An abnormally high mortality from atherosclerotic cardiovascular (CV) accidents has long been reported in patients on maintenance hemodialysis (HD). However, incidence of such complications had not been so far evaluated in chronic renal failure (CRF) patients not yet on dialysis. In a cohort study bearing on 232 predialysis CRF patients, followed as out-patients at Necker hospital, incidence of first myocardial infarction (MI) was three times higher than in the French general population in every age group and in both genders, with a mean (+/- SEM) age at onset of MI of 62.9 +/- 1.2 years. In a retrospective cooperative study involving 748 patients treated in 9 hemodialysis centers in the Ile-de-France area, incidence of first MI episodes did not differ before acid after start of HD therapy acid was similar to that observed in the cohort study. Mean age of patients at first MI, before and after start of HD, was respectively 62.4 +/- 1.6 and 63.7 +/- 1.5 years, a not significant difference. In conclusion, two epidemiologic studies confirm the existence of accelerated atherosclerosis in CRF patients, the incidence of MI being 3 times higher in uremic patients than in the general population in every age group and in both genders. The fact that incidence of first MI episodes and age at onset was similar in predialysis and in dialyzed patients suggests that the uremic stale per se is a main determinant of such accelerated atherosclerosis. It results that therapeutic measures aimed at preventing development of atherosclerosis should be initiated from the early stage of CRF, long before start of renal replacement therapy.

Artificial OrgansVolume 22, Issue 7 p. 523-526 In Memoriam: Jean-Louis Funck-Brentano 1924–1997 Monique Funck-Brentano, Monique Funck-Brentano Clinical Pharmacology Saine-Antoine Medical School,Search for more papers by this authorChristian Funck-Brentano Prof., Christian Funck-Brentano Prof. Clinical Pharmacology Saine-Antoine Medical School,Search for more papers by this authorClaude Griscelli Prof., Claude Griscelli Prof. Director Institut National de la Santé et de la Recherche Medicale,Search for more papers by this authorBéatrice Descamps-Latscha Dr., Béatrice Descamps-Latscha Dr. Necker Hospital Paris, FranceSearch for more papers by this authorTilman Drüeke Dr., Tilman Drüeke Dr. Necker Hospital Paris, FranceSearch for more papers by this authorN.-K. Man Dr., N.-K. Man Dr. Necker Hospital Paris, FranceSearch for more papers by this authorJean-Pierre Grünfeld Dr., Jean-Pierre Grünfeld Dr. Necker Hospital Paris, FranceSearch for more papers by this author Monique Funck-Brentano, Monique Funck-Brentano Clinical Pharmacology Saine-Antoine Medical School,Search for more papers by this authorChristian Funck-Brentano Prof., Christian Funck-Brentano Prof. Clinical Pharmacology Saine-Antoine Medical School,Search for more papers by this authorClaude Griscelli Prof., Claude Griscelli Prof. Director Institut National de la Santé et de la Recherche Medicale,Search for more papers by this authorBéatrice Descamps-Latscha Dr., Béatrice Descamps-Latscha Dr. Necker Hospital Paris, FranceSearch for more papers by this authorTilman Drüeke Dr., Tilman Drüeke Dr. Necker Hospital Paris, FranceSearch for more papers by this authorN.-K. Man Dr., N.-K. Man Dr. Necker Hospital Paris, FranceSearch for more papers by this authorJean-Pierre Grünfeld Dr., Jean-Pierre Grünfeld Dr. Necker Hospital Paris, FranceSearch for more papers by this author First published: 04 January 2002 https://doi.org/10.1046/j.1525-1594.1998.00710.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume22, Issue7July 1998Pages 523-526 RelatedInformation

