Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

BACKGROUND: Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. OBJECTIVES: To assess the predictive value of cTnI in patients with TTP for death or refractoriness. PATIENTS/METHODS: The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. RESULTS: Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 µg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 µg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). CONCLUSIONS: A CTnI level of > 0.25 µg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.

Maribavir use in practice for cytomegalovirus infection in French transplantation centers.

Maribavir (MBV), a UL97 inhibitor, shows good oral bioavailability, low host cell toxicity, and theoretical benefits to inhibit cross-resistant viruses. We herein examined clinical and virological outcomes of 12 patients, including 3 bone marrow recipients and 9 organ recipients infected with resistant cytomegalovirus (CMV) and treated with MBV during 2011-2012. All received at least 800-mg daily doses. They had developed clinical (12/12) and/or virological (11/12) resistance to CMV infection. Based on a decrease of viral load in blood >1.5 log copies/mL half of them responded to MBV treatment. The individual changes varied from a rapid decrease in viral load (n = 4) to no response (n = 3) with some late response slowly decreasing viremia (n = 3). In 2 cases MBV was used as secondary prophylaxis. No clear parameter emerged as a clinical surrogate for nonresponse to MBV. These results contrast with the lack of efficacy in phase III trials of MBV prophylaxis among stem cell recipients, which were possibly due to low doses or inadequate timing of drug initiation in the study. Additional clinical and surrogate laboratory markers are needed to determine antiviral responses to guide MBV use. Dosage ranging studies might benefit future MBV use.

Correlation between Luminex donor-specific crossmatches and levels of donor-specific antibodies in pretransplantation screening.

Before kidney transplantation, recipients are routinely screened for preformed antibodies and prospective crossmatches. In this study, we compared prospective Luminex donor-specific crossmatches (LumXm) with the levels of identified, donor-specific antibodies (DSAs). LumXm was performed for 108 patient sera, 84 of which were positive for preformed antibodies and 24 of which were negative. Although LumXm can detect class I DSAs (anti-A and anti-B) with a mean fluorescence intensity (MFI) as low as 2300, the assay has a 'grey zone' for MFIs up to 4000 with a sensitivity of 54% and a specificity of 100%. LumXm can detect a class II DSA (anti-DRB1) with an MFI as low as 1300 and a sensitivity of 93% and a specificity of 99%. However, these correlations were obtained with two precautions: autocrossmatching and single-antigen bead assay with denaturing buffer were performed in discordant cases. Moreover, LumXm failed to detect anti-Cw and anti-DP in the 10 cases studied. LumXm, therefore, displays certain discrepancies with respect to single-bead assays--especially for antibodies with a low MFI. Unfortunately, LumXm has a low sensitivity for anti-A and anti-B class I antibodies.

Interstitial fibrosis quantification in renal transplant recipients randomized to continue cyclosporine or convert to sirolimus.

Conversion from cyclosporine (CsA) to sirolimus at week 12 after kidney transplantation is associated with a significant improvement in renal function. The aim of this analysis was to investigate the effect of this conversion on interstitial fibrosis (IF), a hallmark of chronic allograft injury, in patients taking part in the CONCEPT trial. This multicenter, prospective, trial included 193 renal recipients randomized at week 12 to switch from CsA to sirolimus or to continue CsA, with mycophenolate mofetil. Routine biopsy with automated, quantified assessment of IF by a program of color segmentation was performed at 1 year in 121 patients. At 1 year, renal function was significantly improved in the conversion group as assessed by estimated GFR (MDRD) and measured GFR. Biopsy results, however, showed no between-group difference in percentage of IF. Calculated GFR at 1 year was significantly associated with the percentage of IF (p = 0.004, R(2)= 0.07). By multivariate analysis diabetic patients had more fibrosis than non-diabetic patients. In conclusion, although kidney transplant patients converted from CsA to sirolimus showed significant improvement in renal function, we found no difference of IF on 1-year biopsies.

Retroperitoneal hematoma compressing a single functioning kidney: an unusual cause of obstructive renal failure.

