Growth differentiation factor 15 : a novel biomarker with high clinical potential

Initially considered as a macrophage inhibitor (macrophage inhibitory cytokine-1), growth differentiation factor 15 (GDF-15) has been identified as a pleiotropic protein that plays key roles in prenatal development, in inflammation, in the regulation of cellular responses to stress signals, and in tissue repair after acute injuries in adult life. Multiple studies have revealed that GDF-15, a distant member of the transforming growth factor beta (TGF-beta) family, acts as a critical hormone to regulate lipid and carbohydrate metabolism. Besides its role in the tumorigenesis and diagnosis of cancer, serum GDF-15 concentrations reflect a systemic response and are predictive of all-cause mortality. Based on the knowledge from animal studies of its involvement in multiple inflammatory processes, we will focus in this review on the current clinical data on GDF-15 as a biomarker for cardiovascular disease, kidney disease, liver disease, the metabolic syndrome, diabetes mellitus, and sepsis

A study of viral infections in renal transplant recipients: Risk factors, clinical profile and outcome analysis

INTRODUCTION: Renal transplantation has become the most effective means of rehabilitating patients with end stage renal disease. In well established centres, 90% 1 year graft survival and 95% patient survival is achieved. Inspite of this, infection occurs more than 60% of renal transplant recipients and being the one of the main cause of death in renal transplant recipients. AIMS AND OBJECTIVES: 1. To study the clinical profile of viral infections in renal transplant recipients. 2. To study the risk factors for viral infections and the effect of viral infections on graft outcome. MATERIALS AND METHODS: Study Place: Department of Nephrology. Study Design: Cross-sectional descriptive prospective and retrospective study. Period of study: Two years. Study population: Patients attending the Transplant clinic, Nephrology Department in Rajiv Gandhi Government General Hospital. Ethical approval: Obtained from ethical committee headed by Dean, Madras Medical College. Consent: Obtained from all patients. Inclusion Criteria: Renal transplant recipients diagnosed with viral infections diagnosed by either clinical or laboratory evidence or serological methods or radiological or by renal biopsy. Exclusion Criteria: Renal transplant recipients with empirical antiviral therapy given. This study was done in prospective and retrospective manner. Retrospective cases selected by examining the case records and examining the patients while coming for follow up and in prospective cases are followed during the time period of study. CONCLUSION: 1. Bacterial, viral, fungal and parasitic infection contributes to 45%, 30.5%, 9.5%, 5.3% respectively to the total infective episodes. 2. Most of the viral episodes occurred after 6 months post transplant. 3. Commonest viral infection is the CMV and its prevalence 17.4% and mean time of onset is between 1-6 months after transplantation. 4. On Univariate analysis, antirejection therapy and NODAT had statistical significant risk factor for developing viral infection (P < 0.05). 5. In patients affected with viral infection on univariate analysis, there is a statistical significance for graft dysfunction, graft loss and death (p < 0.05). 6. CMV infection has a statistical significant risk factor for bacterial, fungal and other viral infections. (p < 0.05). 7. Hepatitis C infection is the second most commonest virus found in our study, mean onset of infection is seen 6 months after transplant. Nearly 50% HCV infected patients developed NODAT. 8. Lamivudine resistance is more common in post transplant situation because prolonged treatment is necessary. 9. All the three patients with BK virus infection had persistent graft dysfunction. 10. Multi dermatomal involvement is commonly seen in our patients with herpes zoster (56%)

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease

Yifang Tang,1,&ast; Tao Liu,2,&ast; Shibo Sun,3 Youbo Peng,1 Xiaoxiao Huang,4 Shuangquan Wang,4 Zhu Zhou1 1Department of Nephrology, the First Affiliated Hospital, Kunming Medical University, Kunming, People’s Republic of China; 2Organ Transplantation Center, the First Affiliated Hospital, Kunming Medical University, Kunming, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Kunming Medical University, Kunming, People’s Republic of China; 4Department of Nephrology, Xishuangbanna Dai Autonomous Prefecture People’s Hospital, Xishuangbanna, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhu Zhou, Department of Nephrology, The First Affiliated Hospital of Kunming Medical University and Yunnan Province Clinical Research Center for Chronic Kidney Disease, No. 295, Xichang Road, Wuhua District, Kunming, People’s Republic of China, Email [email protected] Shibo Sun, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, People’s Republic of China, Email [email protected]: GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease.Keywords: chronic kidney disease, GDF-15, biomarker, inflammation, renal protectio

Clinical outcomes of Renal Transplantation in Hepatitis C virus positive recipients.

