Variables Associated With Hyperkalemic Renal Tubular Acidosis in Solid Organ Transplant Recipients.

INTRODUCTION: The occurrence of hyperkalemic renal tubular acidosis (RTA) in the post-transplantation period is likely underestimated, and its identification remains important to offer adequate medical management. Transplant recipients frequently present with clinical and biological characteristics that may be associated with the occurrence of this complication. METHODS: This was a single-center retrospective study that compared transplanted patients with hyperkalemic RTA and a control group to identify variables associated with the occurrence of this complication. Fisher's exact test and the Mann-Whitney test, followed by multivariate logistic regression, were applied to test whether there was a significant association between hyperkalemic RTA and different variables. RESULTS: Kidney and heart transplant recipients were at greater risk of developing RTA than lung transplant recipients (p = 0.016). There was also a significant association between the development of RTA and kalemia (p < 0.01), chloremia (p < 0.01), and bicarbonatemia (p < 0.01). The significant impact of these last three variables was confirmed by the results of the multivariate logistic regression. Residual serum tacrolimus levels (p = 0.13) and creatinine levels (p = 0.17) of renal transplant patients were not significantly associated with hyperkalemic RTA. CONCLUSION: The type of transplanted organ, kalemia, chloremia, and bicarbonatemia were significantly associated with the occurrence of hyperkalemic RTA. This study calls into question certain approaches to managing this complication proposed in a number of case reports, such as reducing the target serum residual of tacrolimus or discontinuing trimethoprim-sulfamethoxazole (TMP-SMX) in favor of another antibiotic prophylactic agent, potentially exposing patients to graft rejection and opportunistic infections.

5-Year outcomes of the prospective and randomized CISTCERT study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients.

Withdrawal of either steroids or calcineurin inhibitors are two strategies to reduce treatment-related side effects and improve long-term outcomes of kidney transplantation. The CISTCERT study compared the efficacy and safety of these two strategies. In this multicenter, randomized controlled trial, 151 incident kidney transplant recipients received cyclosporine (CsA), mycophenolic acid (MPA), and steroids during three months, followed by either steroid withdrawal (CsA/MPA) or replacement of cyclosporine with everolimus (EVL) (EVL/MPA/steroids). 5-year patient survival (89% vs. 86%; P = NS) and death-censored graft survival (95% vs. 96%; P = NS) were comparable in the CsA/MPA and EVL/MPA/steroids arm, respectively. 51 CrEDTA clearance was comparable in the intention-to-treat analysis, but in the on-treatment population, the EVL/MPA/steroids arm exhibited a superior 51 CrEDTA clearance at 1 and 5 years after transplantation (61.6 vs. 52.4, P = 0.05 and 59.1 vs. 46.2ml/min/1.73 m2 , P = 0.042). Numerically more and more severe rejections were observed in the EVL/MPA/steroids arm, which also experienced a higher incidence of posttransplant diabetes (26% vs. 6%, P = 0.0016) and infections. No significant differences were observed in cardiovascular outcomes and malignancy. Both regimens provide an excellent long-term patient survival and graft survival. Regarding graft function, EVL/MPA/steroids is an attractive strategy for patients with good tolerability who remain free of rejection. (ClinicalTrials.gov number: NCT00903188; EudraCT Number 2007-005844-26).

Treatment of advanced hepatocellular carcinoma with long-acting octreotide: a phase III multicentre, randomised, double blind placebo-controlled study.

BACKGROUND: A previous study reported a significant survival benefit for octreotide compared with no treatment in patients with advanced hepatocellular carcinoma (HCC). This was investigated further in this multicentre study. PATIENTS AND METHODS: Two hundred and seventy two patients with HCC who were ineligible for curative treatments or had relapsed following potentially curative therapies were randomised to receive long-acting octreotide, 30 mg as an intramuscular injection once every 4 weeks for up to 2 years, or placebo. RESULTS: At the time of the final analysis, median overall survival (OS) was 6.53 months (95% confidence interval [CI], 4.8-8.3) for octreotide versus 7.03 months (95% CI, 5.43-8.53) for placebo (p=0.34). Progression-free survival (p=0.26) also did not differ significantly between the two treatment groups. No objective responses were achieved in the octreotide group but 33% of patients achieved disease stabilisation for a mean time of 5.5 months (95% CI, 1.1-9.9). The median time until definitive global health score deterioration (according to QLQ-C30) was 2.3 months (95% CI, 1.4-3.7) in the octreotide and 4 months (95% CI, 2.2-5.7) in the placebo group (p=0.09). There were four objective responses in the placebo group. Octreotide was well tolerated; seven patients reported severe adverse events possibly related to octreotide and there were no cases of haematoma or cholecystitis. CONCLUSIONS: In patients with advanced HCC, octreotide has a favourable safety profile but does not improve OS and could have a negative impact on quality of life.

Incidence of drug-induced hepatic injuries: a French population-based study.

The incidence of hepatic adverse drug reactions (ADRs) remains unknown in the general population. The goal of this population-based study was to assess the incidence and seriousness of hepatic ADRs. All new cases of symptomatic drug-induced hepatic injuries were collected by 139 trained physicians (general practitioners [GPs] and specialists) between November 1997 and November 2000 in an area containing 81,301 inhabitants who could not go elsewhere for medical care. Over 3 years, 34 cases of hepatic ADRs were collected, 82% of them in outpatients. Global crude annual incidence rate was 13.9 +/- 2.4 per 100,000 inhabitants; corresponding standardized annual global rate was 8.1 +/- 1.5. There was no difference between urban and rural areas. Standardized incidence female/male ratio was 0.86 (0.26-2.90) until 49 years of age and 2.62 (1.00-6.92) after this age. Diagnosis was carried out by GPs in half of the cases. The outcome was recovery for 32 patients and death for 2. The main drugs implicated were anti-infectious, psychotropic, hypolipidemic agents, and nonsteroidal anti-inflammatory drugs (NSAIDs). Our results suggest that the number of hepatic ADRs in the French population would be 16 times greater than the number noted by spontaneous reporting to French regulatory authorities. In conclusion, the incidence and seriousness of drug-induced hepatitis are largely underestimated in the general population. These results may be useful for further evaluation of drug-induced hepatotoxicity.