We report a case of a retroperitoneal hematoma occurring in a patient under anticoagulation therapy for deep-venous thrombosis and presenting as an anuric acute renal failure. A coexisting polycythemia vera led to misdiagnosis that could have been life-threatening. A woman, known for polycythemia vera and a single functioning right kidney, was admitted with mild abdominal pain in a context of recent deep venous thrombosis under low-molecular weight heparin. Clinical examination revealed hepatomegaly associated with polycythemia vera. Biochemical evaluation disclosed an acute renal failure, and renal ultrasonography showed no dilation of the renal pelvis. Retroperitoneal hematoma resulted in shock, progressive anemia and obstructive renal failure, related to renal pelvic compression. A right renal indwelling catheter was introduced to restore urine flow after one hemodialysis session, and an inferior vena cava filter was placed because of anti-coagulation contra-indication. However, pulmonary embolism occurred, so that oral anticoagulants were introduced. The hematoma resorbed spontaneously, and a year after this episode, the patient is still alive and well. Retroperitoneal hematoma is a rare cause of obstructive acute renal failure and a life-threatening complication of anti-coagulation therapy.

[Muscular haematoma in Henoch-Schönlein purpura]. / Hématome intramusculaire sévère au cours du purpura rhumatoïde.

INTRODUCTION: Henoch-Schonlein purpura is one of the most frequent systemic vasculitis in children. In adults, muscle involvement is extremely rare and not very well characterized. We report a case of Henoch-Schonlein purpura with severe skin and renal involvement in witch multiple intramuscular haematoma leaded to severe anaemia. Histological examination confirms the muscle localization of the disease. EXEGESIS: A 68 years old man treated by oral anticoagulation for multiple venous thrombosis, was admitted with necrotic vasculitis of the skin, abdominal pain and segmental IgA glomerulopathy. The diagnosis of Henoch-Schonlein purpura was rapidly made and intensive steroid therapy started. After rapid improvement, a haemorrhagic shock due to voluminous intramuscular haematoma was diagnosed by MRI. Histological examination of the muscle, confirms the localization of the disease. CONCLUSION: Intramuscular haematomas are very uncommon in Henoch-Schonlein purpura. There are usually a consequence of muscular immune complex vasculitis. In our patient, high dose corticosteroid was not unable to control the disease.

[Randomized trials in the prevention of recurrent calcium oxalate stones]. / Les essais cliniques randomisés dans la prévention des récidives des lithiases oxalo-calciques.

Kidney stone, with or without lumbar pain, is a major health care problem because of its prevalence and cost for both the patient and the society. Although, surgical procedures are well known, medical treatment and recurrences prophylaxis are uncodified. Fifteen stone recurrence prevention studies have been reviewed, evaluating dietary intake and drugs. The most important factor is a daily diuresis of at least 2 liters. Calcium intake shouldn't be restricted, whereas oxalate, sodium, and protein intakes have to be limited. Hyper and normocalciuretic kidney stone formers improve their outcome with thiazide or indapamide treatment. Hyperuricosuria justifies allopurinol. Potassium citrate (without sodium) may decrease recurrence risk, even in patients without hypocitraturia.

[Progressive renal failure caused by lithium nephropathy]. / Insuffisance rénale évolutive par néphropathie au lithium.

OBJECTIVES: Study the renal consequences of lithium therapy and find out whether lithium-induced chronic renal toxicity can provoke a progressive nephropathy, leading to advanced renal failure, requiring periodical dialysis. METHODS: Fifty-three patients treated with long-term lithium salts were included in the study. They had developed chronic renal failure (creatinine clearance inferior to 80 ml/min) not due to any other cause. RESULTS: These patients had received lithium salts for a mean period of 17.7 years. The mean reduction in creatinine clearance was of 2.23 ml/min/year. Final clearance correlated negatively with the duration of lithium administration. In 7 patients treated a mean of 22 years, progression towards terminal kidney failure required periodical dialysis. Around 30% of patients exhibited mild hypercalcemia. CONCLUSION: Lithium nephropathy inducing progressive renal failure is a reality. Its prevalence in patients treated long-term with lithium should be assessed.

