Microalbuminuria in hypertensive nonproteinuric renal transplant recipients: influence of previous acute rejection episodes and sodium intake.
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Biomedical subjects
Publications and source records attributed to H Nivet.
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BACKGROUND: Lymphocytes are involved in the physiopathologic mechanism of idiopathic nephrotic syndrome (INS). We have recently demonstrated that plasma from patients with INS decreases human glomerular epithelial cell (GEC) glycosaminoglycans (GAGs), particularly heparan sulfates (HS) in vitro. In this study we investigate the effect of peripheral blood lymphocytes (PBL) from INS patients on glomerular cell GAG and HS. METHODS: Human GECs were cultured with total peripheral blood mononuclear cells (PBMCs), PBL, and monocytes from patients and controls. The amounts of GAG and HS were assessed using a cationic membrane after metabolic labeling. RESULTS: In coculture with GECs, mononuclear cells from controls decreased total epithelial cell GAG (-30% with PBMC, P < 0.05; -25% with PBL, P < 0.02; -19% with monocytes, P < 0.05). Particularly HSs were decreased (-36% with PBMC, P < 0.05; -27% with PBL, P < 0.02; and -19% with monocytes, P < 0.05). When GECs were in coculture with PBL from INS patients, the decrease in GAG and HS was significantly greater in comparison to control PBL (-10%, P < 0.02; -10%, P < 0.02, respectively, for GAG and HS). Moreover, supernatants of stimulated PBMCs from patients decreased also GAG and HS in comparison with controls (-13%, P < 0.02; -15%, P < 0.02, respectively, for GAG and HS). CONCLUSION: These data provide direct evidence that PBLs from INS patients are able to decrease GEC HS as previously shown with plasma from patients. This might be instrumental in the onset of albuminuria.
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UNLABELLED: Microalbuminuria (Malb: albuminuria: 30-299 mg/24 h) is associated with many cardiovascular parameters (high systolic (SAP) and diastolic (DAP) arterial pressure, total cholesterol, triglycerides, fasting glucose and body weight, low HDL-cholesterol) and may be a marker of cardiovascular and renal risk in the general population. Whether MAlb could be an integrated marker of cardiovascular and renal risk in transplant recipients is unknown. PATIENTS AND METHODS: 75 hypertensive non-proteinuric renal transplant recipients were selected. Antihypertensive medications were stopped for a month prior to the studies. MAlb (on a 24-hour urine collection), cyclosporine trough levels (CsA-L), fasting glucose and lipids were measured. SAP and DAP were determined with a semi-automatic device. RESULTS: 29 patients (12 W/17M) had normal levels of albuminuria (Nalb: albuminuria < 30 mg/24 h) and 46 had MAlb. As compared to Nalb patients, those with Malb were younger (M +/- SD: 44.3 +/- 13 vs 51.2 +/- 9.7 respectively, p = 0.009), had higher SAP (152 +/- 16 vs 146 +/- 15 mmHg, p = 0.09) et DAP (86 +/- 11 vs 81 +/- 10 mmHg, p = 0.01). No difference in smoking habits, serum creatinine (125 +/- 27 vs 119 +/- 28 mumol/L), total-, HDL- and LDL-cholesterol, triglycerides, fasting glucose, CsA-L (142 +/- 29 vs 144 +/- 26 ng/mL), 24 h-urine urea excretion was observed. History of acute rejection episodes (45.7% vs 17.2%, p = 0.01) was more frequent and 24-hour natriuresis (192 +/- 70 vs 152 +/- 79 mmol/24 h, p < 0.01) was higher in Malb than in Nalb. CONCLUSION: The determinants of microalbuminuria in renal transplant recipients are different from those found in the general population. History of acute rejection episodes was more frequent in renal transplant recipients with Malb than in those with NAlb despite similar renal function, suggesting that Malb may a marker of subclinical renal lesions due to immunological aggression. The relationship between natriuresis and Malb suggests that sodium intake modulates target-organ damage associated with hypertension.
We report two girls with histories of recessive polycystic kidney disease. Both were on maintenance hemodialysis. They had undergone surgical distal portocaval shunt because of portal hypertension. Later, bilateral nephrectomy was performed, and they presented with hepatic encephalopathy (HE) and evolution towards irreversible hepatic coma and death. Portosystemic shunt is the treatment of choice of portal hypertension. The kidney plays a pivotal role in ammonia disposal during portosystemic shunt. Thus, we stress the risk of HE after portosystemic shunt followed by bilateral nephrectomy in patients with end-stage renal failure and suggest that combined liver-kidney transplantation should be considered.
