Nuclear Condensation of CDYL Links Histone Crotonylation and Cystogenesis in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Emerging evidence indicates that epigenetic modulation of gene expression plays a key role in the progression of autosomal dominant polycystic kidney disease (ADPKD). However, the molecular basis for how the altered epigenome modulates transcriptional responses, and thereby disease progression in ADPKD, remains largely unknown. METHODS: Kidneys from control and ADPKD mice were examined for the expression of CDYL and histone acylations. CDYL expression and its correlation with disease severity were analyzed in a cohort of patients with ADPKD. Cdyl transgenic mice were crossed with Pkd1 knockout mice to explore CDYL's role in ADPKD progression. Integrated cistromic and transcriptomic analyses were performed to identify direct CDYL target genes. High-sensitivity mass spectrometry analyses were undertaken to characterize CDYL-regulated histone lysine crotonylations (Kcr). Biochemical analysis and zebrafish models were used for investigating CDYL phase separation. RESULTS: CDYL was downregulated in ADPKD kidneys, accompanied by an increase of histone Kcr. Genetic overexpression of Cdyl reduced histone Kcr and slowed cyst growth. We identified CDYL-regulated cyst-associated genes, whose downregulation depended on CDYL-mediated suppression of histone Kcr. CDYL assembled nuclear condensates through liquid-liquid phase separation in cultured kidney epithelial cells and in normal kidney tissues. The phase-separating capacity of CDYL was required for efficient suppression of locus-specific histone Kcr, of expression of its target genes, and of cyst growth. CONCLUSIONS: These results elucidate a mechanism by which CDYL nuclear condensation links histone Kcr to transcriptional responses and cystogenesis in ADPKD.

Xper computed tomography-guided translumbar inferior vena cava catheterization for long-term hemodialysis: A case report and literature review.

Hemodialysis is the most widely used renal replacement therapy for end-stage renal disease patients. Exhausted vascular access due to repeated indwelling central venous catheters is becoming a challenging clinical problem, which also contributes to reduced survival of the hemodialysis patients. Lack of conventional peripheral and central venous access mandates the use of alternative strategies. We present a case of translumbar dialysis catheter (TLDC) for long-term hemodialysis in a patient with central venous occlusion refractory to conventional endovascular techniques. After a careful literature review, totally 10 cohort studies including 216 cases through TLDC were reported. The incidence of procedure-related complications was very low. The catheter-related infection rate of TLDC was comparable with overall tunneled cuffed catheters (TCCs) reported by clinical practice guidelines for vascular access. Although the patency might be relatively low due to the catheter-related complications, TLDC could be rescued by multiple systemic and topical medications and interventional therapies. Percutaneous translumbar placement of a cuffed tunneled hemodialysis catheter directly into the inferior vena cava (IVC) can provide a relatively safe salvage when traditional central venous sites such as the internal jugular, femoral, subclavian veins are unavailable. Xper computed tomography together with real-time fluoroscopic guidance can reduce the intraoperative risks and complications.

[Research progress on the cardiorenal protection of non-steroid mineralocorticoid receptor antagonists in patients with chronic kidney disease].

Mineralocorticoid receptor antagonists not only are used as a diuretics to treat essential hypertension, but also protect the heart and kidney by inhibiting inflammation and fibrosis. Since the discovery of spironolactone, the first generation of mineralocorticoid receptor antagonist, two types of non-steroid mineralocorticoid receptor antagonists (finerenone and esaxerenone) approved for clinical use have been developed, which have the advantages of high affinity, high selectivity and balanced distribution in heart and kidney, and can be used in clinic as a cardiorenal protective drug. In this paper, the development history of mineralocorticoid receptor antagonists was reviewed, and the pathophysiological mechanism of inflammation and fibrosis caused by mineralocorticoid receptors and the similarities and differences of different generations of mineralocorticoid receptor antagonists were analyzed. In particular, the phase III clinical research evidence of finerenone and esaxerenone was discussed. This paper also reviews the research progress of cardiorenal protection of non-steroid mineralocorticoid receptor antagonists in patients with chronic kidney disease.

PKD2 gene variants in Chinese patients with autosomal dominant polycystic kidney disease.

