Benefits and Harms of Benign Prostatic Obstruction Treatments in Renal Transplanted Patients.

CONTEXT: In an increasingly ageing transplant population, timely management of benign prostatic obstruction (BPO) is key to preventing complications that result in graft dysfunction or compromise survival. OBJECTIVE: To evaluate benefits/harms of BPO treatments in transplant patients by reviewing current literature. EVIDENCE ACQUISITION: A computerised bibliographic search of Medline, Embase, and Cochrane databases was performed for studies reporting outcomes on BPO treatments in transplanted patients. EVIDENCE SYNTHESIS: A total of 5021 renal transplants (RTs) performed between 1990 and 2016 were evaluated. BPO incidence was 1.61 per 1000 population per year. Overall, 264 men underwent intervention. The mean age was 58.4 yr (27-73 yr). In all, 169 patients underwent surgery (n = 114 transurethral resection of the prostate [TURP]/n = 55 transurethral incision of the prostate [TUIP]) and 95 were treated with an un-named alpha-blocker (n = 46) or doxazosin (n = 49). There was no correlation between prostate volume and treatment modality (mean prostate size = 26 cc in the surgical group where reported and 48 cc in the medical group). The mean follow-up was 31.2 mo (2-192 mo). The time from RT to BPO treatment was reported in six studies (mean: 15.4 mo, range: 0-156 mo). The time on dialysis before RT was recorded in only three studies (mean: 47.3 mo, range: 0-288 mo). There was a mean improvement in creatinine after intervention from 2.17 to 1.77 mg/dl. A total of 157 men showed an improvement in the International Prostate Symptom Score (from 18.26 to 6.89), and there was a significant reduction in postvoid residual volume in 199 (mean fall 90.6 ml). Flow improved by a mean of 10 ml/s following intervention in 199 patients. Complications included acute urinary retention (4.1%), urinary tract infections (8.4%), bladder neck contracture (2.2%), and urethral strictures (6.9%). The mean reoperation rate was 1.4%. CONCLUSIONS: Current literature is heterogeneous and of low-level evidence. Despite this, alpha-blockers, TUIP, and TURP showed a beneficial increase in the peak urinary flow and reduced symptoms in transplants patients with BPO. Improvement in the mean graft creatinine was noted after intervention. Complications were under-reported. A multicentre comparative cohort study is needed to draw firm conclusions about the ideal treatment for BPO in RT patients. PATIENT SUMMARY: In this report, we looked at the outcomes for transplant patients undergoing medical or surgical management of benign prostatic obstruction. Although the literature was very heterogeneous, we found that medical management and surgery with transurethral resection/incision of the prostate are beneficial for improving urinary flow and bothersome symptoms. We conclude that further prospective studies are required for better clarity about timing and modality of intervention in transplant patients.

Diets and enteral supplements for improving outcomes in chronic kidney disease.

Protein-energy wasting (PEW), which is manifested by low serum levels of albumin or prealbumin, sarcopenia and weight loss, is one of the strongest predictors of mortality in patients with chronic kidney disease (CKD). Although PEW might be engendered by non-nutritional conditions, such as inflammation or other comorbidities, the question of causality does not refute the effectiveness of dietary interventions and nutritional support in improving outcomes in patients with CKD. The literature indicates that PEW can be mitigated or corrected with an appropriate diet and enteral nutritional support that targets dietary protein intake. In-center meals or oral supplements provided during dialysis therapy are feasible and inexpensive interventions that might improve survival and quality of life in patients with CKD. Dietary requirements and enteral nutritional support must also be considered in patients with CKD and diabetes mellitus, in patients undergoing peritoneal dialysis, renal transplant recipients, and in children with CKD. Adjunctive pharmacological therapies, such as appetite stimulants, anabolic hormones, and antioxidative or anti-inflammatory agents, might augment dietary interventions. Intraperitoneal or intradialytic parenteral nutrition should be considered for patients with PEW whenever enteral interventions are not possible or are ineffective. Controlled trials are needed to better assess the effectiveness of in-center meals and oral supplements.

Tabebuia avellanedae extracts inhibit IL-2-independent T-lymphocyte activation and proliferation.

In order to identify new, immune modulating compounds, aqueous extracts of plants pre-selected on ethno-pharmacological knowledge were screened for inhibitory effects in an anti-CD3 driven lymphocyte proliferation assay (MTT-assay). We found for the extract of the inner bark of Tabebuia avellanedae (Tabebuia) dose dependent and reproducible inhibitory effects on lymphocyte proliferation. We further analyzed Tabebuia in flow cytometry based whole blood T-cell function assays. We found that Tabebuia inhibited dose dependent ConA stimulated T-cell proliferation. Decreased T-lymphocyte proliferation was associated with dose dependent reduction of CD25 and CD71 expression on T-lymphocytes. In contrast Tabebuia exerted no effects on cytokine expression (Il-2 and TNF-alpha) by PMA/Ionomycin stimulated T-lymphocytes. Concentrations of Tabebuia used were not toxic for lymphocytes as verified by trypan blue exclusion assay. Further experiments showed that the immune inhibitory effects by Tabebuia were not mediated by its pharmacological lead compound beta-lapachone and only observed in aqueous but not in ethanol plant extracts.