BACKGROUND: Smoking may adversely affect the progression of renal diseases. However, it is unknown whether smoking affects renal function in subjects without nephropathy. METHODS: In 1998, 28,409 volunteers from the general population were examined at the Institut Régional pour la Santé (IRSA). Renal function was estimated with creatinine clearance using the Cockcroft formula. Dipstick proteinuria was assessed on an overnight urine sample by a trained technician. RESULTS: Adjusted creatinine clearance was higher in current smokers than in former smokers and never smokers (100.6 +/- 13.6 vs. 98.8 +/- 13.9 mL/min/1.73 m2, P < 0.0001, and vs. 98.5 +/- 14.0 mL/min/1. 73 m2, P < 0.0001, respectively). This difference was predominant in men and weak in women, and was associated with the number of cigarettes smoked daily. The slope of the projected age-related decline in the creatinine clearance accelerated with age, but it was similar in current smokers, former smokers, and never smokers. Creatinine clearance was associated with a relative risk of proteinuria [for each mL/min/1.73 m2, the relative risk was 1.007 (95% CI, 1.000 to 1.015), P = 0.056, for 1+ or higher proteinuria; and 1.018 (1.004 to 1.030), P = 0.0078, for 2+ or higher proteinuria]. Current and former smokers had a marked risk of 2 or higher proteinuria [adjusted RR (95% CI), 3.26 (1.66 to 6.80), P = 0. 0009, and 2.69 (1.24 to 5.99), respectively, P = 0.013, vs. never smoking], which was independent of the daily or cumulative cigarette consumption. CONCLUSIONS: In the general population, smokers do not exhibit lower creatinine clearance than never smokers. In fact, creatinine clearance is slightly higher in current smokers at least in men, even when normotensive and hypertensive subjects are analyzed separately, but the difference is small, especially in women. This effect seems reversible upon smoking discontinuation. Chronic smoking results in a marked risk of irreversible proteinuria that may occur despite moderate smoking.
Former smokers exhibit decreased cardiovascular risk as compared to smokers who continue to smoke. However, smoking discontinuation results in weight gain which may be important and influence arterial pressure. From January 1st to June 30th, 1998, 12,417 volunteers (aged 20 to 69) were examined at the "Institut régional pour la santé" (IRSA, Regional Institute for Health), a group of 9 social medical centres in Western and Central France. The subjects were screened for a routine medical and biological check-up provided by their medical insurance. All of the subjects were interviewed by a trained nurse who completed a standardised questionnaire regarding personal medical history, current treatments and lifestyle behaviours (especially alcohol and smoking habits). A physician recorded clinical parameters including age, weight, height, systolic and diastolic arterial pressure. Body mass index (BMI) was calculated. Non smokers and former smokers represented 40.0% and 23.8% of the population respectively. The prevalence of a BMI 27.0 kg/m2 or greater was higher in former smokers than non smokers and current smokers. Systolic and diastolic arterial pressure in former smokers exceeded those of current smokers and non smokers by 4.2/1.1 mmHg and 2.8/1.6 mmHg respectively. Using logistic regression analysis, the relative risk of hypertension in former smokers was 1.24 (CI 95%: 1.10-1.39, p < 0.001) and 1.13 (0.995-1.29, p = 0.055) as compared to non smokers and current smokers, after adjustment for age and alcohol intake. Differences became non significant when BMI was entered in the model. The results of the present study suggest that former smoking status is associated with a higher prevalence of overweight which may cause a higher prevalence of hypertension.
OBJECTIVE: To compare a severe protein restriction diet supplemented with ketoanalogues to a moderate protein restriction diet in order to limit glomerular filtration rate (GFR) decrease in an advanced renal insufficiency stage. DESIGN: Prospective randomised study conducted to compare a severe protein restriction diet (0.30 g/kg/day) supplemented with a preparation of ketoanalogues, hydroxyanalogues of aminoacids and aminoacids (Group A) to a moderate protein restriction diet (0.65 g/kg/day) (Group B). PATIENTS: 50 uremic patients included (25 in each group) with GFR is <20 mL/min/1.73m2. RESULTS: There were no statistically significant differences between the two dietary regimens for the renal survival. But uremia decreased significantly in Group A (22.7+/-5.2 to 18.5+/-6.7 mmol/L) and increased in Group B (26.8+/-9.0 to 34.9+/-9.9 mmol/L). Calcemia increased in Group A from 2.28+/-0.18 to 2.42+/-0.17 mmol/L, p<0.01 with a stable phosphoremia while calcemia decreased in Group B (2.33+/-0.18 to 2.25+/-0.17 mmol/L, p<0.05). At the end of the study, Group A was different from Group B for calcemia (2.42+/-0.17 vs. 2.25+/-0.17 mmol/L, p<0.01), phosphoremia (1.39+/-0.30 vs. 1.80+/-0.65 mmol/L, p<0.02), alkaline phosphatase (61.42+/-22.93 vs. 78.8+/-27.0, p<0.05) and parathormone plasma levels (2.71+/-1.55 vs. 5.91+/-1.41 ng/mL, p<0.001). COMMENTS: Compared to a moderate protein restriction (0.65 g/kg/day), a severe protein restriction (0.3 g/kg/day) supplemented by ketoanologues does not limit GFR decrease when GFR is below 20 mL/min/1.73m2, but improves phosphocalcic plasma parameters.
