Is renal allograft dysfunction a risk factor for severe infection in kidney transplant recipients?

The ANTICIPE study is a cross-sectional, multicenter, French study. The aim of this study was to describe clinical and biological parameters observed in a cohort of 1446 stable renal transplant recipients, according to the stage of chronic kidney disease. Severe infection was defined as an infection necessitating ≥ 7 days of hospital stay. We observed a negative correlation between declining glomerular filtration rate and occurrence of severe infection (P < .0001). In multivariate analysis, severe infection was associated with age, female gender, chronic kidney disease stage (Kidney Disease Outcomes Quality Initiative classification), and number of acute rejection episodes. Our study suggested that renal allograft function is a predictor not only of cardiac death and cardiovascular complications, but also of severe infections.

[Cinacalcet treatment for secondary hyperparathyroidism in dialysis patients in real-world clinical practice - the ECHO observational study: French experience]. / Efficacité du cinacalcet en pratique clinique chez les patients dialysés présentant une hyperparathyroïdie secondaire : observatoire ECHO - Expérience française.

UNLABELLED: In chronic kidney disease patients with secondary hyperparathyroidism (SHPT), the recommended K/DOQI™ target serum levels of parathyroid hormone (PTH), calcium (Ca) and phosphorus (P) are difficult to reach and maintain stable. We present the results of the French cohort from the European study ECHO which investigated the use and effectiveness of cinacalcet in real-world clinical practice. METHODS: An observational study of the SHPT management in dialysis patients, partially retrospective (from 6 months prior to cinacalcet initiation) and partially prospective (up to 12 months of cinacalcet treatment). RESULTS: Four hundred and eighty-five French patients were enrolled from 44 centres. Cinacalcet was given in combination with active vitamin D treatment (39%) and phosphate binders (87%). After 12 months, the proportion of patients reaching recommended K/DOQI™ target levels had increased from 2.5% to 28.8% for PTH, from 46.8% to 50.1% for Ca, from 40.0% to 49.9% for P and 54.8% to 77.7% for the CaxP product. The proportions of patients using active vitamin D and sevelamer decreased by 6% and 20% respectively. Adverse events were reported in 37 (7.6%) patients, mainly nausea (2.1%), vomiting (2.1%) and dyspepsia (1.2%). CONCLUSIONS: The results of this study are consistent with data from controlled and randomized studies showing that cinacalcet increases the proportion of patients achieving the K/DOQI™ targets for PTH, Ca, P and CaxP in real-world clinical practice.

Longer duration of predialysis nephrological care is associated with improved long-term survival of dialysis patients.

BACKGROUND: Late nephrological referral of chronic renal failure patients has been shown to be associated with high morbidity and short-term mortality on dialysis. However, the impact of predialysis nephrological care duration (PNCD) on the long-term survival of dialysis patients had not been evaluated. METHODS: We studied data from all 1057 consecutive patients who started dialysis treatment at the Necker Hospital from 1989 to 1998 (mean age at start of dialysis 53.8+/-17.2 years (range 18-91 years), excluding from analysis patients who presented with acute renal failure (n=60) or advanced malignancy (n=35). We evaluated the effects of PNCD and clinical risk factors on all-cause mortality after long-term follow-up on dialysis. RESULTS: Among the 1057 patients analysed (13.2% diabetics), PNCD was <6 months in 258 patients, 6-35 months in 267 patients, 36-71 months in 227 patients and >or=72 months in 307 patients. Cardiovascular (CV) morbidity, namely a history of myocardial or cerebral infarction, peripheral arteriopathy, and/or cardiac failure, before starting dialysis was 39.6% and 37.4%, respectively, in patients followed for <6 months or 6-35 months, compared with 24.4% in those followed for 36-71 months and 19.9% in those followed for >or=72 months (P<0.001). Five-year survival was significantly lower in patients with a PNCD of <6 months (59+/-4.1%) than for 36-71 months or >or=72 months (77.1+/-3.7 and 73.3+/-3.6%, respectively, P<0.001), but similar to those followed for 6-35 months (65.3+/-3.9%, NS). By Cox proportional hazard analysis, PNCD <6 months, age, diabetes and prior CV disease were independent predictive factors of all-cause death on dialysis. CONCLUSIONS: This study provides suggestive evidence that longer duration of regular nephrological care in the predialysis period, at least for several years prior to the start of dialysis, is associated with a better long-term survival on dialysis. Such data strongly support the argument for early referral and regular nephrological care of chronic renal failure patients.

