Leptin and serum erythropoietin in hemodialyzed and peritoneally dialyzed uremic patients during rHuEPO therapy

Leptin produced by fat cell has an unanticipated role in hematopoietic system development. We examined the relationships between leptinemia and requirements of erythropoietin (Epo), endogenous Epo levels as well as markers of inflammation: C-reactive protein, tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1) in rHuEPO-treated patients maintained on chronic hemodialyses or peritoneal dialyses. The studies were performed on 51 chronically hemodialyzed patients, 20 of them did not receive rHuEPO, 31 subjects received rHuEPO, and 22 patients on CAPD, 13 of them did not receive rHuEPO, 9 subjects were given rHuEPO. In hemodialyzed patients (Epo and Non-Epo group) leptin levels were significantly higher when compared to CAPD patients (Epo and Non-Epo group, respectively). Leptin in peritoneal fluid was significantly higher in the Non-Epo group. In ultrafiltrate, leptin levels were below the detection limit of 0.5 ng/ml. Epo levels in the HD + Epo group were significantly lower than in the HD + Non-Epo group and CAPD + Epo group. TNFalpha and IL-1 concentrations were significantly lower in both groups of CAPD patients when compared to respective HD groups. Treatment with rHuEPO resulted in nonsignificant decline in serum leptin (p = 0.07 in HD and p = 0.08 in CAPD) and significant leptin loss in peritoneal fluid. It may be of clinical relevance in dialyzed patients. In both groups of Epo-treated patients, positive physiological correlation between leptinemia and BMI disappeared. Leptin levels do not correlate with rHuEPO requirements and serum Epo in dialyzed patients.     

Osteoprotegerin and its correlations with new markers of bone formation and bone resorption in kidney transplant recipients

Osteoprotegerin (OPG), a natural decoy receptor for osteoclast differentiation factor, is produced by osteoblasts in response to PTH. OPG and its ligand RANKL constitute a complex mediator system involved in the regulation of bone resorption, probably playing an important role in the homeostasis of bone turnover. At present, little is known about the effects of OPG on uremic bone. Successful kidney transplantation reverses many abnormalities of bone metabolism; however, the improvement is often incomplete. The aim of the study was to assess OPG and RANKL concentrations in long-term kidney allograft recipients and their correlations with biochemical markers of bone resorption and formation. The present studies on 48 kidney transplant recipients and 25 healthy volunteers included concentrations of parathormone, osteocalcin, bone-specific alkaline phosphatase, serum CrossLaps, calcidiol, calcitriol, ICTP, PICP, tartrate-resistant acid phosphatase, beta2 microglobulin, IGF-1, IFGBP-1, IGFBP-3, OPG, and RANKL using commercially available kits for measurements. Among kidney transplant recipients OPG and RANKL did not differ between transplant patients and healthy volunteers, whereas other markers of bone formation and resorption were significantly higher in the former group. OPD was related to age, time on dialysis prior transplantation, urea, platelet count, CSA dose, azathioprine dose, 25(OH)D(3), TRAP, IGF-1, IGFBP-3, whereas RANKL was related to leukocyte count, CSA concentration and dose, urine DPD, and beta2 microglobulin content. In healthy volunteers OPG correlated only with CrossLaps, whereas RANKL correlated only with osteocalcin and TRAP. Correlations between OPG, IGF system components, and some markers of bone metabolism may indicate the role of OPG/RANKL system in the pathogenesis of bone metabolism disturbances following renal transplantation.     

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.     

Importance of serotonergic mechanisms in the thrombotic complications in hemodialyzed patients treated with erythropoietin

