Chronic kidney disease stages 3-5 and cardiovascular disease in the veterans affairs population.

AIM: Cardiovascular complications are common in patients with chronic kidney disease in the general population. The study aims to investigate the prevalence and prognosis of CKD stages 3-5 in the veterans affairs (VA) population, which is sicker with more co-morbid conditions. METHODS: In this case-controlled study of 6,432 men the associations of risk factors with CKD and its risk of mortality were estimated using, primarily, logistic regression analysis. RESULTS: The 1,045 (16.2%) patients with CKD stages 3-5 were older (72 +/- 10 vs. 59 +/- 13 years, P < 0.0001) with more hypertension (53.6 vs. 39.6%, P < 0.0001), diabetes (24.9 vs. 19.8%, P < 0.0002), and CVD (35.3 vs. 17.8%, P < 0.0001) at baseline. Age > or =65 years (odds ratio [95% CI]) (4.95 [4.22-5.82]), hypertension (1.56 [1.34-1.79]), diabetes mellitus (1.21 [1.03-1.43]), CVD (1.71 [1.47-2.00]), and White not Hispanic (1.57 [1.32-1.85]) were independently associated with CKD. The prevalence of CVD at baseline increased with decreasing renal function. Old age (1.98 [1.66-2.35]), CKD (1.94 [1.61-2.33], CVD (1.46 [1.23-1.74]) and tobacco use (1.91 [1.05-3.47]) were independently associated with the 750 (11.7%) deaths. CONCLUSION: Among veterans, traditional cardiovascular risk factors, CVD, and CKD are highly prevalent. CKD is associated with increased risk of baseline CVD and follow-up mortality.

A case of Weber-Christian disease with collapsing glomerulopathy.

We report a case of Weber-Christian disease confirmed by skin biopsy in a patient who presented with collapsing glomerulopathy and lipophagic interstitial nephritis. On renal biopsy, glomerular visceral epithelial cells, tubular cells, and interstitial macrophages were loaded with inclusions that were morphologically consistent with oxidized lipoproteins, suggesting that lipids derived from the panniculitis may have an etiopathogenic role.

Maintenance therapies for proliferative lupus nephritis: mycophenolate mofetil, azathioprine and intravenous cyclophosphamide.

For the treatment of proliferative lupus nephritis, long-term cyclophosphamide (CY) regimens are efficacious, however, at the expense of substantial toxicity. In the last decade, sequential regimens of short-term CY induction followed by either mycophenolate mofetil (MMF) or azathioprine (AZA) maintenance have shown to be efficacious and safe reducing the long-term exposure to CY. In a maintenance study including predominantly Hispanics and African-Americans, the patients who received MMF and AZA maintenance had a higher cumulative probability of remaining free of the composite of death or chronic renal failure (CRF) compared to quarterly intravenous CY (IVCY) maintenance (89% in MMF, 80%, in AZA and 45% in IVCY). Likewise, MMF and AZA maintenance were associated with significantly lower incidence of severe infections (2% in each MMF or AZA, and 25% in IVCY), sustained amenorrhea (6% in MMF, 8% in AZA, and 32% in IVCY), and hospitalizations (one hospital-days per patient-year in each MMF or AZA, and 10 in IVCY). In a European induction study including predominantly Caucasians, patients who received any of two sequential regimens, low dose versus high dose IVCY induction both followed by AZA maintenance, had a high cumulative probability of remaining free of treatment failure (84% in low dose IVCY and 80% in high dose IVCY; treatment failure defined as a composite of free of corticosteroid resistant flare, nephrotic syndrome, doubling creatinine, and persistent elevated creatinine). Low dose IVCY and high dose IVCY induction were associated with low incidence of sustained amenorrhea (4% in each group) and severe infections (11% in low dose and 22% in high dose IVCY induction). Of interest, most of the severe infection episodes occurred while patients were receiving IVCY induction. Finally an Asian study demonstrated that patients with proliferative lupus nephritis could be effectively treated with short-term oral CY induction followed by AZA maintenance. The cumulative probability of complete remission was 76%. The relapse rate was only 11%. The incidence of permanent amenorrhea and infection were 8% and 33%, respectively. None of the Asian patients had an increase in serum creatinine level to double the baseline value. Maintenance therapies with MMF or AZA following short-term CY induction in a sequential regimen are efficacious and safe for the treatment of high-risk patients with proliferative lupus nephritis.

Ethanol promotes T cell apoptosis through the mitochondrial pathway.

Clinical reports suggest that acute ethanol intoxication is often associated with lymphopenia. Previously, ethanol was reported to invoke thymocyte apoptosis. We studied the effect of ethanol on T cell apoptosis. In addition, we evaluated the molecular mechanism of ethanol-induced T cell apoptosis. Human T cells harvested from healthy subjects after an alcohol drinking binge showed enhanced T cell apoptosis (before, 0.4 +/- 0.2% versus after, 19.6 +/- 2.5% apoptotic lymphocytes/field; P < 0.001). In in vitro studies, ethanol in a concentration of 50 mm and higher enhanced the apoptosis of Jurkat cells. DNA isolated from ethanol-treated Jurkat cells displayed integer multiples of 180 base pairs. Ethanol decreased Jurkat cell expression of Bcl-2, whereas ethanol increased Jurkat cell expression of Bax. Jurkat cells treated with ethanol also showed translocation of cytochrome C into cytosol. Moreover, a caspase-9 inhibitor partially inhibited ethanol-induced Jurkat cell apoptosis. In in vivo studies, after binge drinking, T cell expression of Bcl-2 also decreased. In addition, binge drinking induced the cleavage of caspase-3, suggesting activation of caspase-3 in T cells. These results suggest that ethanol promotes T cell apoptosis through the activation of intrinsic or mitochondrial pathway.