An abnormally high mortality from atherosclerotic cardiovascular (CV) accidents has long been reported in patients on maintenance hemodialysis (HD). However, incidence of such complications had not been so far evaluated in chronic renal failure (CRF) patients not yet on dialysis. In a cohort study bearing on 232 predialysis CRF patients, followed as out-patients at Necker hospital, incidence of first myocardial infarction (MI) was three times higher than in the French general population in every age group and in both genders, with a mean (+/- SEM) age at onset of MI of 62.9 +/- 1.2 years. In a retrospective cooperative study involving 748 patients treated in 9 hemodialysis centers in the Ile-de-France area, incidence of first MI episodes did not differ before and after start of HD therapy and was similar to that observed in the cohort study. Mean age of patients at first MI, before and after start of HD, was respectively 62.4 +/- 1.6 and 63.7 +/- 1.5 years, a not significant difference. In conclusion, two epidemiologic studies confirm the existence of accelerated atherosclerosis in CRF patients, the incidence of MI being 3 times higher in uremic patients than in the general population in every age group and in both genders. The fact that incidence of first MI episodes and age at onset was similar in predialysis and in dialyzed patients suggests that the uremic state per se is a main determinant of such accelerated atherosclerosis. It results that therapeutic measures aimed at preventing development of atherosclerosis should be initiated from the early stage of CRF, long before start of renal replacement therapy.

OBJECTIFS: Nous avons cherche si une prise en charge nephrologique precoce des patients atteitns d'insuffisance renale chronique (IRC) ameliorait les conditions de mise en oeuvre et les resultats de la dialyse de suppleance, ainsi que ses consequences, socio-economiques. METHODES: Dans une etude prospective portant sur la totalite des 900 patients atteints d'IRC ayant commence la dialyse de suppleance a l'hopital Necker entre 1989 et 1996, nous avons evalue les caracteristiques cliniques et biologiques, la duree d'hospitalisation et l'evolution chez les patients regulierement suivis et prepares, par comparaison avec les patients vus au stade terminal sans suivi regulier prealable. RESULTATS: Parmi les 900 patients, 731 (81,2 p.100) avaient eu un suivi nephrologique regulier, 632 (70,2 p. 100) ayant beneficie d'une preparation optimale a la dialyse (groupe IA) et 99 (11 p. 100, groupe IB) ayant eu une evolution compliquee du fait de la comorbidite, tandis que 169 patients (18,8 p. 100, group II) n'avaient pas eu de suivi regulier prealable. la proportion des patients non suivis n'a pas diminue avec le temps au cours de la periode d'observation de 8 ans. Les patients non suivis avaient une pression arterielle plus elevee, des signes de surcharge hydrosodee plus frequents, de taux plasmatiques d'uree, de creatinine, d'acide urique et de phosphates plus eleves, et des taux de bicarbonates, de calcium et d'albumine plus faibles que les patients bien prepares. La duree d'hospitalisation necessaire a ete chez eux en moyenne (±SD) de 29,7 ± 15,8 jours, contre 4,8±3,3 jours dans le group IA (p<0,001). Le surcout entraine par l'absence de suivi nephrologique peut etre estime a pres de 0,25 million de francs par patient. La mortalite au cours des 3 premiers mois en dialyse a ete plus elevee (7,1 vs 1,6 p.100, p<0,05) et la proportion des patients ulterieurement traites hors centre plus faible (20,1 vs 40,7 p.100, p<0,05) dans le groupe II que dans le group IA. CONCLUSION: Une prise en charge nephrologique trop tardive de l'IRC, observee encore dans pres de 20 p.100 des cas en dehors de tout probleme d'acces aux soins, se revele prejudiciable pour les patients dont elle obere la qualite de vie et qu'elle oblige a une longue hospitalisation. De plus, elle induit un surcout important. Une cooperation precoce entre medecins feneralistes et nephrologues est souhaitable pour optimiser la prise en charge des patients atteints d'IRC et leur preparation au traitement de suppleance.

