Lilian M. Pereira

The dynamics of glucose metabolism under calcineurin inhibitors in the first year after renal transplantation in nonobese patients

Background. The incidence of glucose metabolism disturbances after transplantation often is based on the use of hypoglycemic agents and not on the results of glucose tolerance tests (GTTs), which may camouflage the real incidence. A lack of information also exists regarding the profile of glucose metabolism during the first year after transplant. Methods. Oral GTT along with insulin measurements and drugs pharmacokinetics were prospectively performed at days 30, 60, 180, and 360 after transplant to diagnose disturbances of glucose metabolism after renal transplantation, in nonobese patients receiving either tacrolimus (n=55) or cyclosporine (n=29), along with mycophenolate mofetil and steroids. Results. The incidence of impaired glucose tolerance or diabetes mellitus reached a peak at 60 days and decreased at 1 year. It could not be adequately diagnosed using fasting plasma glucose in a decreased abnormal (>99 ng/mL) range. In both groups, insulin secretion, evaluated by the Homeostasis Model Assesment (HoMA-β), decreased (P<0.005) from the condition of normal GTT (101±56%) to impaired glucose tolerance (72±35%) and diabetes mellitus (54±25%). In the cyclosporine group, insulin secretion was normal and stable throughout the study period, but in the tacrolimus group, insulin secretion recovered over time and was inversely correlated with tacrolimus exposure. Insulin resistance (HoMA-IR) did not change. Conclusions. This study shows the need to perform an oral GTT at 60 days and at the end of the first year of renal transplantation to adequately diagnose impaired glucose metabolism.

Seroprevalence of antibodies against varicella-zoster virus and response to the varicella vaccine in pediatric renal transplant patients

Abstract:  The severity of varicella‐zoster virus (VZV) in immunocompromised children, especially in those receiving renal transplants, is well known. However, the use of live attenuated virus vaccine in this population is controversial. This study aimed to: (i) assess the immunization status of pediatric renal transplant recipients at our center; (ii) determine the anti‐VZV antibody titers in such patients; (iii) evaluate the response to VZV vaccine in seronegative children and in those who present low antibody titers (defined as <500 mAU/mL).Vaccinated children were monitored for adverse effects for 8 wk after vaccination. Fifty patients with a mean age of 13.7 yr (range, 3–17 yr) were enrolled. In 49, blood samples were collected and antibodies were screened using ELISA. Seropositivity to VZV was found in 43 (88%), and antibody titers were ≥500 mAU/mL in 37 (75.5%). Of the 12 children who were eligible for vaccination and had antibody titers <500 mAU/mL, one developed varicella before vaccination, two did not meet the inclusion criteria, and three parents refused the vaccination. In the six vaccinated children, there were no adverse reactions to the vaccine, and four (66.6%) responded with anti‐VZV titers ≥500 mAU/mL 6–8 wk after vaccination. In conclusion, after renal transplantation, varicella vaccine is safe with a 66% rate of conversion to high antibody titers.

The need of mycophenolic acid monitoring in long-term renal transplants.

Abstract:  Background:  There is little information regarding the 12‐h mycophenolic acid (MPA) pharmacokinetics (PK), a way to monitor the drug and the need of frequent monitoring, in stable patients.

Phylogenetic analysis of a near-full-length sequence of an erythrovirus genotype 3 strain isolated in Brazil

Human parvovirus B19 is the only member of the genus Erythrovirus that causes human disease. Recent findings of several strains with considerable sequence divergence from B19 have suggested a new classification for parvovirus genotypes as 1 (B19), 2 (A-6 and LaLi) and 3 (V9). In their overall DNA sequence, the three genotypes differ by ~10%. Here, we report the isolation of a genotype-3-related strain named BR543 during a prospective study conducted in Sao Paulo, Brazil. Analysis of the nearly full-length genome sequence of BR543 indicates that this B19 variant sequence clusters with Gh2768, a strain from Ghana belonging to subtype 3b, and showed mostly synonymous substitutions.

Bioequivalence of a new cyclosporine a formulation to Neoral.

New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral®, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.7 ± 12 years). They received their renal allografts from 13 cadaver and 5 living donors. Before enrollment, all patients were receiving a third generic CsA for a mean of 48 months. Nine patients were also under azathioprine and 9 under mycophenolate mofetil; 17 received prednisone. A single oral dose of either Zinograf or Neoral was administered. The first PK study was performed with one formulation, and 1 week later, a second PK was done with the other formulation. During the washout period, patients continued taking the third CsA formulation. The drug substitution was done milligram-for-milligram. The CsA whole-blood level was measured by TDx immunoassay. Mean ± SD of area under the curve (AUC), maximum concentration (C max), and concentration at the second hour (C2) of Zinograf were not statistically different from those with Neoral (4019 ± 1466 vs 3971 ± 1325 ng·h/mL, 998 ± 376 vs 1021 ± 356 ng/mL, and 707 ± 254 vs 734 ± 229 ng/mL, respectively). In the same way, the Zinograf 90% confidence interval for either C max (−123, +77 ng/mL) or AUC (−214, +311 ng·mL/h) were within the Neoral bioequivalence interval for the same parameters (±204 ng/mL and ±794 ng·mL/h, respectively). These data demonstrate that the ZinografME CsA formulation is bioequivalent to Neoral.