The transplantation of organs from one species to another introduces a question of compatibility not seen in allotransplantation, the ability of a kidney to perform its physiological function in the new host environment. It has been assumed that an allotransplanted organ will function normally if is not rejected; ample experience supports this assumption. This luxury will not exist in the field of xenotransplantation, where the issues of comparative physiology will assume great importance. From many standpoints, the pig kidney seems an ideal donor for xenotransplantation. They are of similar size and have remarkably similar internal anatomy. Even if the immunological problems could be overcome, there is almost no direct experimental evidence to answer the question of whether or not a pig kidney can function in a human body.
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A cluster of four patients (1 girl, 3 boys) from a French village (2,000 inhabitants) had acute haemolytic uraemic syndrome (HUS) between March 1992 and May 1993. All had prodromes with fever and diarrhoea, then acute renal failure, anaemia, schistocytosis and thrombocytopenia. Peritoneal dialysis was carried out in three children (duration 3-12 days). The verotoxin VT2 gene was identified by polymerase chain reaction in the stools of two children. Some days prior to the diarrhoea, all children had eaten a cheese made with unpasteurised mixed cows' and goats' milk from the same farm. A case control study showed that the occurrence of HUS was linked to the consumption of this milk product (P = 0.006). The VT 2 gene was isolated from the cheese and from the stools of goats and cows from the farm, but not from the stools of farm employees.
To determine the risk factors predictive of graft loss from chronic rejection in pediatric renal allograft recipients, we reviewed the collaborative study database of the Société de Néphrologie Pédiatrique which registered 314 grafts from January 1987 to December 1991. Of the 289 grafts analyzed, 71 failed during follow-up, chronic rejection being the most common cause of graft loss (35%). The clinical features of the chronic rejection group (n = 25) were compared with those of the group without failure (n = 218). The variables tested by monovariate analysis were cyclosporine dose at 1 year, donor type, donor and recipient age, and acute rejection episodes. The incidence of graft loss due to chronic rejection was 4% (4/109) in patients who had no acute rejection and 16% (21/134) in those with at least one acute rejection episode (P = 0.002). Donor age (< or = 5 years) was a risk factor for chronic rejection (P = 0.024). Recipient age and donor type were not significantly different between the chronic rejection group and the control group. Using time-dependent covariates, the risk factors were an acute rejection episode (P = 0.003) and low cyclosporine doses at 1 year (P = 0.02). We conclude that acute rejection and low cyclosporine doses in these pediatric patients were risk factors for graft loss due to chronic rejection.
The authors report a case of an acute renal failure secondary to an obstructive bilateral ureteral endometriosis. They show the limits of the clinical diagnosis as well as the limits of additional explorations and discuss the therapeutic management at the time and in the after effects of the initial acute period.
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Considering that in the allogeneic situation the adhesion of recipient lymphocytes to donor endothelial cells initiates the cellular rejection, we questioned the possible occurrence of a similar process in the xenogeneic situation. The adhesion of human peripheral blood lymphocytes (PBL) to porcine aortic endothelial cells (PAEC) was thus studied in an in vitro porcine-to-human xenogeneic model. It was found that 25.9% of human PBL adhered to resting PAEC. Furthermore, this adhesion increased significantly when the PAEC were stimulated by the human cytokine TNF-alpha (tumor necrosis factor-alpha). The effect of human TNF-alpha was concentration- and time-dependent and was maximal (from 25.9% to 35.6%) with 100 U/ml during 6 h. Moreover, blocking experiments with monoclonal antibody (mAb) demonstrated the role of the PBL adhesion molecules LFA-1 and especially VLA-4. Indeed, an anti-CD11a mAb decreased PBL adhesion to resting PAEC by 17.1% and to TNF-alpha stimulated PAEC by 16.9%, whereas an anti-CD49d mAb decreased dramatically PBL adhesion to resting PAEC by 53.1% and to TNF-alpha stimulated PAEC by 41.0%. Finally, phenotypic analysis of the adherent PBL showed that 50.5% of adherent cells to resting PAEC were NK (natural killer) cells, whereas 50.7% of adherent cells to TNF-alpha stimulated PAEC were T lymphocytes, showing the preferential adhesion of NK cells to resting PAEC, and that the stimulation of the PAEC with human TNF-alpha affects predominantly T lymphocyte adhesion. These results indicate that human PBL could bind to xenogeneic PAEC and that this interaction could be a first step of a xenogeneic cellular rejection.
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