Glomerulonephritis and granulomatous vasculitis in kidney as a complication of the use of BRAF and MEK inhibitors in the treatment of metastatic melanoma: A case report.

RATIONALE: BRAF and MEK inhibitors have significantly improved the prognosis of metastatic melanoma, by inhibiting both the mitogen-activated protein kinase (MAP-kinase) pathway. They are associated with infrequent adverse kidney events. Most of these are related to the use of BRAF inhibitors and involve interstitial nephritis with acute tubular necrosis. PATIENT CONCERNS: We report a unique case of glomerulonephritis with renal granulomatous vasculitis in a patient diagnosed with metastatic melanoma treated with BRAF and MEK inhibitors. The patient was a 55-year old woman, who presented a melanoma of the right thigh with pulmonary metastasis. Treatment started in November 2015, with Encorafenib and Binimetinib, new BRAF and MEK inhibitors, respectively. Two months after the beginning of the treatment, there was a worsening of her renal function with significant proteinuria. DIAGNOSES: Kidney biopsy showed extracapillary proliferation in the glomeruli with a granulomatous reaction. INTERVENTIONS AND OUTCOMES: Renal function recovered completely after withdrawal of the chemotherapy. LESSONS: All the reported kidney adverse events secondary to BRAF and MEK inhibitors in the literature are related to the use of BRAF inhibitors. Some previous reported mechanistic investigations also provide insight between BRAF inhibitors and podocytes injuries. Therefore, encorafenib most likely is the main responsible of the disease. However, evidence has emerged that inhibition of the MAP kinase pathway could also enhance autoimmunity. Thus, binimetinib may also have played a role and the combination of BRAF and MEK inhibitors may have facilitated this autoimmune kidney disease.

Risk factors for Pneumocystis pneumonia after the first 6 months following renal transplantation.

Pneumocystis pneumonia (PCP) incidence was decreased in renal transplant thanks to prophylaxis, recommended during the first months after transplantation. However, many late PCP cases are observed after the first 6 months and recommendations to maintain or reintroduce prophylaxis are lacking. The objective of the study was to identify risk factors to guide the individual prescription of prophylaxis, 6 months after transplantation. Thirty-three late PCP cases were identified between 1995 and 2012 in Lille Hospital, France, and were compared to 72 randomized controls transplant recipients. In univariate analysis, age of donor (>48 years), retransplantation, a decrease glomerular filtration rate (≤45 mL/min), induction therapy mediated by anti-thymocyte globulin (ATG), steroid maintenance, high calcineurin inhibitors (CNI) doses (tacrolimus ≥0.5 mg/kg/day and cyclosporine ≥2.1 mg/kg/day), and cytomegalovirus (CMV) infection were significantly associated with PCP. In multivariate analysis, ATG (hazard ratio [HR]: 2.4 [1.1-5.4]), steroid therapy (HR: 3.1 [1.20-7.84], CNI (HR: 2.9 [1.28-6.38], and CMV (HR: 6.1 [2.74-16.33] remained associated with late PCP. In conclusion, we confirm that intensive immunosuppressive regimen and CMV infection are critical risk factors for late PCP and should be taken into account to decide on maintenance or reintroduction of a prophylactic treatment.

Renal Function and Remission of Hypertension After Bariatric Surgery: a 5-Year Prospective Cohort Study.

PURPOSE: This study examines the effect of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) on renal function for at least 5 years post-operatively in a tertiary referral center for bariatric surgery. MATERIALS AND METHODS: This prospective cohort study of patients undergoing RYGB and LAGB measured renal function, blood pressure, and diabetes status pre-operatively and then 1 and 5 years post-operatively. Renal function was assessed using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault formulae. Hypertension and diabetes were defined by the European Society of Hypertension and European Society of Cardiology joint guidelines and American Diabetes Association guidelines, respectively. A sub-group who had completed 10 years post-operative follow-up was also included. RESULTS: Estimated glomerular filtration rate (eGFR) increased over 5 years after RYGB (N = 190; 94 ± 2 mL/min/1.73 m2 to 102 ± 22 mL/min/1.73 m2, p = 0.01) and LAGB (N = 271; 88 ± 1 to 93 ± 22 mL/min/1.73 m2, p = 0.02). In a sub-group with up to 10 years post-operative date, this trend was maintained. In patients with renal impairment, eGFR improved over 5 years (52 ± 2 to 68 ± 7 mL/min/1.73 m2, p = 0.01). Remission of hypertension was greater after RYGB than LAGB at 1 year (32 vs. 16 %, p = 0.008) and at 5 years post-operatively (23 vs. 11 %, p = 0.02). CONCLUSIONS: Bariatric surgery stabilizes eGFR post-operatively for at least 5 years. In a sub-group with renal impairment, eGFR is increased in the first post-operative year and this is maintained for up to 5 years. RYGB is an effective procedure in achieving blood pressure control.

