Zhiguo Mao

Urinary Interleukin 18 for Detection of Acute Kidney Injury: A Meta-analysis

BACKGROUND Interleukin 18 (IL-18) has been proposed as a biomarker for the early detection of acute kidney injury (AKI), but a broad range of its predictive accuracy has been reported. STUDY DESIGN Meta-analysis of diagnostic test studies. SETTING & POPULATION Various clinical settings of AKI, including after cardiac surgery, after contrast infusion, in the emergency department, or in the intensive care unit. SELECTION CRITERIA FOR STUDIES Prospective studies that investigated the diagnostic accuracy of IL-18 level to predict AKI. INDEX TESTS Increasing or increased urinary IL-18 excretion. REFERENCE TESTS The primary outcome was AKI development, mainly based on serum creatinine level (definition varied across studies). The other outcome was in-hospital mortality. RESULTS We analyzed data from 23 studies and 7 countries involving 4,512 patients. Of these studies, 18 could be included in the meta-analysis. Across all settings, the diagnostic odds ratio (DOR) for urinary IL-18 level to predict AKI was 4.22 (95% CI, 2.90-6.14), with sensitivity and specificity of 0.58 and 0.75, respectively. The area under the receiver operating characteristic curve (AUROC) of urinary IL-18 level to predict AKI was 0.70 (95% CI, 0.66-0.74). Subgroup analysis showed the DOR/AUROC of urinary IL-18 was 5.32 (95% CI, 2.92-9.70)/0.72 (95% CI, 0.68-0.76) in cardiac surgery patients and 3.65 (95% CI, 1.88-7.10)/0.66 (95% CI, 0.62-0.70) in intensive care unit or coronary care unit patients. After stratification for age, IL-18 level had better diagnostic accuracy in children and adolescents versus adults: 8.12 (95% CI, 3.79-17.41)/0.78 (95% CI, 0.75-0.82) versus 3.31 (95% CI, 2.28-4.80)/0.66 (95% CI, 0.62-0.70). There was no significant difference in predictive performance of urinary IL-18 level among various times. LIMITATIONS Various clinical settings; different definition of AKI and serum creatinine level as the reference standard test for the diagnosis of AKI. CONCLUSIONS Urinary IL-18 is a useful biomarker of AKI with moderate predictive value across all clinical settings.

Intravascular administration of mannitol for acute kidney injury prevention: a systematic review and meta-analysis.

Background The effects of mannitol administration on acute kidney injury (AKI) prevention remain uncertain, as the results from clinical studies were conflicting. Due to the lack of strong evidence, the KDIGO Guideline for AKI did not propose completely evidence-based recommendations on this issue. Methods We searched PubMed, EMBASE, clinicaltrials.gov and Cochrane Controlled Trials Register. Randomized controlled trials on adult patients at increased risk of AKI were considered on the condition that they compared the effects of intravascular administration of mannitol plus expansion of intravascular volume with expansion of intravascular volume alone. We calculated pooled risk ratios, numbers needed to treat and mean differences with 95% confidence intervals for dichotomous data and continuous data, respectively. Results Nine trials involving 626 patients were identified. Compared with expansion of intravascular volume alone, mannitol infusion for AKI prevention in high-risk patients can not reduce the serum creatinine level (MD 1.63, 95% CI −6.02 to 9.28). Subgroup analyses demonstrated that serum creatinine level is negatively affected by the use of mannitol in patients undergoing an injection of radiocontrast agents (MD 17.90, 95% CI 8.56 to 27.24). Mannitol administration may reduce the incidence of acute renal failure or the need of dialysis in recipients of renal transplantation (RR 0.34, 95% CI 0.21 to 0.57, NNT 3.03, 95% CI 2.17 to 5.00). But similar effects were not found in patients at high AKI risk, without receiving renal transplantation (RR 0.29, 95% CI 0.01 to 6.60). Conclusions Intravascular administration of mannitol does not convey additional beneficial effects beyond adequate hydration in the patients at increased risk of AKI. For contrast-induced nephropathy, the use of mannitol is even detrimental. Further research evaluating the efficiency of mannitol infusions in the recipients of renal allograft should be undertaken.

Multislice Computed Tomographic Angiography in Evaluating Dysfunction of the Vascular Access in Hemodialysis Patients

Aims: To introduce our preliminary experience in using multislice computed tomographic (CT) angiography (MSCTA) to assess stenoses of the hemodialysis vascular access and to guide revising operation or percutaneous transluminal angioplasty (PTA). Methods: Contrast-enhanced 16-slice spiral CT was used to examine 22 hemodialysis patients with various dysfunctions of their vascular access. The transverse source images were reformatted as maximum intensity projection, volume-rendering, and multiple/curved planar reconstruction images. Results: The whole spectrum of arteriovenous fistulas (AVF) with the feeding artery, anastomoses, and outflow tract up to the superior caval vein was clearly displayed in all patients. According to the results of MSCTA, AVF-revising surgery was done in 11 patients, and PTA under the guide of digital subtraction angiography (DSA) was done in 5 patients. The results of MSCTA coincide with the findings of surgery or DSA in these 16 patients. Conclusions: In our opinion, MSCTA is a good noninvasive diagnostic technique to detect various hemodialysis vascular access abnormalities. It is more economical than DSA in the present medical settings and could replace DSA in the imaging of hemodialysis vascular access and provide important information for further AVF-revising surgery or PTA.