Background. Accelerated atherosclerosis resulting in an abnormally high incidence of coronary and cerebrovascular occlusive accidents has been repeatedly reported in dialysis patients, but incidence and risk factors of such complications in chronic renal failure (CRF) predialysis patients are debated.Methods. We prospectively assessed the incidence of first myocardial and cerebral infarction episodes in a cohort of 147 CRF patients (99 male) followed from January 1985 to December 1994. Relevant clinical and laboratory risk factors for atherogenesis were determined at yearly intervals. They included blood pressure, smoking, blood lipids, fibrinogen, and homocysteine which were compared in patients with (CVA+) or without (CVA-) occurrence of cardiovascular (CV) atherosclerotic accidents.Results. Incidence of CV accidents was nearly three times higher in CRF patients than in the French general population in both genders. In particular, incidence of myocardial infarction in male patients aged 45-55, 55-65 and >65 years was 7.6, 18.2, and 27.8/1000 patient-years, respectively, compared to 3.4, 8.9, and 10.4/1000 subject-years in the general population. Although age and degree of renal failure at onset of CV events or at end of follow-up did not differ between CVA+ and CVA- groups, cigarette smoking (24.5 [SD 24.3] vs 8.2 [14.7] pack-years, P<0.0001) and systolic blood pressure (159 [19] vs 148 [19] mmHg, P<0.001) were markedly higher in CVA+ patients. Similarly, mean plasma HDL-cholesterol was lower, whereas LDL-cholesterol, triglycerides, apoB, Lp(a), fibrinogen, and homocysteine levels all were significantly higher in CVA+ than in CVA-patients. Multivariate Cox analysis identified cigarette smoking, systolic pressure, HDL cholesterol, and fibrinogen as independent risk factors for developing CV accidents.Conclusions. Incidence of atherosclerotic CV complications is abnormally high in predialysis CRF patients, suggesting that the uraemic state per se is associated with atherogenesis. As several of the identified clinical and metabolic risk factors for such accidents are potentially remediable by specific therapeutic interventions, prophylactic measures should be initiated long before start of renal replacement therapy.

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.

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 refer red 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.

In order to assess the incidence of chronic renal failure (CRF) and the demographic characteristics of affected patients, a prospective, multicenter epidemiologic study was conducted with the cooperation of all nephrology and dialysis units in the Ile-de-France district, the total population of which is 10660000 inhabitants (source: national census, march 1990). Included were patients with a plasma creatinine (Pcr) concentration > or = 200 mumol/l referred during the one-year period from July 1, 1991 until June 30, 1992. The overall response rate was 98.5%. A total of 2775 adult patients were recorded, including 1780 males (64%) with a mean (+/- SD) age of 58.1 +/- 16.3 years and a mean Pcr of 447 +/- 214 mumol/l, and 995 females (36%) with a mean age of 59.2 +/- 16.4 years and a mean Pcr of 425 +/- 185 mumol/l. Age of patients was < 40 in 16%, 40-59 in 31%, 60-74 in 34% and > or = 75 years in 19%. Pcr was 200-399 mumol/l in 54%, 400-599 mumol/l in 25%, 600-799 mumol/l in 12% and > or = 800 mumol/l in 9%. The overall incidence of CRF was 260/million population/year, twice higher in males than in females (348 vs 179/10(6)/year, p < 0.001). Incidence of CRF dramatically rose with age in both genders, with figures as high as 1124 and 356/10(6)/year respectively in male and female patients aged > or = 75 years, vs 288 and 151/10(6)/year in patients aged < 40 years. A sequential evaluation was performed in a representative sample of 251 patients with initial Pcr > or = 300 mumol/l. End-stage renal failure (ESRF) was reached within one year in 99% of patients with PCr > 600, 49% with Pcr 500-599, 24% with PCr 400-499 and 11% with PCr 300-399 mumol/l. Based on these figures, the predicted incidence of ESRF within one year of referral was 864 out of the 2775 patients, an estimated annual incidence of 81 patients per million population. In conclusion, this prospective study affords the first direct information on the incidence of chronic renal failure and the demographic characteristics of patients with CRF in the Ile-de-France district. Due to the design of the study conducted only in nephrology units, the estimated figure of 81 new patients per million population per year reaching ESRF is a minimal evaluation. In view of the relentless aging of population in France, an incidence of at least 100 ESRF patients per million population per year is to be expected in the next future.