[Community pharmacists' interventions to prevent and screen chronic kidney disease patients]. / Implication du pharmacien d'officine dans le parcours de soins de la maladie rénale chronique.

Chronic kidney disease (CKD) is a major concern of public health. The pharmacist is known as a health practitioner involved in prevention and therapeutic education. Our study aimed at defining the impact of community pharmacists' interventions for preventing and screening CKD. In our observational prospective study of 5 months conducted in 109 community pharmacy, we included 2 groups of patients: A (therapeutic optimization): CKD patients and B (CKD screening): population at risk. In group A, we included 354 patients, mainly women (51.2%), in stage 3 of CKD, mean age 73 years old, with hypertension alone (40.6%) or associated with diabetes (44%). About 70% of the patients had a follow up by a nephrologist and 45% of them were good adherent according to the Morisky-Green self-report. However, approximately 20% of patients did not have nephroprotective treatments in their regimen although they were on stage 3 or 4 CKD patients, and about half of them were not aware of medical situations at risk. Concerning group B, 532 patients were included. The pharmaceutical interventions screened 10% of patients with a GFR<60mL/min/1.73m2. The community pharmacists' interventions helped to optimize the therapeutic management of CKD patients and in the early screening of patients at risk. More studies are needed to extrapolate our observations to a larger population.

Collapsing glomerulopathy is common in the setting of thrombotic microangiopathy of the native kidney.

Thrombotic microangiopathy (TMA) is a poorly recognized cause of collapsing glomerulopathy. The frequency and significance of collapsing glomerulopathy associated with renal TMA have not been specifically studied in native kidney biopsy specimens. Here we retrospectively documented clinicopathologic features of 53 patients with histologically proven TMA in the native kidney, with special emphasis on changes due to focal segmental glomerulosclerosis (FSGS). Histological TMA was related to hypertensive nephropathy in 21 patients, genetic complement abnormalities in 9, drugs in 7, and to other causes in 16 patients. Almost half (26 patients) presented with arteriolar, 6 with glomerular, and 21 with mixed TMA. Using the Columbia classification system for the 53 patients with histological TMA, 33 had concurrent FSGS lesions with collapsing glomerulopathy the dominant variant in 19 patients (58% of the FSGS cases), not otherwise specified in 9 patients, cellular in 3, and perihilar or tip lesions in 1 patient each. The presence of FSGS was associated with a poor renal prognosis, with no prognostic difference between collapsing glomerulopathy and other FSGS variants. Thus, collapsing glomerulopathy is frequently found in native kidney biopsies with TMA, suggesting that endothelial injury may play an important role in the pathophysiology of FSGS.

miR-21-5p renal expression is associated with fibrosis and renal survival in patients with IgA nephropathy.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, whose prognosis is highly variable. Interstitial fibrosis is a strong independent prognosis factor. Among microRNA involved in renal fibrogenesis, only few have been investigated in IgAN. In the context of IgAN, we aimed to analyze the role of miR-21-5p, miR-214-3p and miR-199a-5p, three established "fibromiRs" involved in renal fibrosis. Fifty-six IgAN biopsy specimens were retrospectively scored according to Oxford classification. Renal expression of miR-21-5p, miR-214-3p and miR-199a-5p were significantly associated with T score (miR-21-5p T0 RQ median = 1.23, T1 RQ = 3.01, T2 RQ = 3.90; miR-214-5p T0 RQ = 1.39, T1 RQ = 2.20, T2 RQ = 2.48; miR-199a-5p T0 RQ = 0.76, T1 RQ = 1.41, T2 RQ = 1.87). miR-21-5p expression was associated with S score (S0 RQ median = 1.31, S1 RQ = 2.65), but not miR-214-3p nor miR-199a-5p. In our cohort, poor renal survival was associated with high blood pressure, proteinuria and elevated creatininemia, as well as T and S scores. Moreover, renal expression of miR-21-5p, miR-214-3p were associated with renal survival. In conclusion, miR-21-5p, miR-214-3p and miR-199a-5p are three "fibromiRs" involved in renal fibrosis in the course of IgAN and miR-21-5p and miR-214-3p are associated with renal survival.

