Intu is known as a ciliogenesis and planar polarity effector (CPLANE) protein. Although roles for Intu have been reported during embryonic development and in the context of developmental disorders, its function and regulation in adult tissues remain poorly understood. Here we show that ablation of Intu specifically in kidney proximal tubules aggravates renal ischemia-reperfusion injury, and leads to defective post-injury ciliogenesis. We identify signal transducer and activator of transcription 1 (STAT1) as a novel interacting partner of Intu. In vitro, Intu and STAT1 colocalize at the centriole/basal body area, and Intu promotes proteasomal degradation of STAT1. During cell stress, Intu expression preserves cilia length and cell viability, and these actions are antagonized by STAT1 expression. Thus, we propose a role for Intu in protecting cells and tissues after injury by targeting STAT1 for degradation and maintaining primary cilia.

Drug-induced autoimmunity occurs when exposure to a causative agent leads to serologic or clinical autoimmune responses. Syndromes that may be associated with drug-induced autoimmunity include antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) and drug-induced lupus (DIL). When drug-induced autoimmunity involves the kidney, histological patterns of injury include pauci-immune glomerulonephritis (GN), which occurs with AAV, and immune complex-mediated GN, which is associated with DIL. We present a case of hydralazine-induced dual ANCA-positive vasculitis and nephritis. Categories: Internal Medicine, Nephrology, Rheumatology Keywords: hydralazine, drug-induced lupus (dil), antineutrophil cytoplasmic antibody (anca), antineutrophil cytoplasmic antibody (anca) associated vasculitis (aav), pauci-immune glomerulonephritis (gn), acute kidney injury (aki), dual anca aav and dil, hydralazine induced dual aav and dil Open Access Case Report

Introduction: Hemodialysis patients (HD pts) with atrial fibrillation (AF) have increased risk of stroke. The HASBLED (Hypertension (HTN), Abnl Renal/Liver Function, Stroke, Bleeding Hx, Labile INR, Elderly, Drugs/Alcohol) risk score predicts bleeding in the general AF population. It is unknown whether the HASBLED score can be applied to HD pts who are at additional bleeding risk due to uremic platelet dysfunction and the regular use of heparin. Hypothesis: To address this question, we queried the United States Renal Data System (USRDS) for bleeding events in HD pts with AF, and correlated those events with a modified HASBLED (mHASBLED) score. Methods: All incident HD pts with AF from the USRDS for 2006-2010 were queried for major bleeding events and mHASBLED parameters using ICD-9 diagnosis codes and data from CMS form 2728. For mHASBLED, the HTN parameter was defined as "HTN as the cause of renal failure", and labile INR as > 16 INRs/yr, but all other parameters could be derived from the dataset. Logistic regression (LR) analysis was used to estimate the odds ratio (OR) for the mHASBLED score to predict major bleeding events. Results: 74,631 HD pts had AF, and 9.8% had a major bleeding event (GI bleeding and hemorrhagic stroke). By univariate analysis, those who bled were more likely to be elderly, have an underlying cause of renal disease due to HTN, prior bleeding event, hepatitis C, labile INR, and be on oral anticoagulants. By LR, variables with the greatest impact on bleeding were HTN as a cause of underlying renal disease, prior bleeding history, and labile INR (OR of 1.10, 2.20 and 2.24, respectively). The OR for bleeding events increased by 1.28 for each unit increase in mHASBLED. Older age, prior stroke, abnormal renal or liver function, and drug use had the least effect. Note that the lowest possible score in this cohort is 1, given that all patients had renal failure. Conclusions: In HD pts with AF, the mHASBLED predicts major bleeding events. The universal presence of renal disease, and the lack of specific clinical data from the USRDS may limit the clinical precision of a given score, however mHASBLED may remain a useful indicator of bleeding risk in this population.

Background Patients with human immunodeficiency virus (HIV) or end-stage renal disease receiving dialysis have an increased risk of developing malignancies, but few data are available on cancer in patients with both conditions. Thus, the objective of this study was to determine the incidence of selected malignancies and identify their potential risk factors in HIV-infected dialysis patients. Methods This study was a nationwide cohort analysis using the US Renal Data System. Participants included all HIV-infected patients starting dialysis from 2005 to 2011. HIV status, comorbidities and malignancies were identified using International Classification of Diseases, Ninth Revision codes. Descriptive statistics and generalized linear models quantifying risk factors were performed for the overall cohort and the three most common malignancies. Results Overall, 6641 HIV-infected dialysis patients were identified, with 543 (8.2%) carrying a malignancy diagnosis. The most common malignancies were non-Hodgkin’s lymphoma (NHL, 25%), Kaposi sarcoma (KS, 16%) and colorectal cancer (13%). Factors increasing the risk of any malignancy diagnosis included: history of cancer [adjusted relative risk (aRR) = 5.37], two or more acquired immunodeficiency syndrome-defining opportunistic infections (ADOIs) (aRR = 3.11), one ADOI (aRR = 2.23), cirrhosis (aRR = 2.20), male sex (aRR = 1.54) and hepatitis B (aRR = 1.52). For NHL and colorectal cancer, history of cancer (aRR = 7.05 and 9.80, respectively) was the most significant risk factor. For KS, two or more ADOIs (aRR = 6.78) was the largest risk factor. Conclusions Over 8% of HIV-infected dialysis patients developed a malignancy. History of cancer and ADOIs were major risk factors, underscoring the significance of immune dysregulation in malignancy development.