In order to assess the incidence of chronic renal failure (CRF) and the demographic characteristics of affected patients, a prospective, multicenter epidemiologic study was conducted with the cooperation of all nephrology and dialysis units in the Ile-de-france district, the total population of which is 10 660 000 inhabitants (source: national census, march 1990). Included were patients with a plasma creatinine (Per) concentration greater than or equal to 200 mu mol/l referred during the one-year period from July 1, 1991 until June 30, 1992. The overall response rate was 98.5%. A total of 2775 adult patients were recorded, including 1780 males (64%) with a mean (+/- SD) age of 58.1 +/- 16.3 years and a mean Per of 447 +/- 214 mu mol/l, and 995 females (36%) with a mean age of 59.2 +/- 16.4 years and a mean Per of 425 +/- 185 mu mol/l. Age of patients was < 40 in 16%, 40-59 in 31%, 60-74 in 34% and greater than or equal to 75 years in 19%. Per was 200-399 mu mol/l in 54%, 400-599 mu mol/l in 25%, 600-799 mu mol/l in 12% and greater than or equal to 800 mu mol/l in 9%. The overall incidence of CRF was 260/million population/year, twice higher in males than in females (348 vs 179/10(6)/year, p < 0.001). Incidence of CRF dramatically rose with age in both genders, with figures as high as 1124 and 356/10(6)/year respectively in male and female patients aged greater than or equal to 75 years, vs 288 and 151/10(6)/year in patients aged < 40 years. A sequential evaluation was performed in a representative sample of 251 patients with initial Per greater than or equal to 300 mu mol/l. End-stage renal failure (ESRF) was reached within one year in 99% of patients with PCr > 600, 49% with Per 500-599, 24% with PCr 400-499 and 11% with PCr 300-399 mu mol/l. Based on these figures, the predicted incidence of ESRF within one year of referral was 864 out of the 2775 patients, an estimated annual incidence of 81 patients per million population. In conclusion, this prospective study affords the first direct information on the incidence of chronic renal failure and the demographic characteristics of patients with CRF in the Ile-de-France district. Due to the design of the study conducted only in nephrology units, the estimated figure of 81 new patients per million population per year reaching ESRF is a minimal evaluation. In view of the relentless aging of population in France, an incidence of at least 100 ESRF patients per million population per year is to be expected in the next future.

OBJECTIVE:To determine the age- and gender-related incidence of chronic renal failure in a French urban area.METHODS:Prospective study of adult patients newly identified as having established, chronic renal failure defined by serum creatinine (Scr) > or = 200 mumol/l, with the cooperation of all nephrology and dialysis units in the Ile de France district (10,660,000 inhabitants) during a 1-year period.RESULTS:2775 patients (1780 males, 995 females) were referred with Scr > or = 200 mumol/l between July 1991 and June 1992, an overall incidence of 260/million population. 847 had advanced renal failure (Scr > or = 500 mumol/l) and 541 patients (19.5%) were > or = 75 years of age. The age-related incidence was 92, 264, 523 and 619/million population in the age groups 20-39, 40-59, 60-74 and > or = 75 years old, respectively. The annual incidence was twice as high in males than in females up to 75 years and three times as high in patients > or = 75 years (1124 vs 356/million population). Based on the proportion of patients reaching end-stage renal failure within one year of referral, the minimal estimation of the need for supportive therapy is 81/million/year.CONCLUSIONS:This epidemiological study in a large French urban area indicates an incidence of 260 patients per million population annually referred to nephrology units for chronic renal failure defined by Scr > or = 200 mumol/l, with a marked preponderance of males and a dramatic increase of incidence with age in both genders.

Hypothalamic-pituitary gonadal function is commonly altered in dialysis patients. Even though an improvement in general status and well-being has been noted after recombinant human erythropoietin supplementation, no significant changes were observed in the sex hormone profile. Pituitary gonadal axis as well as 5 alpha-reduced androgen glucosiduronates (i.e. 5 alpha-androstane,3 alpha,17 beta-diol and androsterone) profiles were studied in 23 young male stable dialyzed patients and compared to an age-matched group of healthy subjects. 5 alpha-Reduced androgen glucosiduronates are products of peripheral testosterone (T) metabolism and seem to be a useful tool in assessment of the male androgen status. Their polarity facilitates their urinary excretion, and their clearance is similar to the glomerular filtration rate in healthy men. We observed 1) a pituitary-Leydig cell dysfunction supported by normal serum estradiol and T levels, low free T, and increased LH levels; 2) an alteration of the dehydroepiandrosterone (DHEA) sulfate-DHEA interconversion, reflected by a dramatic decrease in DHEA while DHEA sulfate levels remained in the normal range; 3) an accumulation of 5 alpha-reduced androgen glucosiduronates, whose removal was impaired as shown by their very low sieving coefficients (< 0.012). Taken together, the above observations are consistent with alteration of spermatogenesis with respect to dialysis duration in which earlier elevated baseline serum LH levels indicate a primary defect in Leydig cell function.