FDG PET/CT allowing detection and follow-up of tumor cell transplantation.

After detection of small cell lung cancer in a 67-year-old patient who had donated a kidney 7 months earlier, the graft recipient underwent FDG-PET/CT to determine the presence/absence of tumor cell transmission. It showed abnormal increased uptake of the renal graft, associated with hypermetabolic lymph nodes and hepatic, pulmonary and bone lesions. Emergency graft resection was performed 5 days after PET/CT, permitting immunosuppressive therapy withdrawal. Pathologic examination of the kidney showed parenchymal infiltration by tumor cells compatible with small cell lung cancer. Thereafter, pathologists proved that the recipient's and donor's tumor cells matched using microsatellite markers. FDG-PET/CT was performed in the follow-up and showed progression in the donor despite chemotherapy and radiotherapy. He died a few months later. However, FDG-PET/CT showed a complete metabolic response after only 3 courses of chemotherapy in the recipient.

CKD and Its Risk Factors among Patients with Cystinuria.

BACKGROUND AND OBJECTIVES: Cystinuria is an autosomal recessive disorder affecting renal cystine reabsorption; it causes 1% and 8% of stones in adults and children, respectively. This study aimed to determine epidemiologic and clinical characteristics as well as comorbidities among cystinuric patients, focusing on CKD and high BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective study was conducted in France, and involved 47 adult and pediatric nephrology and urology centers from April 2010 to January 2012. Data were collected from 442 cystinuric patients. RESULTS: Median age at onset of symptoms was 16.7 (minimum to maximum, 0.3-72.1) years and median diagnosis delay was 1.3 (0-45.7) years. Urinary alkalinization and cystine-binding thiol were prescribed for 88.8% and 52.2% of patients, respectively, and 81.8% had at least one urological procedure. Five patients (1.1%, n=4 men) had to be treated by dialysis at a median age of 35.0 years (11.8-70.7). Among the 314 patients aged ≥16 years, using the last available plasma creatinine, 22.5% had an eGFR≥90 ml/min per 1.73 m(2) (calculated by the Modification of Diet in Renal Disease equation), whereas 50.6%, 15.6%, 7.6%, 2.9%, and 0.6% had an eGFR of 60-89, 45-59, 30-44, 15-29, and <15, respectively. Among these 314 patients, 28.6% had high BP. In multivariate analysis, CKD was associated with age (odds ratio, 1.05 [95% confidence interval, 1.03 to 1.07]; P<0.001), hypertension (3.30 [1.54 to 7.10]; P=0.002), and severe damage of renal parenchyma defined as a past history of partial or total nephrectomy, a solitary congenital kidney, or at least one kidney with a size <10 cm in patients aged ≥16 years (4.39 [2.00 to 9.62]; P<0.001), whereas hypertension was associated with age (1.06 [1.04 to 1.08]; P<0.001), male sex (2.3 [1.3 to 4.1]; P=0.003), and an eGFR<60 ml/min per 1.73 m(2) (2.7 [1.5 to 5.1]; P=0.001). CONCLUSIONS: CKD and high BP occur frequently in patients with cystinuria and should be routinely screened.

Giant osteoclasts in patients under bisphosphonates.

BACKGROUND: Bisphosphonates have been widely used for treatment of high bone resorption states. It lowers bone turnover by inhibiting osteoclasts bone resorption with various mechanisms of actions: inhibition of osteoclast formation and attachment to the bone surface, induction of metabolic injury, alteration of vesicle trafficking and induction of osteoclast apoptosis. Bone biopsies studies from patients under bisphosphonates have shown that some resorption parameters are decreased as expected but the number of osteoclasts seems not to be necessarily decreased. The description of osteoclasts morphology from patients treated with bisphosphonates has rarely been reported in the literature. CASE PRESENTATION: We describe in this paper two patients treated with bisphosphonates from whom iliac crest bone biopsies have shown large, multinucleated and apoptotic osteoclasts that were not associated with bone resorption activities. The characteristics of these osteoclasts are described and the literature reviewed. CONCLUSION: The appropriate recognition of these giant osteoclasts in bone tissues from patients treated with bisphosphonates is of primary importance for bone pathologists and should not be interpreted as signs of increased bone resorption as seen in hyperparathyroidism, bone cancer or Paget's disease of bone.

