High initial blood levels of tacrolimus in overweight renal transplant recipients.

For the purpose of both efficacy and safety, exposure to tacrolimus and other immunosuppressive drugs must be monitored, since initial levels influence the development of acute rejection episodes, nephrotoxicity, and posttransplantation diabetes mellitus. The aim of this study was to identify risk factors for developing high initial tacrolimus blood levels. We analyzed clinical and biochemical parameters of 85 renal transplant recipients receiving tacrolimus-based immunosuppressive therapy by stratifying into subgroups of patients who displayed first tacrolimus concentrations higher and lower than 15 ng/mL. Patients with a first level of tacrolimus higher than 15 ng/mL were older (52 +/- 13 vs 40 +/- 12 years, P < .05) and had a larger body mass index (27 +/- 4 vs 23 +/- 3 kg/m2, P < .05) than patients with lower levels, despite receiving a lower weight-adjusted cumulative steroid dose (8.2 +/- 2.2 vs 9.3 +/- 2.5 mg/kg, P < .05). Upon logistic regression, age (RR 1.047, 95% CI 1.007 to 1.08, P = .021) and body mass index (RR 1.176, 95% CI 1.009 to 1.371, P = .036) remained significant risk factors for high initial blood levels of tacrolimus. As these subgroups of patients are most prone to develop posttransplantation glycemic disorders, attention must be paid to avoid high tacrolimus blood levels by diminishing initial tacrolimus doses or estimating them from ideal body weight.

Higher initial tacrolimus blood levels and concentration-dose ratios in kidney transplant recipients who develop diabetes mellitus.

Posttransplantation diabetes mellitus (PTDM) is a common complication of kidney transplantation, associated with poorer graft and patient outcomes. Tacrolimus is a strong immunosuppressive drug associated with low acute rejection rates, but a higher risk for PTDM. High trough levels of tacrolimus during the first month after transplantation have been found to be a significant risk factor for the development of PTDM. The aim of this single-center study was to identify the risk factors for the development of PTDM among kidney transplant recipients under tacrolimus therapy. We examined 73 cadaveric kidney transplant recipients receiving tacrolimus between 1994 and 2003. Age, donor and recipient gender, dialysis method, body mass index (BMI), first year weight gain, mismatches, incidence of acute rejection and delayed graft function, hepatitis C serology, first year cumulative steroid dose, first tacrolimus blood level, first tacrolimus blood level <15 ng/mL, and corresponding tacrolimus daily doses and concentration/dose ratios (CDR) were also collected. PTDM was defined as at least 2 fasting blood glucose values > or =126 mg/dL, according to the World Health Organization criteria. Incidence of first year PTDM was 27.4%. Patients with PTDM showed significantly higher age, BMI, first tacrolimus blood level, first tacrolimus CDR, and CDR with tacrolimus blood level <15 ng/mL as well as less 1-year weight gain. After logistic regression, age (relative risk [RR] 1.060, confidence interval [CI] 95%, 1.001-1.122; P = .043) and first tacrolimus blood level (RR 1.154; CI 95%, 1.038-1.283; P = .008) remain significant risk factors for developing PTDM. Older age and initial tacrolimus blood levels were the main risk factors for PTDM among our group of patients. Kidney transplant recipients who develop PTDM maintain a high CDR of tacrolimus.

Subclinical renal toxicity in rheumatic patients receiving longterm treatment with nonsteroidal antiinflammatory drugs.

OBJECTIVE: To study the possible renal toxicity of longterm treatment with nonsteroidal antiinflammatory drugs (NSAID), in a population of patients with rheumatic diseases. METHODS: Comparative study of 104 patients treated for more than 2 years with NSAID and 123 healthy controls, nonusers of these drugs. After fasting during 12 h the following tests were performed in both groups: urinalysis, creatinine clearance, osmolar clearance, negative free water clearance, and urinary excretion of sodium. RESULTS: In the patient group the urinary pH was higher than in the controls (5.9 +/- 0.7 versus 5.2 +/- 0.6 p < 0.05) and in addition, they had an impaired renal concentration capacity, as it is shown by a significant decreased urinary density (1018.6 +/- 4.7 vs 1026.3 +/- 5.4 in the controls p < 0.05), a decreased urinary osmolality (502.1 +/- 150.7 vs 661.6 +/- 157.6 mOsm/ml p < 0.001), a lower osmolar clearance (1.26 +/- 0.25 ml/min vs 1.83 +/- 0.4 ml/min p < 0.001) and an increased free water clearance (-0.21 +/- 0.40 ml/min vs -0.98 +/- 0.41 ml/min, p < 0.001). This renal impairment was related to the cumulative intake of NSAID: CONCLUSION: The longterm treatment with NSAID is able to produce a subclinical renal dysfunction, consistent with the early stages of analgesic nephropathy.

Erythromycin-induced hypoacusis: 11 new cases and literature review.

OBJECTIVE: To report 11 cases of possible erythromycin-induced hearing loss and to review all cases reported in the literature. CASE SUMMARY: In the 11 cases reported, the following are reviewed: age, gender, time to onset of and recovery from hypoacusis in relation to erythromycin administration, presence or absence of renal or hepatic disease, underlying disorders, and concurrent administration of other drugs. Hypoacusis appeared with dosages equal to or higher than 4 g/d in patients with a mean age of 52.5 +/- 19 years, a high percentage of whom (45 percent) presented with renal impairment. The hearing loss was reversible in all cases, and subsided a few days (median = 3) after dosage reduction or drug discontinuation. DISCUSSION: Our patients' characteristics are similar to those of patients reported in the literature. Most data indicate that erythromycin-induced hypoacusis is a dose-dependent effect; however, its occurrence in patients otherwise free from disposing factors suggests that it is idiosyncratic. CONCLUSIONS: Erythromycin administered for appropriate indications and dosage adjustments in patients with impaired renal and/or liver function may prevent or reduce the incidence of erythromycin-induced hypoacusis.

Time course of trough serum gentamicin concentrations in preterm and term neonates.

Trough serum concentrations (Cmin) of gentamicin were followed during up to 96h of treatment in 44 neonates (17 preterm and 27 term), treated with intramuscular gentamicin 2.5 +/- 0.3 mg/kg (mean +/- SD) twice daily, a dosage that was not changed during the follow-up period. Relationships with patients' gestational age, postnatal age, postconceptional age and bodyweight were analysed to identify circumstances in which gentamicin should be monitored. Gentamicin Cmin values after 24h correlated better with neonate's postconceptional age (r = -0.42) or gestational age (r = -0.37) than with postnatal age or bodyweight. Correlations with postconceptional age and gestational age improved after 96h (r = -0.71 and r = -0.67, respectively). From 24 to 96h Cmin increased from 1.5 to 2 mg/L (p < 0.001) in the preterm neonates and from 1.5 to 2.5 mg/L (p < 0.01) in those preterm neonates < or = 32 weeks of gestational age, while differences between neonates < or = 3 days and > 3 days of postnatal age were nonsignificant. The Cmin at 24h was potentially toxic (> 2 mg/L) in 9% of the neonates (12% of preterm and 7% of term neonates). At 96h, the percentage of neonates with toxic Cmin values increased to 25% (65% of all preterm neonates and 100% of preterm neonates < or = 32 weeks of gestational age), whereas in term neonates it decreased to 0%. In conclusion, in preterm neonates < or = 32 weeks of gestational age a dosage of 2.5 mg/kg every 24h should be used, and gentamicin concentrations should be monitored. However, in term neonates > 7 days of postnatal age a dosage of 3.5 mg/kg twice daily should be recommended.