Effect of double-filtration plasmapheresis for antibody-mediated rejection on hemostasis parameters and thrombin generation.

INTRODUCTION: Donor-specific alloantibodies (DSAs) cause kidney-allograft loss in chronic antibody-mediated rejection (CAMR). Treatment relies on blocking antibody-producing cells and removing DSAs by apheresis: e.g., double-filtration plasmapheresis (DFPP). MATERIALS AND METHODS: To determine the impact of DFPP (6 or 8 sessions/patient) on clotting factors and natural anticoagulants, and on thrombin generation, we performed a prospective and observational study in five CAMR kidney-transplant patients who received DFPP plus rituximab therapy. Thrombin generation was performed in poor platelet plasma (PPP) with 5 pM tissue factor without and with 2 nM recombinant human thrombomodulin. RESULTS: After the first DFPP session, median levels of high molecular-weight proteins (fibrinogen, FV, FVIII, FXI, FXIII, von Willebrand factors and α2-MG) decreased significantly to <50% of baseline values, whereas levels of low molecular-weight factors (<100 kDa) were not significantly modified, except for protein S and TFPI. Of note, binding-protein (BP) S, i.e., C4BP, was significantly decreased. Over the course of successive DFPP sessions, both high and lower molecular-weight proteins (<100 kDa) with longer half-lives (>2 days, prothrombin and factor XII) were significantly decreased. DFPP also highly affected thrombin generation in the absence of thrombomodulin but not significantly in the presence of thrombomodulin. After the first DFPP session, mean endogenous thrombin potential (ETP) and peak thrombin (PH) significantly decreased when the thrombin generation assay was performed without thrombomodulin (respectively, 1084 nM·min for ETP and 210 nM for PH after the first DFPP session compared to 1616 nM·min and 264 nM at baseline). In the presence of thrombomodulin, there was only a slight decrease in ETP and PH (respectively 748 nM·min, and 172 nM after the first DFPP session compared to 822 nM·min and 179 nM at baseline). After the last session, median ETP and PH decreased respectively to 646 nM·min and 143 nM without thrombomodulin, and, to 490 nM·min and 117 nM with thrombomodulin. CONCLUSIONS: DFPP significantly removed high molecular-weight proteins from the haemostatic system and profoundly decreased levels of protein S and TFPI. Overall thrombin-generation balance was only moderately affected in the presence of thrombomodulin. Nevertheless, high depletion of fibrinogen, FXIII and Von Willebrand Factor may expose patients to an increased risk of bleeding.

[Two cases of iatrogenic cutis and subcutis calcinosis after calcium-containing heparin injection]. / Calcinose cutanée et sous-cutanée après injection d'héparine calcique : à propos de deux cas.

BACKGROUND: Subcutis calcinosis, characterized by abnormal calcium deposition in the skin, is a rare side effect of calcium containing heparins. PATIENTS AND METHODS: Two patients with renal failure presented skin lesions after receiving a calcium-containing heparin treatment. The first patient exhibited erythematous nodules on the abdomen and the second a large erythematous induration of the abdomen and nodules on the thighs. Both had normal blood analysis. The diagnosis of subcutis calcinosis was confirmed by the histological exam showing calcium deposit in the dermis and hypodermis. Outcome was unfavourable in one of the patients who developed a superinfection and skin necrosis lesion requiring surgery at 2 months. DISCUSSION: Subcutis calcinosis is a rare and probably underdiagnosed disease. To our knowledge, only 10 cases have been reported. The pathogenesis is not well-known, tissue damage and calcium disorders are considered as risk factors. The differential diagnoses that can be suspected include calciphylaxis, such as calcifying panniculitis and other local side effects of heparins. Outcome is usually favourable without treatment. CONCLUSION: We describe two cases of iatrogenic subcutis calcinosis after injections of calcium-containing heparins, including the second case of poor outcome. Clinicians should be aware of this adverse effect since other heparins such as fondaparinux or low-weight molecular heparins are contraindicated in patients with renal failure, leading to a large prescription of calcium-containing heparins in this population.

[Mesenteric ischemia in hemodialyzed patients]. / L'ischémie mésentérique chez le sujet dialysé.

OBJECTIVES: Mesenteric ischemia is uncommon in the general population but is frequently encountered in chronic hemodialysis patients. We present here four cases which occurred in our unit within one year while only six cases had been observed in the preceding twenty years. OBSERVATIONS: Four chronic hemodialysis patients (age: 57 to 76 years) with renal failure due to diffuse atheromatous disease, presented non-occlusive mesenteric ischemia. One patient died and one underwent resection of the colon. For the final two patients, prophylactic therapy was initiated. DISCUSSION: Mesenteric ischemia is a severe condition which appears to occur more frequently in end-stage renal disease. In the chronic hemodialysis patient excessive ultrafiltration or a too rapid filtration rate can favor ischemia. Prophylactic measures must be taken at the first sign of ischemia, especially since clinical and biological features of mesenteric ischemia remain largely non-specific.

[Twenty one years of hemodialysis in a patient with primary hyperoxaluria]. / Vingt et un ans d'hémodialyse chez un patient atteint d'hyperoxalurie primitive.

