Role of erythropoietin in the reversal of anemia of renal failure with continuous ambulatory peritoneal dialysis

We report serum erythropoietin levels in a patient who showed significant improvement in hematocrit when switched from hemodialysis to continuous ambulatory peritoneal dialysis (CAPD) treatment. This 22-year-old woman had severe anemia and low serum immunoreactive erythropoietin levels (8.0 +/- 1.2 mU/ml; n = 5) while on hemodialysis for 7 years. Serum erythropoietin levels were 80 and 177 mU/ml, 2 and 3 weeks, respectively, after starting CAPD. This was followed by an increase in reticulocyte count from 3.9 to 22% and hematocrit from 19 to 48%. The serum erythropoietin concentration obtained on CAPD treatment (62.7 +/- 15.2 mU/ml; n = 9) was significantly higher than that obtained on hemodialysis. Our findings indicate that CAPD facilitates increased erythropoietin production compared to hemodialysis and that the anemia of uremia may reverse if sufficient erythropoietin is available.     

Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency

The relative importance of erythropoietin (Ep) and inhibition of erythropoiesis in the anemia of chronic renal insufficiency has been investigated. Sixty patients with varying degrees of renal insufficiency, 40 normal subjects and 40 patients with anemia and normal renal function, were studied. Erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell colony formation were assayed in fetal mouse liver and human bone marrow cultures, respectively. Erythropoietin was measured by radioimmunoassay. Hematocrit and plasma creatinine concentration correlated with the degree of serum inhibition of CFU-E formation (r = 0.69, P less than 0.001, and r = 0.62, P less than 0.001, respectively). Serum erythropoietin levels in patients with renal insufficiency (34.4 +/- 6.7 mU/ml) were slightly higher than normal values (23.1 +/- 0.98 mU/ml), but showed no relationship to plasma creatinine, hematocrit, or inhibition of CFU-E formation. In contrast, serum erythropoietin concentrations increased exponentially as the hematocrit decreased below 32% (r = 0.61, P less than 0.001), and CFU-E formation was stimulated by serum in anemia patients with normal renal function. Studies of granulopoiesis showed uremic sera supported in vitro CFU-GM growth more efficiently than sera from normal subjects. These results suggest that inhibition of erythroid, but not granulocytic, progenitor cell formation, in addition to a relative erythropoietin deficiency, are the primary factors responsible for the anemia of chronic renal failure.     

Serum erythropoietin levels and hematocrit in end-stage renal disease: influence of the mode of dialysis

Serum erythropoietin (Ep) levels were measured by radioimmunoassay in 70 patients with end-stage renal disease (ESRD) to evaluate the influence of the mode of dialysis on the relationship between serum Ep levels and the severity of anemia. Thirty-five patients were on hemodialysis (HD), seven were on intermittent peritoneal dialysis (IPD), and 28 were on continuous ambulatory peritoneal dialysis (CAPD). Compared to HD, CAPD patients had higher serum Ep (CAPD), 46.1 +/- 13.4 v HD, 16.9 +/- 2.2 mU/mL) and hematocrit (CAPD, 33.9 +/- 2.5 v HD, 24.8 +/- 1.4%; P less than 0.05). The Ep and Hct values for IPD patients were intermediate between the other two groups. Serum Ep levels were higher in CAPD patients in the first 4 weeks of initiation of CAPD (144 +/- 35 mU/mL, n = 6) than later (39 +/- 6.4 mU/mL, n = 24). A significant fluctuation in serum Ep and Hct values was noted in patients on all three modes of dialysis, when multiple samples were obtained at different time intervals. There was a weak correlation between serum Ep and Hct in the three groups of dialysis patients; r = 0.36, P less than 0.005. The data suggest that CAPD provides a better biochemical milieu for Ep production and responsiveness than HD treatment of ESRD.     

