Parathyroid hormone status does not influence blood and bone lead levels in dialysis patients

Elevated blood lead levels, a risk factor for cardiovascular disease, have been reported among patients with end-stage renal disease. We evaluated whether these higher levels are due to release of lead from the skeleton because of uremic bone disease. Fifty-one African-American patients with end-stage renal disease were recruited from 3 Tulane University dialysis programs between January and July 2005. An interviewer-administered questionnaire, blood specimen collection and 109Cd-based x-ray fluorescence measurement of tibia lead occurred during a single study visit. Levels of serum parathyroid hormone (PTH), calcium, phosphorus, and albumin were abstracted from the patients' charts. The distributions of tibia and blood lead were similar across levels of serum PTH. Specifically, for participants with serum PTH <300 pg/mL and > or =300 pg/mL, median tibia lead was 21 microg/g and 17 microg/g, respectively, and geometric mean blood lead levels were 6.7 microg/dL and 6.6 microg/dL, respectively (P = 0.70 and 0.87, respectively). After adjustment for age, gender, education, cigarette smoking, and dialysis vintage, natural log transformed blood lead was 0.022 lower in patients with serum PTH > or =300 pg/mL (P = 0.87). There were no differences in tibia and blood lead across levels of serum calcium, serum phosphorus, and the calcium phosphorus product (all P > 0.40). The high blood lead levels observed among dialysis patients do not appear to be the result of increased bone turnover. The causes of higher blood lead levels for these patients need to be identified and attenuated.     

Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology

Thrombocytopenia is a substantial clinical problem for patients with myelodysplastic syndromes (MDS). Cytokine treatment for granulocytopenia and anaemia may further reduce the platelet counts. We studied serum thrombopoietin levels (S-TPO) in 52 patients with MDS and 96 healthy controls and related the results to clinical and morphological variables. S-TPO was also assessed after treatment with granulocyte-CSF (G-CSF) and erythropoietin (EPO) in 30 of these patients. S-TPO in MDS was not a normally distributed variable; mean value was 394 pg/ml, SD +/-831 and median value 123 (12-5000 pg/ml). The controls showed lower S-TPO levels than the patients (median 78 pg/ml, P = 0.003) whereas no differences between the MDS subgroups were observed (P = 0.86). Patients with ringed sideroblastic anaemia (RARS) showed the highest platelet counts and higher S-TPO levels than the controls (P = 0.005). No association between platelet counts and S-TPO levels was found in the patients (P = 0.67). TPO levels were generally low in patients with refractory anaemia with an excess of blasts (RAEB), but very high levels were found in five patients. Patients with a high transfusion need had higher S-TPO levels, whereas bone marrow blast counts, cellularity or megakaryocytes showed no correlation with S-TPO. Patients with 5q- showed lower TPO levels than the other patients, indicating that thrombopoietin is not a mediator of thrombocytosis in these cases. Treatment with G-CSF + EPO significantly reduced the platelet counts (P = 0.0002), but this change was not related to significant changes in S-TPO levels or morphology. Patients with RARS and thrombocytosis who normalized their platelet counts showed a concomitant reduction in S-TPO. This may suggest that the increased platelet counts observed in RARS may be caused by increased S-TPO levels. In conclusion, our study shows that platelet, megakaryocyte and thrombopoietin regulation is rather complex in myelodysplastic syndromes and that spontaneous or induced thrombocytopenia are not usually mirrored by increased S-TPO levels.     

Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes

To evaluate the diagnostic value of thrombopoietin (TPO, c-mpl ligand) measurements, and clarify the regulatory mechanisms of TPO in normal and in thrombocytopenic conditions, the plasma TPO concentration was determined in normal individuals (n = 20), umbilical cord blood (n = 40), chronic idiopathic thrombocytopenic purpura (ITP; n = 16), in severe aplastic anaemia (SAA; n = 3), chemotherapy-induced bone marrow hypoplasia (n = 10), myelodysplastic syndrome (MDS; n = 11), and sequentially during peripheral blood progenitor cell transplantation (n = 7). A commercially available ELISA and EDTA-plasma samples were used for the analysis. The plasma TPO concentration in the normals and umbilical cord blood were 52 ± 12 pg/ml and 66 ± 12 pg/ml, respectively. The corresponding values in patients with SAA and chemotherapy-induced bone marrow hypoplasia were 1514 ± 336 pg/ml and 1950 ± 1684 pg/ml, respectively, and the TPO concentration, measured sequentially after myeloablative chemotherapy and peripheral blood progenitor cell transplantation, was inversely related to the platelet count. In contrast, the plasma TPO recorded in patients with ITP (64 ± 20 pg/ml) and MDS (68 ± 23 pg/ml) were only slightly higher than normal levels. In conclusion, TPO levels were significantly elevated in patients in which bone marrow megakaryocytes and platelets in circulation were markedly reduced, whereas TPO levels were normal in ITP patients, and only slightly increased in the MDS patients. These latter patients displayed a preserved number of megakaryocytes in bone marrow biopsies. Our data support the suggestion that megakaryocyte mass affects the plasma TPO concentration. In thrombocytopenic patients a substantially increased plasma TPO implies deficient megakaryocyte numbers. However, TPO measurements do not distinguish between ITP and thrombocytopenia due to dysmegakaryopoiesis, as seen in MDS patients.     

Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure

Although myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Plasma thrombopoietin levels were measured in 120 patients who had myelodysplastic syndrome with thrombocytopenia (< 100 × 10⁹/L) to determine any correlation to markers associated with immune pathophysiology and outcome. Thrombopoietin levels were consistently low for patients with refractory anemia with excess of blasts, while patients with other myelodysplatic syndrome subsets had more variable results. Patients with thrombopoietin levels of 320 pg/mL and over had increased glycosylphosphatidylinositol-anchored protein-deficient blood cells (49.1% vs. 0%), were more likely to have a low International Prognostic Scoring System (IPSS) score (≤1.0, 100% vs. 65.5%), a higher response rate to immunosuppressive therapy (84.2% vs. 14.3%), and a better 5-year progression-free survival rate (94.1% vs. 63.6% for refractory cytopenia with unilineage dysplasia; 100.0% vs. 44.4% for refractory cytopenia with multilineage dysplasia). In conclusion, increased plasma thrombopoietin levels were associated with a favorable prognosis of bone marrow failure and could, therefore, represent a reliable marker for a benign subset of myelodysplastic syndrome.     

Leptin levels in peripheral blood and bone marrow in orthopedic patients

Leptin is a protein with hormonal activity and is produced mainly by adipocytes. Its primary function in the human organism is regulation of the calorie intake via the anorectic action in the hypothalamus. Leptin participates also in the regulation of haematopoiesis and immunity processes. There are many data on leptin production by peripheral adipose tissue and it is also known that leptin is produced by adipocytes of bone marrow. It was assumed for a long time that adipocytes of bone marrow are not only a passive source of energy but have, similarly as stromal cells, a regulatory function. However, it is not clear in what way the adipose tissue of bone marrow participates in the regulation of haematopoiesis and what role is played in this relationship by leptin production. The authors attempted to assemble in their small study data on leptin production in bone marrow and at the same time parameters of lipids of bone marrow which can be assessed by cytological examination. The authors examined 16 patients (9 men and 7 women) subjected to orthopaedic surgery. They assessed leptin concentrations in sera obtained from peripheral blood and bone marrow, and at the same time they assessed by morphological examination in smears of bone marrow some parameters associated with lipids. The authors found that serum leptin levels from bone marrow are significantly lower than in peripheral blood (p < 0.0005). These values correlate closely (r = +0.77, p < 0.0005). The authors found also a positive correlation between serum leptin (r = +0.56, p < 0.02) and bone marrow leptin (r = +0.72, p < 0.002) and the body mass index (BMI). A positive correlation was found also between serum (r = +0.65, p < 0.006) and bone marrow leptin (r = +0.80, p < 0.0002) and age. The authors did not detect any significant correlations between parameters of the lipids of bone marrow and leptin levels in serum and bone marrow. The assembled results can in combination with data from the literature indicate that the actual amount of leptin in bone marrow is influenced rather by its consumption by haematopoietic tissue than by its production.     

New insights into the regulation of megakaryocytopoiesis by haematopoietic and fibroblastic growth factors and transforming growth factor β1

Effects of cytokines on murine megakaryocyte (MK) colony formation from either unfractionated marrow cells or purified early haematopoietic cells were studied. Recombinant interleukin-3 (IL3), interleukin-6 (IL6), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo) and acidic and basic fibroblast growth factor (aFGF and bFGF) each was able to stimulate MK colony growth although they varied somewhat in their potential. IL6 and FGFs, in addition to their effect on MK colony growth, increased the size of individual MK. The combination of IL3 with IL6 or FGF resulted in an additive action. Monoclonal anti-IL6 antibody completely neutralized the activity of mouse IL6 and FGFs but had no effect on human IL6, mouse IL3 and GM-CSF. When using purified lineage negative marrow cells, only IL3 and IL6 promoted MK colony formation. Transforming growth factor beta 1 (TGF-beta 1) at 10-200 pg/ml selectively inhibited IL3-induced MK colony formation, and at 0.2-0.5 ng/ml it still had no obvious effect on the activity of IL6 or GM-CSF but caused an inhibition of FGF-induced MK colony formation. These data suggest that differential mechanisms are involved in the regulation of megakaryocytopoiesis by IL3, IL6, FGFs and GM-CSF, and that TGF-beta 1 negatively regulates MK development mainly by interfering with the action of IL3.     

Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl

Mice with a null mutation in the thrombopoietin (TPO) receptor c-Mpl were generated by gene targeting. c-mpl-deficient mice developed normally but were deficient in megakaryocytes and severely thrombocytopenic. The hematocrit and numbers of mature circulating leukocytes were normal in mpl-/- mice, as was the distribution of morphologically identifiable precursors in hematopoietic tissues. Bone marrow and spleen cells of adult mpl-/- mice lacked specific binding sites for TPO, were unresponsive to TPO in culture, and displayed a marked deficiency in progenitor cells with megakaryocytic potential. Significantly, total hematopoietic progenitor cell numbers were also reduced in mpl-/- mice including multipotential, blast cell, and committed progenitors of multiple lineages. The megakaryocyte deficiency was evident as early as 14 days of gestation in mpl- deficient mice, although reductions in progenitor cell numbers arose only later in development. The data suggest that the critical function of c-Mpl signalling in megakaryocytopoiesis is in maintenance of mature megakaryocyte numbers through control of progenitor cell proliferation and maturation. Moreover, our results also imply an important role for TPO and c-Mpl in the production of primitive pluripotent progenitor cells as well as progenitor cells committed to nonmegakaryocytic lineages.     

Differential mechanisms in the regulation of endogenous levels of thrombopoietin and interleukin-11 during thrombocytopenia: insight into the regulation of platelet production

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship of endogenous thrombopoietic cytokine levels and circulating platelet (PLT) counts, we measured the levels of thrombo-poietin (TPO), interleukin-11 (IL-11), and interleukin-6 (IL-6) in patients with significant thrombocytopenia secondary to both marrow hypoplasia and increased PLT destruction. Increased endogenous levels of TPO and IL-11, but not IL-6, were detected in bone marrow transplant patients with thrombocytopenia following myeloablative therapy (BMT/MAT) (TPO: 1,455.5 +/- 87.3 pg/mL, [PLT 39,600 +/- 7,800/microL], P < .001, n = 12; IL-11: 227.9 +/- 35 pg/mL, [PLT 32,900 +/- 57,000/microL], P < .05, n = 19; IL-6: 25.8 +/- 8.4 pg/mL, [PLT 32,800 +/- 5,057/microL], P > .05, n = 4] v normal donors [TPO < 150 pg/mL, n = 8; IL-11 < 50 pg/mL, n = 9; IL-6 < 10 pg/mL, n = 5 [PLT 203,000 +/- 7,500/microL]. There was a significant inverse correlation between endogenous levels of TPO and IL-11, but not IL-6, and PLT counts in the MAT/BMT patients (TPO: r = -0.57, P < .0001, n = 188; IL-11: r = - 0.329, P < .0001, n = 249; IL-6: r = -0.1147, P > .05, n = 62). In patients with immune thrombocytopenia purpura (ITP), with decreased PLT survival, but intact bone marrow megakaryocytopoiesis, endogenous IL-11 levels were significantly increased (328.0 +/- 92.6 pg/mL, [PLT: 20,900 +/- 3,000/microL], P < .05, n = 25). However, endogenous TPO levels remained undetectable (< 150 pg/mL, [PLT 30,500 +/- 5,500/microL], n = 15). These results suggest that there may be differential mechanisms regulating endogenous TPO, IL-11, and IL-6 levels during acute thrombocytopenia and suggest that the absolute number of circulating PLTs may not always be the sole regulator of endogenous TPO levels. Other mpl-expressing cells of the megakaryocyte lineage may contribute to the regulation of circulating TPO levels as well. Our results also suggest IL-11 levels may in part, be regulated by a negative feedback loop based on circulating PLT counts, but also may, in part, be regulated by a variety of inflammatory agonists. Both TPO and IL-11, therefore, appear to be active thrombopoietic cytokines regulating, in part, megakaryocytopoiesis during states of acute thrombocytopenia.     

New insights into iron homeostasis through the study of non-HFE hereditary haemochromatosis

Non-HFE haemochromatosis is a negative definition applied to all those haemochromatosis disorders that are unrelated to HFE mutations. Four genes are responsible for the distinct types of non-HFE haemochromatosis: hepcidin and hemojuvelin are the genes involved in type 2 or juvenile haemochromatosis, transferrin receptor 2 is involved in type 3 haemochromatosis, and ferroportin 1 is mutated in type 4, the atypical dominant form of primary iron overload. Molecular genetic studies of these conditions have greatly contributed to our understanding of the regulation of iron absorption. A milestone was the discovery that hepcidin, the key iron regulator in mice, is the gene mutated in the most severe, juvenile form of haemochromatosis. This finding indicates a fundamental role of hepcidin in inhibiting both iron absorption from duodenal cells and iron release from macrophages, and has opened up a new view of haemochromatosis as a disorder of hepcidin.     

