Xiaohua Pei

Bone marrow stem cells‐derived microvesicles protect against renal injury in the mouse remnant kidney model

Aims:  Several studies have demonstrated administration of mesenchymal stem cells (MSC) could reverse kidney injury by paracrine mechanisms rather than by MSC transdifferentiation. Recently, a few researchers found microvesicles (MV) derived from MSC might be a paracrine mechanism for cell‐to‐cell communication. The aim of this study was to investigate the repair effects of MV in a 5/6 subtotal nephrectomy (Nx) mice model.

Systematic review and meta-analysis of mesenchymal stem/stromal cells therapy for impaired renal function in small animal models

The meta‐analysis of recent small animal experiments of mesenchymal stem/stromal cells (MSC) therapy for impaired kidney could provide significant clues to design large animal experiments as well as human clinical trials.

Comparisons between the 2012 New CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equations and Other Four Approved Equations

Objective The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) reported two equations in 2012: one based on cystatin C concentration (CKD-EPI2012cys) and the other using both serum creatinine and cystatin C concentrations (CKD-EPI2012Scr-cys). We compared the adaptability of new formulae with other four equations. Methods Participants (n = 788; median age, 54 [range, 19–94] years) were recruited from the First Affiliated Hospital of Nanjing Medical University. The reference glomerular filtration rate (rGFR) was measured by a 99mTc-DTPA renal dynamic imaging method, and the estimated glomerular filtration rate (eGFR) was calculated separately by the Chinese adapted Modification of Diet in Renal Disease equation (C-MDRD), MacIsaac, Ma, serum creatinine-based CKD-EPI equation (CKD-EPI2009Scr), CKD-EPI2012cys and CKD-EPI2012Scr-cys equations. We compared the performance of six equations with rGFR. Results Median rGFR was 76.35 (interquartile range, 59.03–92.50) mL/min/1.73 m2. Compared with CKD-EPI2009Scr, CKD-EPI2012Scr-cys formula had better diagnostic value with larger area under the receiver operating characteristic curve (ROCAUC, 0.879, p = 0.006), especially in young participants (ROCAUC, 0.883, p = 0.005). CKD-EPI2012cys equation did not perform better than other available equations. Accuracy (the proportion of eGFR within 30% of rGFR [P30]) of the CKD-EPI2012Scr-cys equation (77.03%) was inferior only to MacIsaac equation (80.2%) in the entire participants, but performed best in young participants with normal or mildly-injured GFR. Neither of the two new CKD-EPI equations achieved any ideal P30 in the elderly participants with moderately-severely injured GFR. Linear regression analysis demonstrated a consistent result. In this study, CKD-EPI2012Scr-cys had a relatively better diagnosis consistency of GFR stage between the eGFR and rGFR in the whole cohort. Conclusion CKD-EPI2012Scr-cys appeared less biased and more accurate in overall participants. Neither of the new CKD-EPI equations achieved ideal accuracy in senior participants with moderately-severely injured GFR. A large-scale study with more subjects and cooperating centers to develop new formulae for the elderly is assumed to be necessary.

Micro-vesicles derived from bone marrow stem cells protect the kidney both in vivo and in vitro by microRNA-dependent repairing

Micro‐vesicles (MVs) from bone mesenchymal stem cells (MSCs) have been shown to contribute to the recovery of damaged kidney. The aims of the present study are to investigate the biological effects and repair mechanisms of MVs.

Evaluation of serum creatinine- and cystatin C-based equations for the estimation of glomerular filtration rate in a Chinese population

Abstract Objective. This study aimed to evaluate the applicability of a selection of glomerular filtration rate (GFR) estimating equations based on serum creatinine (SCr) and serum cystatin C in a Chinese population. Material and methods. Estimated GFR values from 10 equations were compared with reference GFR (rGFR) from the 99mTc-DTPA renal dynamic imaging method. The study enrolled 569 Chinese participants (41.5% women, 53.5 ± 16.9 years, range 19–92 years), with mean rGFR 74.80 ± 26.10 (range 9.8–146.8 ml/min/1.73 m2). Results. Bland–Altman analysis illustrated that the 95% agreement limits of all the equations surpassed the acceptable tolerance (<60 ml/min/1.73 m2), of which the MacIsaac equation was the closest one, reaching 71.7 ml/min/1.73 m2. Linear regression analysis also demonstrated a consistent result. When assessed in all participants, the accuracy of the six equations reached and exceeded the acceptable level (≥70%), of which the Shanghai and MacIsaac equations gained more accuracy than others. When compared in subgroups, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), MacIsaac and Cockcroft–Gault (CG) equations were optimal for rGFR stages ≥ 90 ml/min/1.73 m2, 30–89 ml/min/1.73 m2 and < 30 ml/min/1.73 m2, respectively. Conclusion. The results demonstrated that further improvement is needed for the selected 10 equations. Not all the cystatin C equations were superior to SCr equations. They have their own applicability at various GFR levels. At present, the CKD-EPI, MacIsaac and CG equations may be applied to evaluate GFR in normal, mild to moderate and severe kidney function, respectively.

