Excess risk of renal allograft loss associated with cigarette smoking.

BACKGROUND: Cigarette smoking contributes to a number of health-related problems, but its impact on renal transplant survival beyond accelerated patient death is unclear. METHODS: We performed a cohort study of 645 adult renal allograft recipients from 1985 to 1995 to evaluate the relationship between smoking and graft outcome. RESULTS: Twenty-four percent of recipients (156/645) were smokers at the time of transplant evaluation. Of these, 90% continued to smoke after transplantation. Pretransplant smoking was significantly associated with reduced overall graft and death-censored graft survival. Patients who were smokers at the time of pretransplant evaluation had kidney graft survival of 84%, 65%, and 48% at 1, 5, and 10 years, respectively, compared with graft survival in nonsmokers of 88%, 78%, and 62% (P=0.007). Pretransplant smoking adversely affected death-censored graft survival in recipients of cadaveric (P=0.02) and of living donor kidneys (P=0.02). Reduced graft survival in pretransplant smokers could not be accounted for by differences in rejection (64% vs. 61%, P=0.35). In a multivariate analysis, pretransplant smoking was associated with a relative risk of 2.3 for graft loss. Among patients with a smoking history before transplantation, death-censored graft survival was significantly higher for those who quit smoking before transplant evaluation. CONCLUSIONS: Cigarette smoking before kidney transplantation contributes significantly to allograft loss. The effect of smoking on graft outcome is not explained by increases in rejection or patient death. Smoking cessation before renal transplantation has beneficial effects on graft survival. These effects should be emphasized to patients with end-stage renal disease who are considering renal transplantation.

Peripheral vascular occlusive disease in renal transplant recipients: risk factors and impact on kidney allograft survival.

BACKGROUND: This study evaluated the relationship between renal transplantation and the evolution of lower extremity peripheral vascular occlusive disease (PVOD). METHODS: A total of 664 adult renal allograft recipients from 1985-1995 were retrospectively reviewed for atherosclerotic risk factors and peripheral vascular occlusive disease (PVOD). PVOD events were defined as bypass, major amputation, claudication, or percutaneous angioplasty. Follow-up ranged from 2-12 years. RESULTS: The cumulative 5- and 10-year incidences of lower extremity PVOD after renal transplantation were 4.2 and 5.9%. Eight of 14 patients (57%) with pretransplant PVOD had additional PVOD events versus de novo appearance of PVOD in 21/650 patients (3.2%; P<0.0001). In a proportional hazards model, age, preoperative PVOD, diabetes, and postoperative smoking were independent risk factors for the development of PVOD after transplantation. Recipients with lower extremity PVOD had significantly lower 10-year patient and graft survival. Increased graft failure was due to an excess of deaths with a functioning graft. A total of 34 major interventions were performed. One- and two-year limb salvage rates were 64.2 and 53.8%. CONCLUSIONS: Lower extremity PVOD after renal transplantation is associated with diminished patient survival, and affects kidney graft survival via disproportionate patient attrition. Age, preoperative PVOD, diabetes, and postoperative smoking are important risk factors. Transplantation does not appear to either accelerate or retard the progression of disease. An aggressive approach towards limb salvage in properly selected patients is justifiable.

The molecular evolution of G protein-coupled receptors: focus on 5-hydroxytryptamine receptors.

Phylogenetic comparisons between homologous proteins can provide information on the rates of molecular evolution of the proteins. G protein-coupled receptors are a "superfamily" of proteins which exist in species ranging from yeast to man. Based on an analysis of the percentage of amino acid homology between various species, the rate of molecular evolution of G protein-coupled receptors can be estimated at approx 1% per 10 million years. Based on this assumption, the primordial 5-HT receptor must have evolved more than 700-800 million years ago since the 3 major classes of G protein-coupled 5-HT receptors (i.e. 5-HT1, 5-HT2 and 5-HT6 receptors) are less than 25% homologous. 5-HT5, 5-HT7, 5-HTsnail, 5-HTdro and 5-HT1A receptors differentiated approx 600-700 million years ago, the time period during which vertebrates diverged from invertebrates. The mammalian 5-HT receptor subtypes have differentiated over the past 90 million years. Thus, although a recent flurry of "new" 5-HT receptors have appeared in the literature, the first "primordial" 5-HT receptor evolved over 750 million years ago, a date which likely predates the evolution of muscarinic, dopaminergic and adrenergic receptor systems. This analysis also predicts that a significant number of both mammalian and invertebrate G protein-coupled 5-HT receptor subtypes remain to be identified.