Recombinant human erythropoietin corrects anaemia during the first weeks after renal transplantation: a randomized prospective study

BACKGROUND.: Studies on the effect of recombinant human erythropoietin (rHuEpo)on haematopoiesis in patients with kidney transplants, havebeen limited to progressive chronic graft failure, late aftertransplantation. In the present prospective randomized study,the efficacy of rHuEpo in the correction of anaemia during thefirst weeks after renal transplantation (RTP) was evaluated. METHODS.: Patients were allocated to either an Epo-(n=14) or a non-Epo-treatedgroup (n=15). Epo (150 U/kg.week s.c.) was started at a haematocrit(Hct) <30% and was increased at weekly intervals by 30 U/kg.week,as long as Hct remained <25%. RESULTS.: In the Epo group, Hct increased from a nadir of 22±4%2 weeks after RTP to 30±4% at week 4 and to 36±4%at week 6 (P<0.001 and P<0.0001 respectively vs week 2).Corresponding values in the non-Epo group were 25±6%,28±6% (P=NS) and 32±6% (P<0.05 vs week 2) (overallevolution Epo vs non-Epo: P=0.038 by variance analysis). Thedifferences in Hct between the Epo and non Epo group were evenmore marked in patients without major complications (varianceanalysis P=0.009). The Epotreated patients required fewer post-surgicalblood transfusions (0.005 vs 0.014/days follow-up, P<0.05),in spite of greater post-surgical blood losses, especially atday 1 (P<0.05) and the presence of more major complications(7 vs 4) and a higher number of ganciclo vir-treated patients(4 vs 0; P<0.05). The maximum Epo dose after RTP was >2xhigher than the one required before RTP (197.1±45.1 vs85.0±76.0 U/kg.week; P<0.05). CONCLUSIONS.: It is concluded that rHuEpo during the first weeks after RTPis of benefit in the correction of the Hct in the early post-surgicalperiod, in spite of relative Epo resistance.     

Should CAPD be the first choice for dialysis in Romania? Audit of the Iasi 'C. I. Parhon' Dialysis Center: 1995-2000.

Peritoneal dialysis was first introduced in Romania in 1995.We are reporting data on patient and technique outcomes, basedon the 5-year experience of one of the first two Romanian continuousambulatory peritoneal dialysis (CAPD) centres. During this period,Romania had the highest rate of increase in renal replacementtherapy (RRT) and CAPD (28 times over baseline) in Europe: CAPDincrease in Romania vs Eastern Europe was 6.7 compared to asimilarly defined ratio of 5.6 for haemodialysis (HD). Between 1995 and 2000, at the ‘C. I. Parhon’ Hospitalin Iasi, 259 patients were started on HD and 102 on CAPD. The90 CAPD patients we followed were treated for a total of 1896months. 86.7% of the patients were alive on 31 July 2000—67.8%continuing on CAPD, 15.6% on HD and 3.3% transplanted. The 61patients still on PD on that date, represented 11.1% of theactual Romanian CAPD population and 31% of our RRT population(compared to 13.7% nationwide). The gross mortality rate was comparable to the mean calculatedfor the HD population nationwide. Mean survival of the CAPDpatients was 45.4±2.6 months (95% CI=40.4–50.4months). One-year and 5-year patient survival rates were 97.5%and 52.7% respectively, superior and similar to mean figuresnationwide. Mean technique survival was 36.6±0.6 months(95% CI=31.5–41.6 months). One- and 5-year technique survivalrates were 83.1% and 34.3% respectively. Technique failure wasmainly due to dialysis inefficiency: 50% of cases. Mean weeklyKt/V for the 5-year period was 1.92±0.21 while mean weeklycreatinine clearance was 61.2±12.4 ml/1.73 m²/week. Eighty-four episodes of peritonitis were recorded in 46 patients(0.25 episodes/patient/year); mean duration to peritonitis was23 months (95% CI=18.2–27.5). Malnutrition was noted (SGAscore) in 25.5% of the cases. Blood pressure (assessed by 24-hABPM) was adequately controlled in 83.3% of the patients. Leftventricular hypertrophy was ubiquitous (77.7%), but left ventriculardilatation and systolic dysfunction (fractioning shorteningindex <25%) were rare—4.4% and 3.3% respectively (similarin prevalence to the Iasi HD population). No statistically significantchanges in echocardiographic parameters were recorded betweenthe first and subsequent years on CAPD treatment. Peritoneal dialysis had a rapid increase in the last 5 yearsin Romania and particularly in the region of Moldova. Outcomesand complication rates are equal or superior to nationwide HDdata and comparable to distinguished centres of CAPD in economicallydeveloped countries. We conclude that, provided that optimalmedical practice is available, CAPD should be the RRT of choicein Romania, and that it represents the only solution to thecountry's limited dialysis resources.     