Long-term reproducibility of diurnal intraocular pressure patterns in patients with glaucoma.

PURPOSE: To evaluate the long-term reproducibility of diurnal intraocular pressure (IOP) patterns in patients with primary open-angle glaucoma (POAG). DESIGN: Database study. PARTICIPANTS: Ninety-two patients with POAG. METHODS: We reviewed the records of patients with POAG who underwent 4 diurnal IOP curve measurements 6 months apart with Goldmann applanation tonometry recorded in the sitting position at 9 am, 10 am, 11 am, noon, 2 pm, 3 pm, 4 pm, and 5 pm. MAIN OUTCOME MEASURES: Intervisit agreement of IOP by time point and of diurnal IOP curve parameters (mean, standard deviation, range, maximum, maximum hour, minimum, and minimum hour) was assessed using intraclass correlation coefficients (ICCs). Analyses were performed in all eyes and separately in eyes with and without hypotensive medications, and in eyes naïve and non-naïve of filtering surgery. RESULTS: Between-visit agreement of IOP values at each time point was generally poor, with ICCs ranging from 0.26 to 0.77 in all patients (1 of 8 time points with ICC >0.75), from -0.07 to 0.60 in patients without hypotensive medications (zero time points with ICC >0.75), from 0.29 to 0.80 in patients with hypotensive medications (3 time points with ICCs >0.75), from 0.21 to 0.68 in filtering surgery-naïve patients (zero time points with ICC >0.75), and from 0.21 to 0.87 in patients with previous filtering surgeries (5 time points with ICCs >0.75). The predictive value of the first diurnal IOP curve to estimate the risk of IOP fluctuations during the 3 subsequent curves was limited (only 6.4% of the patients with an IOP range ≥30% of the mean IOP on the first curve presented similar fluctuations on the 3 subsequent curves; 77.1% of the patients who did not have an IOP range ≥30% of the mean IOP on the first curve had an IOP range ≥30% of the mean IOP on at least 1 of the 3 subsequent curves). CONCLUSIONS: Patients with POAG do not manifest a reproducible diurnal IOP pattern from month to month. A single diurnal IOP curve in patients with POAG poorly characterizes IOP fluctuations and has limited value in clinical practice.

Osteomalacia induced by vitamin D deficiency in hemodialysis patients: the crucial role of vitamin D correction.

Vitamin D deficiency/insufficiency is significantly prevalent in chronic kidney disease. Data in the literature are however scarce about the effects of this deficiency on bone metabolism in hemodialysis (HD) patients. Moreover, it is still debated whether low vitamin D levels should be normalized in HD patients. In this paper, we report two cases showing the deleterious consequences of vitamin D deficiency in HD patients which is characterised by hypophosphatemia, hypocalcemia and osteomalacia (OM) leading to bone fractures. As vitamin D repletion is an easy way to treat OM, this report underlines the importance of monitoring and correction of vitamin D deficiency in this population.

Crohn's disease and nontropical endomyocardial fibrosis.

The pathogenesis of endomyocardial fibrosis (EMF) is poorly understood. EMF may result from autoimmune scarring of the endocardium. Clinically, EMF presents as a restrictive cardiomyopathy. EMF is commonly reported in tropical countries. In Western countries, EMF is associated with hypereosinophilia and reported as Loeffler endocarditis. We report a Caucasian patient with Crohn's disease and EMF, and discuss a possible linkage between the two conditions.

Renal involvement in MELAS syndrome - a series of 5 cases and review of the literature.

