Clinical Journal of The American Society of Nephrology 

About: Clinical Journal of The American Society of Nephrology is an academic journal published by American Society of Nephrology. The journal publishes majorly in the area(s): Medicine & Kidney disease. It has an ISSN identifier of 1555-9041. Over the lifetime, 5110 publications have been published receiving 265849 citations. The journal is also known as: CJASN.

Normal Bone Anatomy and Physiology

Abstract: This review describes normal bone anatomy and physiology as an introduction to the subsequent articles in this section that discuss clinical applications of iliac crest bone biopsy. The normal anatomy and functions of the skeleton are reviewed first, followed by a general description of the processes of bone modeling and remodeling. The bone remodeling process regulates the gain and loss of bone mineral density in the adult skeleton and directly influences bone strength. Thorough understanding of the bone remodeling process is critical to appreciation of the value of and interpretation of the results of iliac crest bone histomorphometry. Osteoclast recruitment, activation, and bone resorption is discussed in some detail, followed by a review of osteoblast recruitment and the process of new bone formation. Next, the collagenous and noncollagenous protein components and function of bone extracellular matrix are summarized, followed by a description of the process of mineralization of newly formed bone matrix. The actions of biomechanical forces on bone are sensed by the osteocyte syncytium within bone via the canalicular network and intercellular gap junctions. Finally, concepts regarding bone remodeling, osteoclast and osteoblast function, extracellular matrix, matrix mineralization, and osteocyte function are synthesized in a summary of the currently understood functional determinants of bone strength. This information lays the groundwork for understanding the utility and clinical applications of iliac crest bone biopsy.

Diabetic Kidney Disease: Challenges, Progress, and Possibilities

Abstract: Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide Although ESRD may be the most recognizable consequence of diabetic kidney disease, the majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy The natural history of diabetic kidney disease includes glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately, ESRD Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis Despite current therapies, there is large residual risk of diabetic kidney disease onset and progression Therefore, widespread innovation is urgently needed to improve health outcomes for patients with diabetic kidney disease Achieving this goal will require characterization of new biomarkers, designing clinical trials that evaluate clinically pertinent end points, and development of therapeutic agents targeting kidney-specific disease mechanisms (eg, glomerular hyperfiltration, inflammation, and fibrosis) Additionally, greater attention to dissemination and implementation of best practices is needed in both clinical and community settingsIntroduction

Calcineurin Inhibitor Nephrotoxicity

Abstract: The use of the calcineurin inhibitors cyclosporine and tacrolimus led to major advances in the field of transplantation, with excellent short-term outcome. However, the chronic nephrotoxicity of these drugs is the Achilles' heel of current immunosuppressive regimens. In this review, the authors summarize the clinical features and histologic appearance of both acute and chronic calcineurin inhibitor nephrotoxicity in renal and nonrenal transplantation, together with the pitfalls in its diagnosis. The authors also review the available literature on the physiologic and molecular mechanisms underlying acute and chronic calcineurin inhibitor nephrotoxicity, and demonstrate that its development is related to both reversible alterations and irreversible damage to all compartments of the kidneys, including glomeruli, arterioles, and tubulo-interstitium. The main question--whether nephrotoxicity is secondary to the actions of cyclosporine and tacrolimus on the calcineurin-NFAT pathway--remains largely unanswered. The authors critically review the current evidence relating systemic blood levels of cyclosporine and tacrolimus to calcineurin inhibitor nephrotoxicity, and summarize the data suggesting that local exposure to cyclosporine or tacrolimus could be more important than systemic exposure. Finally, other local susceptibility factors for calcineurin inhibitor nephrotoxicity are reviewed, including variability in P-glycoprotein and CYP3A4/5 expression or activity, older kidney age, salt depletion, the use of nonsteroidal anti-inflammatory drugs, and genetic polymorphisms in genes like TGF-beta and ACE. Better insight into the mechanisms underlying calcineurin inhibitor nephrotoxicity might pave the way toward more targeted therapy or prevention of calcineurin inhibitor nephrotoxicity.

World incidence of AKI: a meta-analysis.

Abstract: Summary Background and objectives The burden of AKI around the globe has not been systematically examined. Design, setting, participants, & measurements A systematic review (2004–2012) of large cohort studies was conducted to estimate the world incidence of AKI and its stages of severity and associated mortality, and to describe geographic variations according to countries, regions, and their economies. AKI definitions were reclassified according to the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Random-effects model meta-analyses and meta-regressions were used to generate summary estimates and explore sources of heterogeneity. Results There were 312 studies identified ( n =49,147,878) , primarily in hospital settings. Most studies originated from North America, Northern Europe, and Eastern Asia, from high-income countries, and from nations that spent ≥5% of the gross domestic product on total health expenditure. Among the 154 studies ( n =3,585,911) that adopted a KDIGO-equivalent AKI definition, the pooled incidence rates of AKI were 21.6% in adults (95% confidence interval [95% CI], 19.3 to 24.1) and 33.7% in children (95% CI, 26.9 to 41.3). The pooled AKI-associated mortality rates were 23.9% in adults (95% CI, 22.1 to 25.7) and 13.8% in children (95% CI, 8.8 to 21.0). The AKI-associated mortality rate declined over time, and was inversely related to income of countries and percentage of gross domestic product spent on total health expenditure. Conclusions Using the KDIGO definition, 1 in 5 adults and 1 in 3 children worldwide experience AKI during a hospital episode of care. This analysis provides a platform to raise awareness of AKI with the public, government officials, and health care professionals.

Acute Kidney Injury Associated with Cardiac Surgery

Abstract: Acute renal failure (ARF) occurs in up to 30% of patients who undergo cardiac surgery, with dialysis being required in approximately 1% of all patients. The development of ARF is associated with substantial morbidity and mortality independent of all other factors. The pathogenesis of ARF involves multiple pathways. Hemodynamic, inflammatory, and nephrotoxic factors are involved and overlap each other in leading to kidney injury. Clinical studies have identified risk factors for ARF that can be used to determine effectively the risk for ARF in patients who undergo bypass surgery. These high-risk patients then can be targeted for renal protective strategies. Thus far, no single strategy has demonstrated conclusively its ability to prevent renal injury after bypass surgery. Several compounds such as atrial natriuretic peptide and N-acetylcysteine have shown promise, but large-scale trials are needed.