The effects of the CYP3A5*3 variant on tacrolimus pharmacokinetics and outcomes in Tunisian kidney transplant recipients.

INTRODUCTION: Tacrolimus, exhibits interindividual pharmacokinetic variability and a narrow therapeutic index. The influence of the CYP3A5 6986A>G single nucleotide polymorphism (SNP) on this variability remains a topic of debate. AIM: To assess the impact of the aforementioned SNP on tacrolimus area under curve (AUC0-12h), adverse drug reactions (ADRs), and kidney graft outcomes. METHODS: Blood samples were collected from Tunisian kidney transplants over a five-year period during either the early (<3 months) or late (>3 months) post-transplant phases. Through blood concentration (C0) and AUC0-12h of tacrolimus were measured. Patients were prospectively followed to assess graft outcomes. Polymerase chain reaction of restriction fragment length polymorphism was used for CYP3A5 6986A>G genotyping. RESULTS: Fifty Tunisian kidney recipients receiving tacrolimus were enrolled in the study. Acute and chronic graft rejections were observed in eight and three patients, respectively. Twenty-one patients (42%) reported ADRs. C0 and AUC0-12h, showed a significant difference between CYP3A5*1 carriers (mean C0=4 ng.mL-1 and AUC0-12h=94.37 ng.h.mL-1) and CYP3A5*3/3 or poor metabolizers carriers (mean C0=7.45 ng.mL-1; AUC0-12h=151.27 ng.h.mL-1) (p=0.0001; p=0.003, respectively). Supratherapeutic tacrolimus levels were significantly more common in poor metabolizers (p=0.046; Odds-ratio =1.3; confidence interval 95% [1.12-1.66]). The impact of SNP was significant on C0, AUC0-12h, C0/Dose and AUC0-12h/Dose, only in the late phase (p=0.01, 0.002, 0.012, 0.003 respectively). CONCLUSION: CYP3A5*3 variant was significantly associated with tacrolimus pharmacokinetics but had no impact on graft outcomes.

[Successful treatment with paclitaxel of a visceral relapse of post-transplant Kaposi's sarcoma]. / Succès du traitement par paclitaxel d'une rechute viscérale d'un sarcome de Kaposi après transplantation rénale.

We report the observation of a patient who presented with post-transplant Kaposi's sarcoma after a delay of eight months with a dual cutaneous and palatal localisation. The reduction in immunosuppressive treatment and the introduction of Rapamune® allowed good clinical progress initially with regression of the skin lesions. He subsequently presented later a skin relapse with visceral localisation. Chemotherapy was conducted based on weekly paclitaxel infusions allowing partial remission and maintenance of renal graft function with good clinical tolerance.

[Etiologies and prognostic factors of acute interstitial nephritis]. / Étiologies et facteurs pronostiques des néphropathies interstitielles aiguës.

INTRODUCTION: Acute interstitial nephritis represents a clinically and etiologically heterogeneous group of kidney diseases. The aim of our study was to explore the main causes of biopsy-proven acute interstitial nephritis and to identify predictive factors of renal outcome. METHODS: We conducted a retrospective monocentric study which included patients with biopsy proven AIN, followed in our department during the period between 1980 and 2018. The non-recovery of kidney function or an estimated glomerular filtration rate˂60 mL/min/1.73 m2 were considered as a worse renal outcome. RESULTS: A total of 65 acute interstitial nephritis patients were enrolled. The mean age of patients was 41.3±16 years with a female predominance (78%). Drug-induced etiology was the most common (29%). The most frequent culprit drugs in our study were NSAID followed by antibiotics. The renal prognosis was unfavorable in 21 cases (32%). The independent predictive factors for renal outcome were : a percentage of sclerotic glomeruli greater than 15% (P=0.004), absence of interstitial edema (P˂0.001), non-use to corticosteroid therapy (P=0.02) and a delay in initiating corticosteroid therapy greater than 21 days (P=0.02). CONCLUSION: Drugs currently represent the most common cause of acute interstitial nephritis. The renal prognosis is often favorable, but the progression can be towards chronic renal failure in the event of diagnostic and therapeutic delay. Our data suggest a beneficial influence of steroids on the outcome of acute interstitial nephritis.

Peritoneal dialysis in diabetes patients.

INTRODUCTION: Peritoneal dialysis (PD) is a renal replacement therapy (RRT) in end stage kidney disease patients with several advantages and disadvantages. AIM: To evaluate the epidemiological, clinical, biological and outcome of diabetic patients in PD in our service and to determine the factors influencing overall survival and technique. METHODS: This was a retrospective study that included 90 diabetic patients supported on PD in our Department of Nephrology and Internal Medicine A in Charles Nicolle Hospital of Tunis from 1983 to 2016. RESULTS: There were 90 patients with mean age of 57 years. The sex ratio M/W was 1.3. Diabetes was type 2 in 84.44%. Complications were decreased ultrafiltration (26.66%), displacement of the catheter (20%), umbilical hernia (3.33%), malnutrition (2.22%) and peritonitis (45.55%). The number of peritonitis was 1 episode every 38.64 patient months. Transfer to hemodialysis was indicated in 37.78% of cases. Death occurred in 33 patients. Causes were cardiovascular (21.11%), septic shock (10%) and complicated peritonitis (5.55%). A statistically significant correlation was found between patient survival and death from cardiovascular events (p = 0.048), type 2 diabetes and high peritoneal permeability (p = 0.033) and technical survival and systolic arterial pressure> 139.5mmHg (p = 0.01). Overall survival at 5 years was 66% and technical survival was 28%. CONCLUSION: PD is an interesting way of RRT in diabetic patients. Good control of diabetes complications and those of PD technique is essential to increase survival.