Oxalate elimination via hemodialysis or peritoneal dialysis in children with chronic renal failure

. Oxalate elimination and oxalate dialysance via hemodialysis (HD) or peritoneal dialysis (CAPD) has not been studied in detail in pediatric patients. We studied plasma oxalate, oxalate elimination, and oxalate dialysance in 15 infants and children undergoing CAPD (9 female, 6 male, aged 9 months to 18 years) and in 10 children on HD (4 female, 6 male, aged 7 – 18 years). Two children in each group had primary hyperoxaluria (PH). The mean duration of dialysis prior to examination was 12±11 months in CAPD and 31±23 months in HD patients. Bicarbonate HD was performed 5 h three times a week, CAPD consisted of five daily exchanges in 5 patients and four changes in the remaining 10 children (dwell volume 40 ml/kg body weight, 2.3 g/l glucose). Although oxalate dialysance was significantly higher in HD (mean 115.6 ml/min per 1.73 m² in HD versus 7.14 ml/min in CAPD), mean oxalate elimination per week was not different between both renal replacement therapies (3,478 μmol/1.73 m² surface area/week in CAPD versus 3,915 μmol/1.73 m² per week in HD). Oxalate elimination in patients with PH was between 6,650 and 9,900 μmol/week. Plasma oxalate remained elevated in both procedures [28 – 84 μmol/l in CAPD (92/148 in PH) and 33 – 101 μmol/l in HD (70/93 in PH)]. Oxalate elimination can be increased by a more frequent hemodialysis regimen. Received May 24, 1995; received in revised form and accepted October 31, 1995     

Pharmacokinetics of recombinant human erythropoietin in children with chronic renal failure

Basal erythropoietin (Epo) levels and single dose-pharmacokinetics of recombinant human erythropoietin (rhuEpo) were investigated in 8 predialysis (PD) patients (mean age 11.6±1.4 years) and in 8 patients on continuous ambulatory peritoneal dialysis (CAPD) (mean age 12.7±0.6 years). Basal Epo levels were found to be 1.0±0.0 mu/ml in PD group, 1.6±0.7 mu/ml in CAPD group and 8.5±1.8 mu/ml in control group. Following administration of 50 μ/kg rhuEpo (s.c.) serum Epo concentration (C_max) was 23.2±2.5 mu/ml in 18.5±2.6 hours (t_max) in PD patients and 9.9±0.8 mu/ml in 26.8±7.7 hours in CAPD patients. Mean elimination half-lives (t_1/2) were 13.3±1.9 hours and 13.5±3.0 hours in PD patients and CAPD patients, respectively. The volume of distribution (Vd) was 840.0±100.0 ml/kg; the clearance (Epo Cl) was 37.0±5.5 ml/kg/hour in PD patients. These values were significantly lower in PD patients than in CAPD patients (p<0.05) (Vd; 1500±240.0 ml/kg; Epo Cl 110±30.0 ml/kg/hour). During the course of CAPD, more efficient clearance of uraemic toxins that inhibit erythropoiesis and more rapid extraction of erythropoietin by erythroid precursors may cause higher Vd in CAPD patients than in PD patients.     

Recombinant human erythropoietin dosage in children undergoing hemodialysis and continuous ambulatory peritoneal dialysis

The efficacy of erythropoietin (EPO) in 11 children on hemodialysis (HD) and 8 on continuous ambulatory peritoneal dialysis (CAPD) (mean age 11.8 years) was compared. The initial EPO dose was 50 U/kg s.c. once a week; the time of observation was 24 weeks. In the CAPD group, the mean hemoglobin (Hb) level increased from 7.7±0.2 to 11.2±0.6 g/dl (P< 0.001) and hematocrit (Hct) from 22.3±1.0 to 32.6±1.4% (P<0.001), while in the HD group the mean Hb rose from 7.7±0.6 to 9.3±0.8 g/dl (P<0.001) and mean Hct from 22.7±2.3 to 27.6±2.8% (P<0.001) after 12 weeks of observation. An increase in Hb to over 10 g/dl was obtained in 87.5% of children on CAPD but in only 10% on HD after 8 weeks of EPO treatment. After 12 weeks of treatment, all children on CAPD had the target Hb level of more than 10 g/dl, while 7 children on HD required increased doses of EPO (100 U/kg per week). We conclude that the EPO dose of 50 U/kg given s.c. once a week is effective for children with anemia on CAPD but is insufficient for children on HD. Received June 17, 1996; received in revised form January 24, 1997; accepted March 4, 1997     

