Gene/Protein Disease Symptom Drug Enzyme Compound
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Haemodialysis patients with iron overload sometimes develop resistance to erythropoietin therapy due to 'functional iron deficiency'. It is known that this resistance may be overcome by iron supplementation; however, the latter could worsen haemosiderosis. Therefore, we treated four iron-overloaded haemodialysis patients who had developed relative resistance to erythropoietin (among whom three had features of 'functional iron deficiency') with ascorbic acid (500 mg intravenously after haemodialysis, 1-3 times a week). The erythropoietin doses were voluntarily kept unchanged during the study. After a latency of 2-4 weeks, haematocrit and haemoglobin had increased respectively from 26.5 +/- 0.7 to 32.7 +/- 0.4 vol% and from 8.8 +/- 0.3 to 10.8 +/- 0.2 g/dl (means +/- SEM, P < 0.001). While serum ferritin remained unchanged, transferrin saturation increased from 27 +/- 7 to 54 +/- 12% (P < 0.05), suggesting that ascorbic acid supplementation had allowed mobilization of iron from tissue burdens. In one patient, haematocrit declined after withdrawal of vitamin C and increased again after rechallenge. Also, ascorbate supplementation was continued after the study in two patients and allowed the erythropoietin doses to be decreased, 8 and 11 weeks, respectively, after the start of the trial. When a control group of seven patients with normal iron status and without resistance to erythropoietin were challenged in the same manner with ascorbate, no elevation of haematocrit or transferrin saturation was noted. We conclude that ascorbate supplementation may circumvent resistance to erythropoietin that sometimes occurs in iron-overloaded patients, in particular, in the setting of 'functional iron deficiency'.
Nephrol Dial Transplant 1995
PMID:Resistance to erythropoietin in iron-overloaded haemodialysis patients can be overcome by ascorbic acid administration. 852 94

The migration of leukocytes, including polymorphonuclear neutrophils and monocytes, into the peritoneal cavity is a key event of intraperitoneal inflammation. We investigated the levels of two members of the chemokine family, interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), in the dialysate effluent of 18 continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis and compared them with chemokine levels in noninfected CAPD effluent. Being a major source of inflammatory cytokines, we also isolated peritoneal macrophages from peritonitis effluent to determine the mRNA expression directly after isolation. The mean (SEM) concentrations of IL-8 and MCP-1 were significantly higher in the effluent of peritonitis patients than in noninfected effluents MCP-1: 22.5 +/- (6.27) versus 0.37 +/- (0.1) ng/mL and IL-8: 2.39 +/- (1.15) versus 0.04 +/- (0.01) ng/mL. Northern blot analysis of isolated effluent macrophages revealed strong signals for MCP-1 and IL-8. Our findings showed that CAPD effluent from patients with peritonitis contains markedly elevated MCP-1 and IL-8 levels, suggesting that these chemokines participate in leukocyte recruitment during CAPD peritonitis. Isolation of mRNA of peritonitis-derived peritoneal macrophages revealed strong signals for MCP-1 and IL-8, suggesting that macrophages are a major source of these inflammatory mediators.
Adv Perit Dial 1995
PMID:MCP-1 levels are elevated in peritonitis fluid from CAPD patients due to secretion by peritoneal macrophages. 853 2

The relationship between insulin-like growth factor-I (IGF-I), body weight, and serum albumin was studied in 17 patients on continuous ambulatory peritoneal dialysis (CAPD) and 17 patients on hemodialysis. Patients were matched for gender, age (33-83 years), body mass index (16.7-36.1 kg/m2), hematocrit, concentrations of serum growth hormone, and duration of dialysis (1-210 months). Serum IGF-I concentration was measured by radioimmunoassay (Incstar) and albumin by a standard laboratory technique. CAPD patients had significantly lower serum albumin concentrations than hemodialysis patients, whereas IGF-I levels in the two groups were similar and did not differ from those in 18 normal subjects. We did not find significant positive correlations between IGF-I and serum albumin levels in CAPD or in hemodialysis patients. On the other hand, IGF-I showed a strong positive correlation with body weight (for the CAPD group r = 0.523; for both groups together r = 0.493). Both groups (CAPD and hemodialysis) and CAPD patients who weighted less than 60 kg (44%) had significantly lower serum IGF-I levels (113.5 +/- 10.2 and 108.8 +/- 15.7 micrograms/l +/- SEM, respectively) than patients who weighed 60-80 kg (38.3%; 181.2 +/- 20.9 and 196.6 +/- 27.2 micrograms/L +/- SEM, respectively) or above 80 kg (17.6%; 205.2 +/- 37.7 and 229.5 +/- 43.5; micrograms/L +/- SEM, respectively). It therefore appears that a low serum IGF-I level is a better indicator of malnutrition in CAPD and hemodialysis patients than low serum albumin.
Adv Perit Dial 1995
PMID:Insulin-like growth factor-I in patients on CAPD and hemodialysis: relationship to body weight and albumin level. 853 12

