C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection.

C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9-indicative of complement-mediated injury-is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25-73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9- ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients.

[Therapeutic education of patients taking oral chemotherapy at home]. / Éducation thérapeutique des patients sous chimiothérapie orale à domicile.

Oral cancer drugs make the patient more active and autonomous. They reduce the number of hospital appointments and the risk of infection. However, they result in new problems such as the management of side effects. In this context, therapeutic education is essential. The first French therapeutic education programme for patients taking oral cancer drugs at home has been set up.

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.

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

BACKGROUND: Persistent hyperparathyroidism (HPT) is observed in approximately 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.

[Delayed graft function: a frequent but still unsolved problem in renal transplantation]. / La reprise retardée de fonction: une complication fréquente, non résolue, en transplantation rénale.

Delayed graft function (DGF) is a frequent and well-known complication of renal transplantation, which occurs in 30% of cadaver kidney allografts. It has an economic cost that is the result of prolonged patient hospitalization and the need for hemodialysis sessions; it also increases the risk of acute allograft rejection and may affect long-term graft survival. Lots of risk factors were identified, like donor hemodynamic compromise or prolonged cold ischemia time; however, incidence of DGF remains high due to the frequent use of marginal donors due to organ shortage. Recent advances in the pathophysiology of DGF point the importance of the ischemia-reperfusion injury mechanisms and some therapeutics that may reduce them are under investigation, like the use of new solutions to improve organ preservation and the use of some antioxidant and anti-inflammatory drugs.

Prevalence and risk factors of noncontrolled and resistant arterial hypertension in renal transplant recipients.

BACKGROUND: Arterial hypertension (HT) is common in renal transplant recipients (RTRs). Control of HT is not optimal in this high-risk population despite recommendations for target blood pressure levels under 130/80 mm Hg. METHODS: We performed a cross-sectional analysis of the prevalence of uncontrolled HT, and using a Cox regression model, we identified the risk factors associated with resistant HT. RESULTS: Eight hundred eleven RTRs (>1 year after transplantation) were included. A total of 10.5% were normotensive (<130/80 mm Hg without treatment), 41% had controlled HT, 32.5% uncontrolled HT, and 16% resistant HT. In univariate analysis, compared to controlled HT, the RH group had significantly higher body mass index and older donors, delayed graft function, prevalence of metabolic syndrome (69.2 vs. 51.9%), fast glycemia and glycated hemoglobin, albuminuria, triglycerides and uric acid levels, and worse measured glomerular filtration rate (mGFR). In multivariate analysis, recipient age (P < 0,001), mGFR (P = 0.037), albuminuria (P < 0.001), and metabolic syndrome (P = 0.007) were significantly associated with RH. Association of metabolic syndrome with RH was much stronger than each of its components. CONCLUSION: Our data show that despite the recommendations issued by scientific societies, blood pressure control in RTRs is far from the recommended targets. At least a third of our patients (uncontrolled HT) did not receive optimal treatment and suffered therapeutic inertia. Decreased mGFR, metabolic syndrome, and urinary albumin excretion emerged as strong predictors of poor HT control. Whether prevention and management of the metabolic syndrome and reduction of albuminuria could help to more consistently reach the blood pressure recommended targets deserves further investigation.

[Toxoplasma infection, a rare but life-threatening complication after kidney transplantation: report of two cases]. / La toxoplasmose, une complication exceptionnelle mais grave chez le transplanté rénal : à propos de deux observations.

Toxoplasma infection is uncommon after renal transplantation. As a result, Toxoplasma gondii is often missed from the list of microbial agents which may be responsible of an infectious complication after renal transplantation. However, establishing this diagnosis is very important because toxoplasmosis can be life-threatening in an immunocompromised host, particularly when the diagnosis is too delayed. Here we report two cases of severe toxoplasmosis after renal transplantation. In the first case, primary infection transmitted by a cat developed in a seronegative recipient five years after renal transplantation. In the second case, reactivation of latent infection developed in a seropositive recipient 9 months after transplantation. In both cases, systematic screening for Toxoplasma gondii using polymerase chain reaction (PCR) in biological fluids was essential to suggest the diagnosis. Both recipients rapidly recovered after institution of antiparasitic therapy.

Post-transplantation lymphoproliferative disorder after kidney transplantation: report of a nationwide French registry and the development of a new prognostic score.

PURPOSE: Post-transplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. We conducted a prospective survey of the occurrence of PTLD in a French nationwide population of adult kidney recipients over 10 years. PATIENTS AND METHODS: A French registry was established to cover a nationwide population of transplant recipients and prospectively enroll all adult kidney recipients who developed PTLD between January 1, 1998, and December 31, 2007. Five hundred patient cases of PTLD were referred to the French registry. The prognostic factors for PTLD were investigated using Kaplan-Meier and Cox analyses. RESULTS: Patients with PTLD had a 5-year survival rate of 53% and 10-year survival rate of 45%. Multivariable analyses revealed that age > 55 years, serum creatinine level > 133 µmol/L, elevated lactate dehydrogenase levels, disseminated lymphoma, brain localization, invasion of serous membranes, monomorphic PTLD, and T-cell PTLD were independent prognostic indicators of poor survival. Considering five variables at diagnosis (age, serum creatinine, lactate dehydrogenase, PTLD localization, and histology), we constructed a prognostic score that classified patients with PTLD as being at low, moderate, high, or very high risk for death. The 10-year survival rate was 85% for low-, 80% for moderate-, 56% for high-, and 0% for very high-risk recipients. CONCLUSION: This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.

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.

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.