Increased renal allograft thrombosis in CAPD patients

In a retrospective analysis of 202 renal transplant proceduresin the years 1989–1992 we identified an excess of graftslost from primary renovascular thrombosis in patients receivingcontinuous ambulatory peritoneal dialysis (CAPD) compared tohaemodialysis (HD) patients (9 CAPD versus 0 HD, Chi-squared=9.63;P<0.01). All graft losses from thrombosis occurred within16 days of surgery. Possible predisposing causes were identifiedin three patients. Donor age was greater in CAPD patients losingtheir kidneys from thrombosis compared to the overall CAPD group[means (SD) years, 43.0(12.9) versus 29.1(15.8); P=0.01] whereasno significant difference in haematocrit, platelet count, antibodystatus, cyclosporin use, perioperative hypotension, primarydiagnosis, smoking, or diabetes mellitus was found. Data fromthe EDTA registry for 1990–91 show that graft loss fromprimary renovascular thrombosis in UK-treated patients was reportedin 7.1% of CAPD recipients compared with 1.8% in haemodialysis.We suggest that CAPD patients are at greater risk of graft lossfrom renovascular thrombosis than HD patients and may requiremore intensive fluid and anticoagulant treatment in the perioperativeperiod.     

Effects of haemodialysis and continuous ambulatory peritoneal dialysis on the plasma clearance of an albumin-bound furan dicarboxylic acid

Organic acids that are strongly bound to albumin are not removedby dialysis and the plasma concentrations of one such substance,a furan dicarboxylic acid (3-carboxy-4-methyl-5-propyl-2-furan-propanoicacid; 5-propyl FPA) have been measured by HPLC in healthy subjects(n=21), patients on regular haemodialysis (n=30), and patientstreated by continuous ambulatory peritoneal dialysis (n=21).The mean (±SD) concentrations of 5-propyl FPA were significantlyhigher in haemodialysis (95±44 µM) compared toCAPD patients (28±19 µM)) and both were higherthan in healthy individuals (14±7 µM). Haemoglobinconcentrations in CAPD patients were significantly higher thanin those on haemodialysis while these patients had significantlyhigher albumin concentrations than CAPD patients. The concentrationof 5-propyl FPA was positively correlated with the durationof dialysis for haemodialysis patients but not for CAPD patients.The lower concentrations of 5-propyl FPA in CAPD patients mayat least partly explain the higher haemoglobin levels foundin these patients.     

Survey of Blood Lead and Plasma Aluminium Concentrations in Patients of a Renal Unit

Blood lead and plasma aluminium concentrations have been measuredin patients with end-stage chronic renal failure treated byhaemodialysis (HD) or by continuous ambulatory peritoneal dialysis(CAPD) and in a control group of non-dialysed patients withchronic renal failure (CRF). Data on a group of subjects withnormal renal function is included for comparison. We have foundsignificantly increased mean blood lead and plasma aluminiumconcentrations in all patients with chronic renal failure comparedto a group with normal renal function. All blood lead concentrations were within the accepted safeexposure range of less than 1.8 µmol/l (380 µg/l)).There were significant differences among the patient groups:home HD, 0.60±0.25 µmol/l (124±52 µg/l);hospital HD, 0.39±0.31 µmol/l (81±64 µg/l);CAPD, 0.32±0.17 µmol/l (66±35 µg/l);CRF, 0.38±0.20 µmol/l (79±41 µg/l);normal, 0.24±0.11 µmol/l (50±23 µg/l).Correction of the blood lead results for haemoglobin accentuatesthese differences (i.e. hospital HD, 4.61±3.25 nmol/g(0.96±0.67 µg/g); CRF, 3.05±1.46 nmol/g(0.63±0.30 µg/g); normal, 1.65±0.70 nmol/g(0.34±0.14 µg/g). Plasma aluminium concentrations show a similar pattern: homeHD, 1.09±0.70 µmol/l (29.4±18.9 µg/l);hospital HD, 0.81±0.58 µmol/l (21.9±15.7µg/l); CAPD, 0.34±0.34 µmol/l (9.2±9.2µg/l); CRF, 0.18±0.09 µmol/l (4.9±2.4µg/l); normal, 0.09±0.07 µmol/1 (2.4±1.9µg/l). The duration of dialysis treatment is an important determinantof metal accumulation: there is a significant positive correlationbetween the duration of dialysis treatment and both blood lead:haemoglobinratio (r=0.48, P<0.01) and plasma aluminium (r=0.61, P<0.01)concentrations. There is also a significant negative correlation(r= –0.59, P<0.01) between urine volume and plasmaaluminium for haemodialysis patients, but not for peritonealdialysis patients. Urine volume shows no relationship to bloodlead. Age has no effect on lead accumulation in any of the patientgroups, but there is a significant correlation of age to bloodlead in the normal renal function group (r=0.47, P<0.01).The effect of sex and hypertension on metal concentrations isalso discussed. It is considered probable that the dialysate is a major factorcontributing to the accumulation of both elements. The possiblelong-term clinical significance of these findings remains tobe determined.     

