Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients.

OBJECTIVES: To describe presentation and outcome of patients with scleroderma renal crisis (SRC). METHODS: SRC was defined as rapidly progressive oliguric renal insufficiency and/or rapidly progressive arterial hypertension occurring during the course of systemic sclerosis (SSc). Chronic dialysis-free survival was analysed using multivariate Cox proportional hazards regression models. The risk for developing SRC associated with corticosteroid (CS) exposure during the preceding 1- or 3-month periods was analysed according to a case-crossover design. RESULTS: A total of 50 SSc patients aged 53.3 (14.5) (mean (SD)) years were included in the study. SRC occurred between 1979 and 2003, after a mean (SD) disease duration of 27.7 (49.1) months. A total of 43 (86%) patients had diffuse SSc, 5 (10%) had limited cutaneous SSc and 2 (4%) had SSc sine scleroderma. At the time of SRC, 10 (20%) patients were taking angiotensin converting enzyme inhibitors, and mean creatininaemia was 468 (293) micromol/l. A total of 28 (56%) patients required haemodialysis. In all, 11 patients underwent a renal biopsy, all of them had specific vascular lesions of SRC. Multivariate analyses retained age >53 years and normal blood pressure as independent predictors of decreased dialysis-free survival. Exposure to CS prior to SRC was identified in 30 (60%) patients. The odds ratios for developing SRC associated with CS exposure during the preceding 1- or 3-month periods were 24.1 (95% CI 3.0-193.8) and 17.4 (95% CI 2.1-144.0), respectively. CONCLUSION: SRC remains associated with severe morbidity and mortality. CS might increase the risk of developing SRC. Further studies are needed to confirm these results.

Relapse of membranous glomerulopathy after kidney transplantation: sustained remittance induced by rituximab.

Membranous glomerulopathy (MG) is a rare cause of chronic kidney disease. However, after kidney transplantation (KT), despite immunosuppression, it often relapses on the allograft. Herein, we report on a male kidney-transplant patient, aged 27 years, who developed overt nephrotic syndrome 11 months after KT. This was related to relapsing MG, as evidenced by the allograft biopsy, which, in addition, showed CD3 (+) and CD20 (+) interstitial lymphocyte infiltration. The patient was treated with rituximab: 375 mg/m2/week for 4 consecutive weeks, followed by one additional injection every 3 months for one year. Remission was observed before the third rituximab injection. After a follow-up of 42 months, the patient was still in remission, i.e., microalbuminuria of 107 mg/day.

Hypercalciuria induced by a high dose of cinacalcet in a renal-transplant recipient.

The successful use of cinacalcet in dialysis patients and in patients with primary hyperparathyroidism has prompted transplant physicians to use it to treat renal-transplant patients with persisting hyperparathyroidism. However, in the setting of kidney transplantation, many questions remain unanswered, i.e. the time of initiation of cinacalcet after transplantation, its dosage and the side effects on kidney function all remain unknown. Herein, we report on a kidney-transplant recipient with persisting hyperparathyroidism who developed hypercalciuria afterreceiving high doses of cinacalcet. Cinacalcet was started 3 months after transplantation at a once-daily dose of 60 mg. Thereafter, the dosage was increased progressively because of persistant hyperparathyroidism and hypercalcemia. At a dose of 90 mg b.i.d, hypercalciuria occurred. The latter disappeared after reduction of cinacalcet dosage. Cinacalcet might be responsible for urinary calcium excretion, either by reduction of tubular calcium reabsorption via the reduction of PTH level, or by its direct effect on the calcium sensor receptor located in the upper thick ascending limb of the loop of Henle. We conclude that cinacalcet should be used with caution in renal-transplant patients. Further investigations are required to determine the best way to use this drug in this setting.

Linezolid-induced interstitial nephritis in a kidney-transplant patient.

Linezolid is a recent oral antibiotic used in drug-resistant Gram-positive cocci infections. Herein, we report on the first case of linezolid-related acute renal failure in a kidney-transplant patient. A 60-year-old male having autosomic polycystic kidney disease with liver involvement, on cyclosporin A, mycophenolate mofetil and very low dose prednisolone, presented with an Enterococcus faecium abscess of a huge liver cyst, which was treated by percutaneous drainage and linezolid therapy. Eight days after starting linezolid, he presented with acute renal failure, i.e. serum creatinine increased from 136- 221 micromol/l, associated with mild hypereosinophilia, anemia and thrombocytopenia. There was no skin rash, arthralgia, eosinophiluria or proteinuria. The transplant kidney biopsy, performed 15 days after the beginning of linezolid therapy, showed interstitial nephritis and focal tubular atrophy. After linezolid withdrawal and increasing prednisolone daily dose to 20 mg/d, within a few days, serum creatinine had decreased; after 2 and 4 weeks post linezolid withdrawal, his serum creatinine was 166 and 159 micromol/l, respectively. Because of the potential side effects of linezolid, i.e. myelosuppression and possibly nephrotoxicity, we recommend close monitoring of these parameters when linezolid therapy is attempted in kidney transplant patients.

