Coadministration of tacrolimus and ketoconazole in renal transplant recipients: cost analysis and review of metabolic effects.

BACKGROUND: The high cost of tacrolimus is a major problem in Mexico. Ketoconazole increases tacrolimus bioavailability by inhibiting cytochrome P450 3A4 and glycoprotein-p. OBJECTIVE: To demonstrate that the coadministration of tacrolimus and ketoconazole allows a significant dose and cost reduction. PATIENTS AND METHODS: This prospective study administered tacrolimus and ketoconazole to renal transplant recipients with dose adjustment according to tacrolimus blood levels. At 0-1, 1-6, 6-12, and 12-24 months posttransplant demographic, transplant type, immunosuppression, and clinical data were reviewed. The cost of tacrolimus treatment was calculated based on the dose used as compared to the recommended dose (0.15-0.20 mg/kg/d). RESULTS: Eleven patients with an age of 40 years (range, 13-71) were studied from May 2000 to August 2002. Follow-up was 15 +/- 10 months. Graft source was living donor in six patients and cadaveric in five. All patients received tacrolimus + mycophenolate mofetil + prednisone. The mean ketoconazole dose was 87 mg/d. Since the dose of tacrolimus was 0.04 mg/kg/d versus the recommended dose of 0.15-0.20 mg/kg/d, there was a 78% cost reduction (P =.000). Tacrolimus blood levels remained in the therapeutic range. There were no drug-related side effects. CONCLUSIONS: The co-administration of tacrolimus and ketoconazole results in a substantial dose and cost reduction while maintaining therapeutic levels. No adverse metabolic consequences were seen with this combination.

[Percutaneous kidney biopsy, analysis of 26 years: complication rate and risk factors; comment]. / Biopsia renal percutánea, análisis de 26 años: tasa de complicaciones y factores de riesgo.

UNLABELLED: Percutaneous renal biopsy is an invasive procedure that can result in major and minor complications. The objective of this study was to know the frequency and type of complications in relation with this procedure, as well as the efficacy to obtain enough material for diagnosis. METHODS: Retrospective study. We review the charts of patients to whom a percutaneous renal biopsy of native kidneys was done between January 1970 and March 1996. The following data were obtained: age, gender, clinical and histopathological diagnosis, complications associated with the procedure (minor: hematuria, local infections, hematoma; major: transfusions, severe infections, surgery, nephrectomy, arteriography, embolism and death). RESULTS: We analyzed 1,005 renal biopsies in 840 patients, mean age 37.7 +/- 13.1 years, 67% female. There were no complications in 88.8% (893 biopsies), minor complications in 8.65% (87 biopsies) and only in 2.4% of the procedures major complications. We divided the cases in two groups: percutaneous renal biopsy without complications (n = 893, 89%) and with complications (n = 112, 11%). The most frequent complications were hematuria (91 cases, 9.1%) and perirenal hematoma (29 cases, 2.7%). In these cases transfusion was required in 2.4% (26). Infectious complications were: urosepsis in 7 cases (0.7%), bacteremia, sepsis and perirenal abscesses (1 case each, 0.1%). One patient died because of multiple complications (0.1%). We observed greater risk of major complications on patients in those who biopsy was done because of acute renal failure (OR 4.03, p < 0.003). DISCUSSION: In our experience percutaneous renal biopsy is a low risk procedure. Most complications are minor and without clinical repercussion. There must be a strict selection criteria of the patients to whom percutaneous renal biopsy is going to be done because of the risk of severe complications.

Prevalence of ectopic ventricular activity after left ventricular mass regression.

To assess the effects of left ventricular mass reduction on the prevalence of ventricular ectopic activity, we conducted a double-blind, placebo-controlled trial measuring ambulatory 48 h premature ventricular depolarizations in 27 patients with mild-to-moderate hypertension and an increased left ventricular mass index. Data was obtained at baseline and 6 +/- 2 months after randomization to either 25 mg captopril or placebo twice a day. Patients on captopril attained reduction in blood pressure from 167 +/- 11/103 +/- 6 to 136 +/- 10/85 +/- 5 mm Hg (P = .001), left ventricular mass index regression from 149 +/- 17 to 96 +/- 23 g/m2 (P = .001), and ventricular ectopic activity reduction from 413 +/- 172 to 77 +/- 27 ventricular extrasystoles/day (P = .001). Patients on placebo had no significant change in blood pressure (from 162 +/- 11/101 +/- 6 at baseline to 160 +/- 8/100 +/- 8 mm Hg after 6 months; P = NS). In the placebo group left ventricular mass index increased from 155 +/- 40 to 182 +/- 51 g/m2 (P = .01), and ventricular ectopic activity decreased from 634 +/- 293 to 562 +/- 260 ventricular extrasystoles/day (P = NS). Eight out of 14 patients on captopril (57%) and 1 out of 13 patients on placebo (8%) achieved reduction > 85% in ventricular ectopic activity per day (P = .004). Using multivariate logistic regression analysis, left ventricular mass index regression and reduction in systolic blood pressure were the most important correlates for this effect.(ABSTRACT TRUNCATED AT 250 WORDS)