Kidney transplantation decreases the tissue level of advanced glycosylation end-products

We have studied the effect of chronic renal failure (CRF) andkidney transplantation on advanced glycosylation end-products(AGE) measured as collagen-linked fluorescence (CLF) in theskin and peritoneum of non-diabetic patients. Of 34 patientswith CRF, 18 were studied before the commencement of peritonealdialysis (CRF group), and 16 were studied 5–31 weeks afterkidney transplantation (transplant group). The control groupconsisted of 24 patients with normal renal function. Skin CLFin the CRF group (20.9 ± 2.02 U/mg) was higher than inthe control (8.52±1.08 U/mg, P = 0.0001) and transplantgroups (10.7 ± 2.43 U/mg, P=0.003). Peritoneal CLF inthe CRF group (30.5 ± 5.64 U/mg) was higher than in thecontrol group (16.1 ±2.25 U/mg, P=0.031) but was notdifferent from the transplant group (19.4 ± 3.66 U/mg,P=0.11). Peritoneal CLF of control and transplant groups werenot different (P= 0.45). The results of this study suggest thatrestoration of renal function affects tissue AGE levels.     

The effect of isolated ultrafiltration on Doppler-derived indices of left ventricular diastolic function

Background. Haemodialysis (HD) is associated with acute changessimultaneously in fluid status (ultrafiltration) and in manybiochemical parameters (dialysis). Reports on the effects ofthese changes on left ventricular (LV) diastolic function arescant. This study evaluated the effect of isolated ultrafiltration(UF) and subsequent HD with minimal fluid removal on Doppler-derivedindices of LV diastolic function in patients who were asymptomaticand stable on HD. Methods. In 11 HD cases, the 5 h treatment session was dividedinto a 2.5 h period of fluid removal without dialysis (UF phase)and 2.5 h of dialysis with minimal fluid removal (HD phase).We examined the following parameters of LV diastolic functionechocardiographically: early rapid filling (Emax), atrial peakfilling (Amax), Emax/Amax ratio, isovolumic relaxation time(IVRT) and deceleration time of the E-wave (DT). Results. During the UF phase, Emax decreased from 0.82±0.2to 0.62±0.2 m/s (P = 0.003), Amax decreased from 0.72±0.2to 0.63±0.2 m/s (P = 0.042) and the ratio Emax/Amax didnot change (P = NS). During the HD phase, Emax increased from0.62±0.2 to 0.72±0.2 m/s (P = 0.018), Amax increasedfrom 0.63±0.2 to 0.70±0.3 m/s (P = NS) and theEmax/Amax ratio remained unchanged (P = NS). IVRT was prolongedin 10 out of 11 patients at the start of the UF phase and itwas further prolonged from 142±40 to 171±55 ms(P = 0.03) during the UF phase. IVRT did not alter during theHD phase (P = NS). During the UF phase, DT increased from 175±83to 244±119 and it decreased from 244±119 to 209±98in the HD phase, but both changes were statistically insignificant.No statistically significant correlations were observed betweenthe changes in the Doppler indices of diastolic function andchanges in biochemical parameters during the HD phase. Conclusions. UF affects the parameters Emax, Amax and IVRT usedto evaluate LV diastolic function. The changes in Emax and Amaxduring the HD phase are due to fluid refilling from tissuesinto the blood space, HD as such having no effect on Dopplerindices. However, isolated UF or HD does not affect the Emax/Amaxratio. Emax and IVRT seem to be the most volume-sensitive parameters.     

A registry of haemodialysis patients and the progress of haemodialysis services in Lithuania.