Intraperitoneal production of erythropoietin with continuous ambulatory peritoneal dialysis

Higher hematocrit and serum erythropoietin (EPO) levels have previously been shown in end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD) compared with hemodialysis. We investigated whether EPO was produced intraperitoneally in CAPD patients. EPO concentration was 3.5±0.3 mU/ml by radioimmunoassay in 26 samples of peritoneal dialysis effluent obtained from 15 CAPD patients. EPO was not detectable in the fresh unused dialysate. No correlation was observed between EPO levels in the serum and dialysis effluent. Peritoneal macrophages were isolated from the dialysis effluent of 9 CAPD patients after an overnight dwell. The culture supernatant obtained after 24 h of in vitro culture of a million cells yielded EPO of 3.5±0.3 mU/ml. Our study demonstrated that peritoneal macrophages from CAPD patients produce EPO on in vitro stimulation, and EPO is present in the dialysis effluent of CAPD patients.     

Regulatory mechanisms of erythropoietin levels in dialysis patients

We described a radioimmunoassay system for measuring blood erythropoietin (Epo) levels using recombinant human Epo and evaluated the regulatory mechanisms of Epo in dialysis patients. A satisfactory dose-response relationship for Epo levels was observed within the wide range of 3-250 mU/ml with a sensitivity of approximately 5 mU/ml. The Epo levels were found to be 16.1 +/- 8.6 mU/ml (m +/- SD) in 422 uremic patients on maintenance dialysis and 17.1 +/- 7.2 mU/ml in 86 normal subjects. The Epo levels were not statistically different between the two groups, although the hematocrit was significantly lower in the dialysis patients. No correlation was observed between the Epo levels and hematocrit in the dialysis patients. Patients with polycystic kidneys had higher hematocrits and Epo levels than patients with chronic nephritis. No changes in Epo levels were observed with age and with the period of dialysis. Diurnal variations in the Epo levels revealed a significant increase after hemodialysis, and an acute reduction in hematocrit following massive hemorrhage raised the Epo levels up to 3,180 mU/ml. These findings indicate that the Epo levels in dialysis patients are inappropriately low for the severity of anemia and suggest that a negative feedback mechanism of the hematocrit on the Epo secretion may exist in uremic patients as well as in normal subjects and that the threshold for Epo secretion might be 'reset' at a low hematocrit level.     

Polyamines in the anemia of end-stage renal disease

The improvement in the anemia in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) suggests that dialyzable substances present in the sera of uremic patients either inhibit erythropoiesis directly or inactivate erythropoietin (EPO). In the present study predialysis sera from patients with ESRD inhibited erythroid colony (CFU-E) (N = 10) formation to a significantly (P less than 0.01) greater degree than granulocyte-macrophage (CFU-GM) (N = 7) colony formation in mouse bone marrow (MBM) cultures. The polyamines spermine (SP) (18 to 560 nm/ml) and spermidine (SD) (4 to 648 nm/ml) exerted a more significant (P less than 0.05) inhibition of CFU-E (N greater than or equal to 5) than that of CFU-GM (N greater than or equal to 5) growth. Concentrations of 0.80, 1.0, and 1.5 nm/ml of putrescine (PU) were 92%, 85%, and 77% of erythroid colony (CFU-E) controls (N = 4) and 104%, 130%, and 127% of CFU-GM controls (N = 4). Putrescine (PU) at 1.5 nm/ml also produced a significant (P less than 0.05) inhibition of CFU-E, whereas CFU-GM were stimulated by PU. These data suggest that predialysis sera from uremic patients, as well as SP, SD, and PU, are selectively more inhibitory to CFU-E than CFU-GM growth. The immunoreactivity of EPO was not significantly changed when it was coincubated with SP, SD and PU and measured by radioimmunoassay. PU was found to inhibit noncompetitively the bioactivity of EPO in a CFU-E assay. These data support the hypothesis that polyamines may be important uremic toxins in the anemia of ESRD.     

Insulin-like growth factor I: a modulator of erythropoiesis in uraemic patients?