INTRODUCTION : Hepatitis C virus(HCV) infects 20-50% of chronic kidney disease patients(47). The number of chronic kidney disease patients is on increasing trend . The number of chronic kidney disease patients undergoing dialysis is also increasing. Various studies have shown that 3.4-43% of chronic kidney disease patients undergoing maintenance hemodialysis test positive for anti HCV antibodies. Hepatitis C virus infection confers 1.62-2.39 fold increase in risk of death for hemodialysis patients. Various studies have shown that quality of life, morbidity and mortality of chronic kidney disease patients on maintenance hemodialysis is worse when compared to the quality of life, morbidity and mortality of patients undergoing renal transplantation. For these reasons, renal transplantation is better therapeutic option for hepatitis C virus infected patients on maintenance hemodialysis. Anti viral therapy for hepatitis C virus should be given before transplantation. The recommendation is to screen for hepatitis C virus infected patients on transplant programme by testing antibodies for hepatitis C virus. If antibodies to hepatitis C virus is detected, we should proceed testing hepatitis C virus RNA . If hepatitis C Virus RNA is detected, genotyping should be done. Based on the genotype , interferon should be given before transplant. Patients attaining sustained viral response after interferon therapy should be taken for renal transplant, after ruling out clinical and biochemical evidence of liver cirrhosis. AIMS AND OBJECTIVES : To study of clinical outcomes of renal transplantation in hepatitis C virus positive renal transplantation recipients . To assessing the all cause mortality among hepatitis c virus positive recipients. CONCLUSION : The short term patient and graft survival of HCV positive recipients was better. There was high incidence of NODAT in HCV positive recipients, and occurrence of NODAT was within 3 months after transplant. The incidence of sepsis and cytomegalovirus in HCV positive recipients was higher, it is better to keep minimal level of immunosupression. The incidence of acute rejection, interstitial fibrosis, fungal infection and graft survival in HCV positive recipients was not statistically significant from HCV negative recipients. The short duration of follow up is a main limitation of the study

Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role in cell-cell communications. Exosomes have evolved as potential biomarkers for aging-related diseases. Aging, a physiological process, involves a progressive decline of function of organs with a loss of homeostasis and increasing probability of illness and death. The review focuses on the classic view of exosome biogenesis, biology, and age-associated changes. Owing to their ability to transport biological information among cells, the review also discusses the interplay of senescent cell-derived exosomes with the aging process, including the susceptibility of the aging population to COVID-19 infections

Kidney Inflammation, Injury and Regeneration 2020

Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of chronic kidney disease in the sequel. Whereas the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function—in both the short- and long-term—is urgently needed. This Special Issue includes papers investigating the pathological mechanisms of renal inflammation and AKI and diagnostics using new biomarkers. Furthermore, experimental in vitro and in vivo studies examining potential new approaches to attenuate kidney dysfunction are included, as well as review articles

Etiology and determinants of allograft dysfunction.

INTRODUCTION : Treatment option for Chronic Kidney Disease-Stage5 (CKD-stage5) patients fall into three categories viz., Haemodialysis, Peritoneal dialysis and Renal Transplantation. Many studies proved that the kidney transplantation is distinctly superior and it is associated with reduced mortality and morbidity compared to haemodialysis or peritoneal dialysis. The renal donors are of three types viz. live related, live unrelated and cadaver. Due to shortage organs and long waiting period in cadaver transplant prevention of second or re transplant is more important. To improve the graft survival identifying etiology of graft dysfunction or loss is more important. Once we identified the etiology we have to evaluate for immunologic, nonimmunologic, modifiable, non modifiable risk factors to improve the graft and patient survival. METHODS : All renal transplant recipients on regular follow up are included - September 2009 to march 2011. Those who died and those who are in irregular follow up during the period of study are excluded from the study. All the patient having graft dysfunction underwent renal biopsy. CONCLUSION : According to Univariate analysis following conclusion were made Tacrolimus gives a better graft survival than cyclosporine for both live and cadaveric transplants. Donor age has significant impact on long term graft survival; younger the donor better the outcome. With female donors the graft dysfunction is more, may be due to difference in antigencity and smaller renal mass. The Male recipients do worse than female recipients; probably due to female recipients has higher degree of sensitization to HLA antigen. Blood group, cross match results, day one urine output, First post operative day creatinine, discharge creatinine are not having significant association with cause graft dysfunction. Delayed graft function has significant impact on long term graft survival according to Univariate analysis. Side of the kidney , number of blood vessels, post operative events are not statistically significant to cause graft dysfunction

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%),