Background. Until 1990, haemodialysis (HD) in Lithuania wasunderdeveloped, but after independence, development of HD started.Until 1996, no precise data about HD patients in Lithuania wereavailable. In order to create a registry of HD, we started tocollect data about dialysis services and HD patients in 1996.Every collection of data was followed by distribution and discussionof the results within the nephrological community. This studydescribes the changes of Lithuanian HD between 1996–2002. Methods. Between 1996 till 2002 all HD centres in Lithuaniawere annually visited and data were collected about all HD patients(response rate of 100%). The evaluation of the results duringour observational study was made according to the European BestPractice Guidelines. During annual conferences for nephrologists,the guidelines and data of our HD registry were presented. Results. There was an increase in the number of HD stations(from 25 p.m.p. to 75 p.m.p., P<0.001), in HD patients (from60 p.m.p. to 237 p.m.p., P<0.001) and in the incidence ofnew HD patients (from 54.3 p.m.p. to 103 p.m.p., P<0.01).The mean age of HD patients increased from 47.2±16.1years in 1996 to 56.0±14.9 in 2002 (P<0.001). Themain underlying cause of ESRD was chronic glomerulonephritis,but its rate decreased from 54.5% in 1996 to 27.5% in 2002 (P<0.001).The percentage of diabetics increased from 7.1% to 16.4%, P<0.05,and in hypertensive nephropathy from 3.1% to 10.9%, P<0.05.We observed improvement of the quality of HD in Lithuania duringthese 5 years. The percentage of patients on bicarbonate HDincreased from 7.1% in 1996 to 100% in 2002 (P<0.001). Thepercentage of patients receiving more than 12 h HD/week increasedfrom 30.8% in 1996 to 53.5% in 2002 (P<0.001). The mean Kt/Vin 1999 was 0.81±0.53, but it increased in 2002 to 1.22±0.27,P<0.001. In 2002, 84.6% of all HD patients were examinedfor HB_sAg, 82.3% for anti–HCV, 31.2% for anti-HB_s and57.1% for anti-HB_c. The percentage of patients receiving phosphatebinders increased from 65.2% in 1996 to 84.4% in 1997 and 90.5%in 2002. Serum parathyroid hormone (PTH) levels were measuredin 27.3% of HD patients in 1999 but in 85.2% of patients in2002. The mean haemoglobin (Hb) concentration increased from92±15.4 g/l to 105±14.7 g/l; the percentage ofpatients with Hb>100 g/l increased from 27.5% to 64% in 2001.The percentage of HD patients receiving epoetin was 94.6% in2001 as compared with 78% in 1997. There was a marked increasein the use of intravenous iron (from 7.5% patients in 1997 to70.8% in 2000). The mean weekly dose of Epo was lower in HDpatients receiving intravenous iron than in patients receivingoral iron. Conclusions. Over the period of 1996–2002 the HD servicessignificantly expanded in Lithuania. The introduction of EuropeanBest Practice Guidelines and the establishment of a HD registrywith feedback of the results stimulated the significant progressin the quality of HD and in the management of the patients.     

Increased prevalence of HCV antibodies in dialyzed Ashkenazi Jews--a possible ethnic predisposition

BACKGROUND.: The prevalence of hepatitis C (HCV) antibodies in dialysis patientsis considerably higher than that found among healthy blood donors.This increased seroprevalence has been correlated to increasedduration of dialysis, mode of dialysis and to the number ofblood transfusions administered. However, factors other thannosocomial ones also seem to play a part in disease transmission.The role of the patient's ethnic origin, possibly reflectingon his/her genetic makeup has received scant attention. In thisstudy, HCV seroprevalence in our dialysis population, whichconsists of three major ethnic subgroups (Ashkenazi Jews, SephardiJews and Arabs), was examined. METHODS AND RESULTS.: Altogether HCV seropositivity was determined in 120 dialysedpatients—65 males/55 females (76 hemodialysis, 44 CAPD),using second generation ELISA confirmed by RIBA-2. Mean agewas 59.7±15.7 (range 16–86 years). Patients hadto have been on dialysis for a minimum of 3 months (mean duration45.2±44.5 months). Patients whose end-stage renal diseasewas due to diabetic nephropathy (DN) or those who had previouslybeen transplanted (TP) were considered as separate groups andcompared to the group as a whole. Of the 120 patients, therewere 49 Ashkenazi Jews (40.8%), 57 Sephardi Jews (47.5%) and14 Arabs (11.7%). Overall HCV prevalence was 21.7% (26/120)with a significantly greater prevalence in HD compared to CAPD(30.3 vs. 6.8%, P>0.01). Respective values for AshkenaziJews, Sephardi Jews and Arabs were 30.6, 15.8, and 14.3% (P>0.01,Ashkenazi Jews vs. Sephardi Jews and Arabs). DN had a lower3.7% while TP had a higher 46.1% prevalence compared to thegroup as a whole (P>0.01). In general, the increased frequencyof anti HCV antibodies was significantly correlated to the durationof dialysis and the number of blood transfusions administered.This, however, was not the case in the greater prevalence ofHCV found in Ashkenazi Jews compared to Sephardi Jews and Arabswhich was independent of the above factors and the mode of dialysis. CONCLUSION.: Our results showing increased HCV seropositivity in AshkenaziJews compared to Sephardi Jews and Arabs, suggest that ethnicfactors might predispose to HCV transmission and infectivity.     

Alternative strategies to evaluate the cost-effectiveness of peritoneal dialysis and hemodialysis

Background Dialysis treatment requires considerable resources and it is important to improve the efficiency of care. Methods Files of all adult end-stage renal disease (ESRD) patients who entered dialysis therapy between 1991 and 1996, were studied and all use of health care resources was recorded. A total of 138 patients started with in-center hemodialysis (HD) and 76 patients with continuous ambulatory peritoneal dialysis (CAPD). Four alternative perspectives were applied to assess effectiveness. An additional analysis of 68 matched CAPD-HD pairs with similar characteristics was completed. Results Cost-effectiveness ratios (CER; cost per life-year gained) were different in alternative observation strategies. If modality changes and cadaveric transplantations were ignored, annual first three years’ CERs varied between $41220–61465 on CAPD and $44540–85688 on HD. If CAPD-failure was considered as death, CERs were $34466–81197 on CAPD. When follow-up censored at transplantation but dialysis modality changes were ignored, CERs were $59409–95858 on CAPD and $70042–85546 on HD. If observation censored at any change of primarily selected modality, figures were $57731–66710 on CAPD and $74671–91942 on HD. There was a trend of lower costs and better survival on CAPD, the only exception was the strategy in which technical failure of modality was considered as death. Figures of the matched CAPD-HD pairs were very close to the figures of the entire study population. Conclusions Compared to HD, CERs were slightly lower on CAPD.     