[Course of chronic renal failure epidemiology and prediction of maintenance dialysis needs in France]. / Evolution de l'épidémiologie de l'insuffisance rénale chronique et prévision des besoins en dialyse de suppléance en France.

Epidemiology of diseases leading to end-stage renal disease (ESRD) in France has greatly changed over the past decades, with the disappearance of type 1 primary membranoproliferative glomerulonephritis, and the increased incidence of both vascular and diabetic nephropathies. The incidence of ESRD is continuously growing, by about 4% per year, with a present rate of more than 100 new patients per million population (pmp) per year. The rise in incidence is mainly observed in older subjects. As a consequence, one may predict a relentless increase in the next years, in parallel with the relentless ageing of the population. The number of ESRD patients on maintenance dialysis is also growing, by nearly 4% per year. The present prevalence is 433 pmp in the Ile de France area, ranging from 268 pmp in subjects aged 15-59 years, to as high as 980 pmp in the population aged 60 years or more. Whereas the number of in-center treated patients has remained quite stable over the past five years, the total number and proportion of out-center treated patients is continuously increasing, as expected, thanks to the development of self-care hemodialysis and of peritoneal dialysis. These data may help predict logistic requirements for maintenance dialysis in the next years.

Clinical outcome following coronary angioplasty in dialysis patients: a case-control study in the era of coronary stenting.

BACKGROUND: Balloon coronary angioplasty has been reported to be ineffective in patients treated for end stage renal disease because of a high restenosis rate. OBJECTIVE: To compare the clinical outcome following coronary angioplasty with provisional stenting in dialysis versus non-dialysis patients. DESIGN: A case-control study. PATIENTS: Of 1428 consecutive patients who underwent coronary angioplasty, 100 (7%) were being treated for end stage renal disease. These were compared with 100 control patients matched for age, sex, coronary lesions, presence of diabetes mellitus, and rate of coronary stenting (40%). MAIN OUTCOME MEASURES: In-hospital and one year clinical outcome. RESULTS: The rates of procedural success (90% v 93%), in-hospital mortality (1% v 0%), stent thrombosis (0% v 0%), and Q wave myocardial infarction (0% v 1%) were similar in dialysis and non-dialysis patients. One year clinical outcome after coronary angioplasty was similar in the two groups in terms of clinical restenosis (31% v 28%) and myocardial infarction (6% v 2%), but cardiac death was more common in dialysed patients (11% v 2%, p < 0.03). CONCLUSIONS: Dialysis does not increase the risk of clinical restenosis after coronary angioplasty with provisional stenting. Coronary angioplasty is a safe and effective therapeutic procedure in selected dialysis patients with culprit lesions accessible to stenting. However, the one year survival is reduced in this high risk population.

[Refractory ascites in hemodialysis: treatment by paracentesis- reinjection during dialysis]. / Ascite réfractaire en hémodialyse: traitement par ponction-réinjection en cours de dialyse.

Two hemodialysis patients, one male and one female, aged 46 and 54 years, were treated with preceed respectively for refractory ascites secondary to hepatic cirrhosis and for large polycystic liver. Preceed was decided because of the rapid reappearance of effusion following repeated puncture and albumin infusion, the poor tolerance to ultrafiltration (UF) and the poor nutritional status of the patients, with severe hypoalbuminemia. Abdominal paracentesis was performed on initiation of the dialysis session. Reinjection of the ascites fluid was made into the arterial line, allowing its UF and control of its flow. The procedure was performed whenever necessary, i.e., when inter-dialysis weight gain and ascites volume were high. In both cases, improvement was quickly obtained, with less rapid and less severe reappearance of the effusion and correction of albuminemia. Dialysis sessions with UF were better tolerated. No notable side effect was observed. The first patient was treated for 2 months, when he died of an unrelated cause. The other patient was treated for 6 months and then could be transferred to a dialysis center near her home. Twenty five months after start of dialysis treatment, kidney and liver transplantation were performed in this same patient. After transplantation, reappearance of moderate ascites and oedema is attributed to e degradation of renal function, without liver dysfunction. Five weeks after transplantation, improvement of renal function and ascites regression were noted. Preceed is an effective method of treating refractory ascites in the hemodialysis patient. Compared to classical paracentesis, it has the advantage of good tolerance, patient comfort and moderate cost.

[Indications of central venous access in the context of acute renal insufficiency]. / Indications des accès veineux centraux dans le contexte de l'insuffisance rénale aiguë.

