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Background: Experience with high-dose ganciclovir for the management of resistant cytomegalovirus (CMV) replication in transplant patients is limited despite its adoption as an effective therapy by some consensus documents., Methods: We studied six cases of CMV replication in solid organ transplant patients whose genotypic testing showed mutations associated with different levels of resistance to ganciclovir. All were treated with high-dose intravenous ganciclovir (7.5-10 mg/kg/12 hr) or oral valganciclovir (1350-1800 mg/12 hr) corrected according to creatinine clearance. The virologic response was considered positive if the CMV plasma viral load was undetectable. Safety was evaluated by clinical assessment, including the review of vital signs and laboratory tests., Results: All patients had asymptomatic replication, except one who had digestive disease. Four patients received universal prophylaxis with valganciclovir. Two patients received preemptive therapy with valganciclovir for individual episodes of replication. Two of the six patients received steroid boluses before the episode of replication by resistant CMV. All patients responded to treatment, including those with mutations associated with a high level of ganciclovir resistance. Four patients had neutropenia (<1.5 × 10/L), but only one received treatment., Conclusions: High-dose ganciclovir/valganciclovir can be an option in the treatment of resistant CMV replication and could be considered an alternative treatment in nonsevere patients for whom the use of foscarnet should be avoided. The toxicity of this regimen does not appear to limit its use.

Background: Clinical data are lacking concerning therapeutic action and systemic exposure of tacrolimus (TAC) and everolimus (EVL) in a combined regimen in renal transplantation., Methods: A prospective randomized phase II pharmacokinetic study was conducted comparing two fixed EVL dosages (0.75 mg two times per day (BID), group A, or 1.5 mg BID, group B) in combination with standard TAC dose. Complete 12-hr pharmacokinetic curves of both drugs were performed at days 4, 14, and 42 posttransplant., Results: A higher TAC Cmin was observed with EVL dose of 0.75 mg BID (TAC 11.1+/-6.4 group A vs. 9.4+/-5.0 ng/mL group B, P=0.03), with equivalent TAC area under the curves (162+/-61 vs. 171+/-75). The exposure to TAC was lower in group B despite higher TAC doses were required to maintain target concentrations (day 14: 9.5 vs. 12.5 mg and day 42: 6 vs. 9 mg, P<0.05). Cmin-TAC/dose and area under the curve-TAC/dose ratios were significantly lower, from day 4 to day 42, in group B. Both groups achieved good graft function and acute rejection rate was similar (20% and 15%, respectively)., Conclusions: We conclude that in adult renal transplant recipients, EVL significantly decreases TAC oral bioavailability in a dose-dependent manner. Doses higher than 1.5 mg BID would be probably needed for TAC-minimization strategies because 3 mg/day is not enough to achieve levels more than 3 ng/mL during the first 2 weeks. Therapeutic drug monitoring is mandatory to adjust the dose and prevent low TAC exposure. This regimen of low EVL exposure plus standard TAC exposure avoids wound healing problems with good efficacy.

Background: Kidney transplant recipients are considered to have chronic kidney disease (CKD) irrespective of glomerular filtration rate (GFR) or presence or absence of markers of kidney damage. The aim of this work was to investigate the prevalence of CKD-stages and whether the guidelines for general population (Kidney Disease Outcomes Quality Initiative) are routinely followed in kidney transplant in Spain., Patients and Methods: Two thousand one hundred sixty renal transplant recipients followed up at the outpatient clinics in 4 University Hospitals were included. The estimated GFR (eGFR) was calculated according to the abbreviated modification of diet in renal disease equation, and the patients were classified following the Kidney Disease Outcomes Quality Initiative stages., Results: Chronic kidney failure (eGFR <60 mL/min/1.73 m) was present in 1505 patients (69.7%), 54.4% were 3T-stage (eGFR 30-59); 13.0% were 4T-stage (eGFR 15-30), and 2.3% were 5T-stage. The prevalence of severe anemia increased from 4.1% in 1T-stage to 44% in 5T-stage (P=0.000) as did the percentage of patients on erythropoiesis-stimulating agents from 1.3% to 68% (P=0.000). The intact parathyroid hormone levels increased as graft function declined and 45% of 5T-stage patients had intact parathyroid hormone levels more than 300. Calcium and vitamin D supplements were administered to 50% and 40% of patients, respectively. Hypertension was quite common and increased with the progression of CKD. The mean total cholesterol was 192+/-39 mg/dL, and the levels did not increase with the decline in graft function. Approximately 60% had suboptimal cholesterol despite 50% being on statins treatment., Conclusions: CKD and their complications were prevalent in renal transplant recipients. The control of some of these complications is far below targets established for nontransplant CKD patients despite a progressive intensification of therapy as graft function declines.

Background: Long-term maintenance immunosuppression with cyclosporine (CsA) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile. Several nonrandomized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil (MMF; CellCept)., Methods: A randomized, controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF (2 g/day), CsA (Neoral), and corticosteroids. The primary endpoint was creatinine clearance at 6 months after complete withdrawal., Results: In the intent-to-treat population, CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol (-0.3 mmol/L, P=0.02; -0.4 mmol/L, P=0.015). There was a trend toward improved creatinine clearance (4.5 mL/min, P=0.16) and serum creatinine (-1 vs. +4 micromol/L, P=0.34). In the per-protocol population, which excluded patients with acute rejections, the improvements in creatinine clearance and serum creatinine were statistically significant (7.5 mL/min, P=0.02; -11 vs. +4 micromol/L, P=0.0003). Reversible acute rejections, the majority of which were mild, occurred in nine CsA withdrawal versus two CsA continuation patients (10.6% vs. 2.4% of each group, P=0.03), with no graft loss., Conclusion: Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections, without graft loss.