Anaemia is a feature almost invariably complicating chronic renal failure. Its pathophysiology is multifactorial but the most important cause is erythropoietin (Epo) deficiency. However, either no relation or even a weakly positive relation generally exists between serum immunoreactive (i) Epo and haematocrit values in uraemic anaemia, whereas in anaemias of non-renal origin the correlation is most often strongly negative. Recent evidence indicates that growth hormone also stimulates erythropoiesis. Moreover, late erythroid progenitor cells (CFU-E) require insulin and/or insulin-like growth factor I (IGF-I) for development in vitro. IGF-I has been shown to have a synergistic action with Epo. We have measured serum iEpo and IGF-I levels in 17 haemodialysis patients with severe hyperparathyroidism (mean +/- SEM serum iPTH, 988 +/- 88 pg/ml). Mean age and duration of dialysis treatment were 46.1 +/- 3.4 and 8.8 +/- 1.0 years respectively. Mean haematocrit and haemoglobin values wer 28.1 +/- 1.7% and 9.39 +/- 0.54 g/dl respectively. Mean serum iEpo and IGF-I levels were 20.3 +/- 4.7 mU/ml and 320 +/- 20 ng/ml respectively (normal values for serum iEpo and IGF-I, 17.9 +/- 6 mU/ml and 91 +/- 23 ng/ml respectively). We found that serum IGF-I concentrations were well correlated with haematocrit values (r = 0.68, n = 15, P less than 0.004) whereas serum iEpo values were not (r = 0.41, n = 12, P = 0.18). IGF-I could therefore be an important factor regulating erythropoiesis in uraemic patients, at least when associated with severe hyperparathyroidism.     

Effect of different modes of dialysis on serum erythropoietin levels in pediatric patients

The relative importance of erythropoietin (Ep) and inhibitors of erythropoiesis in the development of anemia in pediatric patients with end-stage renal disease (ESRD) was assessed in 82 patients: 41 treated with peritoneal dialysis (PD) and 41 with hemodialysis (HD). Serum Ep was determined with a sensitive radioimmunoassay. Potential serum inhibition of erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell growth was assessed using human bone marrow cell cultures. The mean Ep level for all 82 patients was 33.1±3.1 mU/ml, which was significantly higher (P<0.05) than the values obtained in 29 normal children (26.2±2.4 mU/ml). Serum Ep in the PD group (41.6±5.6 mU/ml) was significantly higher (P=0.007) than that of the HD group (24.6±2.1 mU/ml). The mean hematocrit in the PD group (25.2±0.8%) was also significantly higher (P<0.002) than that of the HD group (22.2±0.5%). The mean serum parathyroid hormone (PTH) level as measured by a mid-terminal radioimmunoassay was not significantly different (P=0.79) in the HD group (17,298±3,998 pg/ml) from that of the PD group (15,747±4,227 pg/ml). Neither serum Ep nor PTH concentration correlated with hematocrit or degree of inhibition of erythroid progenitor cell colony (CFU-E) formation in either group of dialysis patients, nor did the hematocrit correlate, with the degree of serum inhibition of CFU-E formation. The higher level of Ep in the PD group may indicate more effective removal by PD of some enzymatic substance which reduces the immunologic and biologic activities of Ep. The higher hematocrit in the PD group may be due to the higher serum level of biologically active Ep in the PD patients. The lack of any difference in PTH level in the HD and PD groups suggests that differences in PTH activity are not responsible for the higher hematocrit in PD patients. Southwest Pediatric Nephrology Study Group (SPNSG Central Office, Baylor University Medical Center at Dallas, Tex. USA): Director, Ronald J. Hogg; Statistician, Joan S. Reisch; Administrative Assistant, Kaye Green. SPNSG Centers and Clinicians participating in this study: Baylor College of Medicine, Houston, Tex, Phillip L. Berry, L. Leighton Hill, Sami A. Sanjad: Tulane University Medical Center, New Orleans, La., Frank Boineau, John E. Lewy, Radhakrishna Baliga; University of Arkansas, Little Rock, Watson Arnold, Eileen Ellis; University of Colorado Health Science Center, Denver, Gary M. Lum; University of Oklahoma Medical Center, Oklahoma City, James Wenzl, James Matson; University of Tennessee Center for the Health Sciences, Memphis, F. Bruder Stapleton, Shane Roy, III, Robert J. Wyatt, Charles McKay; University of Texas Health Science Center at Dallas, Billy S. Arant, Jr.; University of Texas Medical School, Houston, Susan B. Conley, Ann Ince; University of Texas Health Science Center at San Antonio, Michael Foulds, Fred A. McCurdy; University of Texas Medical Branch, Galveston, Ben H. Brouhard, Alok Kalia, Luther B. Travis, Lisa Hollander; University of Utah Medical Center, Salt Lake City, Eileen Brewer, Richard Siegler. Offprint requests to: R. J. Hogg, Department of Pediatrics, Baylor University Medical Center, 3500 Gaston Avenue, Dallas TX, 75246, USA     