So far it is not clear how erythropoietin affects the anticoagulant properties of vascular endothelium in uremia. Since serotonin is also thought to play a role in the pathogenesis of thrombosis, the aim of the study was to evaluate major components of extrinsic coagulation pathway, markers of endothelial cell injury, lipoprotein (a) and peripheral serotonergic mechanisms during rHuEPO therapy in hemodialyzed patients. The study was performed on chronically hemodialyzed patients divided into two groups: with rHuEPO treatment and without rHuEPO therapy in relation to the control group. In uremic patients, thrombomodulin and von Willebrand factor, activity of factor VII, tissue factor pathway inhibitor (TFPI) activity, TFPI and tissue factor (TF) concentrations, lipoprotein (a) level were significantly higher when compared to healthy volunteers. Treatment with rHuEPO resulted in a further significant rise in markers of endothelial cell injury: thrombomodulin and von Willebrand factor and TFPI concentration. Extrinsic coagulation factors: activities of factor VII and X, TFPI activity and TF activity and concentration, lipoprotein (a) and vitronectin remained unchanged during rHuEPO therapy. Platelet serotonin content and whole blood serotonin were significantly lower in uremic patients relative to healthy volunteers and during rHuEPO treatment they increased significantly. Whole blood serotonin reached normal values. Plasma serotonin, significantly elevated in uremia, did not change during rHuEPO therapy. Serotonin uptake by uremic platelets was significantly impaired and remained unaltered during rHuEPO administration. Serotonin release by uremic platelets was also significantly depressed but a significant improvement was observed in rHuEPO-treated patients. Our data suggest that endothelial injury, TF pathway components and peripheral serotonergic system disturbances may predispose to thromboembolic complications and play a role in the pathogenesis of atherosclerosis in uremic patients, particularly treated with rHuEPO. Increase in TFPI may compensate the increase in TF in these patients.     

Elevated IGFBP-1 cause high bone turnover in growth-restricted monochorionic twins with discordant birth weight

OBJECTIVE: To test the hypothesis that low birth weight twins have a higher risk of osteoportotic fracture in later life, we investigated the association between fetal IGF axis and type-1 collagen markers of bone turnover in monochorionic (MC) twins with or without discordant birth weight of >or=20%. METHODS: Maternal and cord bloods were collected from gestational age matched MC twins of discordant (n = 16) and concordant birth weights (n = 16). The samples were assayed for cross linked carboxyl terminal telopeptide (ICTP, a marker of bone resorption) and pro-peptide (PICP, a marker of bone formation) of type I collagen, IGF-1, and IGFBP-1 by radio-immunoassay. RESULTS: The growth-restricted twins (IUGR) of discordant group had higher fetal IGFBP-1 and ICTP (P < 0.001) levels, while PICP (P < 0.001) was lower than the co-twins with normal weight (AGA). In contrast, cord blood levels of IGF-1, IGFBP-1, ICTP, and PICP in concordant twin pairs were comparable to AGA twins. The concordant and AGA twins had a positive correlation between ICTP and PICP levels (y = 23x - 711; r = 0.84; P < 0.001; n = 48) but no such association was found in IUGR twins. Instead, IGFBP-1 levels in IUGR twins had a negative association with PICP (r = 0.81; P < 0.001; n = 16) and a positive correlation with ICTP (r- = 0.51; P < 0.05; n = 16). No such association was found in concordant and AGA twins. CONCLUSION: These data suggest that growth-restricted twins had high bone turnover, due to elevated IGFBP-1. This association seems to be independent of maternal and genetic factors.     

Thyroid function, endothelium, and inflammation in hemodialyzed patients: possible relations?

OBJECTIVE: Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and inflammation are common complications of kidney diseases. Endothelial dysfunction may link these two processes. DESIGN AND PATIENTS: A cross-sectional study on thyroid hormones in relation to markers of endothelial damage and inflammation in 96 hemodialyzed (HD) patients and 39 healthy volunteers was performed. SETTING: The study took place in the dialysis unit at a university hospital. INTERVENTION: Thyroid hormones, markers of endothelial damage (von Willebrand factor, thrombomodulin, intracellular adhesion molecule, and CD146), markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor alpha), other hemostatic parameters (thrombin-antithrombin complexes, prothrombin fragments 1 + 2 - F1 + 2, plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, tissue factor pathway inhibitor, and platelet glycoprotein V) were measured using commercially available kits. RESULTS: Free T3 and total T3 were lower in HD patients compared with controls. Markers of endothelial dysfunction and inflammation were significantly elevated in HD patients compared with controls. In multiple regression analysis T3 was independently related to time on dialyses, albumin, iron, ferritin, C-reactive protein (CRP), and F1 + 2 in HD patients. Free T3 was also independently related to total protein, total calcium, and triglycerides. In patients with CRP less than 6 mg/L in multiple regression analysis the only correlates of T3 were albumin and ferritin, whereas the only correlates of free T3 were albumin and time on dialyses. Multiple regression analysis showed that in HD patients with CRP greater than equal to 6 mg/L predictors of free T3 were CRP, F1 + 2, and dose of erythropoietin. In healthy volunteers T3 was related to tissue factor pathway inhibitor and platelet glycoprotein V was related to thyroid-stimulating hormone. CONCLUSIONS: We described novel relations between thyroid hormones and markers of endothelial dysfunction and inflammation in HD patients. Thyroid dysfunction is related to time on dialyses, endothelial damage, and inflammatory state, frequently encountered in uremia. Therefore, the relations between thyroid axis and endothelium in HD subjects merit additional studies.     