Renal dysfunction is increasingly recognized as a potential clinical feature of mitochondrial cytopathies such as mitochondrial encephalomyopathy, lacticacidosis and stroke-like episodes (MELAS) syndrome. Five cases of MELAS syndrome with renal involvement from 4 unrelated families are presented in this case series. Three of the 5 patients had a history of maternally-inherited diabetes and/or deafness. Focal and segmental glomerulosclerosis and arteriolar hyaline thickening were the most striking findings on renal biopsy. In addition to clinical presentation with the typical symptoms of MELAS syndrome, genetic testing in these patients identified the A3243G point mutation in the tRNALeu gene of the mitochondrial DNA (mtDNA). The diagnosis of MELAS syndrome was thus considered to be unequivocal. The incidence of kidney disease in MELAS syndrome may be underestimated although a study is required to investigate this hypothesis. As the A3243G mtDNA mutation leads to a progressive adult-onset form of focal segmental glomerulosclerosis (FSGS), screening for the MELAS A3243G mtDNA mutation should therefore be performed especially in patients with maternally-inherited diabetes or hearing loss presenting with FSGS.

Three-year outcome of isolated glomerulitis on 3-month protocol biopsies of donor HLA antibody negative patients.

Transplant glomerulitis (TG) can lead to the diagnosis of acute humoral rejection when associated with C4d. Recent data have shown that, in patients with donor-specific antibodies, TG is a sign of humoral rejection, even in the absence of C4d. However, the clinical significance of isolated TG, i.e. TG without C4d deposition or morphological evidence of rejection, has not been specifically studied in protocol biopsies of recipients without donor-specific antibodies. We compared 20 isolated TG-patients with 44 selected recipients without TG or any rejection-associated change. The two groups had similar baseline characteristics. After a 3 year follow-up, renal function, acute rejection rate, and development of HLA antibodies were not significantly different between the two groups. Isolated TG had no deleterious consequences on the 3 year graft outcome. Eleven patients of the glomerulitis-group had another allograft biopsy during follow-up: glomerular lesions returned to normal in six patients whereas the persistence of glomerulitis or features consistent with chronic transplant glomerulopathy were noticed in the remaining five patients. Four of these five patients had pretransplant non-donor specific HLA antibodies. In conclusion, although isolated TG had no impact on allograft function at 3 year, histological outcome could be related to patient sensitization.

Maturity onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience.

The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicêtre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 ± 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients.

Epithelial-to-mesenchymal transition predicts cyclosporine nephrotoxicity in renal transplant recipients.

Maintenance immunosuppression with cyclosporine A (CsA) can cause nephrotoxicity in renal transplant recipients. Identifying patients at increased risk for CsA nephrotoxicity may allow interventions to prolong graft survival. Here, we studied the effect of early CsA withdrawal or maintenance among 96 kidney recipients at risk for interstitial fibrosis and tubular atrophy (IF/TA) on the basis of tubular expression of vimentin and ß-catenin in a protocol biopsy performed 3 months after transplant. In this retrospective analysis of biopsies collected during a randomized trial of early withdrawal of CsA or mycophenolate mofetil, the semiquantitative score of early phenotypic changes suggestive of epithelial-to-mesenchymal transition (EMT) progressed with time among those maintained on a CsA-containing regimen. EMT-positive grafts displayed a significantly higher IF/TA score and greater progression of the IF/TA score at 12 months (P=0.001 and 0.008, respectively). EMT-positive grafts exposed to CsA also had a greater decrease in estimated GFR compared with EMT-negative grafts exposed to CsA and EMT-positive grafts withdrawn from CsA exposure. Multivariable analysis revealed that the presence of EMT was an independent risk factor for a 10% decline in graft function up to 4 years posttransplant (odds ratio 4.49; 95% confidence interval 1.02 to 19.9). Collectively, these data demonstrate that changes consistent with EMT are strong prognostic biomarkers in renal transplant recipients exposed to CsA.

CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation.

BACKGROUND: The effect of potentially relevant genetic polymorphisms, CYP3A5 6986A>G and ABCB1 3435C>T, on Tacrolimus pharmacokinetics and graft clinical outcome was investigated in donor and recipient DNA samples from 209 kidney transplant patients. METHODOLOGY/PRINCIPAL FINDINGS: The mean follow-up was 21.8 ± 9 months. The Tacrolimus dose, trough blood concentrations (C0) and C0/dose ratio were only statistically correlated with the recipient CYP3A5 genotype. CYP3A5 and ABCB1 genotypes appeared to have no influence on the incidence of Biopsy Proven Acute Rejection and Delayed Graft Function. Renal function was not affected by CYP3A5 and ABCB1 genotypes. Histological evaluation of biopsies revealed also no significant association between Tacrolimus toxicity features and donor or recipient CYP3A5 and ABCB1 polymorphisms. Tacrolimus sparing appeared to be independent of CYP3A5 and ABCB1 genotypes. CONCLUSIONS/SIGNIFICANCE: Recipient CYP3A5 6986A>G polymorphism explains part of the interindividual variability of the pharmacokinetics of Tacrolimus. The clinical outcome at 2-year follow-up does not appear to be related to the donor or recipient CYP3A5 6986A>G and/or ABCB1 3435C>T polymorphisms.