Using Mathematical Algorithms to Modify Glomerular Filtration Rate Estimation Equations

Background The equations provide a rapid and low-cost method of evaluating glomerular filtration rate (GFR). Previous studies indicated that the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease-Epidemiology (CKD-EPI) and MacIsaac equations need further modification for application in Chinese population. Thus, this study was designed to modify the three equations, and compare the diagnostic accuracy of the equations modified before and after. Methodology With the use of 99 mTc-DTPA renal dynamic imaging as the reference GFR (rGFR), the MDRD, CKD-EPI and MacIsaac equations were modified by two mathematical algorithms: the hill-climbing and the simulated-annealing algorithms. Results A total of 703 Chinese subjects were recruited, with the average rGFR 77.14±25.93 ml/min. The entire modification process was based on a random sample of 80% of subjects in each GFR level as a training sample set, the rest of 20% of subjects as a validation sample set. After modification, the three equations performed significant improvement in slop, intercept, correlated coefficient, root mean square error (RMSE), total deviation index (TDI), and the proportion of estimated GFR (eGFR) within 10% and 30% deviation of rGFR (P10 and P30). Of the three modified equations, the modified CKD-EPI equation showed the best accuracy. Conclusions Mathematical algorithms could be a considerable tool to modify the GFR equations. Accuracy of all the three modified equations was significantly improved in which the modified CKD-EPI equation could be the optimal one.

Reference Intervals for Serum Cystatin C and Factors Influencing Cystatin C Levels Other than Renal Function in the Elderly

Objective The present study aimed to establish reference intervals for serum cystatin C (Scys-C) stratified by stages of chronic kidney disease, explore factors influencing Scys-C and compare the performance of Scys-C with serum creatinine (Scr) in the young and elderly. Methods A total of 800 participants, 516 young (<60 years) and 284 old (≥60 years) subjects were included in this study. Scys-C and Scr were assayed by the partical-enhanced immunoturbidimetry method and enzymatic method respectively. 95% reference interval was adopted to evaluate reference intervals. Influencing factors were characterized by multivariate linear regression analysis. Relationship between reference glomerular filtration rate (rGFR) and Scys-C or Scr was determined by correlation coefficient. Results Reference intervals for Scys-C were calculated to be 0.71–1.38 mg/L, 0.83–1.67 mg/L, 1.02–2.61 mg/L, 1.32–4.48 mg/L, 1.95–6.11 mg/L in the aged in CKD G1, G2, G3a, G3b and G4-5 stages, respectively. Body mass index(BMI), nephritis, kidney neoplasm and hypertension were demonstrated as factors affecting Scys-C in the elderly while gender, nephritis and kidney neoplasm were clarified as influencing factors in the young group. Scr levels were affected by more factors, such as body surface area and hematological disease. Correlation coefficient between rGFR and Scys-C or Scr showed that serum Scys-C was superior to Scr, especially in the subjects with mildly decreased renal function (−0.593 vs. −0.520). Conclusions Factors other than renal function influenced Scys-C when applying to evaluate glomerular filtration rate (GFR), such as BMI, nephritis, kidney neoplasm and hypertension, and Scys-C had higher correlation with GFR than Scr in the elderly.