Peroxisome Proliferator-Activated Receptor Gamma Agonists in Kidney Disease – Future Promise, Present Fears

The peroxisome proliferator-activated receptor superfamily (PPARs) comprises a class of nuclear receptors with significant effects in regulating multiple cellular pathways. Much research and clinical interest has surrounded the PPAR-γ isoform because of its key role in the transcriptional regulation of metabolic pathways and the efficacy of thiazolidinediones, the most clinically used PPAR-γ agonist, in the management of type 2 diabetes mellitus. In this review, we discuss the pathogenic role of PPAR-γ in experimental models of kidney disease, clinical trials of thiazolidinediones in diabetic and non-diabetic kidney disease, recent safety concerns surrounding PPAR-γ agonists and reflect on their potential use in ‘orphan’ kidney diseases.

Clinical characteristics and disease predictors of a large Chinese cohort of patients with autosomal dominant polycystic kidney disease

Objective Autosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration. Methods To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥30 ml/min/1.73 m2. Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI). Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). A linear regression model was developed to analyze the factors which determine eGFR and TKV changes. Results The age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3±10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline log10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (r = 0.222) and higher TKV (r = 0.134). Conclusions This large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression.

Immunosuppressive treatment for nephrotic idiopathic membranous nephropathy: a meta-analysis based on Chinese adults.

Background Idiopathic membranous nephropathy (IMN) is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial. Objectives To assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN. Methods PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs) meeting the criteria was performed using Review Manager. Main Results 17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008), partial or complete remission (effective) (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003), and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC) was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX), leflunomide (LET) showed no beneficial effect, mycophenolate mofetil (MMF) showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006) but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15). Conclusions This analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.

Metabolic abnormalities in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder and is known to affect all ethnic groups with a prevalence of 1:400-1:1000 live births. The kidney in ADKPD is characterized by the formation of numerous cysts which progressively expand and eventually destroy normal kidney structure and function. Cysts occur in other organs outside the kidney, most commonly in the liver, pancreas and spleen. Important non-cystic features include intracranial aneurysms and cardiac valve defects. Less well recognized are a range of metabolic abnormalities, which could be involved in cystic disease progression or be associated with other disease complications. In this review, we summarize the literature suggesting that metabolic abnormalities could be important under-recognised and under-treated features in ADPKD.

Non-pharmacological interventions for improving sleep quality in patients on dialysis: systematic review and meta-analysis

We conducted a meta-analysis to summarise and quantify the effects of non-pharmacological interventions on sleep quality improvement in uraemic patients on dialysis. We defined the primary outcome as the change of sleep quality before and after interventions (evaluated by polysomonography or subjective questionnaires such as Pittsburgh sleep quality index, PSQI). The change of fatigue scales, inflammatory cytokines and adverse events were analysed as secondary outcomes. Twelve eligible randomised controlled trials and one prospective cohort study were identified. All three identified non-pharmacological interventions could result in a greater PSQI score reduction compared to controls: 1) cognitive-behavioural therapy (CBT) versus sleep hygiene education (standardised mean difference (SMD) 0.85, 95% CI 0.37-1.34); 2) physical training versus no training (SMD 3.36, 95% CI 2.16-4.57) and 3) Acupressure (including other acupoints massages) versus control (SMD 1.77, 95% CI 0.80-2.73). In terms of subscores, we found that CBT may shorten sleep latency, alleviate sleep disturbance and reduce the use of sleep medications. The finding of the cohort study suggested that intradialytic aerobic exercise training improved sleep quality in haemodialysis patients with restless leg syndrome. In conclusion, in dialysis-dependent patients, CBT could shorten sleep latency, alleviate sleep disturbance and reduce the use of sleep medications. Acupressure (including other acupoints massages) and exercise training are promising interventions but the results in these subgroups should be interpreted cautiously due to the concern of methodological quality and potential confounding factors.

Autosomal dominant polycystic kidney disease: recent advances in clinical management.

The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 st century. In this commentary, we consider how clinical management is likely to change in the coming decade.

Scientific Publications in Nephrology and Urology Journals from Chinese Authors in East Asia: A 10-Year Survey of the Literature

Background Diseases of the kidneys and genitourinary tract are common health problems that affect people of all ages and demographic backgrounds. In this study, we compared the quantity and quality of nephrological and urological articles published in international journals from the three major regions of China: the mainland (ML), Hong Kong (HK), and Taiwan (TW). Methods Nephrological and urological articles originating from ML, TW, and HK that were published in 61 journals from 1999–2008 were retrieved from the PubMed database. We recorded the numbers of total articles, clinical trials, randomized controlled trials, case reports, impact factors (IF), citations, and articles published in the leading general-medicine journals. We used these data to compare the quantity and quality of publication output from the three regions. Results The total number of articles increased significantly from 1999 to 2008 in the three regions. The number of articles from ML has exceeded that from HK since 2004, and surpassed that from TW in 2008. Publications from TW had the highest accumulated IF, total citations of articles, and the most articles published in leading general-medicine journals. However, HK publications had the highest average IF. Although ML produced the largest quantity of articles, it exhibited the lowest quality among the three regions. Conclusion The number of nephrological and urological publications originating from the three major regions of China increased significantly from 1999 to 2008. The annual number of publications by ML researchers exceeded those from TW and HK. However, the quality of articles from TW and HK was higher than that from ML.