Intrarenal IFN-γ mRNA expression differentiates clinical and subclinical glomerulitis in renal transplant recipients.

BACKGROUND: Transplant glomerulitis, characterized by mononuclear cell infiltration of glomeruli, is likely to occur during clinical or subclinical antibody-mediated rejection. METHODS: To determine whether T-cell phenotype influences the clinical presentation of this pathologic condition, we used reverse transcription quantitative polymerase chain reaction to analyze expression of Treg cells (Foxp3), cytotoxic CD8 T cells (Granzyme B), Th1 cells (INF-γ,T Bet), Th2 cells (GATA3, IL-4), and Th17 pathway (IL-17). Our study included 20 renal transplant recipients exhibiting subclinical glomerulitis (SG) diagnosed after a routine 3-month posttransplant biopsy. Results were compared with those observed in 22 patients with normal routine biopsies at 3 months (N) and 17 patients with clinical glomerulitis occurring during early acute renal dysfunction within the first year after transplantation in a context of acute antibody-mediated rejection. RESULTS: Our results show that expression of IL-4 mRNA was significantly higher in SG patients than in N patients (P = 0.02). Expression of IFN-γ was significantly higher in patients with clinical glomerulitis than in patients with SG (P<0.001) and was associated with a clinical expression of glomerulitis. CONCLUSION: Our results suggest that the balance of Th1/Th2 is likely to differentiate clinical expression of transplant glomerulopathy. They also indicate that therapeutic approaches in cases of SG should be defined with caution and take into account transcriptional criteria.

Daclizumab versus antithymocyte globulin in high-immunological-risk renal transplant recipients.

Nondepleting anti-CD25 monoclonal antibodies (daclizumab) and depleting polyclonal antithymocyte globulin (Thymoglobulin) both prevent acute rejection, but these therapies have not been directly compared in a high-risk, HLA-sensitized renal transplant population. We randomly assigned 227 patients, who were about to receive a kidney graft from a deceased donor, to either Thymoglobulin or daclizumab if they met one of the following risk factors: current panel reactive antibodies (PRA) >30%; peak PRA >50%; loss of a first kidney graft from rejection within 2 yr of transplantation; or two or three previous grafts. Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and steroids. Compared with the daclizumab group, patients treated with Thymoglobulin had a lower incidence of both biopsy-proven acute rejection (15.0% versus 27.2%; P = 0.016) and steroid-resistant rejection (2.7% versus 14.9%; P = 0.002) at one year. One-year graft and patient survival rates were similar between the two groups. In a comparison of rejectors and nonrejectors, overall graft survival was significantly higher in the rejection-free group (87.2% versus 75.0%; P = 0.037). In conclusion, among high-immunological-risk renal transplant recipients, Thymoglobulin is superior to daclizumab for the prevention of biopsy-proven acute rejection, but there is no significant benefit to one-year graft or patient survival.

[First acute rejection episode after renal transplantation: study of the histopathological characteristics according to the immunological risk]. / Premier épisode de rejet aigu après transplantation rénale: étude des caractéristiques histopathologiques en fonction du risque immunologique du patient.

Renal allograft biopsies (n=34) of two different populations of patients according to the immunological risk (high versus low-risk) have been compared retrospectively. The presence of polymorphonuclear leukocytes in peritubular capillaries was more frequent in the high-risk group. The C4d staining was positive in 10% of the low-risk patients and in 50% of the high-risk patients (P=0.03). There were more early graft loss, renal infarctions, interstitial hemorrhage, severe glomerulitis, neutrophilic glomerulitis and Banff III grade rejection in the positive C4d group. In conclusion, half of the immunized patients had a humoral rejection, patients with a C4d positive rejection had more early graft loss and more severe histological lesions.