Does diurnal variation in blood pressure exist in CAPD patients?

The existence of diurnal variation in CAPD remains controversial.We therefore attempted to delineate the blood-pressure (BP)pattern in CAPD patients by ambulatory blood-pressure monitoring(ABPM). Initially ABPM was performed in 31 patients (21 M, 10F), mean age 65.4 years (26–87) using the Spacelabs model90207. The maximal normal BP preset on the recorder was 140/90mmHg. Daytime and night-time readings, recorded every 30 min,were defined as those from 0600 to 2100 and 2100 to 0600 hoursrespectively. Mean duration of dialysis was 15.2 months (3–76). There were 14 hypertensive patients, defined as a basal BP >140/90 mmHg, or those on antihypertens-ive medications. Takingthe group as a whole a significant difference between day andnight-time readings was found as regards minimal systolic BP(118 versus 107.6 mmHg), maximal systolic BP (181.6 versus 171.2mmHg), mean diastolic BP (83.9 versus 79.6 mmHg), and maximaldiastolic BP (121.7 versus 104.5 mmHg), P<0.05. Diurnal variation,defined in the initial study as a 10% decrease of MAP occurringduring any consecutive 4-h period, was present in 21 patients.In three the diurnal variation manifested as a paradoxical reductionof BP during the day. The only significant difference betweenthose with diurnal variation and those without was the durationof dialysis, being 19.2 ±19.9 versus 13.3 ±17.3months respectively, (P<0.05). In a second study 18 hypertensive CAPD patients were subjectedto ABPM. Nine of them had participated in the first study. Thesepatients were specifically asked to detail their periods ofsleep and arousal. Diurnal variation was here defined as a 10%decrease of MAP occurring 2 h after the onset of sleep. Diurnalvariation was found to exist in 10 patients (55%). Comparingthe day to night-time readings in this group, no significantdifferences were found in mean systolic and MAP. When, however,the arousal versus sleep period readings were compared, a significantdifference was observed in mean diastolic BP (83±14 versus77±17mmHg, P<0.01), and in the MAP (104 ± 18versus 98±20.5 mmHg, P<0.01). The mean systolic BPjust failed to reach statistical significance (141±26versus 137±30 mmHg) due probably to the small samplesize. We conclude that diurnal variation exists in the majority ofCAPD patients. Our findings support the concept that the setpoint model of diurnal variation, in which the major determinantis activity or arousal is the operative one in these patients.Due to disordered sleep patterns in patients on CAPD, diurnalvariation might thus be better elicited when taking into accounta decrease of MAP occurring during any consecutive 4-h period.     

Serum concentrations and peritoneal loss of growth hormone and growth-hormone-binding protein activity in older adults undergoing continuous ambulatory peritoneal dialysis: comparison with haemodialysis patients and normal subjects

Serum concentrations and peritoneal losses of growth hormone(GH) and of growth-hormone-binding protein (GH-BP) activityin 13 patients undergoing continuous ambulatory peritoneal dialysis(CAPD) were compared with those of 13 patients on haemodialysisand 13 normal subjects. The individuals in the three groupswere matched by age (40–83 years), gender, and serum glucoseconcentration. In addition CAPD and haemodialysis patients werematched by haematocrit, serum creatinine and albumin concentrations,and period of time on dialysis (0.5–127 months). GH inthe serum and in the peritoneal effluent were measured by radioimmunoassay(RIA) and NB2 bioas-say. GH-BP activity was analysed by bindingassay and expressed as a percentage of the specific bindingof GH. In the haemodialysis patients, serum GH was significantlygreater and serum GH-BP activity significantly less than inthe CAPD patients and control subjects. Between the two lattergroups no significant differences in GH or in GH-BP activitywere observed. GH bioactive/immunoactive ratios in the threegroups were similar. Both GH and GH-BP were detected in theperitoneal effluent of CAPD patients, in whom an overnight (8-h)peritoneal loss of GH (8.0±1.4x 10^–3 ug/h/1.73m2) was strongly correlated with serum GH (r= 0.840). CirculatingGH and GH-BP activity were influenced by serum creatinine andhaematocrit. In addition a positive relationship was observedbetween GH-BP activity and body mass index and between GH andtime on dialysis. These data reaffirm that older adults undergoinghaemodialysis, unlike CAPD patients, exhibit persistent abnormalitiesin GH-GH-BP axis. The peritoneal losses of GH and GH-BP thatoccur during CAPD do not affect their respective serum concentrations.     

