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.

[Epidemiology of end-stage renal failure: comparison between 2 Swiss cantons]. / Epidémiologie de l'insuffisance rénale terminale: comparaison entre deux cantons suisses.

Since a previous survey in the Valais Canton had shown a disparity in the prevalence of chronic dialysis patients compared to the national mean, an epidemiological survey was conducted in the cantons of Valais (VS) and Vaud (VD) among all the dialysis units (VS 6, VD 6) and all adult dialysis patients (VS 130, VD 187). The survey confirms the disparity in prevalence: VS 476, VD 340 and Switzerland 329 per million inhabitants (p.m.h.). This disparity also exists among different parts of the VS canton: Haut-Valais 316, Valais Central 650 and Bas-Valais 409 per million d'habitants. The mean age at start of therapy and at the time of the survey are comparable: 57 +/- 17 vs 55 +/- 15 years and 62 +/- 15 vs 61 +/- 14 respectively. Among the different etiological diseases, vascular nephropathies are less frequent and hereditary diseases more frequent in the VS canton. Co-morbidity factors were comparable. In VS there are less patients on peritoneal dialysis (6 vs 19%) and on the transplant waiting list (12 vs 16%). Globally, disparities exist in the prevalence of dialysis patients between the 2 cantons; they can be explained by both medical factors (type of nephropathies) and different options in the treatment modalities.

Cholestatic hepatitis A complicated by acute renal insufficiency.

31 cases of non-fulminant hepatitis A complicated by acute renal insufficiency are reported in the literature. Two-thirds of those patients needed dialysis, usually when depending on the severity of their hyperbilirubinemia. This report concerns the first published case of non-fulminant cholestatic hepatitis A complicated by acute renal insufficiency in which a spontaneous remission of renal function occurred without need for dialysis despite a very severe hyperbilirubinemia.

[Living donors in kidney and liver transplantation]. / Le donneur vivant: transplantation de rein et de foie.

The shortage of organs available for transplantation has rekindled the interest for the kidney living donor, and has recently induced the use of living donors for liver transplantation too. Both methods raise many medical and ethical interrogations. The aim of this paper is to analyse this type of organ harvesting, and to report our experience and results with kidney and liver living donors.

Is there a place for duplex screening of brachial artery in haemodialysis patients with vascular access?

BACKGROUND: Vascular access (VA) stenosis with subsequent thrombosis remains one of the major causes of morbidity and hospitalization in haemodialysis patients. The present cross-sectional study was planned in order to analyze the usefulness of brachial artery duplex ultrasound for detection and prediction of vascular access stenoses. METHODS: Color duplex ultrasound (Apogée Cx200, sectorial probe 7.5 MHz) was used to obtain the anatomical pattern of the VA and flow velocity waveforms of the brachial artery in 77 non-selected VA (47 Ciminio-Brescia fistulae and 30 PTFE grafts). In each VA, the resistance index (RI), the mean blood flow rate (Q) and the blood flow ratio index (QI) (QI = VA flow rate/contralateral flow rate) were calculated at the level of the brachial artery. The sensitivity and specificity of these brachial Doppler parameters were calculated for the detection of VA stenosis. In normal VA, positive (PPV) and negative predictive (NPV) values were calculated for the development of clinical stenotic complications 3 months post ultrasound examination. RESULTS: Thirteen of the 77 VA (17%) were identified as stenosed by duplex ultrasound and confirmed by fistulography and/or during surgical exploration. The best screening tests for VA stenosis detection were a QI threshold < 4.0 with a sensitivity and specificity of 69 and 69% and an RI > 0.55 with a sensitivity and specificity of 62 and 66%, respectively. In the VA considered as normal by ultrasound, the prediction of subsequent stenosis within three months post-ultrasound examination gave a PPV of only 18% and 19% for RI and QI, respectively. NPV for RI and QI were 90% and 88%. CONCLUSIONS: While Doppler ultrasound is a useful non-invasive test for the detection of prevalent VA stenosis, our results do not confirm that abnormal brachial Doppler flow parameters can predict short term development of VA stenosis.

[Laparoscopic nephrectomy in the liver donor: introduction of the method and preliminary results]. / Néphrectomie par laparoscopie chez le donneur vivant: introduction de la méthode et résultats préliminaires.

INTRODUCTION: The shortage of organs available for renal transplantation has focussed attention on the use of live donors. Techniques for laparoscopic nephrectomy have recently been described, which have limited morbidity, duration of hospitalization and the period off work. However, these surgical procedures are difficult, and may be risky for the organ to be transplanted. METHOD: The laparoscopic live donor nephrectomy was introduced in stages, including the use of a videoconference from a reference center. In this article, the prospective analysis of the present authors' preliminary results has been presented. RESULTS: Ten kidneys were removed by laparoscopy, i.e., three from the left and seven from the right side. No conversion of this technique to laparotomy was necessary. The mean warm ischemic time was five minutes, and in the last six operations it did not exceed three minutes. The patients were able to leave hospital between four and eight days following surgery. After a mean follow-up of 10.5 months, organ survival was 100%, and in all grafts excellent function was observed. CONCLUSION: The quality of these preliminary results which may act as a reference and the careful introduction of a live donor laparoscopic program could provide an incentive to potential donors, and thereby increase the pool of organs available for transplantation.

One-year immunological evaluation of chronic hemodialysis in end-stage renal disease patients.

