Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50 µmol/L; ≥80 years, 54.41-96.43 µmol/L. RIs for females were: 18-59 years, 40.42-69.73 µmol/L; 60-79 years, 41.16-73.69 µmol/L; ≥80 years, 46.50-73.20 µmol/L. Q-values were set at 73.82 µmol/L (0.84 mg/dL) for males and 53.80 µmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

Evaluation of serum neutrophil gelatinase-associated lipocalin in older patients with chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is a major health-care burden all over the world, and aging is an important risk factor for end-stage renal disease (ESRD). Neutrophil gelatinase-associated lipocalin (NGAL) has been confirmed as a novel marker for early diagnosis of acute kidney injury. Other studies have found that NGAL takes part in the mechanisms of CKD progression. The aim of this study was to evaluate the expression of serum NGAL in CKD, particularly in elderly patients who rapidly progressed to end-stage renal failure. METHODS: Serum NGAL, cystatin C, creatinine, urea, and other factors were evaluated in a cohort of 160 CKD patients (mean age 75.29 ± 12.08 years) with various etiologies. RESULTS: Serum NGAL was closely related to cystatin C, creatinine, urea, and estimated glomerular filtration rate (eGFR). Special correlations between NGAL and, respectively, anemia and hypoalbuminemia were also found. The cutoff value of NGAL was calculated from Stage 2 to Stage 5. Receiver-operator curve analysis showed good area under the curve (>0.8) and high sensitivity (> 70%) on the cutoff value of NGAL. The NGAL levels increased progressively with the increasing of 2- and 5-year risk of ESRD using the Kidney Failure Risk Equations (KFRE). CONCLUSION: In elderly patients with CKD, serum NGAL reflects renal impairment and presents a strong and independent risk marker for progression of ESRD.

Mild cognitive impairment in maintenance hemodialysis patients: a cross-sectional survey and cohort study.

INTRODUCTION: Few studies focused on mild cognitive impairment (MCI) in maintenance hemodialysis (MHD) patients. This study was conducted to survey the prevalence, the potent risk factors of MCI in MHD patients, and further observe the progress of MCI in a period of 6 months. METHODOLOGY: Mini-Mental State Examination, and Montreal Cognitive Assessment were used to assess cognitive condition. MHD patients were enrolled from The First Affiliated Hospital of Nanjing Medical University, who had a stable hemodialysis history for more than 3 months. RESULTS: Sixty-four MHD patients and 54 general subjects were finally included. The average age of both groups was more than 60 years. The prevalence of MCI in the MHD group was significantly higher than that in general population (60.9% vs 29.6%, P<0.05). Spearman correlation analysis indicated that MCI was related to age, comorbidities, education years, uric acid, serum albumin, and blood pressure. The prevalence and severity of MCI in the MHD group remained unchanged during the 6 months (prevalence: 59.5%-66.6%, MoCA scores: 22.9-22.5). CONCLUSION: MHD patients sustain a fairly high prevalence of MCI. Multiple risk factors influence the incidence and progression of MCI in MHD patients. More attention should be paid to this special population.

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.

Serum protein profiling to identify biomarkers for small renal cell carcinoma.

Diagnostic biomarkers for early detection of renal cell carcinoma (RCC) are in great need. In the present study, we compared the serum protein profiles of patients with small RCC to those of healthy individuals to identify the differentially expressed proteins with potential to serve as biomarkers. Serum samples were collected from 10 patients with small RCC and 10 healthy individuals. The serum protein expression profiles were analyzed by two-dimensional (2-D) gel electrophoresis. Twenty-seven proteins with differences in expression levels between RCC patients and healthy volunteers were identified. Of these, 19 were expressed at different levels and eight were expressed in serum from the RCC group, but not from the control group. Six differentially expressed proteins identified by using mass spectrometry included coagulation factor XIII B, complement C3 and its precursor, misato homolog 1 (isoform CRA_b), hemopexin, and alpha-1-B-glycoprotein. Some of these serum proteins are known regulators of tumor progression in human malignancies. In conclusion, we successfully applied 2-D gel electrophoresis and identified six serum proteins differentially expressed between patients with small RCC and healthy volunteers. These proteins may provide novel biomarkers for early detection and diagnosis of human RCC.