Sylvie Delmas

Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism.

Background. Persistent hyperparathyroidism (HPT) is observed in ∼50% of kidney transplant recipients one year after transplantation. It may result in hypercalcemia, hypophosphatemia, bone demineralization, vascular calcification, lithiasis, and participate in chronic allograft nephropathy. We evaluated the use of the calcimimetic cinacalcet chloride to correct chronic hypercalcemia in posttransplant HPT, in a prospective single-center study. Methods. Nine patients with persistent hypercalcemia (>2.6 mmol/L) and stable graft function were treated with cinacalcet (30 mg/day, thereafter adapted to obtain normal serum Ca levels) for six months. Their immunosuppressive schedule included mycophenolate mofetil (MMF), steroids, and cyclosporine A (4), tacrolimus (4), or sirolimus (2). Results. Serum Ca levels significantly decreased from 2.75±0.15 to 2.59±0.10, 2.42±0.29 and 2.44±0.25 mmol/L by one, two, and six months, respectively (P<0.02, Wilcoxon test for paired data, for all the data points). Parathyroid hormone (PTH) serum levels decreased from 171±102 to 134±63 pg/ml by two months (P<0.05) and stabilized thereafter (148±99 pg/ml at six months; NS). No changes in glomerular filtration rate (49.8±18.6 and 51.3±19 ml/min at initiation and six months, respectively) and no variation in serum concentration of the immunosuppressive drugs were observed. Three patients withdrew the treatment because gastrointestinal intolerance. Conclusion. Cinacalcet allows the correction of hypercalcemia with no interference in immunosuppressive treatment or renal function. However, whether the increased intolerance observed was due to the association of cinacalcet chloride with other drugs required in renal transplantation (e.g., MMF) needs to be assessed.

Outcome of renal transplant recipients admitted to an intensive care unit: a 10-year cohort study.

Background. Epidemiology and prognosis of severe complications related to renal transplantation requiring admission to intensive care unit (ICU) have not been assessed precisely. This study was undertaken to evaluate the outcome in this population and to identify the factors of prognosis. Methods. All records of adult renal transplant recipients admitted to our ICU from 1997 to 2007 were reviewed including transplant variables, clinical and biological parameters, use of mechanical ventilation, catecholamine support, or dialysis or both. Mortality was assessed and data were analyzed to identify predictive factors of outcome. Results. Twenty-seven women and 30 men, median age 54 years, were included in the study. Eighteen patients were oliguric, 35 were mechanically ventilated, 32 underwent hemodialysis, and 36 needed catecholamine. Twenty-three patients died (40.3%), a mortality significantly higher than in a matched by age and gravity scores control group of nontransplant ICU patients. By univariate analysis, survivors had a significantly lower ICU severity scores, a higher mean arterial pressure, a higher Glasgow Coma Score, a higher serum albumin, and a lower serum lactate on ICU admission. The need for catecholamine support, mechanical ventilation or dialysis or both during the ICU stay worsens the outcome significantly. Using the multivariate analysis, only the mean arterial pressure and the need for mechanical ventilation were predictive of mortality. Conclusion. The incidence of severe transplant-related complications requiring an admission to an ICU was at 16 of 1000 patients year with a mortality rate higher than the general ICU population (40% vs. 20%). These data suggest that immunosuppressive treatment of transplant patients with severe complications worsens significantly their outcome.

An epidemic of Pneumocystis jiroveci pneumonia in a renal transplantation center: role of T-cell lymphopenia.

Although only 2 cases of Pneumocystis jiroveci pneumonia were observed in our center between 2004 and 2009, we diagnosed 9 cases in 2010. Each patient had been in contact in the hospital with at least 1 other patient suffering P jiroveci pneumonia. Genotyping of P jiroveci pneumonia strains demonstrates a total homogeneity of the DNA sequences in the 7 patients already analyzed. CD4+ lymphocyte count was significantly lower at M3 in P jiroveci pneumonia patients than in controls. Our clinical and molecular data confirm that interhuman transmission of P jiroveci is possible, particularly to lymphopenic transplant recipients.

Early high pulse pressure is associated with graft dysfunction and predicts poor kidney allograft survival.

Background. Pulse pressure (PP), which reflects the pulsatile component of the blood pressure (BP), is known as a major predictor of cardiovascular events and death. In the elderly and type 2 diabetic patients, PP is associated with low glomerular filtration rate and albuminuria. Because kidney allograft survival is closely related to BP levels, we investigated the impact of early high PP, systolic, diastolic, and mean arterial BP on kidney allograft survival. Methods. Renal hemodynamic and function studies using isotopic methods were prospectively performed in 493 renal transplant patients at 3 months posttransplantation to determine the impact of the different BP components on allograft survival using a proportional hazard model. Results. After a median follow-up of 6.3 years, 91 allografts were lost. High PP was associated with high systolic, diastolic, and mean arterial pressure, heart rate, recipient age, glycemia, and low glomerular filtration rate. Moreover, PP emerged as the strongest BP component influencing overall and death-censored kidney allograft survival. Conclusion. High PP is an early marker of poor allograft outcome that could be corrected by therapeutic intervention.

Stricturing Crohn’s disease-like colitis in a patient treated with belatacept

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) modifying agents have been involved in the development of intestinal inflammation, especially therapeutic monoclonal antibodies directed against CTLA-4. Here we report the appearance of a severe stricturing Crohn’s disease-like colitis in a patient with a kidney allograft who was treated with belatacept, a recombinant CTLA-4-Ig fusion protein.