The clinical status and survival in elderly dialysis: example of the oldest region of France.

BACKGROUND: The number of elderly (≥75 years) patients with end-stage renal disease (ESRD) has increased markedly, including in the Limousin region, which has the oldest population in France. We retrospectively compared outcomes in elderly and non-elderly ESRD patients who started dialysis during two time periods. METHODS: Baseline clinical characteristics, care, and survival rates were assessed in 557 ESRD patients aged ≥75 and <75 years who started dialysis in 2002-2004 and 2005-2007. Survival curves and Cox proportional hazards model were used to assess survival and factors associated with survival. RESULTS: Of the 557 patients, 343 and 214 were <75 years and ≥75 years, respectively. Dialysis was started in 2002-2004 and 2005-2007 by 197 and 146 patients <75 years, respectively, and by 96 and 118 patients ≥75 years, respectively. Median age (73.4 years [interquartile range [IQR] 61.7-79.5 years] vs 69.5 years [IQR 57.4-77.4 years] p = 0.001) and the proportion aged ≥75 years (44.7% vs 32.8%, p = 0.004) were significantly higher in 2005-2007 than in 2002-2004. Improved initial status during 2005-2007 was observed only in patients ≥75 years, with a decrease in some co-morbidities, improved walking and better preparation for dialysis. Mortality rates were significantly lower in 2005-2007 than in 2002-2004 (hazard ratio 0.81, 95% confidence interval 0.69-0.95; p = 0.008), with the difference due to factors associated with clinical status and care. CONCLUSIONS: Improved initial clinical status and better preparation for dialysis, accompanied by increased survival, were observed for patients ≥75 years who started dialysis more recently, perhaps because of early referral to a nephrologist.

Severe sirolimus-induced acute hepatitis in a renal transplant recipient.

Sirolimus is currently used as an immunosuppressive agent in kidney transplantation due to its lack of nephrotoxicity and antiproliferative properties. However, a large number of side effects has been described with the use of m-Tor inhibitors. Most are reversible when treatment is withdrawn. Hepatotoxicity is one of these side effects, considered as a benign condition and resulting generally in a transitory and small increase in transaminase levels. We report here, to the best of our knowledge, the first case of severe sirolimus-induced acute hepatitis confirmed by liver biopsy, in a renal transplant recipient. This condition was completely cured in few weeks after sirolimus withdrawal.

Pharmacological blockade of B2-kinin receptor reduces renal protective effect of angiotensin-converting enzyme inhibition in db/db mice model.

Diabetic nephropathy (DN) can be delayed by the use of angiotensin-converting enzyme inhibitors (ACEi). The mechanisms of ACEi renal protection are not univocal. To investigate the impact of bradykinin B(2) receptor (B2R) activation during ACE inhibition, type II diabetic mice (C57BLKS db/db) received for 20 wk: 1) ACEi (ramipril) alone, 2) ACEi + HOE-140 (a specific B2R antagonist), 3) HOE-140 alone, or 4) no treatment. The development of DN, defined by an increase in albuminuria and glomerulosclerosis, was largely prevented by ACEi treatment (albuminuria: 980 +/- 130 vs. 2,160 +/- 330 mg/g creatinine; mesangial area: 22.5 +/- 0.5 vs. 27.6 +/- 0.3%). The protective effect of ramipril was markedly attenuated by B2R blockade (albuminuria: 2,790 +/- 680 mg/g creatinine; mesangial area: 30.4 +/- 1.1%), whereas HOE-140 alone significantly increased albuminuria. Despite such benefits, glomerular filtration rate remained unchanged, probably because of the combination of the hypotensive effect of diabetes in this model and the renal hemodynamic action of ramipril. Finally, the renal protective effect of ACEi was associated with a marked decrease in glomerular overexpression of insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta pathways, but also in advanced glycation end product receptors and lipid peroxidation assessed by 4-hydroxy-2-nonenal (4-HNE) adducts. Concomitant blockade of B2R partly restored glomerular overexpression of IGF-1 receptor beta and 4-HNE complexes. These results support the critical role of B2R activation in the mediation of ACEi renal protection against DN and provide the rationale to examine the benefit of B2R activation by itself as a new therapeutic approach for DN.