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.

Differentiation of serum-free mouse embryo cells into astrocytes is accompanied by induction of glutamine synthetase activity.

Serum-free mouse embryo (SFME) cells derived in a defined serum-free medium have been cultured for more than 200 generations and display properties of neural progenitor cells. SFME cells express the neuroepithelial stem cell marker nestin in defined serum-free medium. Exposure of SFME cells to transforming growth factor beta (TGF-beta) or serum decreases nestin expression and induces the astrocyte marker glial fibrillary acidic protein, suggesting that SFME cells differentiate into astrocytes upon exposure to TGF-beta or serum. We examined the expression by SFME cells of the functional central nervous system (CNS) astrocyte marker glutamine synthetase (GS). GS activity is induced in SFME cells upon exposure to TFG-beta or serum. The induction of GS activity was dose- and time-dependent and was reversible. Retinoic acid, hydrocortisone, and dibutyryl cyclic AMP also induced GS expression. The induction of GS activity was accompanied by an increase in the level of GS mRNA and protein. This work provides further evidence that SFME cells represent neural progenitor cells which differentiate into functional astrocytes upon exposure to TGF-beta or serum.

Down regulation of nestin by TGF-beta or serum in SFME cells accompanies differentiation into astrocytes.

The serum-free mouse embryo (SFME) cell line, derived from 16-day-old mouse embryos in medium in which serum was replaced by growth factors and other supplements, has been cultured for more than 200 generations. SFME cells are nontumorigenic, lack gross chromosomal abnormalities, and display characteristics of CNS progenitor cells. SFME cells show reversible induction of the astrocyte-specific marker glial fibrillary acidic protein when cultured in the presence of TGF-beta or serum. In order to determine if SFME cells exhibit further characteristics of CNS progenitor cells we investigated the expression of the gene encoding nestin, an intermediate filament protein expressed by neuroepithelial stem cells of the CNS. SFME cells express nestin in serum-free medium, and nestin expression is reversibly down-regulated by TGF-beta or serum. These results demonstrate that nestin expression is regulated by factors present in serum and support the hypothesis that SFME cells represent a CNS progenitor cell.