Cytokines and Their Roles in the Pathogenesis of Systemic Lupus Erythematosus: From Basics to Recent Advances

Systemic lupus erythematosus (SLE) is a complex auto-immune disorder which involves various facets of the immune system. In addition to autoantibody production and immune complex deposition, emerging evidences suggest that cytokines may act as key players in the immunopathogenesis of SLE. These cytokines assume a critical role in the differentiation, maturation and activation of cells and also participate in the local inflammatory processes that mediate tissue insults in SLE. Certain cytokines such as the IL-6, IL-10, IL-17, BLys, type I interferons (IFN) and tumor necrosis factor-α (TNF-α) are closely linked to pathogenesis of SLE. The delineation of the role played by these cytokines not only fosters our understanding of this disease but also provides a sound rationale for various therapeutic approaches. In this context, this review focuses on selected cytokines which exert significant effect in the pathogenesis of SLE and their possible clinical applications

Peritoneal Adipocytes and Their Role in Inflammation during Peritoneal Dialysis

Adipose tissue is a major site of chronic inflammation associated with peritoneal dialysis (PD) frequently complicating peritonitis. Adiposity-associated inflammation plays a significant contributory role in the development of chronic inflammation in patients undergoing maintenance PD. However, the molecular and cellular mechanisms of this link remain uncertain. Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically. In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. An understanding of the inflammatory roles played by adipose tissue during PD and the healing mechanism of injured mesothelium will help to devise new therapeutic approach to slow the progression of peritoneal damage during peritoneal dialysis. This article reviews the roles of peritoneal adipose tissue in chronic peritoneal inflammation under PD and in serosal repair during PD

The pathogenic role of the renal proximal tubular cell in diabetic nephropathy

Abstract A growing body of evidence indicates that the renal proximal tubular epithelial cell (PTEC) plays an important role in the pathogenesis of diabetic nephropathy (DN). Microalbuminuria that intensifies over time to overt proteinuria, a hallmark of DN, is already known to activate the PTEC to induce tubulointerstitial inflammation. In addition to proteins, a number of diabetic substrates including high glucose per se, advanced glycation end-products and their carbonyl intermediates, angiotensin II, and ultrafiltered growth factors activate a number of signaling pathways including nuclear factor kappa B, protein kinase C, extracellular signal-regulated kinase 1/2, p38, signal transducer and activator of transcription-1 and the generation of reactive oxygen species, to culminate in tubular cell hypertrophy and the accumulation in the interstitium of a repertoire of chemokines, cytokines, growth factors and adhesion molecules capable of orchestrating further inflammation and fibrosis. More recently, the kallikreinkinin system (KKS) and toll-like receptors (TLRs) in PTECs have been implicated in this process. While in vitro data suggest that the KKS contributes to the progression of DN, there are conflicting in vivo results on its precise role, which may in part be strain-dependent. On the other hand, there are both in vitro and in vivo data to suggest a role for both TLR2 and TLR4 in DN. In this review, we offer a critical appraisal of the events linking the participation of the PTEC to the pathogenesis of DN, which we believe may be collectively termed diabetic tubulopathy

Acute renal impairment in coronavirus-associated severe acute respiratory syndrome

Acute renal impairment in coronavirus-associated severe acute respiratory syndrome.BackgroundSevere acute respiratory syndrome (SARS) is a newly emerged infection from a novel coronavirus (SARS-CoV). Apart from fever and respiratory complications, acute renal impairment has been observed in some patients with SARS. Herein, we describe the clinical, pathologic, and laboratory features of the acute renal impairment complicating this new viral infection.MethodsWe conducted a retrospective analysis of the plasma creatinine concentration and other clinical parameters of the 536 SARS patients with normal plasma creatinine at first clinical presentation, admitted to two regional hospitals following a major outbreak in Hong Kong in March 2003. Kidney tissues from seven other patients with postmortem examinations were studied by light microscopy and electron microscopy.ResultsAmong these 536 patients with SARS, 36 (6.7%) developed acute renal impairment occurring at a median duration of 20 days (range 5–48 days) after the onset of viral infection despite a normal plasma creatinine level at first clinical presentation. The acute renal impairment reflected the different prerenal and renal factors that exerted renal insult occurring in the context of multiorgan failure. Eventually, 33 SARS patients (91.7%) with acute renal impairment died. The mortality rate was significantly higher among patients with SARS and acute renal impairment compared with those with SARS and no renal impairment (91.7% vs. 8.8%) (P < 0.0001). Renal tissues revealed predominantly acute tubular necrosis with no evidence of glomerular pathology. The adjusted relative risk of mortality associated with the development of acute renal impairment was 4.057 (P < 0.001). By multivariate analysis, acute respiratory distress syndrome and age were the most significant independent risk factors predicting the development of acute renal impairment in SARS.ConclusionAcute renal impairment is uncommon in SARS but carries a high mortality. The acute renal impairment is likely to be related to multi-organ failure rather than the kidney tropism of the virus. The development of acute renal impairment is an important negative prognostic indicator for survival with SARS

Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone

<p>Abstract</p> <p>Background</p> <p>Inhibition of the renin-angiotensin-aldosterone system (RAAS) slows down the progression of chronic renal diseases (CKD) including IgA nephropathy (IgAN). Herein, we studied the pathogenetic roles of aldosterone (Aldo) in IgAN.</p> <p>Methods</p> <p>Human mesangial cells (HMC) was activated with polymeric IgA (pIgA) from IgAN patients and the effects on the expression of RAAS components and TGF-β synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC) was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS).</p> <p>Results</p> <p>Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-β by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis.</p> <p>Conclusions</p> <p>Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.</p

Renal cell carcinoma of native kidney in Chinese renal transplant recipients: a report of 12 cases and a review of the literature

Objectives To present and discuss the epidemiological and clinical aspects, as well as therapeutic options and outcome of de novo renal cell carcinoma (RCC) of the native kidneys in a series of Chinese renal transplant recipients. Patients and Methods A retrospective, cohort study examining all renal transplant recipients with the diagnosis of RCC of native kidney followed up in two major regional hospitals in Hong Kong between January 2000 and December 2009. Clinical data includedage, gender, cause of renal failure, symptoms at presentation, duration of transplantation, immunosuppressive therapy, and history of acquired cystic kidney disease (ACKD). Laboratory, radiographic, operative, and pathology reports were used to assess the tumor extent. Results Among the 1,003 renal transplant recipients recruited, 12 transplant recipients had a nephrectomy for a total of 13 RCC. The prevalence of de novo RCC was 1.3%. The mean age at diagnosis of RCC was 48.4 years, and the median time from transplantation to diagnosis was 6.1 years. ACKD was found in 6 (50%) of the patients. All patients except one were asymptomatic. pT1 disease was found in ten patients with a mean tumor size of 3.2 cm. All patients were treated successfully with radical nephrectomy. After a median follow-up of 38 months, two patients (16.7%) died. One died of sepsis, and the other died of metastatic carcinoma. Conclusions With increasing data showing a better prognosis if RCC is detected early by screening, it is time to consider screening all kidney transplant recipients for ACKD and RCC. © The Author(s) 2011. This article is published with open access at Springerlink.com.published_or_final_versionSpringer Open Choice, 21 Feb 201

Observations on left ventricular function in uraemic patients

published_or_final_versionMedicineMasterDoctor of Medicin