Efficient removal of albumin-bound furancarboxylic acid, an inhibitor of erythropoiesis, by continuous ambulatory peritoneal dialysis

3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid, which cannot be removed by conventional hemodialysis due to its strong albumin binding, was found to be efficiently removed by continuous ambulatory peritoneal dialysis (CAPD), resulting in a lower serum level in uremic patients on CAPD than in those on hemodialysis. 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid was demonstrated in vitro to inhibit erythroid colony formation. The anemia in patients on CAPD was significantly less severe than in those on hemodialysis. These results suggest that the efficient removal by CAPD of 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, an inhibitor of erythropoiesis, is related to an improvement of anemia in patients on CAPD.     

Relationship between erythropoietin and chronic heart failure in patients on chronic hemodialysis.

In the present study, the relationship between the blood erythropoietin level and cardiac function was investigated in 15 patients on chronic hemodialysis who developed chronic heart failure. Another 45 patients without cardiac dysfunction were selected as a control group that was matched for gender, age, and the duration of dialysis. The erythropoietin level was 256.3 +/- 481.8 mU/ml in the heart failure group, which was significantly higher than that in the control group (17.0 +/- 10.0 mU/ml, P < 0.01). Eight of the 15 patients in the heart failure group maintained a hematocrit of more than 30% without receiving recombinant human erythropoietin therapy, whereas 29 of the 45 patients in the control group required erythropoietin. In the heart failure group, the erythropoietin level was significantly correlated with the levels of atrial natriuretic peptide and brain natriuretic peptide (P < 0.01). These results suggest that heart failure can increase the erythropoietin level in proportion to the severity of cardiac dysfunction, even in patients on long-term dialysis.     

Hematopoietic inhibitors in chronic renal failure: lack of in vitro specificity

To assess the potential role of retained inhibitors in the pathogenesis of the anemia of chronic renal failure, we have studied simultaneously the effects of increasing concentrations of normal or uremic sera on the growth of erythroid colonies (from CFU-E), granulocyte-macrophage colonies (from CFU-GM), and megakaryocytic colonies (from CFU-Meg) in mouse marrow cell cultures. As compared to normal human serum, increasing concentrations of uremic sera induced a dose-dependent inhibition in the growth of all colony types. Significant correlations (P less than 0.001) were found between the ability of any individual uremic serum to support CFU-E, CFU-GM, and CFU-Meg growth, and, whenever significant inhibition was seen, all three progenitor types were affected. The inhibitory effect on CFU-E growth was significantly greater (P less than 0.01) in patients with serum creatinine concentrations greater than or equal to 7 mg/dl, but no correlation was found between CFU-E inhibition and hematocrit. Likewise, inhibition of CFU-GM and CFU-Meg growth was not associated with leukopenia or thrombocytopenia, respectively. Sera from patients undergoing chronic intermittent hemodialysis were assayed before and after one hemodialysis session. In each case, the degree of inhibition of CFU-E and CFU-GM growth decreased after hemodialysis, but improvement in CFU-Meg growth was more variable. These data indicate that uremic sera contain dialyzable inhibitors of in vitro hematopoiesis which increase with the severity of renal dysfunction, but these inhibitors lack specificity. If uremic inhibitors of erythropoiesis are of pathophysiologic significance in vivo, there must be unrecognized repair mechanisms for granulopoiesis and thrombopoiesis.     