Thrombotic microangiopathy in a sirolimus-treated renal transplant patient receiving gemcitabine for lung cancer.

BACKGROUND: Many etiologies lead to thrombotic microangiopathy (TMA), amongst which are antineoplastic chemotherapies. Gemcitabine, a nucleoside analogue, has been approved for the treatment ofbladder and advanced non-small cell lung carcinomas (NSCLC). The reported incidence of gemcitabine-associated TMA in the literature is low, ranging from 0.015-0.31%. METHODS: Herein, we describe the first reported case of gemcitabine-induced TMA in a renal transplant patient. This occurred in a 54-year-old male transplant recipient undergoing sirolimus-based immunosuppression. In February 2005, he was diagnosed to have NSCLC, for which he received dual chemotherapy, including carboplatin and gemcitabine. After the third cycle he developed TMA. RESULTS: On admission, he presented with weakness, edema, normal blood pressure, leucopenia (2440/mm3), thrombopenia (11,000/mm3), hemolytic anemia with hemoglobin at 8 g/dl, schistocytes between 18-33% per hundred, increase in lactate dehydrogenase at 600 IU/l (N <380), and decreased haptoglobin at 0.29 g/l. Renal function was stable: serum creatinine was 1.3 mg/dl, albuminemia 30 g/l, proteinuria was present at 3 g/l in association with microscopic hematuria, and sirolimus trough level was 6.4 ng/ml. Treatment included infusions of fresh frozen plasma, withdrawal of sirolimus, which was replaced by mycophenolate mofetil, and suspension of chemotherapy. He fully recovered from TMA within 4 weeks. The concomitant use of sirolimus, which inhibits vascular endothelial growth factor, plus gemcitabine may have resulted in TMA.

An unusual cause of acute renal failure in a kidney transplant recipient: salmonella enteritidis post-infectious glomerulonephritis.

BACKGROUND: Salmonella enteritidis-associated acute renal failure has often been described and is usually a result of dehydration or of rhabdomyolysis. A few cases of acute renal failure with glomerular syndrome, caused by S. enteritidis infection, have been reported in the literature, but none have been proven by histological findings. METHODS: Herein, we report on a case of S. enteritidis-related glomerulonephritis that occurred in a 42-year-old male transplant recipient. He was admitted with fever, signs of urinary infection, diarrhea, and nephritic syndrome, i.e. edema, hypertension, increase in serum creatinine, microscopic hematuria, proteinuria. His urine culture tested positive for S. enteritidis. RESULTS: Under light microscopy, the graft biopsy showed proliferative and exudative endocapillary glomerulonephritis. In addition, there was polymorphonuclear infiltration of the interstitium, and extra-capillary proliferation in one glomerulus. Immunofluorescence showed granular deposits of C3 in the mesangium. Electron microscopy showed electron-dense deposits typical of humps. He fully recovered on a double antibiotic therapy that included ofloxacin and amikacin. CONCLUSION: Although acute renal failure related to non-typhoidal Salmonella infections are often related to dehydration or rhabdomyolysis, this case report shows that it might also be related to immune complex-mediated glomerulonephritis manifesting as nephritic syndrome.

Rituximab therapy for mixed cryoglobulinemia in seven renal transplant patients.

Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in hepatitis C virus-positive immunocompetent patients with rituximab, a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen. Thus, this provides a rationale for the use of rituximab for type III cryoglobulin-related graft dysfunction in renal-transplant patients. Seven patients, of whom five were hepatitis C positive, developed renal function impairment long after transplantation, as well as de novo nephrotic syndrome (n = 5), severe hypertension (n = 5), nephritic syndrome (n = 1), and increased serum creatinine (n = 1). This type III cryoglobulinemia was associated with membranoproliferative glomerulonephritis and with thrombi within the glomeruli in one case. In addition to their baseline standard immunosuppressive medications, the patients were given weekly rituximab infusions: 375 mg/m(2) for 2 weeks in four cases, for 3 weeks in one case, and for 4 weeks in two cases. This treatment resulted in a dramatic improvement in all renal parameters, particularly a sustained remission of nephrotic syndrome in three cases, the disappearance of nephritic syndrome in one patient, and improved nephrotic syndrome in two cases, as well as a sustained clearance of cryoglobulins in six cases. However, it also resulted in severe infectious complications in two cases. We concluded that rituximab therapy is effective in cryoglobulin-related renal dysfunction in renal transplant patients but, due to chronic immunosuppression, this may be achieved at the expense of infectious complications.