Leptin in CAPD patients: serum concentrations and peritoneal loss.

BACKGROUND: To determine whether serum leptin concentrations in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are influenced by peritoneal loss of leptin and to compare serum leptin levels of normal subjects with those of patients receiving renal replacement therapy such as haemodialysis (HD), CAPD, or kidney transplantation. SUBJECTS AND METHODS: Eighty-four individuals were investigated: six females and 14 males on standard CAPD; 13 females and 13 males on chronic HD; 10 female and eight male kidney transplant recipients, and 10 female and 10 male subjects as controls. Morning serum, 8-h and 24-h samples of peritoneal fluid concentrated to 6-20-fold by Centricon 3 (cutoff 3000 daltons), and 24-h urinary concentrations of leptin were measured with commercial RIA (Linco Research, Inc., USA). Venous blood and peritoneal fluid samples of albumin, beta2-microglobulin, glucose, urea, and creatinine were determined by standard laboratory techniques. Serum insulin levels were measured by radioimmunoassay. RESULTS: Patients (men and women) on CAPD and after kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/BMI ratios than control subjects. These increased values did not reach statistical significance in HD patients. Serum leptin concentrations were correlated very significantly with BMI in all cases (r=0.380, P<0.001). Moreover, in CAPD patients (r=0.630, P<0.007) and in HD patients (r=0.668, P<0.005), but not in kidney transplant recipients or control subjects, significant correlations were observed between serum leptin and insulin concentrations. Residual renal function (RRF) in the range 0-12.8 ml/min and serum beta2-microglobulin levels in the range 7.9-47.1 mg/l did not influence serum leptin levels in CAPD and HD patients. As expected, leptin was detected in the peritoneal fluid of CAPD patients. Twenty-four-hour peritoneal loss (30.95+/-21.05 ng/min) and 24-h peritoneal clearance (0.01+/-0.01 ml/kg/min) of leptin account for only 3.9% of estimated whole-body leptin production rate and 0.7% of leptin clearance from plasma respectively. Twenty-four-hour urinary losses of leptin in CAPD patients were negligible, accounting for 5.6+/-1.8% (range 0.3-15.2%) of total (peritoneal and urinary) loss of this hormone. CONCLUSIONS: These findings suggest that serum leptin levels are not affected by continuous peritoneal loss of leptin during CAPD and that insulin resistance and hyperinsulinaemia contribute to elevated serum leptin concentrations in CAPD and HD patients. The aetiology of increased serum leptin levels in kidney transplant recipients is probably different from that in dialysis patients.     

Peritoneal dialysis catheters: a comparison between percutaneous and conventional surgical placement techniques

Percutaneous peritoneal dialysis catheter (PDC) placement isa well-tolerated, rapidly performed side-room procedure thatallows the rapid initiation of dialysis without the delay imposedin co-ordinating a surgeon, theatre time, and theatre staff.We retrospectively reviewed the clinical outcome of 230 PDCinserted over a 30-month period. Fifty were placed percutan-eously(group P) and 180 were placed using conventional surgical techniques,107 in patients commencing CAPD (group A) and 73 in patientspreviously established on CAPD (group B). Total experience accumulatedwas 2563 patient months: 270 patient months group P, 1381 patientmonths group A, 912 patient months group B. Percutaneous PDCinsertion was non-elective, and reserved for patients unfitfor general anaesthesia or haemodialysis. Group P patients wereolder (P<0.001) and had increased early mortality (P<0.005)due to underlying pathology. Death and early mechanical failurecontributed to a shorter mean duration of catheter use in groupP (9.0 ± 2.3 months compared to 15.3 ± 9.6 monthsgroup A and 17.3 ±9.7 group B) (P<0.05). The peritonitisrate was similar in group P (1 per 6.75 patient months) andgroup B (1 per 7.4 patient months) but significantly lower ingroup A (1 per 15.7 patient months) (P<0.01). We concludethat percutaneous PDC placement provides a safe, reliable accessfor peritoneal dialysis and is especially suitable for ill patientswho would not tolerate general anaesthesia.     