Effective peritoneal capillary blood flow (EPBF) was evaluated by calculating the diffusive mass transport coefficient of carbon dioxide during intermittent peritoneal dialysis (IPD) performed with the intraperitoneal administration of sodium nitroprusside (NP), chlorpromazine (CP), or isoproterenol (IP) in the doses 5, 2.5, and 0.5 mg/L, respectively. Peritoneal transfer rates of substances of different molecular size and charge were simultaneously examined and compared with EPBF. EPBF (mL/min) was 220 +/- 40 (+/- SEM) for NP (n = 11), 224 +/- 29 for CP (n = 10), and 243 +/- 35 for IP (n = 10). These values did not differ significantly from those obtained during dialysis without drugs (223 +/- 22 mL/min, n = 20). NP, CP, and IP did not cause any significant changes in peritoneal transfer of carbon dioxide. Transfer rates of bicarbonate and total carbon dioxide were increased only with NP. All drugs enhanced the peritoneal removal of sodium, potassium, urea, and uric acid. Total protein loss was enhanced by all drugs except IP. With statistically similar EPBF during dialysis, the augmenting effect of NP and IP on small solute removal was the most pronounced. These results indicate that EPBF is not a major factor in the changes in peritoneal transfer rates during dialysis performed with NP, CP, or IP.
Adv Perit Dial 1995
PMID:Peritoneal blood flow and peritoneal transfer parameters during dialysis with administration of drugs. 853 23

The effect of different dialysis modes on kinin kinetics was studied in seven stable haemodialysis patients treated with AN69 dialysers and ACE inhibitors (ACEI). AN69 haemodiafiltration with calcium-enriched substitution (HDF), AN69 haemodialysis with 1.75 (HD 1.75) and 1.50 (HD 1.50) mmol/l dialysate calcium, AN69 haemodialysis with 1.25 mmol/l dialysate calcium and substitution of 2.25 mmol/h calcium (HD+Ca), and cellulose acetate haemodiafiltration (CA HDF) were compared. Dialysis was uneventful in all patients. During dialysis, serum calcium, sodium, pH, albumin, and bradykinin were measured at the start and after 5 min at arterial, venous, and postinfusion side of the extracorporeal circuit. Serum predialysis bradykinin was 107 +/- 18fmol/ml (mean +/- SEM) in patients on HDF, 61 +/- 9 fmol/ml in patients on HD 1.50, 49 +/- 13 fmol/ml in patients on HD 1.75, 35 +/- 3 fmol/l in patients on HD+Ca, and 75 +/- 27 fmol/ml in CA HDF. No significant change of mean bradykinin levels occurred after 5 min at the arterial and venous side of the dialyser or postinfusion. Individual high bradykinin levels, up to 2672 fmol/ml, were observed but without clinical consequences, suggesting that the threshold value is difficult to determine. No significant correlations were evidenced between bradykinin levels and any of the biochemical measurements. The present data show an intraindividual variability of the bradykinin levels with variation coefficients ranging from 0.386 to 2.783. The present study illustrates that haemodialysis and haemodiafiltration with AN69 in ACEI-treated patients, under the present conditions, does not result in anaphylactoid reactions or in a clinically significant release of bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1995
PMID:Kinin kinetics during different dialysis protocols with AN69 dialyser in ACEI-treated patients. 855 90