Technetium-labeled heparin kinetics studies were undertaken in 12 hemodialyzed patients, where heparin was used over a long term (1 to 10 years) for anticoagulation of the extracorporeal circuit. The 99mTc-heparin (99mTc VECTOSCINT, Solabco Nuclear, Coutras, France) used has a 10 mCi activity and a labeling efficiency of more than 95%. Two healthy subjects served as control. After an i.v. bolus of 2 ml 99mTc-heparin, corresponding to 170 +/- 10 IU, radioactivity of kidney, liver, knee and shoulder was recorded with a gamma camera at t1-h, t3-h and t6-h during 120, 152 and 215 s, respectively. Radioactivity recorded was computerized, giving quantitative data for comparison. In hemodialyzed patients, accumulation of radioactivity (mean +/- SEM 10(6) x activity count) was significantly higher at the knee (11.3 +/- 1.1 vs. 4.9 +/- 0.4; p < 0.05; 13.4 +/- 1.1 vs. 5.7 +/- 0.7; < 0.02; and 14.7 +/- 0.8 vs. 5.3 +/- 0.6; < 0.001), and on the shoulder (17.3 +/- 1.1 vs. 10.7 +/- 1.4; p < 0.05; 19.9 +/- 1.0 vs. 10.9 +/- 1.7; < 0.01; 20.8 +/- 1.1 vs. 10.1 +/- 0.9; < 0.01) at t1-h, t3-h and t6-h, respectively, than in control subjects at the same areas. Although direct evidence is not in hand, accumulation of heparin in bone tissue due to renal excretion failure could play a role in mineral metabolism resulting in osteopenia in hemodialyzed patients.

The possibility of endotoxin transfer across haemodialysis membranes remains a controversial issue. Additional concern has arisen because of the recent introduction in clinical practice of highly permeable, synthetic dialysis membranes and of bacteria-contaminated bicarbonate concentrate with potential short-term and long-term hazards for haemodialysis (HD) patients. Therefore, we performed experiments in an in-vitro dialysis recirculation system using three different types of HD membranes, namely standard regenerated cellulose (Cuprophan, CU), polyacrylonitrile AN-69 (PAN), and polysulphone F-60 (PS). When radiolabelled lipopolysaccharide (125I M-LPS) from E. coli, together with 10 micrograms/ml unlabelled LPS, was added to the recirculating solution in the dialysis compartment, radioactivity could be detected in the blood compartment after 15 min and increased progressively with time up to respectively 6.7% (CU), 10.3% (PAN), and 10.3% (PS) of initial activity on the dialysate side. The addition of albumin to the solution on the blood side led to a decreased permeability of radioactivity (7.3% vs 10.3%), compared to the absence of albumin (tested only for PS membrane). Furthermore, 73% of 125I M-LPS transferred across the PS membrane in the presence of albumin was TCA-precipitable. In contrast, free iodine (Na 125I) incubated in an albumin-containing solution did not precipitate with albumin after the addition of TCA (precipitation of only 0.6%). Moreover, kinetics of transmembranous transfer of Na-125I were strikingly different from that of 125I M-LPS. Analysis by the method of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the blood side solution, after LPS addition in the dialysis solution and 30 min of back-filtration, revealed the presence of several silver-stainable and autoradiographic bands of low-molecular-weight range, probably LPS fragments. Finally, the presence of LPS in the dialysate compartment led to a moderate increase in interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF) concentrations in plasma as well as in monocyte culture supernatants after isolation from recirculating normal human whole blood exposed to CU, PAN, or PS membrane. In conclusion, our study provides evidence for the permeation of low-molecular-weight LPS subunits across cellulosic and non-cellulosic HD membranes. The clinical significance, if any, of such a transfer has, however, still to be demonstrated.