Central vascular access indications in acute renal failure have never been precised by clinical studies. This is probably due to the epidemiology of acute renal failure and to heterogeneity of acute renal failure patients. Schematically, acute renal failure can be divided into three groups of increasing gravity: isolated non complicated acute renal failure, complicated acute renal failure, and severe acute renal failure that arises in the setting of multiple organ failure syndrome. Central vascular access indications, such as catheters type and vascular sites of insertion are actually based on many clinical and technical considerations. These considerations include the gravity of acute renal failure, the need of emergency extracorporeal renal replacement therapy, the modalities of such therapy, and the expected catheterism duration.

Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy.

UNLABELLED: Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy. BACKGROUND: Folic acid supplementation is only partially efficacious in correcting moderate elevation of plasma total homocysteine (tHcy) concentrations observed in hemodialysis (HD) patients. Experimental and clinical data have suggested that this partial efficacy may be due to impairment of folic acid metabolism to 5-methyltetrahydrofolate (MTHF) and of MTHF transmembrane transport as well. To bypass these difficulties, we assessed the efficacy of intravenous (i.v.) folinic acid, a ready precursor of MTHF, on reducing plasma tHcy concentrations in HD patients. METHODS: In a cohort of 37 patients on intermittent HD treatment, plasma tHcy concentrations were determined before and during i.v. supplementation of folinic acid (50 mg once per week), together with i.v. pyridoxine (250 mg 3 times per week), to prevent vitamin deficiency, particularly in those treated by recombinant erythropoietin. RESULTS: Folinic acid and pyridoxine i.v. supplementation was given for 11.2 +/- 2.45 months (range 7.5 to 17 months). The mean plasma tHcy levels decreased significantly from 37. 3 +/- 5.8 microM at baseline to 12.3 +/- 5.4 microM on folinic acid treatment (P < 0.001). Moreover, 29 of the 37 patients (78%) had normal plasma tHcy levels at the end of follow-up (that is, <14.1 microM, mean 9.8 microM, range 6.2 to 13 microM). No adverse effects attributable to folinic acid treatment were observed during this time. CONCLUSIONS: Intravenous folinic acid therapy (50 mg) once per week associated with pyridoxine supplementation appears to be an effective and safe strategy to normalize plasma tHcy levels in the majority of chronic HD patients.

Critical evaluation of plasma and LDL oxidant-trapping potential in hemodialysis patients.

BACKGROUND: We investigated whether the total peroxyl radical-trapping antioxidant potential (TRAP) assay, which has recently been proposed as a gauge of oxidative stress, could serve to evaluate plasma and low density lipoprotein (LDL) antioxidant state in hemodialysis (HD) patients. METHODS: TRAP was determined by the lag time of the chemiluminescence reaction induced by azo-initiator-catalyzed linoleic acid peroxidation in the plasma and corresponding LDL preparations of 23 HD patients and 22 healthy subjects. Antioxidant systems, including glutathione peroxidase (GSH-Px), ascorbate, vitamin E, and uric acid, oxidative stress markers including malondialdehyde (MDA), carbonyls, and advanced oxidation protein products (AOPP), and lipids, including cholesterol and triglycerides, were also determined in the plasma. RESULTS: Both plasma and LDL-TRAP were significantly increased in HD patients despite decreased GSH-Px and ascorbate and increased MDA, carbonyl, and AOPP plasma levels. Plasma TRAP values were closely related to both uric acid and AOPP levels, and LDL-TRAP values were related to triglycerides and AOPP levels. In vitro studies showed that: (a) plasma TRAP of control plasma increased regularly with supplementation of uric acid, although not reaching that of HD plasma with similar uric acid levels; (b) the addition of human serum albumin-AOPP also regularly increased control plasma TRAP, but was close to that of HD plasma with similar AOPP levels; and (c) LDL-TRAP was increased following LDL enrichment with triglycerides. CONCLUSION: Our study demonstrates that TRAP is not a relevant parameter for evaluating plasma or LDL antioxidant capacity in HD patients, due to the high plasma levels of uric acid, triglycerides and AOPP, which by themselves do not exert efficient antioxidant activity in vivo, but in vitro are able to scavenge the peroxyl radicals involved in the TRAP assay.

[Benefits of early nephrological management in chronic renal failure]. / Bénéfices d'une prise en charge néphrologique précoce de l'insuffisance rénale chronique.