Rapid onset of acute peritoneal dialysis (PD) in the infant population is, in part, dependent upon equipment availability. From March 1991 until June 1995, over 200 children at the University of Michigan have undergone dialysis for acute renal failure. Of these children, 29 infants (mean +/- SEM)(age 4.5 +/- 1.3 months; weight 4.8 +/- 0.5 kg) have had placement of an acute 5 French Cook PD catheter for dialysis. Complications including inadequate inflow in one case, bleeding in one case, and accidental removal in one case were infrequent. Duration of the placed catheters was 9.9 +/- 2.7 days, without the problems associated with chronic placement of a stiff catheter. Onset of dialysis occurred within minutes due to rapid access. We conclude that the placement of a 5 French Cook acute PD catheter for acute PD in the infant population is easily performed with minimal risk. Moreover, this allows for more rapid onset of PD when conditions mandate this need.
Perit Dial Int 1996
PMID:Acute peritoneal dialysis access in infant renal failure. 872 58

It is known that serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations are inversely related to insulin levels both in healthy and diabetic subjects. The aim of the present study was to assess serum IGFBP-1 levels in a group of patients undergoing peritoneal dialysis (PD) and to evaluate their relationship with serum insulin concentrations. Thirty-five patients [19 males, 16 females; age (mean +/- SEM) 53.2 +/- 2.5 years; range 18-78; duration of continuous ambulatory peritoneal dialysis 33.1 +/- 6.0 months; Kt/V 2.00 +/- 0.05; normalized protein catabolic rate 1.00 +/- 0.05 g/kg/day] were studied. Nine patients were diabetics. In all patients, baseline IGFBP-1, insulin, and growth hormone (GH) levels were determined. Fasting IGFBP-1 levels were elevated in 19 (54%) patients and were normal in 16 patients. In all patients, high levels of serum insulin levels (> 25 microU/mL) were observed. Baseline IGFBP-1 levels were only slightly higher in diabetic patients (53.7 +/- 14.6 vs 40.5 +/- 8.2 micrograms/L,NS), however, serum levels of GH were similar in both groups (3.0 +/- 1.8 vs 2.9 +/- 0.5 microgram/L, NS). There was no correlation between fasting insulin and IGFBP-1 levels both in the whole group (r = 0.2; NS) and the diabetic (r = 0.2; NS) and nondiabetic (r = 0.3; NS) subgroups, despite high fasting insulin levels. We could only find a significant positive correlation between fasting glucose and IGFBP-1 levels in the diabetic group (r = 0.7, p < 0.05). Our data suggest that adult patients undergoing PD show hyperinsulinemia associated with normal or high serum IGFBP-1 levels. This suggests that insulin does not affect IGFBP-1 production in this group of patients. It could be explained, at least in part, by the insulin resistance present in uremia.
Adv Perit Dial 1996
PMID:Serum insulin and insulin-like growth factor binding protein-1 levels in adult patients undergoing peritoneal dialysis. 886 77

Protein intakes of patients on continuous ambulatory peritoneal dialysis (CAPD) are estimated by protein catabolic rate (PCR) or dietary protein intake assessments (DPI). In this study we compared two approaches suggested by Randerson et al. for calculating PCR. One method incorporates urea generation rate (UG) and estimated dialysate protein losses (PCR), while the other includes UG and measured dialysate protein losses (PCR). We feel that calculating PCR2 is more convenient in practice. We studied 95 patients on CAPD, 49 men and 46 women, with a mean age of 56.5 years (range 26.6-84.5 years) and lean body mass of 41 kg (range 19-71 kg). Mean +/- SEM of PCR1, PCR2, and DPI were: 0.89 +/- 0.02, 0.86 +/- 0.02, and 0.90 +/- 0.04 g/kg standard weight (std wt)/day, respectively. PCR1 and PCR2 were highly and significantly correlated (r = 0.94, p = 0.0001). The difference of PCR1-PCR2 is plotted against dialysate protein loss, which reveals that PCR2 often underestimates PCR1 if dialysate protein loss is > 10 g/day, but this difference is minimum (< 0.1 g/kg standard weight/day) when the dialysate protein loss is < 15 g/day. We conclude that PCR2 is an easy and effective method to monitor nutritional status in the majority of CAPD patients as very few will have dialysate protein losses > 15 g/day.
Adv Perit Dial 1996
PMID:Protein catabolic rate in CAPD patients: comparison of different techniques. 886 20