PKD2 gene variants account for 4.5% to 20% of patients with autosomal dominant polycystic kidney disease (ADPKD). Little is known about the clinical characteristics of PKD2 variants in Chinese patients with ADPKD. Herein, we performed a comprehensive search for variants of PKD2 gene in 44 Chinese ADPKD pedigrees and a total of 37 variants were identified. Of these 37 variants, 18 were nonsense variants, 10 frameshift variants, 4 missense variants, and 5 splice site variants. 11/37 variants were detected for the first time. The median age at diagnosis was 30.5 years, and positive family history was detected in 77.27% patients, liver cysts in 68.18%, hypertension in 45.45%, nephrolithiasis in 31.82%, macro-hematuria in 22.73%, and proteinuria in 13.63%. The level of estimated glomerular filtration rate in 8/39 patients were blow 60 ml/min/1.73m2 . 11/17 patients were classified as rapid progression by Mayo Clinic classification. The end stage renal disease (ESRD) events were reported in 9/22 pedigrees, and the presence of nephrolithiasis and macro-hematuria were significantly associated with ESRD in the pedigrees with PKD2 variants. The identified variants and clinical features will facilitate the early diagnosis and prognosis prediction in Chinese ADPKD patients with PKD2 variants.

Development and validation of a nomogram to predict overall survival for patients with metastatic renal cell carcinoma.

BACKGROUND: Heterogeneity of metastatic renal cell carcinoma (RCC) constraints accurate prognosis prediction of the tumor. We therefore aimed at developing a novel nomogram for accurate prediction of overall survival (OS) of patients with metastatic RCC. METHODS: We extracted 2010 to 2016 data for metastatic RCC patients in the Surveillance, Epidemiology, and End Results (SEER) database, and randomly stratified them equally into training and validation sets. Prognostic factors for OS were analyzed using Cox regression models, and thereafter integrated into a 1, 3 and 5-year OS predictive nomogram. The nomogram was validated using the training and validation sets. The performance of this model was evaluated by the Harrell's concordance index (C-index), calibration curve, integrated discrimination improvement (IDI), category-free net reclassification improvement (NRI), index of prediction accuracy (IPA), and decision curve analysis (DCA). RESULTS: Overall, 2315 metastatic RCC patients in the SEER database who fulfilled our inclusion criteria were utilized in constructing a nomogram for predicting OS of newly diagnosed metastatic RCC patients. The nomogram incorporated eight clinical factors: Fuhrman grade, lymph node status, sarcomatoid feature, cancer-directed surgery and bone, brain, liver, and lung metastases, all significantly associated with OS. The model was superior to the American Joint Committee on Cancer (AJCC) staging system (7th edition) both in training (C-indices, 0.701 vs. 0.612, P < 0.001) and validation sets (C-indices, 0.676 vs. 0.600, P < 0.001). The calibration plots of the nomogram corresponded well between predicted and observed values. NRI, IDI, and IPA further validated the superior predictive capability of the nomogram relative to the AJCC staging system. The DCA plots revealed reliable clinical application of our model in prognosis prediction of metastatic RCC patients. CONCLUSIONS: We developed and validated an accurate nomogram for individual OS prediction of metastatic RCC patients. This nomogram can be applied in design of clinical trials, patient counseling, and rationalizing therapeutic modalities.

Nocturnal Hemodialysis Compared with Conventional Dialysis for End-Stage Renal Disease Treatment in Polycystic Kidney Disease Patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage renal disease (ESRD). Little is known about outcomes after in-center nocturnal hemodialysis (NHD) treatment in ADPKD patients with ESRD. OBJECTIVES: This study aimed to evaluate the effects of in-center NHD compared with conventional hemodialysis (CHD) and peritoneal dialysis (PD) in ADPKD. METHODS: We used data of ADPKD adult patients with ESRD in the hospital database from 2000 to 2016. Propensity score matching, competing-risk regression, and Cox regression models were used for analysis. RESULTS: A total of 170 ADPKD patients were included. The median follow-up time was 5.5 years. In the overall multivariate-adjusted analysis, no significant difference of mortality risk was found in NHD vs. CHD (hazard ratio [HR] 1.33, 95% CI 0.26-6.73, p = 0.31) and PD (HR 1.06, 95% CI 0.14-7.71, p = 0.55), respectively. The overall survival rate also was not significantly different among the 3 groups (p = 0.88). Based on the propensity score, 26 patients on CHD and 26 patients on PD were successfully matched to 13 NHD patients. In the matched analysis, NHD was not associated with a lower risk of mortality compared with CHD (HR 2.14, 95% CI 0.33-14.00, p = 0.31) and PD (HR 0.68, 95% CI 0.52-8.94, p = 0.55). The result was similar when treating renal transplantation as a competing event. However, NHD was associated with a lower rate of complications (38.5 vs. 84.6%, p = 0.003) and a higher level of serum albumin (p < 0.001) compared with PD. CONCLUSIONS: NHD may not be a better choice in survival compared with conventional dialysis modalities for ADPKD patients in this pilot study. Patients in NHD have fewer complications than PD. Future studies with large sample sizes and longer follow-up are required.

CTCF regulates the FoxO signaling pathway to affect the progression of prostate cancer.

The present research focuses on the influence of CCCTC-binding factor (CTCF) on prostate cancer (PC) via the regulation of the FoxO signalling pathway. A bioinformatics analysis was conducted to screen out target genes for CTCF in LNCaP cells and to enrich the relevant pathways in LNCaP cells. It was found that the FoxO pathway was enriched according to the ChIP-seq results of CTCF. The expression of CTCF, pFoxO1a, FoxO1a, pFoxO3a and FoxO3a was tested by RT-qPCR and Western blot. Inhibition of CTCF could lead to the up-regulation of the FoxO signalling pathway. The rates of cell proliferation, cell invasion and apoptosis were examined by MTT assay, cell invasion assay and flow cytometry under different interference conditions. Down-regulation of CTCF could suppress cell proliferation, cell invasion and facilitate cell apoptosis. Lastly, the effect of CTCF on tumour growth was determined in nude mice. Inhibition of CTCF regulated the FoxO signalling pathway, which retarded tumour growth in vivo. In conclusion, CTCF regulates the FoxO signalling pathway to affect the progress of PC.

Ketamine induces reactive oxygen species and enhances autophagy in SV-HUC-1 human uroepithelial cells.

This study was aimed at exploring the underlying mechanisms of ketamine in the SV-40 immortalized human ureteral epithelial (SV-HUC-1) cells. The viability and apoptosis of SV-HUC-1 cells treated with 0.01, 0.1, and 1 mM ketamine were respectively detected via cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Reactive oxygen species (ROS) level was measured through ROS probe staining. Apoptosis-related proteins (B-cell lymphoma 2 [Bcl-2] and Bax) and autophagy-associated proteins (light chain 3-I [LC3-I] and LC3-II) were determined by western blot or immunofluorescent assay. Additionally, transmission electron microscopy (TEM) was used to evaluate the formation of autophagosomes. After cotreatment of 3-methyladenine (3-MA) or N-acetyl-l-cysteine (NAC), the biological functions of SV-HUC-1 cells were analyzed to determine the association of ROS with cell viability and autophagy. CCK-8 assay and TUNEL staining indicated that ketamine effectively decreased the viability of SV-HUC-1 cells and accelerated apoptosis of SV-HUC-1 cells through regulating the expression level of IKBα (phospho), nuclear factor ÐºB (P65), Bcl-2, and Bax proteins. Enhanced ROS production was also confirmed in ketamine-treated SV-HUC-1 cells treated with ketamine. Ketamine-induced autophagosomes in SV-HUC-1 cells were observed by means of TEM, and increased levels of LC3 II/I ratio and Beclin 1 were examined through western blot and immunofluorescent assay. Furthermore, ketamine exerted effects on SV-HUC-1 cells in a dose-dependent and time-dependent manner. Additionally, cotreatment of NAC with 3-MA significantly attenuated the ROS level and suppressed the cell autophagy. Ketamine promoted SV-HUC-1 cell autophagy and impaired the cell viability of SV-HUC-1 cells by inducing ROS.

miR-30c-5p Reduces Renal Ischemia-Reperfusion Involving Macrophage.

BACKGROUND Ischemia-reperfusion (I/R) leads to kidney injury. Renal I/R frequently occurs in kidney transplantations and acute kidney injuries. Recent studies reported that miR-30 stimulated immune responses and reductions in renal I/R related to anti-inflammation. Our study investigated the effects of miR-30c-5p on renal I/R and the relationship among miR-30c-5p, renal I/R, and macrophages. MATERIAL AND METHODS Sprague Dawley rats received intravenous tail injections of miR-30c-5p agomir. Then a renal I/R model were established by removing the left kidney and clamping the right renal artery. Serum creatinine (Cr) was analyzed using a serum Cr assay kit, and serum neutrophil gelatinase associated lipocalin (NGAL) was measured using a NGAL ELISA (enzyme-linked immunosorbent assay) kit. Rat kidney tissues were analyzed using hematoxylin and eosin staining. THP-1 cells treated with miR-30c-5p agomir and miR-30c-5p antagomir were measured with quantitative reverse transcription-polymerase chain reaction. Protein levels were analyzed by western blot. RESULTS MiR-30c-5p agomir reduced serum Cr, serum NGAL, and renal I/R injury. MiR-30c-5p agomir inhibited the expression of CD86 (M1 macrophage marker), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-alpha) and promoted the expression of CD206 (M2 macrophage marker), interleukin (IL)-4, and IL-10 in rat kidneys. MiR-30c-5p agomir reduced the expression of CD86 and iNOS, and increased the expression of CD206 and IL-10 in THP-1 cells. CONCLUSIONS We preliminarily demonstrated that miR-30c-5p agomir might decrease renal I/R through transformation of M1 macrophages to M2 macrophages and resulted in changes in inflammatory cytokines.

Catheterization in a patient with end-stage renal disease through persistent left superior vena cava: a rare case report and literature review.

BACKGROUND: Persistent left superior vena cava (PLSVC) is a common vena cava malformation, and drains blood into the right atrium via the dilated coronary sinus in most cases. It is usually asymptomatic and detected incidentally during invasive procedures or imaging. Whether the hemodialysis catheters can be placed in PLSVC is still controversial now (Stylianou et al. Hemodial Int 11:42-45, 2007). CASE PRESENTATION: Here we report a rare case of catheterization through PLSVC in an end-stage renal disease (ESRD) male patient whose PLSVC connected with pulmonary vein with insufficient blood flow eventually. Among the other 28 cases included in the literature review, 16 cases were non-tunneled catheter and 12 cases were cuffed, tunneled catheter and most of them could provide adequate blood flow. CONCLUSION: PLSVC is a rare malformation and mostly asymptotic, we believe that PLSVC drains blood into the right atrium with enough inner diameter and blood flow can serve as an alternative site for conventional dialysis access. However, the feasibility of hemodialysis catheterization through it and measures to avoid serious complications are still needed to be discussed.

Comparison of Three Methods Estimating Baseline Creatinine For Acute Kidney Injury in Hospitalized Patients: a Multicentre Survey in Third-Level Urban Hospitals of China.

BACKGROUND/AIMS: A lack of baseline serum creatinine (SCr) data leads to underestimation of the burden caused by acute kidney injury (AKI) in developing countries. The goal of this study was to investigate the effects of various baseline SCr analysis methods on the current diagnosis of AKI in hospitalized patients. METHODS: Patients with at least one SCr value during their hospital stay between January 1, 2011 and December 31, 2012 were retrospectively included in the study. The baseline SCr was determined either by the minimum SCr (SCrMIN) or the estimated SCr using the MDRD formula (SCrGFR-75). We also used the dynamic baseline SCr (SCrdynamic) in accordance with the 7 day/48 hour time window. AKI was defined based on the KDIGO SCr criteria. RESULTS: Of 562,733 hospitalized patients, 350,458 (62.3%) had at least one SCr determination, and 146,185 (26.0%) had repeat SCr tests. AKI was diagnosed in 13,883 (2.5%) patients using the SCrMIN, 21,281 (3.8%) using the SCrGFR-75 and 9,288 (1.7%) using the SCrdynamic. Compared with the non-AKI patients, AKI patients had a higher in-hospital mortality rate regardless of the baseline SCr analysis method. CONCLUSIONS: Because of the scarcity of SCr data, imputation of the baseline SCr is necessary to remedy the missing data. The detection rate of AKI varies depending on the different imputation methods. SCrGFR-75 can identify more AKI cases than the other two methods.

Knockdown of mediator subunit Med19 suppresses bladder cancer cell proliferation and migration by downregulating Wnt/ß-catenin signalling pathway.

Mediator complex subunit 19 (Med19), a RNA polymerase II-embedded coactivator, is reported to be involved in bladder cancer (BCa) progression, but its functional contribution to this process is poorly understood. Here, we investigate the effects of Med19 on malignant behaviours of BCa, as well as to elucidate the possible mechanisms. Med19 expression in 15 BCa tissues was significantly higher than adjacent paired normal tissues using real-time PCR and Western blot analysis. Immunohistochemical staining of 167 paraffin-embedded BCa tissues was performed, and the results showed that high Med19 protein level was positively correlated with clinical stages and histopathological grade. Med19 was knocked down in BCa cells using short-hairpin RNA. Functional assays showed that knocking-down of Med19 can suppress cell proliferation and migration in T24, UM-UC3 cells and 5637 in vitro, and inhibited BCa tumour growth in vivo. TOP/FOPflash reporter assay revealed that Med19 knockdown decreased the activity of Wnt/ß-catenin pathway, and the target genes of Wnt/ß-catenin pathway were down-regulated, including Wnt2, ß-catenin, Cyclin-D1 and MMP-9. However, protein levels of Gsk3ß and E-cadherin were elevated. Our data suggest that Med19 expression correlates with aggressive characteristics of BCa and Med19 knockdown suppresses the proliferation and migration of BCa cells through down-regulating the Wnt/ß-catenin pathway, thereby highlighting Med19 as a potential therapeutic target for BCa treatment.

Fibroblast Growth Factor 23 Predicts All-Cause Mortality in a Dose-Response Fashion in Pre-Dialysis Patients with Chronic Kidney Disease.

BACKGROUND: Quantitative dose-response associations between fibroblast growth factor 23 (FGF23) and risks of mortality, cardiovascular disease (CVD), and renal events in chronic kidney disease (CKD) are not known. This study aimed to summarize and quantify the predictive effects of FGF23 among the pre-dialysis CKD stages 1-5 population. METHODS: Data sources included PubMed, EMBASE, and Web of Science. Prospective cohort studies assessing the associations between FGF23 and all-cause mortality, CVD, and renal events in CKD patients were selected. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. The composite higher or the highest level in FGF23 categories of each study was considered the high level. The reference level was regarded as the low level in the overall analysis. The restricted cubic spline model was used to estimate dose-response associations. RESULTS: Fifteen prospective cohort studies centered around 15,355 subjects were analyzed. A high FGF23 level was associated with increased risks of all-cause mortality (RR 1.46, 95% CI 1.38-1.55, p < 0.001), CVD (RR 1.37, 95% CI 1.15-1.63, p < 0.001), and renal events (RR 1.31, 95% CI 1.07-1.59, p = 0.008), respectively. There was a positive, nonlinear, dose-response relationship between FGF23 and all-cause mortality. The reference level in dose-response analysis was defined as 51 RU/mL of c-terminal FGF23. We then calculated RRs for increments of 20 RU/mL, which was associated with increased risks of mortality (RR 1.04, 95% CI 1.00-1.07, p = 0.038), CVD (RR 1.02, p < 0.001), and renal events (RR 1.01, p < 0.001), respectively. CONCLUSIONS: There may be positive dose-response predictive effects of FGF23 on all-cause mortality, CVD, and renal events in patients with CKD.

The mutation-free embryo for in vitro fertilization selected by MALBAC-PGD resulted in a healthy live birth from a family carrying PKD 1 mutation.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD, autosomal dominant PKD or adult-onset PKD) is the most prevalent and potentially lethal kidney disease that is hereditary and lacks effective treatment. Preimplantation genetic diagnosis (PGD) of embryos in assistant reproductive technology (ART) helps to select mutation-free embryos for blocking ADPKD inheritance from the parents to their offspring. However, there are multiple pseudogenes in the PKD1 coding region, which make blocking ADPKD inheritance by PGD complicated and difficult. Therefore, this technique has not been recommended and used routinely to ADPKD family plan. METHODS AND RESULTS: Here, we report a new strategy of performing PGD in screening (target-) mutation-free embryos. We firstly used a long-range PCR amplification and next generation sequencing to identify the potential PKD1 mutant(s). After pathogenic variants were detected, multiple annealing and looping-based amplification cycles (MALBAC), a recently developed whole genome amplification method, was used to screen embryo cells. We successfully distinguished the mutated allele among pseudogenes and obtained mutation-free embryos for implantation. The first embryo transfer attempt resulted in a healthy live birth free of ADPKD condition and chromosomal anomalies which was confirmed by aminocentesis at week 18 of gestation, and by performing live birth genetic screening. CONCLUSIONS: The first MALBAC-PGD attempt in ADPKD patient resulted in a healthy live birth free of ADPKD and chromosomal anomalies. MALBAC-PGD also enables selecting embryos without aneuploidy together and target gene mutation, thereby increasing implantation and live birth rates.

Estrogen receptor α in cancer-associated fibroblasts suppresses prostate cancer invasion via modulation of thrombospondin 2 and matrix metalloproteinase 3.

The prostate cancer (PCa) microenvironment contains active stromal cells known as cancer-associated fibroblasts (CAF) that may play important roles in influencing tumor progression. Here we studied the role of CAF estrogen receptor alpha (ERα) and found that it could protect against PCa invasion. Immunohistochemistry on prostatectomy specimens showed that PCa patients with ERα-positive stroma had a significantly lower risk for biochemical recurrence. In vitro invasion assays further confirmed that the stromal ERα was able to reduce PCa cell invasion. Dissection of the molecular mechanism revealed that the CAF ERα could function through a CAF-epithelial interaction via selectively upregulating thrombospondin 2 (Thbs2) and downregulating matrix metalloproteinase 3 (MMP3) at the protein and messenger RNA levels. Chromatin immunoprecipitation assays further showed that ERα could bind to an estrogen response element on the promoter of Thbs2. Importantly, knockdown of Thbs2 led to increased MMP3 expression and interruption of the ERα mediated invasion suppression, providing further evidence of an ERα-Thbs2-MMP3 axis in CAF. In vivo studies using athymic nude mice injected with CWR22Rv1 (22Rv1) PCa epithelial cells and CAF cells ± ERα also confirmed that mice coimplanted with PCa cells and CAF ERα+ cells had less tumor foci in the pelvic lymph nodes, less metastases, and tumors showed less angiogenesis, MMP3, and MMP9 (an MMP3 downstream target) positive staining. Together, these data suggest that CAF ERα could play protective roles in suppressing PCa metastasis. Our results may lead to developing new and alternative therapeutic approaches to battle PCa via controlling ERα signaling in CAF.

Idiopathic nodular glomerulosclerosis in Chinese patients: a clinicopathologic study of 20 cases.

BACKGROUND: The objective of this study is to investigate the frequency and clinicopathological features of idiopathic nodular glomerulosclerosis (ING) in Chinese patients, on which there has been no previously published information. METHODS: Native kidney biopsies performed at a kidney histopathological center in Shanghai between January 1, 2009 and December 31, 2011 were retrospectively examined and relevant clinical data were reviewed. RESULTS: All kidney biopsy specimens (3,480) were examined. After excluding specimens from patients with diabetes, fasting hyperglycemia or hemoglobin A1c elevation and other known entities associated with nodular glomerulosclerosis, 20 ING cases (1 in 174 biopsies) were identified. Patients with ING had a median age of 55.5 years, 16 (80 %) were male, 19 (95 %) had a body mass index (BMI) ≥25 kg/m(2) [BMI ≥30 in 8 (40 %)], 18 (90 %) were hypertensive, 17 (85 %) had a history of cigarette smoking (mean pack-years 19.8 ± 2.4), and 10 (50 %) had hyperlipidemia. All 20 patients had >1 g/day proteinuria with a mean of 2.85 ± 0.33 g/day (seven had nephrotic-range proteinuria). Mean serum creatinine at the time of kidney biopsy was 4.23 ± 0.53 mg/dL (338.2 ± 44.7 µmol/L). Histopathologically, all specimens showed varying degrees of nodular glomerulosclerosis, glomerular basement membrane thickening, foot process effacement, interstitial fibrosis and arterial hyalinosis/sclerosis. Immunofluorescence was non-specific. At follow-up of 22.1 ± 1.15 days post-biopsy, six patients had developed end-stage renal failure and five had worsening serum creatinine concentrations not requiring dialysis. CONCLUSION: ING is rare and appears to be associated with overweight, hypertension and cigarette smoking in Chinese patients.

Carcinosarcoma of native renal pelvis in recipient after a renal transplant: a case report.

BACKGROUND: Carcinosarcoma is a malignancy that rarely occurs in the renal pelvis. MATERIALS AND METHODS: We present a case of histologically proven, native renal pelvis carcinosarcoma in a 65-year-old woman who had accepted a renal transplant. We performed a laparoscopic ureterectomy, combined with lymph node dissection and immunosuppression with sirolimus (SRL), which was alternated with the conventional immunosuppressant--cyclosporine. RESULTS: This patient was still alive 34 months after renal transplantation. CONCLUSIONS: Operation is still the best choice, and the SRL may be beneficial for preventing the progression of a tumor.

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.