Update on role of direct renin inhibitor in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renin-angiotensin-aldosterone system (RAAS) plays a critical role in the development of DKD with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) being the mainstay of treatment. Systemic RAAS activity has been implicated in the pathogenesis of DKD, but lately interest has shifted to intrarenal RAAS effect. With the discovery of the (pro)renin receptor and ACE independent pathways of angiotensin II production, our understanding of role of renin in end organ damage has improved significantly. SUMMARY: We summarize our current understanding of ACE dependent and independent pathways in the development of DKD and the preclinical models demonstrating renal effects of direct renin inhibitors (DRIs). We then review clinical studies and trials performed so far evaluating the efficacy of aliskiren on renal outcomes and safety in DKD. KEY MESSAGE: At present, there is little evidence for renal benefit of aliskiren in DKD beyond that offered by ACEIs or ARBs. Combining aliskiren with ACEI or ARB in DKD did not significantly improve renal outcomes in comparison with ACEI or ARB monotherapy in clinical trials. Slightly more adverse events including hyperkalemia, acute kidney injury and hypotension were observed in the combination therapy as compared to the monotherapy. Thus, current evidence suggests that aliskiren, because of its antihypertensive and antiproteinuric effects, maybe used as monotherapy in DKD and considered an equivalent alternative to ACEIs or ARBs. Careful monitoring for renal adverse effects would allow safe clinical use of DRI.

The thiazide-sensitive NaCl cotransporter is targeted for chaperone-dependent endoplasmic reticulum-associated degradation.

The thiazide-sensitive NaCl cotransporter (NCC, SLC12A3) mediates salt reabsorption in the distal nephron of the kidney and is the target of thiazide diuretics, which are commonly prescribed to treat hypertension. Mutations in NCC also give rise to Gitelman syndrome, a hereditary salt-wasting disorder thought in most cases to arise from impaired NCC biogenesis through enhanced endoplasmic reticulum-associated degradation (ERAD). Because the machinery that mediates NCC quality control is completely undefined, we employed yeast as a model heterologous expression system to identify factors involved in NCC degradation. We confirmed that NCC was a bona fide ERAD substrate in yeast, as the majority of NCC polypeptide was integrated into ER membranes, and its turnover rate was sensitive to proteasome inhibition. NCC degradation was primarily dependent on the ER membrane-associated E3 ubiquitin ligase Hrd1. Whereas several ER luminal chaperones were dispensable for NCC ERAD, NCC ubiquitination and degradation required the activity of Ssa1, a cytoplasmic Hsp70 chaperone. Compatible findings were observed when NCC was expressed in mammalian kidney cells, as the cotransporter was polyubiquitinated and degraded by the proteasome, and mammalian cytoplasmic Hsp70 (Hsp72) coexpression stimulated the degradation of newly synthesized NCC. Hsp70 also preferentially associated with the ER-localized NCC glycosylated species, indicating that cytoplasmic Hsp70 plays a critical role in selecting immature forms of NCC for ERAD. Together, these results provide the first survey of components involved in the ERAD of a mammalian SLC12 cation chloride cotransporter and provide a framework for future studies on NCC ER quality control.

Reflex anuria: a rare cause of acute kidney injury.

BACKGROUND: Acute Kidney Injury results from pre renal, post renal or intrinsic renal causes. Reflex anuria is a very rare cause of renal impairment which happens due to irritation or trauma to one kidney or ureter, or severely painful stimuli to other nearby organs. CASE PRESENTATION: Here we present a case of acute kidney injury secondary to reflex anuria in a patient who underwent extensive gynecological surgery along with ureteral manipulation which recovered spontaneously. CONCLUSION: Reflex Anuria is a rare and often not considered as cause of acute kidney injury. This case illustrates that this should be kept as a differential in potential cause of acute kidney injury in patient undergoing urogenital or gynecological surgeries.

Tackling the readmission epidemic: a resident teaching service perspective.

BACKGROUND: Readmission rates are projected to serve as quality measures that have the potential to negatively impact hospital and physician reimbursement. Individual physicians and hospitals are developing plans to reduce readmission rates. Successful plans should be based on specific data obtained from each individual type of practice. OBJECTIVE: To analyze the etiological factors responsible for readmissions to various teaching services in a community hospital. This will serve to identify potentially correctable factors that will be the basis for developing practice-specific plans to reduce readmissions. DESIGN: Retrospective detailed chart review. SETTING: Community teaching hospital affiliated with a large academic health care system. PARTICIPANTS: Patients admitted to teaching services at a community hospital. MEASUREMENTS: Data are presented as descriptive analysis. RESULTS: Advanced chronic medical conditions (31%), patients' lifestyle choices (28%), and new unrelated diagnoses (21%) are the major causes of readmissions. The remaining small percentage of readmissions is attributed to premature discharge, poor discharge planning, poor post-discharge follow-up, medication errors, and failure to implement medical care guidelines. LIMITATIONS: Retrospective study from a single center. CONCLUSIONS: Causes of readmission are diverse. Although most are universal, the relative contribution of each factor is unique to each population. Institutions should generate their own data in order to direct their resources toward 'high return' areas. Current studies emphasize the role of physicians and health systems in reducing readmission rates. However, the area of readmissions related to patients' behaviors is not well explored. Our study identified the role of patients' lifestyle choices as a major cause of readmission.