclerosis in healthy postmenopausal women.

OBJECTIVE: This study aims to evaluate the potential effects of renal function variations on vascular structure before the development of hypertension. METHODS: This pilot study included 141 postmenopausal women without evidence of renal dysfunction or hypertension. Markers of renal function and levels of glomerular filtration rate (GFR)--using standard calculations (GFR based on levels of creatinine [GFR(epi)]) and newer creatinine and/or cystatin calculations (GFR based on levels of creatinine and cystatin [GFR(cr cystatin)] and GFR based on levels of cystatin [GFR(cystatin)])--were associated with hemodynamic parameters and markers of vascular structure (intima-media thickness [IMT] and presence of atheromatous plaques in carotid and femoral arteries). RESULTS: Levels of GFR(epi), GFR(cr cystatin), and GFR(cystatin) exhibited a significant negative correlation with femoral artery IMT, whereas levels of GFR(epi) correlated significantly with mean carotid bulb (CB) IMT. Multivariate analysis showed that CB-IMT was predicted by GFR(epi) levels and age (ß-coefficient = -0.212, P = 0.020), whereas femoral artery IMT was predicted by GFR(epi) levels (ß-coefficient = -0.293, P = 0.001). GFR(epi) levels lower than the 25th percentile were associated with higher CB-IMT (P = 0.009), femoral artery IMT (P = 0.001), and combined IMT (P = 0.035) compared with higher GFR(epi) levels. Moreover, GFR(epi) levels greater than the 25th percentile were associated with lower odds for the presence of atherosclerotic plaques at the CB and carotid arteries combined (CB: odds ratio, 0.146; P = 0.006; combined: odds ratio, 0.249; P = 0.043) compared with lower GFR(epi) levels. CONCLUSIONS: A mild decrease in renal function within normal limits of GFR is independently associated with the presence of subclinical atherosclerosis in a sample of apparently healthy young postmenopausal women. Assessment of GFR using creatinine (vs cystatin C) levels is a more sensitive marker of its association with IMT and atherosclerotic plaques in this postmenopausal population.

Type of uromodulin mutation and allelic status influence onset and severity of uromodulin-associated kidney disease in mice.

Uromodulin-associated kidney disease (UAKD) is a dominant heritable renal disease in humans which is caused by mutations in the uromodulin (UMOD) gene and characterized by heterogeneous clinical appearance. To get insights into possible causes of this heterogeneity of UAKD, we describe the new mutant mouse line Umod(C93F), leading to disruption of a putative disulfide bond which is also absent in a known human UMOD mutation, and compare the phenotype of this new mouse line with the recently published mouse line Umod(A227T). In both mutant mouse lines, which were both bred on the C3H background, the Umod mutations cause a gain-of-toxic function due to a maturation defect of the mutant uromodulin leading to a dysfunction of thick ascending limb of Henle's loop (TALH) cells of the kidney. Umod mutant mice exhibit increased plasma urea and Cystatin levels, impaired urinary concentration ability, reduced fractional excretion of uric acid and nephropathological alterations including uromodulin retention in TALH cells, interstitial fibrosis and inflammatory cell infiltrations, tubular atrophy and occasional glomerulo- und tubulocystic changes, a phenotype highly similar to UAKD in humans. The maturation defect of mutant uromodulin leads to the accumulation of immature uromodulin in the endoplasmic reticulum (ER) and to ER hyperplasia. Further, this study was able to demonstrate for the first time in vivo that the severity of the uromodulin maturation defect as well as onset and speed of progression of renal dysfunction and morphological alterations are strongly dependent on the particular Umod mutation itself and the zygosity status.

[The established and reintroduced markers of kidney functions].

The article considers different techniques supporting clinician in evaluation of kidney function and kidneys damage. The actual studies data can assist to determine usefulness of many new markers and to clarify their role in treatment of patients with risk of development of kidneys diseases.

Surface Plasmon Resonance Imaging biosensor for cystatin determination based on the application of bromelain, ficin and chymopapain.

A Surface Plasmon Resonance Imaging (SPRI) sensor based on bromelain or chymopapain or ficin has been developed for specific cystatin determination. Cystatin was captured from a solution by immobilized bromelain or chymopapain or ficin due to the formation of an enzyme-inhibitor complex on the biosensor surface. The influence of bromelain, chymopapain or ficin concentration, as well as the pH of the interaction on the SPRI signal, was investigated and optimized. Sensor dynamic response range is between 0-0.6 µg/ml and the detection limit is equal to 0.1 µg/ml. In order to demonstrate the sensor potential, cystatin was determined in blood plasma, urine and saliva, showing good agreement with the data reported in the literature.

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury.