Handgrip strength and mortality in a cohort of kidney failure patients: Comparative analysis of different normalization methods.

OBJECTIVES: Reduced handgrip strength (HGS) is associated with adverse clinical outcomes. We analyzed and compared associations of HGS with mortality risk in dialysis patients, using different normalization methods of HGS. METHODS: HGS and clinical and laboratory parameters were measured in a cohort of 446 incident dialysis patients (median age 56 y, 62% men). The area under the receiver operating characteristic curve (AUROC) was used to compare different normalization methods of HGS as predictors of mortality: absolute HGS in kilograms; HGS normalized to height, weight, or body mass index; and HGS of a reference population of sex-matched controls (percentage of the mean HGS value [HGS%]). Multivariate linear regression analysis was used to assess HGS predictors. Competing risk regression analysis was used to evaluate 5-year all-cause mortality risk. Differences in survival time between HGS% tertiles were quantitated by analyzing the restricted mean survival time. RESULTS: The AUROC for HGS% was higher than the AUROCs for absolute or normalized HGS values. Compared with the high HGS% tertile, low HGS% (subdistribution hazard ratio [sHR] = 2.36; 95% CI, 1.19-3.70) and middle HGS% (sHR = 1.79; 95% CI, 1.12-2.74) tertiles were independently associated with higher all-cause mortality and those with high HGS% tertile survived on average 7.95 mo (95% CI, 3.61-12.28) and 18.99 mo (95% CI, 14.42-23.57) longer compared with middle and low HGS% tertile, respectively. CONCLUSIONS: HGS% was a strong predictor of all-cause mortality risk in incident dialysis patients and a better discriminator of survival than absolute HGS or HGS normalized to body size dimensions.

The role of irisin in kidney diseases.

Irisin is a hormone that is produced mainly by skeletal muscles in response to exercise. It has been found to have a close correlation with obesity and diabetes mellitus for its energy expenditure and metabolic properties. Recent research has revealed that irisin also possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, which make it associated with major chronic diseases, such as chronic kidney disease (CKD), liver diseases, osteoporosis, atherosclerosis and Alzheimer s disease. The identification of irisin has not only opened up new possibilities for monitoring metabolic and non-metabolic diseases but also presents a promising therapeutic target due to its multiple biological functions. Studies have shown that circulating irisin levels are lower in CKD patients than in non-CKD patients and decrease with increasing CKD stage. Furthermore, irisin also plays a role in many CKD-related complications like protein energy wasting (PEW), cardiovascular disease (CVD) and chronic kidney disease-mineral and bone disorder (CKD-MBD). In this review, we present the current knowledge on the role of irisin in kidney diseases and their complications.

Interleukin-6-to-Albumin Ratio as a Superior Predictor of Mortality in End-Stage Kidney Disease Patients.

INTRODUCTION: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients. METHODS: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time. RESULTS: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40-3.52) and 1.85 (95% CI 1.16-2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality. CONCLUSIONS: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD.

RNA-Seq-based transcriptomics analysis during the photodynamic therapy of primary cells in secondary hyperparathyroidism.

BACKGROUND: The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. METHODS: Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. RESULTS: In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM-receptor interaction, focal adhesion and protein digestion and absorption. Protein-protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. CONCLUSIONS: The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT.

Cardiovascular Risk Prediction in Chronic Kidney Disease.

BACKGROUND: As one of the main complications of chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) in CKD patients is high. CVD risk is markedly increased even at early stages of CKD, and CVD deaths account for half of all known causes of mortality in end-stage renal disease patients. The alarming rate of CVD in CKD patients demands accurate risk prediction to identify individuals at greater risk and therefore needing intensive surveillance and treatment in order to improve their prognosis. SUMMARY: Since the CVD risk prediction models used in general population did not perform well in CKD patients, novel CVD risk biomarkers and improved risk predictive models adapted to CKD are receiving increasing attention in recent years. In this article, we review the applicability and performance of some of the available cardiovascular risk prediction tools in CKD. KEY MESSAGES: Cardiovascular risk prediction in CKD needs and deserves continued attention and in-depth research that helps clinicians set out timely and effective interventions.

Progress in volume assessment for the hemodialysis patients. / è¡€æ¶²é€æžæ‚£è€ å®¹é‡è¯„ä¼°æ–°è¿›å±•.

Volume overload is widespread in the hemodialysis (HD) patients, which is closely related to cardiovascular complications, hospitalization rates, hospitalization costs, and mortality. Meanwhile it is an important independent prognostic risk factor. Some new technologies for volume assessment have made some progress and are gradually applied in clinical practice, such as blood volume monitoring, lung ultrasound examination, bioelectrical impedance analysis, and corrected flow time. The new technologies can provide clinicians more objective and efficient methods for assessing the volume status of the HD patients, which is beneficial to the HD patients because they can achieve an ideal volume balance and improve the prognosis.

Roxadustat for treatment of erythropoietin-hyporesponsive anemia in a hemodialysis patient: A case report.

BACKGROUND: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is a prevalent problem in patients with chronic kidney disease. It is associated with increased morbidity and mortality in patients who undergo dialysis. A significant proportion of patients do not respond to iron supplementation and conventional ESAs. We report a case of severe ESA hyporesponsiveness-related anemia that was successfully treated with oral roxadustat. CASE SUMMARY: A 59-year-old Chinese woman had high blood glucose for 25 years, maintenance hemodialysis for 7 years, and recurrent dizziness and fatigue for more than 2 years. Laboratory tests showed severe anemia (hemoglobin level of 54 g/L), though bone marrow biopsy, fluorescence in situ hybridization, and hemolysis tests were within normal ranges. We initially administered first-line therapies and other adjuvant treatments, such as blood transfusions, ESAs, and adequate dialysis, but the patient did not respond as anticipated. Her erythropoietin-resistant anemia was probably not only due to chronic renal insufficiency. The patient received the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (100 mg, three times weekly). After 12 wk of treatment, the patient's hemoglobin increased significantly, and her symptoms were alleviated. During the follow-up period, adverse drug reactions were controllable and tolerable. CONCLUSION: Oral roxadustat is effective and tolerable for the treatment of ESA hypores-ponsiveness-related anemia in patients undergoing hemodialysis.

Application of regional citrate anticoagulation in membrane therapeutic plasma exchange.

BACKGROUND: Both regional citrate anticoagulation (RCA) and heparin are used as anticoagulants during membrane therapeutic plasma exchange (mTPE). However, there are few reports of comparisons of the two methods. The aim of this study was to compare different anticoagulants in mTPE and observe the effectiveness, safety, and advantages of RCA. METHODS: We retrospectively included 85 patients who underwent mTPE in the past 1 year, and divided them into three groups. Patients with no bleeding tendency were administered heparin anticoagulation; patients with bleeding tendency/with liver dysfunction/who had undergone an operation were treated with RCA, or did not receive anticoagulation. In the heparin group, low-dose heparin anticoagulation was administered; in the RCA group, 4% sodium citrate solution was administered, and 10% calcium gluconate solution was pumped from the venous circuit tube. The peripheral blood platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and electrolytes were detected before and after treatment in all patients. RESULTS: A total of 255 sessions of mTPE were performed in 85 patients (2-7 times/case) with 120 sessions of heparin anticoagulation, 93 sessions of RCA, and 42 sessions of no anticoagulation. Compared with pretreatment values, the platelet count decreased by 53.7% and the PT and APTT increased (p < 0.05) in the heparin group after treatment. There were no differences in platelet count and PT before and after treatment in the RCA group. In the RCA group, the patients did not experience hypocalcemia or hypercalcemia, and no separator clotting occurred. CONCLUSION: RCA is safe, feasible, and effective in mTPE, especially for patients with bleeding tendency and frequent monitoring is needed. It is worth widely developing and applying it in clinical practice.

MicroRNA-302c modulates peritoneal dialysis-associated fibrosis by targeting connective tissue growth factor.

Long-term peritoneal dialysis (PD) can lead to the induction of mesothelial/epithelial-mesenchymal transition (MMT/EMT) and fibrosis; these effects eventually result in ultrafiltration failure and the discontinuation of PD. MicroRNA-302c (miR-302c) is believed to be involved in regulating tumour cell growth and metastasis by suppressing MMT, but the effect of miR-302c on MMT in the context of PD is unknown. MiR-302c levels were measured in mesothelial cells isolated from the PD effluents of continuous ambulatory peritoneal dialysis patients. After miR-302c overexpression using lentivirus, human peritoneal mesothelial cell line (HMrSV5) and PD mouse peritoneum were treated with TGF-ß1 or high glucose peritoneal dialysate respectively. MiR-302c expression level and MMT-related factors alteration were observed. In addition, fibrosis of PD mouse peritoneum was alleviated by miR-302c overexpression. Furthermore, the expression of connective tissue growth factor (CTGF) was negatively related by miR-302c, and LV-miR-302c reversed the up-regulation of CTGF induced by TGF-ß1. These data suggest that there is a novel TGF-ß1/miR-302c/CTGF pathway that plays a significant role in the process of MMT and fibrosis during PD. MiR-302c might be a potential biomarker for peritoneal fibrosis and a novel therapeutic target for protection against peritoneal fibrosis in PD patients.

[Role of cofilin in kidney disease].

Cofilin is a actin-binding protein in eukaryotic cells. It plays a role in maintaining the steady state of the internal environment through regulating actin dynamics, which contributes to the development of various kinds of diseases. In recent 20 years, cofilin has been widely attracted due to its regulatory effect on cell phenotype, gene transcription, apoptosis and inflammation in renal tissue. Cofilin plays a regulatory role in pathological changes in proteinuria diseases such as minimal change nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy. It could be one of the diagnosis index for glomerular podocyte injury. At the same time, cofilin plays a key role in maintaining the polarity and function of proximal tubular epithelial cells and it is involved in the regulation of kidney inflammation in a variety of kidney diseases, such as renal ischemia/reperfusion injury, diabetic nephropathy, and hypertensive nephropathy reaction. In addition, cofilin plays an important role in epithelial-to-mesenchymal transition (EMT) of tumor cells and epithelial cells in various tissues, suggesting that cofilin may be involved in the regulation of peritoneal dialysis-related EMT and fibrosis. Cofilin might turn into the new diagnosis and treatment target of kidney diseases.

Preliminary study of Huai Qi Huang granules delay the development of primary glomerular diseases in human.

OBJECTIVE: To evaluate the effects of Huai Qi Huang (HQH) granules on primary glomerulonephritis patients, and to discuss its possible mechanisms. METHOD: Sixteen patients diagnosed with primary glomerular disease between December 2011 and December 2012 were enrolled. Their blood and urine samples were collected at day 0 (the baseline levels), 30, and 90 of receiving HQH granules orally. Levels of creatinine and cystatin C (Cys-C) in serum and urine, and total protein and albumin in urine were measured by automatic biochemical analyzer. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine was tested by ELISA; serum malondialdehyde (MDA) was measured by thiobarbituric acid method, the erythrocyte count in urine was calculated under light microscope. RESULTS: Serum levels of creatinine, MDA, Cys-C and NGAL at day 30 and 90 were significantly lower than the baseline levels. Urinary levels of Cys-C, NGAL, total protein, albumin and erythrocyte counts were also decreased; level of estimated glomerular filtration (eGFR) was increased. CONCLUSION: HQH granules have certain effect on delaying the development of primary glomerular disease with mild proteinuria and hematuresis in patients. This study may supply a new treatment for primary glomerular diseases.

Gene delivery in peritoneal dialysis related peritoneal fibrosis research.

OBJECTIVE: To summarize the development of gene delivery vectors in peritoneal fibrosis research and discuss the feasibility and superiority of lentiviral vectors. DATA SOURCES: The data in this article were collected from PubMed database with relevant English articles published from 1995 to 2011. STUDY SELECTION: Articles regarding the gene therapy in peritoneal fibrosis research using non-viral vectors, adenoviral vectors, retroviral vectors, and lentiviral vectors were selected. Data were mainly extracted from 60 articles, which are listed in the reference section of this review. RESULTS: Non-viral vector-mediated gene delivery (including naked DNA for ex vivo, oligonucleotides, ultrasound- contrast agent mediated naked gene delivery, etc.) and viral vector-mediated gene delivery (including adenovirus, helper-dependant adenovirus, and retrovirus vectors) have been successfully applied both in the mechanistic investigation and the potential prevention and treatment of peritoneal fibrosis. CONCLUSIONS: Peritoneal fibrosis is a major complication of peritoneal dialysis (PD). Recently, the wide use of the gene delivery technique made it possible to access and further research peritoneal fibrosis. The use of lentiviral vector is expected to be widely used in PD research in the future due to its advantages in gene delivery.

[Advances in molecular genetics research of IgA nephropathy].

Immunoglobulin A nephropathy (IgAN), which can develop into end-stage renal disease, is the most common primary glomerulonephritis. The pathogenesis of IgAN is not clear. Many studies have confirmed that genetic susceptibility is associated with IgAN, and it belongs to polygenic disease. Some studies have found that IgAN is associated with chromosome 6q22-23, 2q36 by linkage analysis, and several candidate genes have been confirmed to be associated with IgAN, such as angiotensin converting enzyme, Fc fragment of IgA receptor, human leukocyte antigen. In recent years, as the progression of molecular genetics and the Human Genome Project, more attention has been paid to the role of genetic factors in the pathogenesis of IgAN.