Methotrexate should not be used for patients with end-stage kidney disease.

Methotrexate is a widely used disease-modifying anti-rheumatic drug. Its effectiveness has been proven in placebo-controlled trials and in comparison with other disease-modifying anti-rheumatic drugs. The pharmacokinetics of methotrexate are highly variable and unpredictable. In patients with normal renal function, the recommended dose in rheumatoid arthritis ranges between 7.5 and 15 mg/week, but in recent years, even dosages up to 25 mg weekly are used. Toxicity includes myelosuppression, gastrointestinal adverse effects, hepatotoxicity and pneumonitis. Renal impairment and age are considered major risk factors for developing methotrexate toxicity, but studies show conflicting results. Whether methotrexate can be administered to patients with end-stage kidney disease has not been formally tested. The present case illustrates the severe side effects of low-dose methotrexate treatment in a patient with end-stage kidney disease. Seven other cases have reported similar and even more severe and irreversible consequences after low-dose regimen. In view of these side effects we strongly recommend to monitor toxicity rigorously in patients with stage 3 or stage 4 kidney disease and not to use methotrexate in patients with stage 5 kidney disease.

Morphometric analysis of renal vessels. Advantage of the multisector area approach to cross-sections.

OBJECTIVE: To determine the most accurate morphometric approach to overcoming the obstacles of limited number, angle of section and irregular contours of vascular structures in analyzing vascular sections of renal biopsies. STUDY DESIGN: The luminal area of 451 cortical arterioles in 65 Masson-trichrome-stained renal sections was assessed with a computer-assisted imaging system connected to a Leica DMR microscope (Mikroskopie und Systeme GmbH, Wetzlar, Germany). The luminal area measured by the imaging system was used as the gold standard, against which three mathematical sector approaches and one classical approach were evaluated. The accuracy of these approaches was evaluated by means of the relative deviation from the measured value and of the degree of overestimation or underestimation. Intraobserver and interobserver variability were determined for the most accurate mathematical approach. RESULTS: As compared to measured luminal area, the sector elliptical approach yielded the lowest relative deviation (13.4 +/- 12.5%), without significant overestimation or underestimation (-0.6 +/- 18.3%). The intraobserver and interobserver correlation coefficients for this method were 82.3% and 86.5%, respectively. CONCLUSION: The sector elliptical approach is the most accurate mathematical approach to vascular sections in renal biopsies.

Fibrous intimal thickening at implantation as a risk factor for the outcome of cadaveric renal allografts.

BACKGROUND: During the past decade, the donor age of cadaveric renal allografts steadily increased. Because cerebrovascular injury is the main cause of death in this donor population, an increased prevalence of atherosclerotic lesions in the retrieved grafts could be anticipated. In a prospective study, we investigated the predictive value of morphologic lesions at implantation for the functional and morphologic outcome of cadaveric renal allografts at 1 1/2 years. METHODS: In 50 consecutive adult recipients of a cadaveric renal allograft, under cyclosporine-based regimen, implantation biopsies and subsequent protocol biopsies at 18 months were performed, and morphometrically analyzed for the extent of glomerulosclerosis, interstitial fibrosis, and atherosclerosis. Risk factors were assessed at implantation and during the subsequent observation period of 18 months. Endpoints for this study were: the 24-hr creatinine clearance (normalized for body surface area) and the fractional interstitial volume at 1 1/2 years. RESULTS: In multivariate analysis, fibrous intimal thickening at implantation (FIT) was the main determinant of the functional and morphologic outcome at 1 1/2 years. FIT represented a relative risk of 4.55 for interstitial fibrosis (95% CI=1.855-11.138), and 1.89 for impaired renal function (95% CI=1.185-3.007) at 1 1/2 years. FIT adversely affected fractional interstitial volume at 1 1/2 years (34.3 vs. 27.7%, P=0.004), as well as renal function (54 vs. 68 ml/min/1.73 m2, P=0.028). CONCLUSIONS: Fibrous intimal thickening at implantation is a determinant risk factor for the functional and morphologic outcome of cadaveric renal allografts at 1 1/2 years.