Thyroid function and morphology in kidney transplant recipients, hemodialyzed, and peritoneally dialyzed patients

Disturbances in thyroid function are common among patients on renal replacement therapy. The aim of the present study was to compare thyroid stimulating hormone (TSH) and thyroid morphology among patients on hemodialysis (HD), peritoneal dialysis (CAPD), and after kidney transplantation. The study was performed on three groups of patients: 48 transplant recipients (Tx) (receiving cyclosporine, azathioprine, and prednisone); 32 HD, and 26 CAPD patients. The control group included 40 healthy volunteers. Thyroid examinations were performed with a 7.5-MHz probe and the thyroid volume was calculated. Among Tx patients the thyroid volume was 25.16 +/- 12.27mL; 21.60 +/- 10.33mL in HD; 19.70 +/- 8.46 mL in CAPD; and 16.34 +/- 5.46mL in the healthy volunteers. Serum TSH was within the normal range in each group. Goiter was diagnosed in the majority of Tx, most HD patients, and some CAPD patients. Single and multiple nodules were found in 21 Tx, 12 HD, and 2 CAPD patients. Moreover, parathyroid glands were visualized on sonography in 10 Tx, 12 HD, and 8 CAPD subjects. In Tx observed correlations were positive between thyroid volume and creatinine, negative between thyroid volume and TSH. The time after transplantation correlated negatively with TSH. No correlation between TSH, thyroid volume, and time on dialysis was observed. The prevalence in patients on renal replacement therapy was higher than that in the general population. These findings suggest that screening for abnormal thyroid morphology should be performed in kidney patients and that iodide supplementation should be considered in Tx patients.     

Association of prohepcidin and hepcidin-25 with erythropoietin response and ferritin in hemodialysis patients

Hepcidin is a key regulator of iron metabolism. In this study, we examined whether measurement of hepcidin is useful in assessing recombinant human erythropoietin (rHuEPO) responsiveness in regular hemodialysis (HD) patients in a cross-sectional fashion. We examined the association between serum prohepcidin, a prohormone of hepcidin, and rHuEPO dosage and the rHuEPO/hemoglobin (Hb) ratio in 75 HD patients. We also semiquantatively measured the peak intensity of serum hepcidin-25, the major form of mature hepcidin, in 24 HD patients by using surface-enhanced laser desorption ionization time of flight time mass spectrometry, and compared those between rHuEPO-hyporesponsive (rHuEPO 192 +/- 10 [126-252] IU/kg/week, n = 15) and responsive patients (rHuEPO 40 +/- 9 [0-81] U/kg/week, n = 9). A significant but weak relationship was found between serum prohepcidin and rHuEPO dosage (r = 0.24, p < 0.05) and rHuEPO/Hb ratio (r = 0.22, p = 0.06). However, prohepcidin did not become an indicator of hematopoietic parameters by multiple regression analysis. Serum hepcidin-25 intensity was significantly and positively correlated with ferritin (r = 0.51, p < 0.01) but not with log-transformed C-reactive protein. There was no difference in the intensities of serum hepcidin-25 between rHuEPO-hyporesponsive and responsive patients (64 +/- 10 vs. 52 +/- 16 AU, p = NS). It follows from these findings that the assessment of serum hepcidin using currently available assays was not valid in predicting rHuEPO responsiveness in chronic HD patients.     

Circulating levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in patients with severe head injury

There is evidence to suggest that fractures heal more rapidly in patients with a head injury as a result of systemic factors released from the site of this injury. We have measured the circulating level of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum because of their known involvement in the stimulation of the activity of osteoblasts and the healing of fractures. The serum level of IGF-1 was significantly lower in patients with both head injury and fracture and fracture only compared with that in healthy volunteers (p < 0.01 and p < 0.02, respectively). The level of IGFBP-3 was also significantly lower in patients with both head injury and fracture (p < 0.01). Our findings showed, however, that the level of IGF-1 and IGFBP-3 varied from week to week in both the patients and healthy control subjects. These results indicate that the levels of circulating IGF-1 and IGFBP-3 are unlikely to be responsible for the altered healing of fractures seen in conjunction with head injury.     