Outcome of Renal Transplant in Recipients With Vasculitis.

OBJECTIVES: End-stage renal disease develops in a high percentage of patients with vasculitis, in whom kidney transplant has become a therapeutic option. However, limited data are available on the prognosis and outcomes after kidney transplant in these patients. We aimed to compare the long-term graft survival and graft function in 8 renal transplant recipients with vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, Goodpasture syndrome, and Henoch-Schonlein purpura) with the other kidney recipients at a single center. MATERIALS AND METHODS: We conducted a retrospective study of patients followed for chronic renal failure associated with vasculitis before renal transplant. We excluded patients with no biopsy-proven nephropathy. RESULTS: There was no difference in the occurrence of metabolic and cardiovascular complications in our case group compared with the other graft recipients. Infections were frequent and included cytomegalovirus and urinary tract infection. The rates of bacterial and viral infection were equivalent in our population. The incidence of allograft loss was estimated at 1.8%, less than that seen in our entire transplant population. The presence of vasculitis was not significantly related to renal failure (P = .07). Extrarenal relapse occurred in 1 patient with microscopic polyangiitis. Antineutrophil cytoplasmic antibody levels in patients with granulomatosis with polyangiitis and microscopic polyangiitis did not seem to influence the renal outcome (P = .08). Circulating antineutrophil cytoplasmic antibodies were associated with the development of vascular lesions in the graft but were not significantly correlated with graft survival (P = .07). CONCLUSIONS: This study supports the theory that renal transplant is an effective treatment option for patients with end-stage renal disease secondary to vasculitis. These patients fare similarly to, if not better than, other patients.

Outcome of Kidney Transplant in Patients with Polycystic Kidney Disease: A Single-Center Study in Tunisia.

OBJECTIVES: Autosomal dominant polycystic kidney disease is a common cause of end-stage renal disease and a common indication for renal transplant. This study was undertaken to evaluate the demographics, outcomes, and complications of renal transplant in patients with autosomal dominant polycystic kidney disease compared with other nephropathies. MATERIALS AND METHODS: In a retrospective case-control design, we reviewed the records of 7 patients with autosomal dominant polycystic kidney disease from a total of 701 renal transplant patients over a 30-year period (1986-2016). For each patient, a matched control was selected based on sex, age, year of transplant, and type of kidney donor. We excluded patients who underwent kidney transplant abroad and those with a follow-up period of less than 2 years. RESULTS: The number of patients with autosomal dominant polycystic kidney disease requiring transplant at our center was estimated at 0.23 per year, and the condition represented 1.57% of initial nephropathy causes. The mean patient age at transplant was 50.8 ± 8.05 years. There were 5 male and 2 female patients in the case group, with a male-to-female ratio of 2.5. The source of the graft was predominantly a living related donor (5/7). Four patients had extrarenal manifestations, the most common of which were liver cysts (3 patients). Rejection occurred in a single study patient (14.2%) and in 4 control patients (57.1%; P = .51). Two patients did not develop any complications. Complications noted after transplant included infection (3/7 cases vs 2/7 controls; P= .67) and cerebrovascular accidents (2/7 cases vs 0/7 controls). CONCLUSIONS: Further studies with longer follow-up and greater numbers of patients are needed to compare more precisely the complications and results of transplant between patients with autosomal dominant polycystic kidney disease and other kidney transplant recipients.

Tuberculosis After Renal Transplant.

Tuberculosis is one of the leading infections after renal transplant, particularly in developing countries where the incidence and prevalence in the general population are high. Diagnosis requires bacteriologic and histologic confirmation. Interactions among the antitubercular drugs and the immunosuppressive agents have to be considered while prescribing, and surveillance for adverse effects is required. Although rare, case reports are available on extrapulmonary tuberculosis in allograft recipients. Here, we present a 25-year-old kidney transplant recipient who was diagnosed with lymph node tuberculosis under uncommon circumstances but who had a good outcome. This case report illustrates the difficulties in diagnosis of tuberculosis, changes in therapeutic protocols, and prognostic factors and highlights the effects of infectious complications with immunosuppressive therapy in this particular patient population.

[Renal involvement in Behcet's disease]. / L'Atteinte Renale au cours de la Maladie de Behçet.

BACKGROUND: Renal involvement in the Behcet's disease is rare. The clinical features vary from urinary sediment's abnormalities to ESRD. AIM: We propose to study the clinical, biological and histological data, the therapeutic management and the prognosis of patients. METHODS: We report a retrospective study including 8 patients representing 1.23 % of cases. RESULTS: The average age of the patient was of 37 +/- 12. 35 years with a clear male prevalence. Urinary signs were discovered fortuitously by the strips in the majority of the cases after an average of 18 months. It's about proteinuria and hematuria. Renal insufficiency and hypertension were rare. Pathological study highlighted 3 cases of amyloidosis, 2 cases of IgA nephropathy, 1 case of minimal change disease, 1 case of endo and extracapillary glomerulonephritis and 1 case of interstitial nephropathy. Patients having GN were treated by corticoids and immunosuppressive agents and those having an interstitial nephropathy were treated symptomatically with good evolution in the majority of the cases. Only one patient is dead, he had amyloidosis. Prognosis depended on the precocity of the diagnosis, the histological type and the treatment. CONCLUSION: The renal involvement during Behçet's disease is rare. Amyloidosis and Ig A nephropathy are the most frequent. Treatment is still controversial.