Effect of hyperparathyroidism on response to erythropoietin in children on dialysis

The response to recombinant human erythropoietin (rHuEPO), 50 units/kg thrice weekly, was studied prospectively in 17 children and adolescents with end-stage renal disease who were either transfusion dependent or had hematocrits <25%. For convenience, rHuEPO was given intravenously to 12 hemodialysis (HD) patients and subcutaneously to 5 peritoneal dialysis (PD) patients. Blood pressure, hematocrit, iron indices, and serum potassium, calcium, phosphorus, alkaline phosphatase, urea nitrogen, and intact parathyroid hormone (PTH) were monitored serially. When serum ferritin was <100 ng/ml during therapy, 6 patients received iron supplementation. rHuEPO therapy eliminated frequent transfusions in all patients; 11 of 17 patients reached the target hematocrit of 30% – 33% by week 16 of rHuEPO, 50 units/kg thrice weekly. The 5 PD patients treated subcutaneously reached target at week 6±1; 6 HD patients treated intravenously reached target at week 11±3; 6 additional HD patients never reached target at this dose; 5 of 6 had pre-rHuEPO serum PTH levels >400 pg/ml, significantly higher than those of the other patients (P <0.005); 3 of 6 later reached a hematocrit of 30% – 33% after the rHuEPO dose was increased to 120 – 130 units/kg thrice weekly. We conclude that most pediatric dialysis patients can be treated successfully with rHuEPO, 50 units/kg thrice weekly, unless the serum PTH concentration is markedly elevated, in which case a higher dose is likely to be needed. Received May 8, 1997; received in revised form September 16, 1997; accepted September 19, 1997     

Clinical evaluation of an optimized 1.1% amino-acid solution for peritoneal dialysis

A significant percentage of dialysed patients have inadequateprotein intake. One strategy for treating the protein malnutritionin peritoneal dialysis patients is to replace glucose in thedialysis solution by amino acids. A new peritoneal dialysissolution containing 1.1% amino acids in a formulation optimizedfor renal patients and with a lactate concentration of 40 mmol/lhas been evaluated. Fifteen CAPD patients completed a non-randomizedprospective 3-month study. Each patient received 2 litres ofthe optimised 1.1% amino acid solution for the second exchangeof the day with a dwell time of 5–6 h. Indicators of efficacywere serum albumin and transferrin. After 3 months of intraperitonealamino acids, serum albumin levels significantly increased from32.7±2.3 to 35.1±2.2 g/l (mean±SD; p>0.01).This occurred in parallel with a significant increase in transferrinlevels from 2.21±0.26 to 2.39±0.27 g/l (P>0.05).As expected, urea rose from 23.7±6.8 to 29.9±9.4mmol/l. Interestingly bicarbonate did not change (25.5±4.2versus 25.2±3.3 mmol/l). These results suggest that theoptimized formulation is effective in improving nutritionalparameters in CAPD patients while avoiding unwanted side-effectssuch as acidosis.     

Importance of iron supply for erythropoietin therapy

BACKGROUND.: rHuEpo and iron therapy corrects renal anaemia. However, dosage,route of administration, and monitoring of iron and rHuEpo therapyin uraemic patients remains controversial. METHODS.: Therefore a 22-month i.v. iron substitution trial, subdividedinto four study periods, was initiated in 64 iron-depleted chronichaemodialysis (HD) patients receiving i.v. rHuEpo therapy. Withinthe first period (6 months) patients were treated with high-doseiron (100mg at the end of HD treatment, mean cumulative i.v.iron saccharate dosage was 2538±810 mg per patient) inorder to replete the iron stores. During the 2nd period (6 months)the available iron pool was maintained with low-dose iron byadministration of 10, 20, or 40 mg iron at each HD, dependingon haemoglobin, serum ferritin and transferrin saturation levels.During the 3rd period (4 months), the iron-replete patientswere randomized to i.v. or s.c. route of rHuEpo administration.During the 4th period (3 months) iron substitution was omittedto exclude severe iron overload. RESULTS.: In the first study period, high-dose iron therapy dramaticallyreduced the weekly rHuEpo requirement by 70% of the initialdose (from 217±179 to 62.6±70.2 U/kg/week). Inthe 2nd period iron storage pools were easily maintained. Serumferritin and transferrin saturation levels remained stable duringthis study period. Randomization for thrice-weekly i.v. or s.c.administration of rHuEpo in the 3rd study period revealed comparableefficacy for both administration routes in iron-replete patients.In well-nourished patients (serum albumin >40 g/1) withouthyperparathyroidism (parathyroid hormone levels < 100 pg/ml),50–60 U/kg/week rHuEpo were required in contrast to >100 U/kg/week in patients with hyperparathyroidism. In the 4thstudy period, withdrawal of iron administration led to a rapiddecrease of serum ferritin and transferrin saturation levels,indicating the absence of severe iron overload. CONCLUSIONS.: Long-term thrice-weekly i.v. low-dose iron therapy (10–20mg per HD treatment) proved to be a very effective, economicaland safe treatment schedule for iron-replete HD patients. Intravenousand s.c. rHuEpo therapy was equally efficacious in iron-replete,well-nourished patients. HD patients with increased parathyroidhormone levels require significantly more rHuEpo than HD patientswith parathyroid hormone levels values <100 pg/ml).