CAPD的内分泌激素与rHuEPO疗效的相关性

目的：探讨在连续性非卧床腹膜透析(CAPD)干预治疗下慢性肾衰竭尿毒症内分泌激素与人类重组促红细胞生成素(rHuEPO)疗效的关系。方法：对经CAPD治疗的慢性肾衰竭尿毒症患内分泌激素等多重因素及血红蛋白进行多元回归分析。结果：非CAPD组贫血改善程度显低于CAPD组，内生肌酐清除率、甲状旁腺素、甲状腺激素、血皮质酵及透析治疗均与Hb显相关。结论：单用rHuEPO对改善肾衰竭尿毒症的贫血状态存在较大的局限，主要和包括PTH等在内的尿毒症红细胞生长抑制因子(inhibitors of erythropoiesis，IE)有关。rHuEPO配合CAPD是清除IE、改善贫血状态、提高生活质量的很好的组合治疗方法。     

ACE inhibitors or angiotensin II receptor blockers in dialysed patients and erythropoietin resistance

BACKGROUND: To examine whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) are associated with a state of recombinant human erythropoietin (rHuEPO) resistance in hemodialyzed patients. METHODS: Cross-sectional study involving all dialysis facilities in French-speaking Switzerland. All patients treated with rHuEPO in March 2001 were included. Demographic, clinical and laboratory data were collected in 515 patients treated with chronic hemodialysis (HD) and rHuEPO. Patients were classified into five groups according to their antihypertensive treatment. The main outcomes of the study were the mean rHuEPO dosage and the prevalence of erythropoietin EPO resistance among the groups. Erythropoietin resistance was defined as a weekly rHuEPO dosage >300 units/kg/wk. RESULTS: The mean rHuEPO dosage and the prevalence of EPO resistance were similar in patients treated with ACEIs (n = 138, mean EPO dosage 109 units/kg/wk, EPO resistance 12%), ARBs (n = 59, mean EPO dosage 120 units/kg/wk, EPO resistance 7%), both (n = 10, mean EPO dosage 109 units/kg/wk, EPO resistance 10%), other drugs (n = 137, mean EPO dosage 110 units/kg/wk, EPO resistance 10%) and no antihypertensive treatment (n = 171, mean EPO dosage 90 units/kg/wk, EPO resistance 9%). Differences were not statistically significant. Patients with rHuEPO resistance were characterized by a higher frequency of hospitalization and a more pronounced inflammatory state. There was no difference in the use of ACEIs and ARBs between patients with and without EPO resistance (37 vs. 41%, ns). CONCLUSIONS: Neither the use of ACEIs nor ARBs is associated with a state of rHuEPO resistance among hemodialyzed patients.     

Correlations of new markers of bone formation and resorption in kidney transplant recipients

Renal osteodystrophy is a common complication of chronic renal failure and renal replacement therapy. Successful kidney transplantation reverses many of these abnormalities, but the improvement is often incomplete. The evaluation of renal osteodystrophy in everyday practice is based on noninvasive measurements. Taking this into consideration the aim of the present study was to assess new markers of bone metabolism: serum CrossLaps degradation products of C-terminal telopeptides of type I collagen tartrate-resistant acid phosphatase (TRAP) and bone-specific alkaline phosphatase (bALP), as well as their correlations with bone mineral disease (BMD) in kidney transplant recipients. Twenty-six patients (aged 26 to 54 years) receiving a triple immunosuppressive regimen with stable graft function were enrolled in the study. Serum parathormone (PTH) osteocalcin type collagen C-terminal peptides (ICTP), and procollagen type I carboxyterminal extension peptide (PICP) concentrations were measured by radioimmunoassay (RIA), Serum CrossLaps, bALP, beta2-microglobulin, TRAP 5b by enzyme-linked immunoassay (ELISA), and deoxypyridinoline (DPD) in urine immunochemiluminescence. BMD, as measured by dual-energy X-ray absorptiometry (DEXA), correlated negatively with markers of bone formation (bALP, osteoclacin, and PICP) and resorption (TRAP, ICTP, and beta2-microglobulin). The only positive correlation was between urine DPD and BMD at the femoral neck. Interestingly, BMD correlated negatively with CsA concentration. TRAP 5b correlated positively with serum creatinine, ALP, bALP, osteocalcin, iPTH, ICTP, and serum beta2-microglobulin, and negatively with CsA concentration, and azathioprine and prednisone dose. DPD did not correlate with any parameters. Serum CrossLaps correlated with markers of both bone formation and resorption. Because TRAP and serum CrossLaps correlated with markers of both bone formation and or resorption, additional studies are needed to establish the value of these markers of bone resorption to assess renal osteodystrophy.     

