Long-term maintenance of calcineurin inhibitor monotherapy reduces the risk for squamous cell carcinomas after kidney transplantation compared with bi- or tritherapy.

International audienceThe incidence of skin cancer after organ transplantation is mainly related to type, level, and duration of immunosuppression. The immunosuppressive minimization strategy reduces skin malignancies, but no data are available concerning long-term calcineurin inhibitor (CNI) monotherapy compared with bi- or tritherapy. We studied the benefits of long-term CNI monotherapy (>6 years of exposure) with regard to the incidence of squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) compared with bi- or tritherapy, among first renal allograft adult recipients who were more than 6 years posttransplantation. Among 294 renal transplantations performed between 1986 and 1999, 80 patients received CNI monotherapy (MT) and 86 patients bi- or tritherapy (BTT) with a follow-up of more than 6 years. MT patients were older, had longer follow-up, and fewer biopsy-proven acute rejection episodes. The incidence of SCC was 15.9 SCC/1000 patients/year for MT vs 26.2 for BTT (P = .07). The incidence was significantly lower for patients older than 40 years (22.4 vs 56, respectively; P < .01). The incidence of BCC was 28.3 BCC/1000 patients/year for MT and 10.1 for BTT (P = .05), which failed to show a significant difference in patients older than 40 years (39.7 vs 25, respectively; P = .09). The ratio of SCC/BCC in MT was maintained around 1/2 over time, while it exceeded 2/1 in BTT after 12 years posttransplantation. Patient survival was comparable between the 2 groups. A higher graft survival rate was observed in the MT group. CNI monotherapy should be considered to be a beneficial, safe immunosuppressive minimization strategy for SCC in selected recipients

[Quinine-induced renal bilateral cortical necrosis]

International audienceAcute bilateral renal cortical necrosis is a rare cause of renal failure frequently induced by disseminated intravascular coagulation (Dic) following obstetrical complications, sepsis and drugs. We describe a case of Dic with bilateral cortical necrosis after ingestion of only one tablet of quinine. A 41-year-old woman was admitted for severe abdominal pain, melaena, fever and anuria two hours after quinine tablet intake for nocturnal leg cramps. Her medical history included angioneurotic edema caused by chloroquine for malaria prevention. Physical examination was normal. Laboratory data showed acute renal failure, hemolytic anemia without schistocytes and Dic. Platelet antibodies were negative. Ultrasonographic examination showed a complete defect of renal perfusion with permeable renal arteries. Results of abdominal CT scan and MAG3 scintigraphy led to the diagnosis of bilateral renal cortical necrosis. The patient underwent plasma exchanges with fresh frozen plasma which induced rapid resolution of Dic. She remained dependent on chronic hemodialysis. Quinine-induced microangiopathic hemolytic anemia and Dic is a rare described entity. These complications occur typically in quinine-sensitized subjects. The presence of acute renal failure is generally associated with poor prognosis in case of bilateral renal cortical necrosis. Caution is required for the prescription of quinine derivates, which should be avoided in patients experienced on adverse reaction to the drug

Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients.

International audienceCytomegalovirus (CMV) seronegative renal allograft recipients (R-), particularly those with a graft from a CMV-seropositive donor (D+), are at high risk for primary CMV infection. CMV resistance to antiviral oral therapy is an emerging problem in renal transplantation, prompting development of new prophylactic strategies. We retrospectively studied the 1-year posttransplantation incidence of CMV infection in high-risk renal transplant recipients, in whom polyvalent intravenous immunoglobulins (IVIg) were used as prophylaxis. Forty R- patients received immunoprophylaxis by polyvalent IVIg (0.25 g/kg weekly for 8 weeks, starting on the operative day). CMV serological tests remained negative in eight patients (20%). Eight patients (20%) had asymptomatic CMV infection while 24 (60%) developed CMV syndrome and were treated with gancyclovir (10 mg/kg/day intravenously for 3 weeks). None had CMV disease or opportunistic infection. Six patients (15%) had biopsy-proven acute rejection, which followed CMV syndrome in three cases. One-year renal allograft and patient survivals were 95% and 97.5%, respectively. Mean serum creatinine level was 124 +/- 33 micromol/L at 1 year. Clinical tolerance of IVIg was excellent, without any episode of acute renal failure. Polyvalent IVIg provides effective prophylaxis in renal transplant recipients at high risk for CMV infection and is associated with excellent 1-year allograft survival. Because of their immunomodulatory functions, IVIg may have a beneficial effect on the incidence of acute and chronic rejection and allograft survival. A randomized prospective study is required to evaluate long-term effects of CMV prophylaxis with polyvalent IVIg compared to antiviral agents in renal transplant recipients

Acute immuno-allergic interstitial nephritis caused by fluindione.

International audienceFluindione is a vitamin K antagonist that is commonly prescribed for the treatment of cardiovascular disease and venous thromboembolism in France. Bleeding is the most common side effect of fluindione, whereas hypersensitivity reactions are rare. We describe here a patient with acute immuno-allergic interstitial nephritis caused by fluindione. Initial symptoms included fever, eosinophilia, low albuminuria, microscopic hematuria, eosinophiluria and acute renal failure. Kidney biopsy showed severe interstitial nephritis with interstitial edema, inflammatory infiltrates and tubulorrhexis. Fluindione withdrawal and corticosteroid treatment resulted in rapid recovery of renal function. A review of the literature revealed a very low incidence of fluindione-induced interstitial nephritis, with variable renal and extra-renal signs. Early recognition of this rare complication may prevent the development of severe chronic renal injury

Fanconi's syndrome induced by a monoclonal Vkappa3 light chain in Waldenstrom's macroglobulinemia.

Fanconi's syndrome (FS) is a disorder of sodium-dependent proximal tubule reabsorption, which may complicate plasma cell disorders producing a free monoclonal light chain (LC). FS often occurs in the setting of smoldering myeloma and features cytoplasmic crystalline inclusions of monoclonal kappa LC in proximal tubular cells and malignant plasma cells. Although the clinical and pathological presentation may vary, including lack of crystal formation, monoclonal kappa LCs that underlie FS show a striking genetic and biochemical homogeneity: they almost always belong to the Vkappa1 subgroup of variability and originate from 2 germline genes, O2/O12 or O8/O18. Their variable domain sequences present unusual hydrophobic residues, responsible for the resistance to proteolysis, which leads to LC accumulation in the endocytic compartment of proximal tubule cells. We report a patient with slowly progressive Waldenstrom's macroglobulinemia and full-blown FS with accumulation of a monoclonal kappa LC within proximal tubules, but no detectable crystalline organization. This LC, which belonged to the unusual Vkappa3 subgroup and derived from the L2/L16 germline gene, showed no common substitution with previously described FS kappaI LC and was sensitive to trypsin digestion. These data show that molecular and biochemical characteristics of kappa LCs in patients with FS are more heterogeneous than initially suspected. Mechanisms other than resistance of LCs to endosomal proteolysis probably are involved in the pathogenesis of FS-associated plasma cell dyscrasias