Rabi Yacoub

Association between smoking and chronic kidney disease: a case control study

BackgroundThe progression of chronic kidney disease (CKD) remains one of the main challenges in clinical nephrology. Therefore, identifying the pathophysiological mechanisms and the independent preventable risk factors helps in decreasing the number of patients suffering end stage renal disease and slowing its progression.MethodsSmoking data was analyzed in patients with CKD throughout 2005-2009. One hundred and ninety-eight patients who had recently been diagnosed with stage three CKD or higher according to the National Kidney Foundation (NKF) 2002 Classification were studied. The control group was randomly selected and then matched with the case subjects using a computerized randomization technique. The relative risk was estimated by computing odds ratio (OR) by using multinomial logistic regression in SPSS ® for Windows between the two groups.ResultsSmoking significantly increases the risk of CKD (OR = 1.6, p = 0.009, 95% CI = 1.12-2.29). When compared to nonsmokers, current smokers have an increased risk of having CKD (OR = 1.63 p = 0.02, 95% CI = 1.08-2.45), while former smokers did not have a statistically significant difference. The risk increased with high cumulative quantity (OR among smokers with > 30 pack-years was 2.6, p = 0.00, 95% CI = 1.53-4.41). Smoking increased the risk of CKD the most for those classified as hypertensive nephropathy (OR = 2.85, p = 0.01, 95% CI = 1.27-6.39) and diabetic nephropathy (2.24, p = 0.005, 95% CI = 1.27-3.96). No statistically significant difference in risk was found for glomerulonephritis patients or any other causes.ConclusionThis study suggests that heavy cigarette smoking increases the risk of CKD overall and particularly for CKD classified as hypertensive nephropathy and diabetic nephropathy.

Acute Kidney Injury and Death Associated With Renin Angiotensin System Blockade in Cardiothoracic Surgery: A Meta-analysis of Observational Studies

BACKGROUND Acute kidney injury (AKI) is a common complication after cardiovascular surgery. The use of renin angiotensin system (RAS) blockers preoperatively is controversial due to conflicting results of their effect on the incidence of postoperative AKI and mortality. STUDY DESIGN Meta-analysis of prospective or retrospective observational studies (1950 to January 2013) using MEDLINE, EMBASE, the Cochrane Library, conferences, and ClinicalTrials.gov, without language restriction. SETTING & POPULATION Patients undergoing cardiovascular surgery. SELECTION CRITERIA FOR STUDIES Retrospective or prospective studies evaluating the effect of preoperative use of RAS blockers in the development of postoperative AKI and/or mortality in adult patients. INTERVENTION Preoperative use of RAS blockers. RAS-blocker use was defined as long-term use of either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers until the day of surgery. OUTCOMES The primary outcome was the development of postoperative AKI; the secondary outcome was mortality. AKI was defined by different authors using different criteria. Death was ascertained in the hospital, at 30 days, or at 90 days in different studies. RESULTS 29 studies were included (4 prospective and 25 retrospective); 23 of these involving 69,027 patients examined AKI, and 18 involving 54,418 patients studied mortality. Heterogeneity was found across studies regarding AKI (I2 = 82.5%), whereas studies were homogeneous regarding mortality (I2 = 20.5%). Preoperative RAS-blocker use was associated with increased odds for both postoperative AKI (OR, 1.17; 95% CI, 1.01-1.36; P = 0.04) and mortality (OR, 1.20; 95% CI, 1.06-1.35; P = 0.005). LIMITATIONS Lack of randomized controlled trials, different definitions of AKI, different durations of follow-up used to analyze death outcome, and inability to exclude outcome reporting bias. CONCLUSIONS In retrospective studies, preoperative use of RAS blockers was associated with increased odds of postoperative AKI and mortality in patients undergoing cardiovascular surgery. A large, multicenter, randomized, controlled trial should be performed to confirm these findings.

Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult Kidneys

Nephrin is required during kidney development for the maturation of podocytes and formation of the slit diaphragm junctional complex. Because nephrin expression is downregulated in acquired glomerular diseases, nephrin deficiency is considered a pathologic feature of glomerular injury. However, whether nephrin deficiency exacerbates glomerular injury in glomerular diseases has not been experimentally confirmed. Here, we generated mice with inducible RNA interference-mediated nephrin knockdown. Short-term nephrin knockdown (6 weeks), starting after the completion of kidney development at 5 weeks of age, did not affect glomerular structure or function. In contrast, mice with long-term nephrin knockdown (20 weeks) developed mild proteinuria, foot process effacement, filtration slit narrowing, mesangial hypercellularity and sclerosis, glomerular basement membrane thickening, subendothelial zone widening, and podocyte apoptosis. When subjected to an acquired glomerular insult induced by unilateral nephrectomy or doxorubicin, mice with short-term nephrin knockdown developed more severe glomerular injury compared with mice without nephrin knockdown. Additionally, nephrin-knockdown mice developed more exaggerated glomerular enlargement when subjected to unilateral nephrectomy and more podocyte apoptosis and depletion after doxorubicin challenge. AKT phosphorylation, which is a slit diaphragm-mediated and nephrin-dependent pathway in the podocyte, was markedly reduced in mice with long-term or short-term nephrin knockdown challenged with uninephrectomy or doxorubicin. Taken together, our data establish that under the basal condition and in acquired glomerular diseases, nephrin is required to maintain slit diaphragm integrity and slit diaphragm-mediated signaling to preserve glomerular function and podocyte viability in adult mice.

Representation of Patients With Kidney Disease in Trials of Cardiovascular Interventions: An Updated Systematic Review

Conflict of Interest Disclosures: Dr Mor reported performing research in a related area to that of several different paid activities; periodically serving as a paid speaker at national conferences where he discusses trends and research findings in long-term and postacute care but never any specific product or service provider; founding and previously owning stock of unknown value and sitting on the board of PointRight, Inc, an information services company that provides advice and consultation to various components of the long-term care and postacute care industries, including suppliers and insurers, and sells information on the measurement of nursing home quality to nursing homes and liability insurers; chairing the independent quality committee for HRC Manor Care, Inc, a nursing home chain, for which he receives compensation ranging from

Inhibition of RAS in diabetic nephropathy

20 000 to

The Role of SIRT1 in Diabetic Kidney Disease

40 000 per year; serving as chair of a scientific advisory committee for NaviHealth, a postacute care service organization, for which he also receives compensation ranging from

Krüppel-Like Factor 15 Mediates Glucocorticoid-Induced Restoration of Podocyte Differentiation Markers.

20 000 to

Urinary tract infections and asymptomatic bacteriuria in renal transplant recipients

40 000 per year; serving as a compensated speaker at the nonacademic National Long Term Care Quality Meeting in 2014; serving as a technical expert on several Centers for Medicare & Medicaid Services quality measurement panels; and serving as a member of the board of directors for Tufts Health Plan Foundation, Hospice Care of Rhode Island, and the Jewish Alliance of Rhode Island. No other disclosures were reported.

Detection of circulating tumor cells in cancers of biliary origin

Diabetic kidney disease (DKD) is a progressive proteinuric renal disorder in patients with type 1 or type 2 diabetes mellitus. It is a common cause of end-stage kidney disease worldwide, particularly in developed countries. Therapeutic targeting of the renin–angiotensin system (RAS) is the most validated clinical strategy for slowing disease progression. DKD is paradoxically a low systematic renin state with an increased intrarenal RAS activity implicated in its pathogenesis. Angiotensin II (AngII), the main peptide of RAS, is not only a vasoactive peptide but functions as a growth factor, activating interstitial fibroblasts and mesangial and tubular cells, while promoting the synthesis of extracellular matrix proteins. AngII also promotes podocyte injury through increased calcium influx and the generation of reactive oxygen species. Blockade of the RAS using either angiotensin converting enzyme inhibitors, or angiotensin receptor blockers can attenuate progressive glomerulosclerosis in animal models, and slows disease progression in humans with DKD. In this review, we summarize the role of intrarenal RAS activation in the pathogenesis and progression of DKD and the rationale for RAS inhibition in this population.

Comparison of Cutting Balloon Angioplasty and Percutaneous Balloon Angioplasty of Arteriovenous Fistula Stenosis: A Meta‐Analysis and Systematic Review of Randomized Clinical Trials

Sirtuins (SIRTs) are members of the silent information regulator 2 family. In mammals, of the seven known SIRTs, SIRT1 function is most studied and has been shown to regulate wide range of cellular functions that affect metabolic homeostasis and aging. SIRT1 exerts anti-apoptotic, anti-oxidative, and anti-inflammatory effects against cellular injury, and protects the cells through the regulation of mitochondrial biogenesis, autophagy, and metabolism in response to the cellular energy and redox status. SIRT1 also promotes vasodilation and protects vascular tissues. In humans and animal models with diabetic kidney disease (DKD), its expression tends to be decreased in renal cells, and increased expression of SIRT1 was found to play a renal protective role in animal models with DKD. In this review, we discuss the role and potential mechanisms by which SIRT1 protects against DKD.