BACKGROUND: Much research has been devoted to the determination of acute leukocyte activation as well as acute cytokines production during and after blood hemodialysis membrane interaction. In contrast, few studies deal with chronic immunological evaluation of T-cell activation markers in hemodialysis. METHODS: We evaluated different immune parameters using a modified cellulose low-flux hemophan vs. synthetic high-flux polyamide membrane during 1 year in 35 stable chronic hemodialysis patients. Leukocyte counts, lymphocyte subpopulations, T-cell activation markers (CD69, CD25, HLA-DR, CD54, CD62L, CD45RO, CD11a, CD28), complement-activation products (C3a) and serum elastase were measured at 0, 3, 6 and 12 months in the two patient groups and compared to 13 healthy control subjects. RESULTS: Over dialysis time, all patients showed a significant level elevation of CD69/CD3 (p < 0.005) and CD25/ CD3 (p < 0.005) phenotypes. In contrast, HLA-DR and CD45RO remained unchanged suggesting a truncated pattern of activation. T lymphocyte subset analysis showed in both hemodialyzed groups a significant decrease in the expression of CD54 (ICAM-1) when compared to controls (p < 0.005). C3a and elastase measurements showed a significant upward trend with dialysis time in both hemodialyzed groups. CONCLUSION: Although the immunological changes seen in chronic hemodialyzed patients must be interpreted in conjunction with their basal uremic states and the membrane permeability properties, our study suggests that 1-year immunological evaluation of hemodialysis membranes biocompatibility is associated with changes in the pattern of chronic T-cell activation, which is in part related to the use of a particular membrane type. Moreover, some key molecules (CD54) are affected in patients with end-stage renal disease undergoing hemodialysis.

Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

Postprandial hepatic glycogen synthesis in liver transplant recipients.

BACKGROUND: The liver plays a central role in glucose homeostasis by releasing glucose in the fasting state and by taking up and converting into glycogen part of the glucose absorbed from the gastrointestinal tract after meal ingestion. METHODS: To determine whether the hepatic denervation that accompanies liver transplantation interferes with these functions, we assessed glucose tolerance to an oral glucose load in seven patients at 2-6 weeks after orthotopic liver transplantation, in six patients after kidney transplantation, and in six healthy controls. Hepatic glycogen synthesis was non-invasively assessed over the 4 hours after ingestion of a glucose load by monitoring hepatic uridine diphosphoglucose turnover with 13C galactose and acetaminophen. RESULTS: Liver and kidney transplant recipients had increased postprandial glucose concentrations but normal hepatic uridine diphosphoglucose turnover, indicating an unaltered hepatic glycogen synthesis. CONCLUSIONS: These results indicate that denervated liver transplants have an adequate glucoregulatory function. Postprandial hyperglycemia in liver transplant recipients is therefore not due to alterations of liver glucose metabolism.

Chromosomal abnormalities in renal cell neoplasms associated with acquired renal cystic disease. A series studied by comparative genomic hybridization and fluorescence in situ hybridization.

Sporadic renal cell carcinomas (RCCs) display different chromosomal abnormalities according to their morphology; gains of chromosomes 7 and 17 and loss of Y are commonly observed in papillary lesions, whereas loss of 3p sequences and multiple losses of specific chromosomes are found in non-papillary and chromophobe cell carcinomas, respectively. Acquired renal cystic disease (ARCD) is associated with an increased incidence of renal cell tumours, especially papillary lesions. The aim of this study was to examine a series of ARCD-related tumours for chromosomal abnormalities and to compare the findings with those abnormalities commonly observed in sporadic RCCs. Nine tumours from four patients with ARCD were examined using comparative genomic hybridization (CGH) and interphase cytogenetics. Gain of chromosomes 7 and 17 was observed in all four papillary lesions and loss of Y in three. In addition, gain of chromosome 16 was observed in three papillary tumours. Three chromophobe RCCs originating from the same kidney showed different genomic profiles; two had no abnormalities, whereas one showed loss of chromosome 17p. Two non-papillary RCCs failed to show chromosome 3p alterations. In conclusion, renal cell tumours developing in ARCD may show chromosomal abnormalities both similar to and different from those seen in sporadic tumours.

Frequency and impact of autosomal dominant polycystic kidney disease in the Seychelles (Indian Ocean).

BACKGROUND: As little such data is available in African populations, we investigated the prevalence of ADPKD and the impact of the disease in the Seychelles islands, where approximately 65% of the population is of African descent and 30% of Caucasian or mixed descent. METHODS: Prevalent cases were identified over a 3-year period by requesting all the doctors in the country (most of them are employed within a national health system) to refer all presumed or confirmed cases and by systematically examining the family members of all confirmed cases. The diagnosis was based on standard criteria including ultrasonographic findings and family history. RESULTS: Forty-two cases were identified in this population of 74,331 inhabitants, a total prevalence (per 100,000 total population) of 57 (95% CI, 41-76). All but one of the cases were of Caucasian descent so that the prevalence rates of the disease in the populations of Black and Caucasian descents were respectively 2 (0-11) and 184 (132-249). The prevalence rates of the gene(s) carriers were estimated to be 75 (45-117) in the total population respectively 6 (0-33) and 236 (140-372) in the Black and Caucasian populations. Haplotype analysis in 58 cases from three families showed a common DNA fragment in all affected individuals. Cases had significantly higher blood pressure compared to the general population and 21% had serum creatinine higher than 120 mumol/l. Among the established pedigrees, mean age of death between 1960 and 1995 (haemodialysis was introduced in 1992) was younger in subjects with than those without ADPKD (50.5 vs 67.7 years; P < 0.001). CONCLUSIONS: In the Seychelles, ADPKD clusters in the Caucasian population (possibly a founder effect), is rare in individuals of black descent, and is associated with substantial clinical and survival impact.

Hypertension arterielle apres transplantation renale : Influence du profil tensionnel au stade de dialyse

L'objectif de ce travail cooperatif est d'etudier l'influence d'une hypertension pre-existante en dialyse (D); sur la frequence de l'hypertension arterielle (HTA) chez les transplantes renaux (TR); et de definir ses caracteristiques cliniques