OBJECTIVES: We evaluated whether early nephrological referral of patients with chronic renal failure (CRF) resulted in improved condition of patients at initiation of maintenance dialysis and in better outcome on dialysis. PATIENTS AND METHODS: We prospectively recorded clinical status, laboratory parameters, length of hospital stay and outcome of 900 CRF patients who started maintenance dialysis at Necker hospital between January 1989 and December 1996. We compared patients who benefited regular nephrological follow-up, and patients who were referred in emergency conditions at the ultimate stage of CRF. RESULTS: Among the 900 patients, 731 (81.2%) had regular nephrological follow-up, including 632 (70.2%, group IA) with optimal preparation to dialysis and 99 (11%, group IB) whose clinical course was complicated due to heavy comorbidity, whereas 169 (18.8%, group II) had no previous nephrological management. Over the 8-year observation period, the proportion of the latter group did not decrease. Late referred patients had higher blood pressure level, more frequent fluid overload, higher serum levels of urea, creatinine, uric acid and phosphate, and lower levels of bicarbonate, calcium, albumin and creatinine clearance that did well-prepared patients. Mean (+/- SD) hospital stay was 29.7 +/- 15.8 days in the former compared to only 4.8 +/- 3.3 days (p < 0.001) in the latter. Early deaths within 3 months of dialysis initiation were more frequent (7.1 vs 1.6%, p < 0.05) and less patients subsequently were able to be treated out-center (20.1 vs 40.7%, p < 0.05) in group II than in group IA. The overcost induced by late referral may be estimated at 0.25 million French francs per patient. CONCLUSION: An unjustified late nephrological referral of CRF patients still is observed in nearly 20% of cases. Such late referral is detrimental to both patients in terms of altered quality of life and long hospital stay, and to the collectivity due to heavy overcost. Closer cooperation between family physicians and nephrologists is needed to provide optimal management and allow timely preparation to maintenance dialysis of CRF patients.

[Benefits of early nephrological management of chronic renal failure]. / Bénéfices d'une prise en charge néphrologique précoce de l'insuffisance rénale chronique.

OBJECTIVES: We evaluated whether early nephrological referral of patients with chronic renal failure (CRF) resulted in improved condition of patients at initiation of maintenance dialysis and in better outcome on dialysis. PATIENTS AND METHODS: We prospectively recorded clinical status, laboratory parameters, length of hospital stay and outcome of 900 CRF patients who started maintenance dialysis at Necker hospital between January 1989 and December 1996. We compared patients who benefited regular nephrological follow-up, and patients who were referred in emergency conditions at the ultimate stage of CRF. RESULTS: Among the 900 patients, 731 (81.2%) had regular nephrological follow-up, including 632 (70.2%, group IA) with optimal preparation to dialysis and 99 (11%, group IB) whose clinical course was complicated due to heavy comorbidity, whereas 169 (18.8%, group II) had no previous nephrological management. Over the 8-year observation period, the proportion of the latter group did not decrease. Late referred patients had higher blood pressure level, more frequent fluid overload, higher serum levels of urea, creatinine, uric acid and phosphate, and lower levels of bicarbonate, calcium, albumin and creatinine clearance that did well-prepared patients. Mean (+/- SD) hospital stay was 29.7 +/- 15.8 days in the former compared to only 4.8 +/- 3.3 days (p < 0.001) in the latter. Early deaths within 3 months of dialysis initiation were more frequent (7.1 vs 1.6% p < 0.05) and less patients subsequently were able to be treated out-center (20.1 vs 40.7%, p < 0.05) in group II than in group IA. The overcost induced by late referral may be estimated at 0.25 million French francs per patient. CONCLUSION: An unjustified late nephrological referral of CRF patients still is observed in nearly 20% of cases. Such late referral is detrimental to both patients in terms of altered quality of life and long hospital stay, and to the collectivity due to heavy overcost. Closer cooperation between family physicians and nephrologists is needed to provide optimal management and allow timely preparation to maintenance dialysis of CRF patients.

Dialysis-associated amyloidosis.