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.     

Effects of recombinant human erythropoietin on echocardiographic findings in elderly dialysis patients

Summary: Twenty anaemic, normotensive and elderly patients on both haemodialysis and CAPD with left ventricular hypertrophy (LVH) were undergoing systematic echocardiographic analysis during treatment with recombinant human erythropoietin (rHuEPO) for 12 months. Before and after the rHuEPO treatment, M-mode and pulsed Doppler echocardiographic were performed and haemodynamic parameters were closely followed. Partial correction of anaemia resulted in a decrease in the LV end-diastolic diameter (LVEDD) from 56.0±2.0–49.2 ± 2.0mm ( P <0.05) in HD patients and 50.5 ± 4.0-43.6 ± 3.0mm in CAPD patients ( P = NS). Concomitantly the calculated mass index (LVMi) was reduced significantly from 232.3 ± 21.8-185.9 ± 11.4 g/m² in elderly haemodialysis patients. Heart rate and arterial pressure did not change during the study period. However, in CAPD patients there was no significant change in LVMi during the study period. We conclude that long-term amelioration of anaemia in dialysis patients could induce a regression of left ventricular hypertrophy. However, in CAPD patients, both myocardial and haemodynamic effects were less evident. CAPD could possibly modulate the haemodynamic changes associated with the rHuEPO treatment or CAPD itself impose less left ventricular wall stress in these elderly patients.     

Parvovirus B19-induced anemia in renal transplantation: a role for rHuEPO in resistance to classical treatment

Human parvovirus B19 (PVB 19) is responsible for pure red cell aplasia in immunocompromised patients, and particularly solid organ recipients. Intravenous immunoglobulins (IVIG) have been shown to be efficient to achieve the correction of anemia in association with the reduction of immunosuppression. We report a case of kidney transplant recipient with PVB 19-induced anemia that did not respond to recombinant human erythropoietin (rHuEPO) and to a first course of IVIG. After discontinuation of rHuEPO, a second course of IVIG was successful with the resolution of anemia. We discuss the role of rHuEPO that may facilitate PVB 19 replication in erythropoietin-sensitive human erythroid progenitor cells.     

Blood 8-hydroxy-2'-deoxyguanosine is associated with erythropoietin resistance in haemodialysis patients.

BACKGROUND: 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidized DNA, is increased in haemodialysis (HD) patients, but the clinical relevance of enhanced 8-OHdG production in these patients remains unknown. METHODS: We cross-sectionally measured serum 8-OHdG in 73 patients on maintenance HD (age 68+/-2 years, time on HD 85+/-11 months, male/female=42/31), and examined the relationship between blood 8-OHdG and the severity of renal anaemia and the weekly dosage of recombinant human erythropoietin (rHuEPO). RESULTS: There was a significant increase in serum 8-OHdG in HD patients compared with normal subjects. Serum 8-OHdG was positively correlated with the patients' age (r=0.231, P<0.05) but not with the duration of HD. Serum 8-OHdG was significantly higher in diabetic subjects than in non-diabetic subjects (P<0.05). Serum 8-OHdG had a significant inverse correlation with haemoglobin (Hb) (r=-0.526, P<0.01) but a positive correlation with the rHuEPO dose (r=0.443, P<0.01) and the ratio of the weekly rHuEPO dose divided by Hb (r=0.487, P<0.01). Serum 8-OHdG was not correlated with inflammatory and nutritional parameters. CONCLUSIONS: These findings suggest that the elevation of circulating 8-OHdG may be associated, at least in part, with rHuEPO resistance in HD patients.     