We report a male patient with primary hyperoxaluria from childhood who survived more than 21 years on conventional haemodialysis. Despite the severity of his bone disease, he was married and actively employed up until 2 years before his death. His condition really worsened a few months before his death. He presented with only renal and bone involvement and had hardly any cardiovascular complications, that was probably a reason for his prolonged survival. Such an evolution is very unusual and we speculate that the length of haemodialysis sessions in addition to the large surface of the membrane probably contributed to such an outcome. During the time period on HD, anemia was transiently controlled by recombinant erythropoietin despite oxalate involvement of the marrow. He was refused a liver-kidney transplant and died from malnourishment at 43 years of age. To our knowledge, such an outcome has not yet been reported. It shows that careful prolonged hemodialysis sessions should be helped in admet patients without severe cardiovascular involvement.

[Ophthalmologic manifestations of dialysis. Retrospective study on 81 patients]. / Manifestations ophtalmologiques du dialysé. Etude rétrospective sur 81 patients.

In this work, we looked at the results of a retrospective study carried out in our unit on the ocular manifestations in the dialysed chronic renal failure patient. Eighty-one of our 189 patients had an ophtalmic examination. Thirty-six showed a retinopathy, 26 suffered from a corneoconjunctival alterations, 19 from a cataract, 6 a vascular thrombosis, 4 a glaucoma and one motor-ocular paralysis. There was no significant difference for age and sex between the 81 patients and the group of 108 who did not have an ophtalmic examination. But this difference was positive for duration of time on dialysis (p = 0.01). There is a correlation between the presence of a cataract and the age of the patients (p = 0.01). There was no link between the different types of ophtalmic problems on the one hand, and the age, sex, time on dialysis, type of dialysis, original nephropathy, hypertensive history or anterior renal transplantation on the other hand.

Relationship of omega-3 fatty acid supplementation to plasma lipid peroxidation in predialysis patients with hypertriglyceridaemia.

OBJECTIVES: Since it has been suggested that omega-3 polyunsaturated fatty acids (PUFA) may be an efficient treatment for dyslipoproteinaemia and renal function in uraemic patients, this study was carried out to evaluate the potential adverse effects of polyunsaturated acids on lipid peroxidation in patients with chronic renal failure. PATIENTS AND METHODS: Five uraemic predialysis patients with various renal diseases presenting progressive renal failure and moderate hypertriglyceridaemia (1.93 +/- 0.60 g/L) in comparison with the reference values of our laboratory (0.88 +/- 0.20 g/L) were given 6 g of fish oil per day for 6 months in the form of Maxepa capsules containing a low dose of tocopherol acetate (10.5 mg/day). During the treatment we investigated the effect (expected to be beneficial) of n-3 PUFA on triglyceride plasma levels and renal function. We also investigated the potential side effect of such a treatment on lipid peroxidation. RESULTS: A moderate decrease of triglycerides early after the introduction of the treatment (1.93 +/- 0.6 g/L vs 1.33 +/- 0.58 g/L; 0 vs 0.5 months) was observed. In all patients, lipid peroxides measured as thiobarbituric acid reactants increased early after the introduction of the n-3 PUFA therapy (2.8 + 0.8 vs 3.76 +/- 0.15 mumol/L; 0 vs 0.5 months). Organic hyperoxides were significantly different in these patients compared with laboratory values, but they did not increase significantly during the treatment. CONCLUSION: It must be noted that polyunsaturated fatty acids should be used with caution in predialysis patients.

[Diabetic glomerulopathy]. / La glomérulopathie diabétique.

Detecting a microalbuminuria in a diabetic patient is enough to diagnose a diabetic glomerulopathy (which is more properly termed diabetic nephropathy). To appreciate exactly means to know what are the lesions of mesangium matrix and interstitial tissue; therefore, a renal biopsy is useful, (but needs to be examined by quantitative histo-morphometry). Numerous factors facilitate the progression of renal insufficiency in these patients: high blood pressure, poor glycemie control, high protein diet. Avoiding each of these factors allows to delay the time of dialysis and renal transplantation. Now diabetics represent the large group of patients in renal replacement therapy world-wide. These therapies are twice to thrice as expensive as they are for non diabetic patients.

[Mixed cryoglobulinemia with necrotizing angiitis. Apropos of 2 cases]. / Cryoglobulinémies mixtes avec angéites nécrosantes. A propos de deux observations.

Out of a series of 26 personal cases, 2 cases of mixed IgM-IgG cryoglobulinemia, one type II the other type III, are reported because they were associated with histologically proven necrotizing vasculitis. In both cases the numerous symptoms were due to renal damage (the vasculitis was discovered in the kidney) and to peripheral neuropathy. One of the patients died; the other had severely deteriorated general condition and required substitution hemodialysis. Cases of vasculitis associated with mixed cryoglobulinemia have often been published, but there are few reports mentioning necrotizing vasculitis; a search in the literature yielded only 9 cases. This small number does not mean that mixed cryoglobulinemia should not be listed among the causes of necrotizing vasculitis, but it makes it difficult to extract those specific features that would enable to predict which case of mixed cryoglobulinemia is associated or not with necrotizing vasculitis.