Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort.

Cardiovascular disease (CVD) remains the major cause of death in patients with end-stage renal disease (ESRD). Traditional risk factors do not explain the high prevalence of CVD in this population, and other non-traditional cardiovascular (CV) risk markers have now been described. Therefore, the potential relationship between CVD and phenotypic and genotypic risk markers was investigated prospectively in incident dialysis patients cohort. The 279 patients (244 on hemodialysis, 35 on peritoneal dialysis) within the Diamant Alpin Dialysis Cohort Study were investigated. Phenotypic and genotypic parameters were determined at dialysis initiation, patients monitored over a 2-year period, and CV events (morbidity and mortality) recorded. Globally, 82 CV events occurred and 26 patients (9.3%) died from CVD, whereas 28 (10%) died from non-CV causes. Previous CV events were strongly predictive of CV events occurrence, whatever patients had had one (hazard ratio (HR) 2, 95% confidence intervals (CI) 1.1-3.5) or more (HR 3.9, 95% CI 2.1-7.1) CV accidents before starting dialysis. Both lipoprotein(a) (HR 1.67, 95% CI 1-2.5) and total plasma homocysteine at cutoff 30 micromol/l (HR 1.7, 95% CI 1.1-2.8) were independent predictors of CV events outcome. In the subgroup of patients with homocysteine < 30 micromol/l, methylenetetrahydrofolate reductase (MTHFR) TT was the sole biological parameter predictive of CV event outcome (HR 2.5, 95% CI 1.1-10, P = 0.03). ESRD patients who enter chronic dialysis with a previous CV event, high total homocysteinemia levels, or MTHFR 677TT genotype must be considered at high risk of incident CV events.

Low dose antithymocyte globulins in renal transplantation: daily versus intermittent administration based on T-cell monitoring.

BACKGROUND: Despite the long history of use of antithymocyte globulins (ATG) in renal transplantation, ideal doses and duration of ATG administration based on the monitoring of T lymphocytes have yet to be defined. METHODS: Two immunosuppressive regimens based on low-dose rabbit ATG (Thymoglobuline; Imtix-Sang-stat, Lyon, France) were assessed during the first year after transplantation: daily ATG (DATG; n=23) where 50 mg of ATG was given every day and intermittent ATG (IATG; n=16) where similar doses of ATG were given for the first 3 days and then intermittently only if CD3+ T lymphocytes (measured by flow cytometry) were > 10/mm3. Both groups received steroids, azathioprine, and cyclosporine. RESULTS: ATG-induced depletion was similar for peripheral blood lymphocytes and T cells in both groups: it began at day 1 after transplantation, was submaximal at day 3, and reached maximum intensity between days 6 and 8, from which time cell counts progressively increased. However, T-cell depletion was still present at day 20. The total ATG dose per patient (381.5+/-121 vs. 564+/-135 mg/patient) and the mean cumulative daily dose of ATG (0.60+/-0.17 vs. 0.80+/-0.14 mg/kg/day) were significantly lower in the IATG group (P=0.0001 and 0.0006, respectively). The overlap of ATG and cyclosporine treatment was 6.7+/-3 vs. 7.4+/-4.3 days (P=NS), and the mean duration of ATG therapy was 11.3+/-3.2 vs. 11.6+/-2.7 days in the IATG and DATG groups, respectively (P=NS). ATG was given in an average of one dose every 1.6 days in the IATG group compared with one dose daily in the DATG group (P=7 x 10(-7)). There was no significant difference in renal graft function, the number of acute graft rejections, or ATG-related side effects and complications. Despite the daily immunological follow-up, there was a net saving of $760/patient in the cost of treatment in the IATG group. CONCLUSION: IATG had the advantage of a reduction in the dose of ATG and in the cost of treatment, while offering similar T-cell depletion and effective immunosuppression. This approach could be proposed as an induction protocol, particularly for patients with poor graft function in whom cyclosporine introduction has to be delayed or those with increased risk of cytomegalovirus infections or secondary malignancies.

[Secondary hyperparathyroidism and multiple vertebral brown tumors: cure after parathyroidectomy]. / Hyperparathyroïdie secondaire et tumeurs brunes multiples à localisation vertébrale: guérison après parathyroïdectomie.

A 46 year old man was referred for severe left cruralgia and multiple vertebral cystic defects on CT-scan. He was treated by hemodialysis since 1987 for chronic renal failure secondary to focal and segmental glomerulosclerosis, diagnosed in 1960 on renal biopsy. Dialysis schedule consisted of 3 x 4 h/week with a polysulfone dialyser and 1.75 mMol Ca containing bicarbonate dialysate. On early 1995, the patient complained of back pain and cruralgia, which gradually worsened. Vertebral column CT-scan and MRI showed multiple lytic lesions expanding into the medullary canal. Biological hyperparathyroidism was present. To differentiate between hyperparathyroidism with brown tumors, malignancy and amyloid deposition, an iliac biopsy and a biopsy of a corporeal vertebral cyst were done. They showed florid hyperparathyroidism and brown tumors. The patient was submitted to surgical parathyroidectomy. Six months after surgery, cruralgia resumed, CT-scan and MRI showed refilling of the cysts by calcic material.

[Lipoprotein glomerulopathy: a new French case with recurrence on the transplant]. / Glomérulopathie lipoprotéinique: un nouveau cas français avec récidive sur le transplant.

Lipoprotein glomerulopathy is defined by the presence of lipidic deposits in the capillary lumen giving them a dialted and microaneurysmal aspect and the presence of quantitative and/or qualitative alterations of plasma apolipoprotein E. We describe here the long-term follow-up of a young female patient who presented with corticoresistant nephrotic syndrome in 1979 and progressed to chronic renal failure requiring dialysis in 1990. The three renal biopsies performed during the follow-up showed markedly enlarged capillary loops due to intra-luminal fibrinolipidic material deposition forming true intracapillary thrombi. She received a cadaver renal transplant in 1993. One year after transplantation, nephrotic syndrome reappeared and graft biopsy showed recurrence of the initial glomerular disease on the transplant. The plasma lipid profile showed hypercholesterolemia, hypertriglyceridemia, and elevated plasma ApoE levels with an abnormal Apo E phenotype. Our case report is a new typical case of lipoprotein glomerulopathy with recurrence of the initial disease on the renal allograft.

Prognosis of acute renal failure in the elderly.

UNLABELLED: Life expectancy is uncertain in the elderly with ARF. In order to determine whether a costly supportive management is worthwhile, we have studied a group of 68 elderly patients (over 65 years of age) admitted to the ICU with ARF. PATIENTS: 47 male; 21 female; 72 +/- 6 years old. Types of ARF include prerenal 24; obstructive 9; intrinsic 35 (acute tubular necrosis 30; glomerulonephritis 4; vascular 1). The mean simplified acute physiology score (SAPS) was 14 +/- 4; 39 patients (57.3%) had more than two underlying diseases; 42 patients (61.7%) were on mechanical ventilation; 40 patients (60%) underwent haemodialysis. The overall survival rate was 36.7%. Among the parameters studied, organic systemic failure index (OSF), diuresis, blood lactate, systolic blood pressure, urea appearance rate (UAR), differed significantly in survivors and deceased. From these results we conclude that the elderly with non-oliguric ARF, normal blood lactate, low catabolic state, and no more than two organ failures have a fair chance of recovering and should therefore be treated aggressively. In other cases, decisions to proceed with intensive supportive measures should be made according to individual characteristics.