Abstract. NGNG dimethyl-L-arginine (asymmetric dimethyl-L-arginine; ADMA) and NGNG dimethyl-L-arginine (symmetric dimethyl-L-arginine; SDMA) are naturally occurring analogues of L-arginine, the substrate for nitric oxide (NO) synthesis. ADMA is a potent inhibitor of NO synthesis, and accumulates in the plasma of patients with renal failure. However the precise concentration of ADMA and SDMA in renal patients is still controversial. This study was performed to measure plasma ADMA and SDMA concentrations by two different HPLC techniques in nine healthy controls and 10 uraemic subjects, and to investigate the effects of haemodialysis. In controls, the mean (+/-SEM) plasma concentrations of ADMA and SDMA were 0.36 +/- 0.09 and 0.39 +/- 0.05 mumol/l respectively, yielding an ADMA/SDMA ratio of 1.2 +/- 0.17. In uraemic patients, the plasma concentrations of ADMA and SDMA were 0.9 +/- 0.08 mumol/l (P < 0.001 compared to controls) and 3.4 +/- 0.3 mumol/l (P < 0.001 compared to controls) with an ADMA/SDMA ratio of 0.27 +/- 0.015 (P < 0.001). In the course of one 4 h haemodialysis session, ADMA concentrations decreased from 0.99 +/- 0.13 to 0.77 +/- 0.3 mumol/l and SDMA concentrations from 3.38 +/- 0.44 to 2.27 +/- 0.21 mumol/l. The plasma ADMA/creatinine ratio tended to increase from 1.26 +/- 0.20 x 10(-3) to 2.01 +/- 0.41 x 10(-3). It is concluded that there is a modest (3-fold) but definite increase in plasma ADMA concentration in uraemic patients compared to controls. SDMA accumulates to a greater degree (8-fold increase) and more closely parallels creatinine concentration than ADMA. The change in the ADMA/SDMA ratio is not accounted for by greater renal or dialysis clearance of ADMA, and, even though alternative explanations are not excluded, greater metabolism of ADMA than SDMA is the most likely explanation. Although small in magnitude, the increase in ADMA concentration might by biologically significant.
Nephrol Dial Transplant 1996 Dec
PMID:Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure. 901 21

The effects of extracorporeal (urinary plus peritoneal) losses of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) on their respective serum levels were studied in 10 adult patients (aged 42-74 years) with end-stage renal failure and residual renal function of 0-4.5 mL/min. All patients had been on continuous ambulatory peritoneal dialysis (CAPD) for a period of 2-27 months. Morning serum, 24-hour urine, and 8-hour overnight peritoneal concentrations of IGF-I and IGFBP-3 were measured by radioimmuno- (Incstar) and immunoradiometric (Active) assays. CAPD patients showed extracorporeal losses (mean +/- SEM) of 118.7 +/- 10.6 micrograms (urinary 6.4 +/- 2.8 and peritoneal 112.3 +/- 8.5 micrograms) of IGF-I/24 hour and 1.5 +/- 0.1 mg (urinary 0.2 +/- 0.1 mg and peritoneal 1.3 +/- 0.1 mg) of IGFBP-3/24 hour. Extracorporeal losses of IGF-I accounted for about 4% of the daily production rate of this polypeptide, and the peritoneal and urinary concentrations of IGFBP-3 did not exceed 4% and 14%, respectively, of their serum levels. Serum concentrations of IGF-I (227.7 +/- 64.2 micrograms/L) and IGFBP-3 (5.3 +/- 2.4 mg/L) were not significantly correlated with extracorporeal, peritoneal, or urinary losses of these proteins or with residual renal function. We suggest that extracorporeal losses of IGF-I and IGFBP-3 in adult patients on CAPD do not influence their serum levels and that IGF-I may therefore be used as a marker of malnutrition.
Adv Perit Dial 1997
PMID:Extracorporeal losses of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in adult patients on CAPD. 936 Jun 50


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