[Renal osteodystrophy (2): its treatment in renal insufficiency before dialysis]. / Ostéodystrophie rénale (2): Son traitement chez l'insuffisant rénal avant la dialyse.

1. In the patient with renal insufficiency before dialysis, the phosphocalcic disorders appear insidiously. They are dominated by hyperparathyroidism which will be diagnosed on the initially yearly determination of plasma intact PTH as soon as creatinine clearance decreases below 60 ml/min, eventhough there is still no modification in plasma concentrations of calcium and phosphate. Its diagnosis should lead to initiate the therapeutic measures in order to prevent the irreversible thining of the corticals by endosteal resorption and later the occurrence of histological and radiological osteitis fibrosa favoring fractures. 2. Hyperparathyroidism prevention relies on two main measures: prevention of phosphate retention and hypocalcemia is implemented by progressive phosphate and protein restriction (from 1 g/kg/day when Ccr < 60 ml/min to 0.6 g/kg/day when Ccr < 20 ml/min) and administration of CaCO3 (1.5 g at lunch and dinner to better complex the phosphate) as soon as PTH is above normal; optimal vitamin D repeletion will be implemented by systematic supplementation of native vitamin D or 25OH vitamin D3 in order to bring P25OHD between 30-60 ng/ml (75-150 nmol/l) or more generally around the upper limit of the epidemiologic range of the laboratory; these measures should aim at maintaining plasma intact PTH in its optimal range variable with the degree of renal insufficiency: 0.5-1; 1-2.5 and 2-3 folds the upper limit of normal for creatinine clearance respectively at 60-30; 30-10 and < 10 ml/min. 3. Because of their hyperphosphatemic and hypercalcemic effect, 1 alpha-hydroxylated vitamin D derivatives will be regularly efficient and safe only when non-calcemic non-aluminic phosphate binder will be available and proven to be without side-effects. 4. Instrumental (surgical or by alcohol injection) parathyroidectomy should be considered when plasma intact PTH is > 5 to 7 times the upper limit of normal in the presence of hypercalcemia (> 2.60 mmol/l) and/or hyperphosphatemia (> 1.70 nmol/l) in spite of the above measures, the decision being reinforced by coexistence of bone radiologic abnormalities and metastatic calcifications. 5. Adynamic bone diseases are rare before hemodialysis in the absence of aluminum exposition by the drinking water or the aluminum-phosphate binders. In absence of aluminum it will be prevented by maintaining PTH in its optimal range. 6. Osteomalacia before hemodialysis is mainly due, in the absence of aluminum exposition, to vitamin D deficiency, hypocalcemia and acidosis. It is readily cured by physiological doses of native vitamin D or 25OH vitamin D3 bringing plasma 25 OHD above 16 ng/ml, in association with alkaline salts of calcium and if necessary of sodium bicarbonate.

[Collapsing glomerulopathy and cytomegalovirus, what are the links?]. / Glomérulopathie avec collapsus du floculus et cytomégalovirus, quels liens?

BACKGROUND: Collapsing glomerulopathy is a form of focal and segmental glomerulosclerosis which occurs preferentially in black people. It causes severe nephrotic syndrome and quickly progresses towards end-stage renal failure. CASE REPORT: We report the case of a 16-year-old black girl from Guadeloupe who was admitted for tetanus and edema in 1996. She had hypoparathyroidism, renal failure and a nephrotic syndrome as well as cytomegalovirus infection. Renal biopsy showed collapsing glomerulopathy. The renal function improved on glucocorticoid and ganciclovir therapy and her serum creatinine stabilized around 250 mumol/l for two years. DISCUSSION: Collapsing nephropathy is the cellular type of focal and segmental glomerulosclerosis. The main etiology is the human immunodeficiency virus. A viral infection may be involved in its pathogenesis. Other viruses could be linked with this nephropathy. This case report relates a case associated with a cytomegalovirus viruria. The clinical course might be related with the antiviral treatment.