Plasma levels of pancreatic secretory trypsin inhibitor in relation to amylase and lipase in patients with acute and chronic renal failure

Plasma levels of pancreatic secretory trypsin inhibitor (PSTI), lipase and amylase were measured in patients with chronic renal failure (CRF), patients undergoing regular hemodialysis treatment (RDT) or continuous ambulatory peritoneal dialysis (CAPD), patients with acute renal failure (ARF) and patients following successful cadaveric kidney transplantation. Plasma PSTI values were 9.2 +/- 0.8 ng/ml in controls (CO), 156.9 +/- 16.2 ng/ml in CRF patients, 257.6 +/- 22.3 ng/ml in RDT patients, 376.8 +/- 57.5 ng/ml in CAPD patients and 2,300 +/- 276.9 ng/ml in patients with posttraumatic ARF. RDT patients with malignant diseases displayed significantly higher PSTI values (1,014 +/- 148.7 ng/ml; p less than 0.01) than RDT patients without malignancy. Transplant patients with normal kidney function (creatinine 1.25 +/- 0.1 mg/dl) showed significantly lower PSTI values (16.7 +/- 2.1 ng/ml) than transplant patients with impaired renal function (creatinine 4.7 +/- 0.5 mg/dl; PSTI 72.8 +/- 11.8 ng/ml; p less than 0.01). Daily urinary excretion of PSTI increased from 26.7 +/- 3.1 micrograms (CO) to 551.8 +/- 54.8 micrograms in CRF patients. In CAPD patients, daily peritoneal loss of PSTI was 164.3 +/- 58.4 micrograms. Plasma PSTI values increased during hemodialysis with dialyzers made of cuprophan (317.0 +/- 32.6 vs. 422.0 +/- 46.2 ng/ml; p less than 0.05) and decreased with polysulfone dialyzers (226.6 +/- 19.9 vs. 86.6 +/- 18.1 ng/ml). There was no correlation between PSTI and urea, creatinine, lipase or amylase in each tested group. Our results document markedly elevated plasma PSTI values in all forms of renal insufficiency, suggesting extrapancreatic PSTI production and/or reduced renal elimination.     

Prospective evaluation of an anemia treatment algorithm in hemodialysis patients

Current guidelines recommend maintaining the hematocrits of chronic hemodialysis patients in the low to mid-30s. Maintaining patients' hematocrits within a narrow range requires frequent monitoring of their hematocrits and iron studies and periodic adjustment of erythropoietin doses and administration of intravenous iron. We designed a simple anemia treatment algorithm to streamline the management of anemia in hemodialysis patients. The protocol required formal monthly decisions about the administration of intravenous iron or changes in erythropoietin dose. This algorithm was implemented by dialysis nurses and evaluated prospectively for 6 months in a single dialysis unit (30 patients). The proportion of patients whose hematocrits were within the desired target (31% to 35%) increased from 27% at baseline to 61% during months 4 through 6 of the algorithm. Conversely, the proportion of patients whose hematocrit values were below the target decreased from 46% at baseline to 18% during months 4 through 6 of the algorithm (P=0.004). The percentage of patients whose hematocrit values were above the target did not increase. The proportion of patients whose transferrin saturation was less than 18% decreased from 47% at baseline to 20% during months 4 through 6 of the algorithm (P=0.04). The weekly erythropoietin dose administered decreased from 11,200+/-1,400 units at baseline to 9,400+/-1,200 units in month 6 of the algorithm (P=0.06). We conclude that a simple anemia treatment algorithm implemented by dialysis nurses is feasible and efficacious and may increase the proportion of hemodialysis patients whose hematocrit values are within the target range, without increasing erythropoietin requirements.     

Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease.

From a total of 81 patients on maintenance hemodialysis who underwent coronary angiography, 8 patients fulfilled the criteria: significant coronary artery disease, hematocrit less than 27%, reproducible (ECG) positive treadmill test, no disturbance of repolarization in ECG at rest. Exercise stress testing was performed at a hematocrit of 25 +/- 2% and following erythropoietin therapy at a hematocrit of 34 +/- 0.5%. Symptom-limited exercise performance increased in all patients (1.10 +/- 0.3 W/kg b.w. vs. 1.44 +/- 0.31 W/kg b.w., p less than 0.01) as well as exercise duration (489 vs. 362 s, p +/- 0.01). ST segment depression during maximal exercise was reduced from a mean of 2.1 to 0.4 mm (p less than 0.01). It is concluded that amelioration of renal anemia by erythropoietin in dialysis patients with significant coronary artery disease reduces exercise-induced myocardial ischemia.     