Dialysis-related arthropathy represents a major complication of uremic patients treated by hemodialysis or other renal replacement therapies. Nearly 10 years ago, this syndrome was shown to be associated with a new type of amyloid, mainly composed of beta-2 microglobulin (beta 2-M). Retention of the beta 2-M protein due to chronic renal failure, although unquestionably a prerequisite for the occurrence of beta 2-M amyloidosis, appears not to be the unique pathogenetic factor involved in this complication. A role has also been attributed to an enhanced local or systemic generation of inflammatory mediators, an increased production of beta 2-M, and an altered metabolism of the molecule including partial proteolysis and glycation. It is possible that factors related to renal replacement therapy such as dialysis membrane biocompatibility also play a role. However, the clarification of the precise underlying mechanism(s) awaits further study. Because dialysis technology has progressed considerably during the last decade, a significant beta 2-M removal can be achieved at present using high-flux dialyzers. Moreover, a marked reduction in bioincompatibility during the dialysis procedure as manifested by activation of complement and stimulation of mononuclear blood cells can now be attained. Future studies will tell whether technical progress in dialysis technique results in a decrease in the incidence of symptomatic dialysis-associated amyloidosis.

No generation of bradykinin with a new polyacrylonitrile membrane (SPAN) in haemodialysis patients treated with ACE inhibitors.

BACKGROUND: Anaphylactoid reactions occurring in uraemic patients haemodialysed with polyacrylonitrile haemodialysis (HD) membranes and being treated with ACE inhibitors have been attributed to an excessive generation of bradykinin. METHODS: Here we tested in a prospective trial a new type of polyacrylonitrile membrane (SPAN) with respect to bradykinin generation in nine HD patients receiving either captopril or enalapril. Each patient had three consecutive HD sessions with each of the three tested membranes, high-flux SPAN, high-flux polysulphone (F60) and low-flux Hemophan (GFS Plus 16). RESULTS: No clinical signs of anaphylactoid reactions were observed in any of these patients but the number of patients was relatively small and the duration of exposure to different membranes relatively short. At 5 min after the start of HD session, plasma bradykinin levels were significantly higher in the venous than in the arterial line for all three HD membranes: SPAN, 18.5 +/- 11.9 versus 12.4 +/- 5.3 fmol/ml (P < 0.05); F60, 19.0 +/- 13.8 versus 11.5 +/- 6.5 fmol/ml (P < 0.01); and GFS Plus 16, 39.1 +/- 22.9 versus 15.8 +/- 12.4 fmol/ml (P < 0.005), mean +/- SD respectively. Higher venous line levels were still observed at the 15 and 60 min time points for F60 and GFS Plus 16, but not for SPAN. However, these levels were still insignificant compared to levels measured during episodes of anaphylactic shock from the literature. Plasma histamine and C5a anaphylatoxin levels did not show any increase during HD with SPAN. CONCLUSION: The SPAN membrane did not induce significant bradykinin release in dialysis patients on ACE-inhibitor therapy. It may therefore be used for high-flux dialysis in such patients.

Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity.

Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from 12 uremic patients undergoing intermittent hemodialysis were tested for their capacity to produce IL-2 and BCGFs and to respond to these soluble mediators. IL-2 and BCGF activities were determined by means of two biological assays (proliferation of IL-2-dependent cytotoxic T-cell line CTLL-2 and of anti-human IgM (mu chain)-stimulated normal B cells, respectively) in the supernatants of phytohemagglutinin A-stimulated T-cell cultures. IL-2 activity was significantly decreased in patients as compared to normal controls (mean +/- SEM, 0.28 +/- 0.09 unit per ml) in hemodialyzed patients versus 1.02 +/- 0.16 units per ml in normal controls). This profound abnormality contrasted with the normal activity of the BCGFs that was invariably observed in the same supernatants. A similar dissociation was detected when analyzing the sensitivity of uremic B and T cells to exogenous purified lymphokines. Anti-IgM (mu chain)-stimulated uremic B cells exhibited a normal response to recombinant IL-2 and to chromatography-purified BCGF I and BCGF II. Resting B cells did not show any increased reactivity to these lymphokines. In contrast, whereas in normal controls recombinant IL-2 exclusively induced the proliferation of T cells that had been previously activated by a mitogen, resting T cells from uremic patients were highly responsive to exogenous IL-2. This abnormal response was paralleled by significantly increased proportions of peripheral T cells recognized by the anti-Tac monoclonal antibody that specifically binds to the IL-2 receptor. These data clearly show the existence in hemodialyzed patients of abnormally high proportions of T cells presenting phenotypic and functional signs of preactivation. This increased T-cell IL-2 receptor expression may offer an explanation to the deficient IL-2 activity observed in patients' supernatants (by inducing increased absorption of the lymphokine). The potential relevance of these preactivated T cells to the depressed cell-mediated immunity observed in hemodialyzed patients is outlined.