tion’, implying that most patients ‘should’ receive a particular action. In contrast, level 2 guidelines are essentially ‘suggestions’ and are deemed to be ‘weak’ or discretionary, recognising that management decisions may vary in different clinical contexts. Each recommendation was further graded from A to D by the quality of evidence underpinning them, with grade A referring to a high quality of evidence whilst grade D recognised a ‘very low’ evidence base. The overall strength and quality of the supporting evidence is summarised in table 1 . The guidelines focused on 4 key domains: (1) AKI definition, (2) prevention and treatment of AKI, (3) contrastinduced AKI (CI-AKI) and (4) dialysis interventions for the treatment of AKI. The full summary of clinical practice statements is available at www.kdigo.org, but a few key recommendation statements will be highlighted here.

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KDIGO clinical practice guidelines for acute kidney injury.

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature.

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Computational Methods in Drug Discovery

Pathologic Basis of Diseaseby Stanley L. Robbins is really the fourth edition of hisPathology. Appropriate updating and addition enhance the otherwise identical format, sequence, writing, and illustrations. So many medical students have benefited from this source that it may be the best known general book in the field. I recommend it even more now. Like his former texts, this will be enjoyed for its readability. He clearly lays out a great deal of information. When he includes minutiae, the reasons are clear and one feels that all the material is pertinent. Robbins keeps the whole field in perspective—that is, he does not dwell so long or so heavily on pathologic anatomy or pathogenesis as to tempt the reader to overlook clinical presentation or prognosis. A great strength of the subject of pathology is that it bonds strongly with many other medical sciences and specialties and thus occupies the

Pathologic Basis of Disease

142 Summary of Recommendation Statements 143 Chapter 1: Introduction 154 Chapter 2: General principles in the management of glomerular disease 156 Chapter 3: Steroid-sensitive nephrotic syndrome in children 163 Chapter 4: Steroid-resistant nephrotic syndrome in children 172 Chapter 5: Minimal-change disease in adults 177 Chapter 6: Idiopathic focal segmental glomerulosclerosis in adults 181 Chapter 7: Idiopathic membranous nephropathy 186 Chapter 8: Idiopathic membranoproliferative glomerulonephritis 198 Chapter 9: Infection-related glomerulonephritis 200 Chapter 10: Immunoglobulin A nephropathy 209 Chapter 11: Henoch-Schönlein purpura nephritis 218 Chapter 12: Lupus nephritis 221 Chapter 13: Pauci-immune focal and segmental necrotizing glomerulonephritis 233 Chapter 14: Anti-glomerular basement membrane antibody glomerulonephritis 240 Methods for guideline development 243 Biographic and Disclosure Information 252

KDIGO Clinical Practice Guideline for Glomerulonephritis

Central vein stenosis is commonly associated with placement of central venous catheters and devices. Central vein stenosis can jeopardize the future of arteriovenous fistula and arteriovenous graft in the ipsilateral extremity. Occurrence of central vein stenosis in association with indwelling intravascular devices including short-term, small-diameter catheters such as peripherally inserted central catheters, long-term hemodialysis catheters, as well as pacemaker wires, has been recognized for over two decades. Placement of multiple catheters, longer duration, location in subclavian vein, and placement on the left-hand side of neck seem to predispose to the development of central vein stenosis. Endothelial injury with subsequent changes in the vessel wall results in development of microthrombi, smooth muscle proliferation, and central vein stenosis. Central vein stenosis is often asymptomatic in nondialysis patients, but can result in edema of ipsilateral extremity and breast when challenged by increased flow from an arteriovenous fistula or arteriovenous graft. Bilateral central vein stenosis or superior vena cava stenosis can produce a clinical picture of superior vena cava syndrome, associated with engorgement of face and neck. Endovascular interventions are the mainstay of management of central vein stenosis. Percutaneous angioplasty and stent placement for elastic and recurring lesions can restore the functionality of the vascular access, at least temporarily. Frequent or multiple interventions are usually required. In recalcitrant cases, surgical bypass of the obstruction is an option. In resistant cases with severe symptoms, occlusion of the functioning vascular access will usually provide relief of symptoms. Further study of mechanisms of development of central vein stenosis and search for a targeted therapy is likely to lead to better ways of managing central vein stenosis. Prevention of central vein stenosis is the key to avoid access failure and other complications from central vein stenosis and relies upon avoidance of central vein stenosis placement and timely placement of arteriovenous fistula in prospective dialysis patient.

Central vein stenosis: a nephrologist's perspective.

Prevalence of hepatitis C in patients with idiopathic glomerulopathies in native and transplant kidneys

In contrast to hemodialysis (HD), peritoneal dialysis (PD) remains an underutilized form of renal replacement therapy in the United States. Although a variety of factors have been deemed responsible, timely insertion of a PD catheter may also be a contributory factor. We conducted a multicenter analysis to examine whether the establishment of a program for PD catheter insertion by nephrologists has a positive impact on the growth in the number of patients using PD. Data for catheter insertion performed by nephrologists were collected from three centers. Any change in the prevalent PD population at each respective center was compared to the number of PD patients during the period having the traditional surgical approach. Nephrologists at the three centers used the peritoneoscopic technique and performed catheter insertion under local anesthesia. In center 1, the PD population remained stable at between 38 and 45 patients (approximately 16% of the total end-stage renal disease [ESRD] population) from 1993 to 2001. Nephrologists initiated a program for PD catheter insertion in 2001. The number of PD patients has increased to 101 (32% of the ESRD population). In center 2, the PD population remained stable at between 70 and 78 patients (approximately 17%) between 1988 and 1990. Catheter insertion by interventional nephrologists began in 1991. The number of PD patients has increased to 125 (22%). In center 3, the PD population remained at 20-30 patients (approximately 18%) between 1988 and 1991. Catheter placement by nephrologists was initiated in 1991. The number of PD patients increased to 97 (27%). Catheter insertion by interventional nephrologists was suspended in 2001. The number of PD patients has gradually declined to 25 (6%). This study suggests that catheter insertion by the nephrologist can have a positive impact on the utilization of PD.

Does catheter insertion by nephrologists improve peritoneal dialysis utilization? A multicenter analysis.

Two hundred and thirty three cases of ovarian tumours and tumour like lesions were studied. Of these 233 cases, 96 cases were of ovarian tumours and 137 were tumour like lesions of the ovary. Of the 96 cases of ovarian tumours, 72.9% were benign, 4.1% were borderline and 22.9% were malignant. Histologically surface epithelial tumours were the commonest (48.8%) followed by germ cell tumours (23.9%), sex cord stromal tumours (8.3%) and metastatic tumours (2.0%). Ultrasound guided FNAC done in cases of ovarian tumours showed an accuracy of 100% for malignant lesions and 100% for benign and borderline lesions when compared with histopathological diagnosis. Of the non neoplastic lesions follicular cysts and corpus leuteal cysts were commonest (80.2%). Tuberculosis constituted (2.9%) cases and was the major cause of clinical diagnostic pitfalls for cases in which a clinical diagnosis of ovarian neoplasm was made.

Anil Agarwal

Papers

Central vein stenosis: a nephrologist's perspective.

Prevalence of hepatitis C in patients with idiopathic glomerulopathies in native and transplant kidneys

Does catheter insertion by nephrologists improve peritoneal dialysis utilization? A multicenter analysis.

Retrospective and prospective study of ovarian tumours and tumour-like lesions

Pregnenolone sulphate-independent inhibition of TRPM3 channels by progesterone