Anemia of chronic renal failure: inhibition of erythropoiesis by uremic serum

The pathogenesis of anemia in patients with end-stage renal disease was studied by assessing the effect of uremic serum on the proliferation and maturation of erythroid progenitor cells, BFU-E and CFU-E, into colonies in vitro. Nucleated peripheral blood cells from 10 anemic patients produced normal or increased numbers of BFU-E colonies in response to added erythropoietin when cultured in control serum, but declined a mean of 63% when autologous uremic serum was substituted. Uremic sera from 90 patients cultured with normal human marrow produced a mean decrease in BFU-E colony growth of 72%, and of CFU-E colony growth of 82%, compared to control serum. Neither hemodialysis nor peritoneal dialysis was effective in removing the inhibitor. We conclude that patients with uremia have adequate circulating erythroid progenitors that respond to erythropoietin normally when removed from the uremic environment, and that uremic serum is toxic and inhibitory to erythropoiesis. This may be an important mechanism in the anemia of chronic renal failure.     

Dynamics of erythropoiesis following renal transplantation

We examined the temporal dynamics of the correction of anemia following renal transplantation in 65 recipients using a sensitive radioimmunoassay for erythropoietin to determine the effects of modern immunosuppressive agents, delayed graft function, and early acute rejection. Pretransplant mean erythropoietin (25.6 +/- 3.3 mU/ml) was only 25% of the expected value at the mean hematocrit of 27.2 +/- 0.7, and erythropoietin correlated positively with hematocrit (r = 0.37, P less than 0.05). Following onset of graft function, erythropoietin increased to 109 +/- 13 mU/ml and then decreased in a negative feedback fashion over the next several months. Delayed graft function was associated with delay in the assumption of this orderly process irrespective of the immunosuppressive regimen used. Cyclosporine A produced a biphasic response despite delayed graft function in recipients with underlying adult polycystic kidney disease. Correction of anemia required resumption of graft function. Onset of acute graft rejection within the first month posttransplantation (14 episodes in 11 patients) abrogated the hematopoietic response until the rejection was successfully reversed. We conclude that a major cause for the anemia of renal failure is subnormal production of erythropoietin. Following transplantation, anemia corrects in an orderly manner with restoration of the normal biofeedback process between erythropoietin and red cell mass. This process is delayed by failure of graft to function initially and interrupted by acute early rejection, re-commencing following successful reversal.     

Randomized prospective comparison between erythropoietin and androgens in CAPD patients

BACKGROUND: Anemia and malnutrition are significant complications in peritoneal dialysis (PD) patients. Previous studies in hemodialysis have shown that androgens are effective as therapy for anemia; however, this has not been tested in a randomized prospective trial in PD patients. Furthermore, the anabolic properties of androgens may exert additional benefits on the nutritional status in this population. METHODS: Twenty-seven stable male patients over 50 years who were under maintenance continuous ambulatory peritoneal dialysis (CAPD) therapy were randomized to receive recombinant human erythropoietin (rHuEPO; N = 14) or nandrolone decanoate (ND; 200 mg/week IM; N = 13) as therapy for anemia. The evolution of hematologic parameters and the impact on both nutritional anthorpometric and biochemical variables were evaluated after six months of treatment. RESULTS: Hemoglobin and hematocrit experienced similar increases in both groups: from 8.5 +/- 0.9 g/dL and 25.8 +/- 2.7% to 11.7 +/- 0.6 g/dL and 34.7 +/- 1.6% (P < 0.001) in patients receiving rHuEPO, and from 8.9 +/- 0.8 and 27 +/- 2.2% to 11.8 +/- 0.4 g/dL and 35.1 +/- 1.5% (P < 0.001) in subjects treated with ND. At the end of the study, out of the diverse nutritional variables included in this investigation, only weight and body mass index significantly increased in the rHuEPO group. Conversely, both anthropometric [weight, body mass index, triceps skinfold, mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC)] and biochemical parameters (serum total proteins, albumin, prealbumin and transferrin) were significantly increased in patients treated with ND. In this group, serum urea nitrogen, urea net excretion and protein equivalent of nitrogen appearance significantly decreased. These facts, together with an increase in serum creatinine and no changes in dietary intake during the study, suggest a rise in muscle mass related to an anabolic effect of nandrolone decanoate. Interestingly, serum levels of insulin-like growth factor type 1 (IGF-1) increased in patients on the androgen group compared to subjects treated with rHuEPO. Moreover, there was a positive and significant correlation between the rise in IGF-1 concentrations and the increase in hemoglobin, hematocrit, MAC and MAMC. CONCLUSIONS: Androgens therapy improved the anemia in elderly male CAPD patients in a similar manner to that observed with rHuEPO. Furthermore, compared with rHuEPO, androgen administration was associated with beneficial effects on nutritional status. The mechanism of action of androgens on hematologic and nutritional parameters might be mediated, at least in part, by IGF-1.     