Application of creatinine- and/or cystatin C-based glomerular filtration rate estimation equations in elderly Chinese

Background No conventional creatinine- or cystatin C-based glomerular filtration rate (GFR) estimation equation performed consistently outstandingly in elderly Chinese in our previous studies. This research aimed to further evaluate the performance of some recently proposed estimation equations based on creatinine and cystatin C, alone or combined, in this specific population. Materials and methods The equations were validated in a population totaling 419 participants (median age 68 [range 60–94] years). The estimated GFR (eGFR) calculated separately by ten equations was compared with the reference GFR (rGFR) measured by the 99mTc-DTPA renal dynamic imaging method. Results Median serum creatinine, cystatin C, and rGFR levels were 0.93 mg/L, 1.13 mg/L, and 74.20 mL/min/1.73 m2, respectively. The Chinese population-developed creatinine- and cystatin C-based (Cscr-cys) equation yielded the least median absolute difference (8.81 vs range 9.53–16.32, P<0.05, vs the Chronic Kidney Disease Epidemiology Collaboration serum creatinine equation), the highest proportion of eGFR within 15% and 30% of rGFR (P15 and P30, 55.13 and 85.44, P<0.05 and P<0.01, vs the Chronic Kidney Disease Epidemiology Collaboration serum creatinine equation), and the lowest root mean square error (14.87 vs range 15.30–22.45) in the whole cohort. A substantial agreement of diagnostic consistency between eGFR and rGFR (with a kappa 0.61–0.80) was also observed with the Cscr-cys equation. Moreover, measures of performance in the Cscr-cys equation were consistent across normal to mildly injured GFR strata and individuals aged ≤80 years. Among all the Cscr-cys equations, the elderly Chinese-developed creatinine-based (CEscr) equation performed best in this specific population. Nevertheless, none of the equations achieved ideal manifestation in the moderately to severely GFR-injured group or in individuals aged ≥80 years. Conclusion The Cscr-cys equation appeared to be optimal in elderly Chinese among the investigated equations. If cystatin C is not available, the CEscr equation is an acceptable alternative. A multicenter study with abundant subjects to develop an apposite formula for elderly Chinese is assumed to be essential.

Predictive value of serum cystatin C for acute kidney injury in adults: a meta-analysis of prospective cohort trials.

The role of serum cystatin C (Scys) for the detection of acute kidney injury (AKI) has not been fully discussed. This meta-analysis was aimed to investigate the overall diagnostic accuracy of Scys for AKI in adults, and further identify factors affecting its performance. Studies before Sept. 2016 were retrieved from PubMed, Embase, Web of Science and the Cochrane Library. A total of 30 prospective cohort studies (involving 4247 adults from 15 countries, 982 patients occurring AKI) were included. The revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tools demonstrated no significant bias had influenced the methodological quality of the included studies. Scys showed a high predictive power for all-cause AKI, that the area under the receiver operating characteristic curve was 0.89. The detailed assessment parameters, such as sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for Scys were 0.82, 0.82, 4.6, 0.22 and 21, respectively. Although Scys could be slightly influenced by the following factors: settings, AKI diagnostic criteria, ethnicity, determination method, age and gender, these factors above did not reach statistically significance. In conclusion, Scys could be a vital promising marker to screen out AKI.

Diagnostic value of cystatin C and glomerular filtration rate formulae in Chinese nonelderly and elderly populations

BACKGROUND Serum cystatin C has been recognized as a surrogate marker for serum creatinine (SCr). However, whether cystatin C and cystatin C-based glomerular filtration rate (GFR) formulae offer any diagnostic value in nonelderly and elderly subjects has rarely been investigated. METHODS Reference GFR (rGFR) values were established using the 99mTc-DTPA renal dynamic imaging method. Nine GFR formulae were used to predict estimated GFR (eGFR). RESULTS A total of 534 Chinese participants were enrolled. Cystatin C had a better diagnostic value than SCr. The superiority of cystatin C was more distinctly observed in the elderly. Combined cystatin C and SCr gave similar diagnostic values to cystatin C alone (p>0.05). Compared with single markers, GFR prediction formulae improved accuracy. Each formula had its own characteristics and applicability. Most formulae predicted with higher accuracy in the elderly than they did in the nonelderly. In chronic kidney disease (CKD) stage 1, the CKD-EPI formula had the least bias and the highest accuracy for the nonelderly, while the Hojs and Ma formulae performed best for the elderly. In the CKD stage 2-3, the Macisaac formula gave the most accurate eGFR. In the CKD stage 4-5, it was the CG formula that gave the closest estimate to the rGFR. CONCLUSIONS Cystatin C could be superior to SCr, particularly in the elderly; however, cystatin C formulae and SCr formulae may possess their own applicability in different CKD stages and age groups. At present, it is not possible to say that cystatin C formulae are superior to SCr formulae.