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Tacrolimus is the cornerstone of immunosuppression following liver transplantation (OLT). However, this agent may cause hyperkalemia by multiple mechanisms affecting potassium in the distal tubule. The purpose of this study was to evaluate the impact of fludrocortisone for the management of tacrolimus-induced hyperkalemia. Hospitalized adult OLT recipients who received fludrocortisone for tacrolimus-induced hyperkalemia were retrospectively identified. Change in serum potassium within 14 days of initiation was the primary endpoint. Secondary endpoints included serum sodium, blood urea nitrogen, serum creatinine, and tacrolimus concentrations up to 14 days after fludrocortisone initiation. Nine patients were evaluated. Outcomes were analyzed with separate repeated-measures analyses of variance. Mean daily fludrocortisone dose was 0.14 ± 0.08 mg. Serum potassium decreased significantly within the 14-day study period (P < .001). Mean potassium decreased from 5.7 ± 1 to 4.3 ± 0.5 mmol/L within 48 hours of fludrocortisone initiation (P = .002). Sodium concentrations were statistically higher (P = .024), while serum creatinine was not significantly different by day 14. Mean tacrolimus concentration at fludrocortisone initiation was 10.2 ± 5.2 and remained stable to 14 days (10.4 ± 4.7 ng/mL; P = .9). This is the first study in OLT recipients demonstrating fludrocortisone significantly decreases serum potassium in patients with stable tacrolimus concentrations. Larger prospective studies are needed to confirm these results.

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BACKGROUND: The new microemulsion formulation of cyclosporine (CsA-ME) is more bioavailable than cyclosporine (CsA) in de novo renal transplant patients. Therefore, it was of interest to compare the safety profile of each formulation in such patients. METHODS: In a multicenter, double-blind, parallel-group study, 101 renal transplant recipients were randomized after transplantation to receive either CsA (n=50) or CsA-ME (n=51) capsules twice daily for 2 years. Of these patients, 54 (CsA, n=26; CsA-ME, n=28) completed 1 year of the study and entered the second-year, double-blind extension. Initial dose at the time of transplantation was 5 mg/kg b.i.d.; doses were titrated to target trough levels. METHODS: The mean (+/- SD) doses at the end of 2 years were 4.6 +/- 1.8 and 3.8 +/- 1.1 mg/kg per day for CsA- and CsA-ME-treated patients, respectively. The mean (+/- SD) CsA trough levels at end point were 187 +/- 63 and 210 +/- 95 ng/ml for CsA- and CsA-ME-treated patients, respectively. At least one adverse event was reported by 25/26 (96%) of CsA- and 27/28 (96%) of CsA-ME-treated patients. No patient discontinued the study because of adverse events. No deaths occurred during the study. Renal function, as measured by serum creatinine levels, and blood pressure were comparable over time in both treatment groups. CONCLUSIONS: There was no significant difference in safety and tolerability between CsA- and CsA-ME-treated kidney recipients for 2 years after transplantation.

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This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability of two cyclosporine (CsA) formulations, cyclosporine emulsion capsules and oral solution for microemulsion and cyclosporine, in the postoperative management of renal transplant patients. Of the 101 patients, aged 18 to 65, who entered the study, 89 were evaluable for pharmacokinetics. Initial dosage was 10 mg/kg per day, administered twice daily in two equal doses. Dosages were adjusted to achieve target CsA concentrations. The pharmacokinetic (PK) parameters (dose-normalized) of greatest interest were maximum blood concentration (C(max)/dose), time to reach maximum concentration (t(max), area under the blood concentration-vs.-time curve (AUC/dose), and trough blood concentrations (Co h/dose). The relative CsA bioavailabilty was found to be significantly enhanced with cyclosporine emulsion compared with cyclosporine with a 16% to 31% increase in AUC and a 32% to 42% increase in C(max). Intrapatient variability of PK parameters was significantly lower with cyclosporine emulsion than with cyclosporine for AUC, C(oh), t(max), and C(max) in many instances. This indicates a more consistent, rapid, and more complete total absorption of CsA. Despite higher CsA C(max) levels and AUCs with cyclosporine emulsion, safety and tolerability (detailed in a parallel report) were comparable to those of cyclosporine. The PK advantages of cyclosporine emulsion over cyclosporine are either independent of food conditions or possibly reflective of more consistent absorption of CsA with cyclosporine emulsion. The findings suggest that de novo use of cyclosporine emulsion may simplify and improve management of organ transplant recipients and that the PK advantages of cyclosporine emulsion may translate into clinical benefits.

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A 12-week, randomized, double-blind, multicenter pharmacokinetics study was conducted to compare the clinical safety and tolerability of cyclosporine capsules and oral solution for microemulsion and cyclosporine in 101 primary renal transplant recipients Cyclosporine emulsion has more complete absorption and improved bioavailability compared with cyclosporine, and dosing of both cyclosporine formulations was adjusted to achieve comparable whole-blood trough levels. Mean serum creatinine values were higher in the cyclosporine emulsion group at baseline, 8, and 12 weeks (P<0.05). The incidence of acute rejection was similar in both treatment groups although fewer patients required monoclonal antibody therapy in the cyclosporine group (31% vs. 82%, respectively). Despite the increased bioavailability of cyclosporine emulsion, no significant differences in the incidence of adverse events were observed; the safety, tolerability, and efficacy of cyclosporine emulsion and cyclosporine were comparable.

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Chronic active hepatitis has been associated with renal abnormalities and immune-mediated glomerulonephritis or vasculitis. We report a case of acute reversible renal failure due to renal interstitial infiltration by lymphocytes, plasma cells, and neutrophils. The acute renal failure responded to the administration of prednisone. It is possible that interstitial nephritis is commonly associated with acute and chronic hepatitis.

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Between July 1, 1979, and July 1, 1980, we treated 64 patients with long-term maintenance hemodialysis. Of these, 11 (17%) had angina pectoris, four of them (6%) chronic stable angina and seven (11%) new onset of crescendo angina. The most common risk factors in the group with unstable angina were cardiomegaly and hypertension. Of the five patients who underwent cardiac catheterization, proximal occlusive disease was seen in four and these four had good left ventricular function. Three patients underwent coronary artery bypass, which successfully improved their functional status to a class I or II without any antianginal medicines. Concurrent hemodialysis was performed during heart-lung bypass in one patient. The need for dialysis postoperatively was easily delayed for 72 hours without detriment to this patient. We reached the following conclusions: (1) The prevalence of angina in a stable hemodialysis population was 17% in a one-year analysis period. (2) The incidence of new onset of crescendo angina, which potentially requires coronary angiography, was 11% over the same one-year period. (3) The presence of surgically correctable lesions in these cases is high. (4) Concurrent hemodialysis during coronary artery bypass simplifies postoperative fluid and electrolyte management and prevents surgical bleeding.

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Frequent hypotensive episodes developed in a 56-year-old man, who was receiving long-term hemodialysis therapy, at the time he had a uremic pericardial effusion. During dialysis with an inadvertent calcium infusion, however, the mean blood pressure (BP) was sustained and even rose from 93 to 133 mm Hg. During continued dialysis to restore the serum calcium level from a peak of 17.4 to 12.0 mg/dL, mean arterial pressure decreased back to 93 mm Hg. In contrast, BP had fallen in three of six preceding dialysis treatments and five of nine subsequent dialysis treatments, all at the same ultrafiltration rate. This report suggests the importance of serum calcium to BP regulation during hemodialysis.

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