Improved sexual function in hemodialysis patients on recombinant erythropoietin: a possible role for prolactin

As it was reported that correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) is associated with improved sexual function, we conducted the present study to further delineate the mechanism(s) by which this is brought about. Serum prolactin, testosterone, and parathyroid hormone (PTH) levels were followed during 4 months of r-HuEPO therapy. Within 4 months of treatment with r-HuEPO, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin increased from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were low in male patients and remained unchanged during r-HuEPO therapy. Baseline PTH values were elevated (1,880 +/- 220 pg/ml) in patients of both sexes and declined to 1,410 +/- 180 pg/ml during treatment with r-HuEPO. However, this difference did not reach statistical significance. Sexual function improved in 4 out of 7 males and 5 out of 9 female patients began to menstruate regularly again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO improves sexual function via normalization of elevated serum prolactin concentrations.     

Concentrations of thyroxine-binding globulin in sera and peritoneal dialysates in patients on chronic peritoneal ambulatory dialysis

Losses in thyroxine-binding globulin (TBG) in peritoneal dialysate and thyroid function were evaluated in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), in comparison to patients on hemodialysis (HD) without TBG loss in the dialysate. The TBG concentration in the peritoneal dialysate was 0.26 +/- 0.09 microgram/ml (mean +/- SD, n = 24), with a daily loss of 2.47 +/- 0.94 mg. The serum TBG level in CAPD patients was 21.0 +/- 4.71 micrograms/ml (n = 24), which was not significantly different from that in HD patients (20.0 +/- 5.72 micrograms/ml, n = 24) or in healthy Japanese subjects. The serum TBG level correlated positively with the TBG loss and TBG level in the peritoneal dialysate (p less than 0.001). The serum T4 level in CAPD patients (4.93 +/- 1.38 microgram/dl, n = 24) was significantly greater than in HD patients (4.08 +/- 1.30 microgram/dl, n = 24, p less than 0.05).     

Alterations in sex hormones and sexual function of patients with renal failure treated with recombinant human erythropoietin.

Since it has been reported that correction of anemia in long-term hemodialysis patients by using human recombinant erythropoietin (r-HuEPO) is associated with improve sexual function, we conducted the present study to evaluate the changes in sex hormones as well as sexual function after r-HuEPO administration (1500 to 4500 IU per dialysis) for a year in patients on regular hemodialysis. Thirteen patients receiving regular hemodialysis entered this study. Their median age was 43 years. Along with correction of anemia (the hematocrit increased from 20 to 28%), testosterone (T) increased from 2.4 +/- 0.1 to 2.6 +/- 0.2 ng/ml, follicular stimulating hormone (FSH) increased (29 +/- 5 to 73 +/- 7 mIU/ml), luteinizing hormone increased (69 +/- 14 to 160 +/- 21 IU/ml) and prolactin decreased (all changes are significant at p less than 0.05). However, the improvement of sexual function was not remarkable. Only 25% of the uremic patients treated with r-HuEPO showed amelioration of this function. From the present data, it does not seem likely that therapy with r-HuEPO induces directly amelioration of sexual function through changes in sex hormones.