Hyperforin content determines the magnitude of the St John's wort-cyclosporine drug interaction.

OBJECTIVE: Hyperforin (HYF) has been discussed as a potential cause of the reduction in the bioavailability of numerous drugs seen with St John's wort (SJW) comedication. This study compared the effects of 2 SJW preparations with high and low HYF content on the pharmacokinetics of cyclosporine (INN, ciclosporin) (CSA). METHODS: In a crossover study, 10 renal transplant patients were randomized into 2 groups and received SJW extract (900 mg/d) containing low or high concentrations of HYF for 14 days in addition to their regular regimen of CSA. After a 27-day washout phase, patients were crossed over to the other SJW treatment for 14 days. Blood concentrations of CSA were measured by immunoassay. RESULTS: The study showed a significant difference between the effects of the 2 SJW preparations on CSA pharmacokinetics (area under the plasma concentration-time curve within one dosing interval [AUC 0-12 ], P < .0001, ANOVA). AUC 0-12 values (monoclonal) with high-HYF SJW comedication were 45% lower (95% confidence interval [CI], -37% to -54%; P < .05, Student-Newman-Keuls test) than for low-HYF SJW. The dose-corrected AUC 0-12 for CSA (monoclonal) decreased significantly compared with baseline by 52% (95% CI, -46% to -56%; P < .05) after 2 weeks of comedication with high-HYF SJW. Values of peak concentration in plasma and drug concentration at the end of one dosing interval were affected to a similar extent, with reductions by 43% (95% CI, -36% to -48%) and 55% (95% CI, -48% to -60%), respectively. In addition, a 65% (95% CI, 53% to 85%; P < .05) increase in daily CSA doses was required during high-HYF SJW treatment. In contrast, coadministration of low-HYF SJW did not significantly affect CSA pharmacokinetics and did not require CSA dose adjustments compared with baseline. CONCLUSION: HYF content of SJW extracts significantly affects the extent of the pharmacokinetic interaction between CSA and SJW.

Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients.

BACKGROUND: This study investigated the effect of St John's wort (SJW) extract on the pharmacokinetics of the immunosuppressants tacrolimus (TAC) and mycophenolic acid (MPA). METHODS: Ten stable renal transplant patients received 600 mg SJW extract for 14 days in addition to their regular regimen of TAC and mycophenolate mofetil. RESULTS: Dose-corrected AUC((0-12)) of TAC decreased significantly from 180 ng/ml/h at baseline to 75.9 ng/ml/h after 2 weeks of SJW treatment. To maintain therapeutic TAC concentrations, dose adjustments from a median 4.5 mg/day at baseline to 8.0 mg/day under SJW treatment were required. Two weeks after discontinuation of SJW, TAC doses were reduced to a median of 6.5 mg/day. MPA pharmacokinetics remained unaffected by comedication with hypericum extract. CONCLUSIONS: Administration of SJW extract to patients receiving TAC treatment can result in a serious drug interaction leading to markedly reduced TAC blood concentrations associated with the risk of organ rejection.

Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients.

AIM: This study investigated the effects of St John's wort extract (SJW) on the pharmacokinetics and metabolism of the immunosuppressant cyclosporin A (CSA). METHODS: In an open-label study, 11 renal transplant patients received 600 mg SJW extract daily for 14 days in addition to their regular regimen of CSA. Blood concentrations of CSA and its metabolites AM1, AM1C, AM9, AM19, and AM4N were measured by HPLC. RESULTS: After 2 weeks of SJW coadministration, dose-corrected AUC0-12, Cmax and Ctrough values for CSA decreased significantly by 46%[geometric mean ratio baseline/SJW (95% CI): 1.83 (1.63-2.05)], 42%[1.72 (1.42-2.08)], and 41%[1.70 (1.17-2.47)], respectively. CSA doses were increased from a median of 2.7 mg day(-1) kg(-1) at baseline to 4.2 mg day(-1) kg(-1) at day 15, with the first dose adjustment required only 3 days after initiation of SJW treatment. Additionally, the metabolite pattern of CSA was substantially altered during SJW treatment. Whereas dose-corrected AUC values for AM1, AM1c and AM4N significantly decreased by 59%, 61%, and 23% compared with baseline, AUC values for AM9 and AM19 were unchanged. Following the increase in CSA dose, observed AUC and Cmax values for AM9, AM19, and AM4N increased by 20-51% and 43-90%, respectively. CONCLUSION: Administration of SJW extract to patients receiving CSA treatment resulted in a rapid and significant reduction of plasma CSA concentrations. Additionally, the substantial alterations in CSA metabolite kinetics observed may affect the toxicity profile of the drug.