The relationship of circulating insulin-like growth factor 1, its binding protein-3, prostate-specific antigen and C-reactive protein with disease stage in prostate cancer

OBJECTIVE: To assess the relationships among circulating insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), prostate-specific antigen (PSA) and C-reactive protein (an indicator of inflammatory systemic response) in patients with prostate disease and cancer of different stages. PATIENTS AND METHODS: Circulating IGF-1, IGFBP-3, PSA and C-reactive protein concentrations were measured in patients with BPH (17) or stages T1/T2 (15), T3/T4 (16) and metastatic prostate cancer (12 patients). RESULTS: IGF-1 and IGFBP-3 concentrations were similar between patients with BPH and those with cancer, and there was no difference between the groups with cancer. In the latter patients there was a significant correlation between age and IGFBP-3 concentrations (r = -0.400, P = 0.008) but not with IGF-1 concentrations. Controlling for age, there were significant partial correlations between C-reactive protein and IGF-1 (r = -0.412, P = 0.008) and IGFBP-3 (r = -0.277, P = 0.05). CONCLUSIONS: These results indicate that circulating IGF-1 and IGFBP-3 concentrations do not change with disease stage in prostate cancer, but that they decrease with an increase in the systemic inflammatory response.     

良性前列腺增生病人血清IGF-1、IGFBP-3水平分析

目的 :检测良性前列腺增生 (BPH)病人血清胰岛素生长因子 Ⅰ(IGF 1 )及其结合蛋白 3 (IGFBP 3)的水平 ,探讨IGF 1、IGFBP 3对揭示BPH病因及治疗方面的价值。　方法 :采用免疫放射分析法 (IRMA)测定 64例BPH病人血清中IGF 1、IGFBP 3水平 ,并以 30例健康男性作对照。BPH病人按照其前列腺总体积 (PV)的大小分为 3组 :A组PV≤ 30ml,1 8例 ;B组　PV 31～ 50ml,2 4例 ;C组　PV≥ 50ml,2 2例。　结果 :BPH组血清IGF 1、IGFBP 3含量与对照组比较 ,差异均无显著性。BPH组中 ,C组与A组比较 ,IGF 1、IGFBP 3水平均显著升高 (P<0 .0 5) ,C组与B组比较 ,IGF 1水平显著增高 (P =0 .0 0 3) ,IGFBP 3水平无统计学差异。IGF 1、IGFBP 3的水平随PV的增加而升高 ,均呈正相关 (r =0 .58,r =0 .48)。　结论 :IGF 1、IGFBP 3水平的高低与前列腺增生的程度有关 ,对BPH病因的揭示及BPH的非手术治疗均有一定的临床价值     

维持性血液透析患者血浆sTWEAK蛋白表达

目的观察维持性血液透析（maintain hemodialysis,MHD）患者血浆soluble TNF-like weak inducer of apoptosis（sTwEAK）蛋白的表达。方法将研究对象分为3组：健康人群40例（健康对照组）,MHD患者46例（MHD组）,慢性肾脏病（chronickidneydisease,CKD）5期患者40例（CKD组）。ELISA法检测血浆sTWEAK、超敏C反应蛋白（high-sensitive C-reactiveprotein,hs-CRP）、白细胞介素6（IL-6）及血浆胰岛素生长因子1（insulin growth factor-I,IGF-1）。观察重组人红细胞生成素（rHuEP0）对MHD及CKD5期患者sTwEAK、hs—CRP及IL-6的影响。根据对照组血浆sTwEAK水平为基线,将MHD患者46例再分2组：高sTWEAK组20例、低sTWEAK组26例;分析MHD患者透析时间、透析器及IGF-1等临床资料。结果CKD组血浆sTWEAK蛋白较对照组低（P〈0．01）,rHuEPO治疗后sTwEAK升高（P〈O．05）,hs-CRP降低（P〈0．05）,IL-6无变化（P〉0．05）。MHD组sTwEAK蛋白较对照组高（P〈0．05）,高sTwEAK组26例中,20例（占77％）使用三醋酸膜透析器,透析时间长,IGF-1低;低sTWEAK组20例,16例（占80％）使用聚砜膜透析器,透析时间短,IGF-1高。结论CKD5期患者血浆sTWEAK蛋白低于健康对照组,rHuEPO治疗后升高。MHD组sTWEAK蛋白高于健康对照组,可能与rHuEPO、透析膜种类、透析时间及IGF-1有关。     

Underrecognition and Underestimation of Disturbances in Calcium-Phosphate Balance in Kidney Transplant Recipients

Disturbances in mineral metabolism, namely chronic kidney disease-metabolic bone disease, became more profound with impairment of renal function.The aim of the study was to assess how often calcium, phosphate, alkaline phosphatase, and parathyroid hormone (PTH) were measured in kidney transplant recipients relative to hemodialyzed patients. In addition, prevalence of hypercalcemia defined as calcium concentration over 10.5 mg/dL was assessed.