In vivo adenovirus vector-mediated transfer of the human thrombopoietin cDNA maintains platelet levels during radiation-and chemotherapy- induced bone marrow suppression

Thrombopoietin (TPO, c-mpl ligand) has emerged as a major hematopoietic cytokine stimulating megakaryocyte proliferation, endomitosis, and platelet production. This study shows that a single administration of an adenovirus (Ad) vector encoding TPO (AdCMV.TPO) abrogates thrombocytopenia induced in mice by carboplatin and irradiation. Normal Balb/c mice receiving the vector had increased platelet counts peaking at 7 days and returning to baseline by day 15. Mice rendered pancytopenic with 500 rads and 1.2 mg of carboplatin had a nadir platelet count of five percent of the baseline. Mice receiving AdCMV.TPO 3 days before receiving irradiation and chemotherapy achieved a platelet nadir fourfold higher, and had significant reduction in duration of thrombocytopenia, than mice receiving the control Ad vector. Introduction of AdCMV.TPO the same day of chemotherapy and irradiation was equally effective in acceleration of platelet recovery, but administration of AdCMV.TPO 3 days after chemotherapy-radiation had little effect on platelet recovery. At 30 days after therapy bone marrow and spleen of mice treated with AdCMV.TPO were populated with a large number of polyploid megakaryocytes, but there was no evidence of circulating megakaryocytes in the liver or lungs and no pathologic bone abnormalities such as osteosclerosis or myelofibrosis. These observations suggest that an Ad vector may be an excellent delivery system to provide adequate TPO production to maintain platelet levels in circumstances associated with life-threatening thrombocytopenia.     

The synergistic effect of thrombopoietin in erythropoiesis and myelopoiesis from human bone marrow cells

We sought to determine whether recombinant human thrombopoietin (TPO) acts synergistically with recombinant human erythropoietin (EPO) and/or recombinant human interleukin-3 (IL-3) on erythroid burst formation and granulocyte-macrophage colony formation from human bone marrow (BM). BM cells were from 5 adults and 15 children who underwent bone marrow examination because of a clinical suspicion of malignancy; their bone marrows as well as the complete blood counts were normal and were cultured in a methylcellulose system. TPO has a synergistic effect with EPO or EPO + IL-3 on erythropoiesis of human BM, as the addition of TPO to EPO significantly gave rise to more erythroid bursts (p = 0.0001) and the addition of TPO to EPO + IL-3 might give rise to more erythroid bursts (p = 0.05). TPO also has a synergistic effect with recombinant human granulocyte colony-stimulating factor (G-CSF) on myelopoiesis of human BM, since the addition of TPO to G-CSF gave rise to significantly more granulocyte-macrophage colonies (p = 0. 0001). Besides its well-known significant role in megakaryopoiesis, TPO also has synergistic effects on erythropoiesis and myelopoiesis.     

Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes

Umbilical cord blood (CB) is a valuable source of stem cells for transplantation, but CB transplantations are frequently complicated by delayed platelet engraftment. The reasons underlying this are unclear. We hypothesized that CB- and peripheral-blood (PB)-derived megakaryocytes (MKs) respond differently to the adult hematopoietic microenvironment and to thrombopoietin (Tpo). To test this, we cultured CB- and PB-CD34(+) cells in adult bone marrow stromal conditioned media (CM) or unconditioned media (UCM) with increasing concentrations of recombinant Tpo and compared the effects of these conditions on CB-versus PB-MKs. PB-MKs reached highest ploidy in response to UCM + 100 ng/mL rTpo, and the addition of CM inhibited their maturation. In contrast, CB-MKs reached highest ploidy in CM without rTpo, and high rTpo concentrations (> 0.1 ng/mL) inhibited their maturation. This is the first evidence that human neonatal and adult MKs have substantially different biologic responses to Tpo and potentially to other cytokines.     

New insights into the role of T cells in the vicious cycle of bone metastases

PURPOSE OF REVIEW: Bone metastases interact with the bone microenvironment. Cancer cells modulate the functions of osteoblasts and osteoclasts to induce new bone formation or bone resorption, leading to secondary stimulation of tumor development. Recent findings suggest the involvement of T cells in this process. RECENT FINDINGS: Bone metastatic cancer cells produce factors such as parathyroid hormone-related protein, interleukin-7, and interleukin-8 that can recruit or activate T cells. T cells are involved in bone remodeling and can induce osteoclastic resorption. Bone resorption releases transforming growth factor-beta, however, which could suppress T-cell antitumor immune responses. Bisphosphonate antiresorptive drugs are the approved treatment for solid tumor bone metastases. They have recently been found to activate the cytolytic activity of gammadelta T cells. Thus, inhibitors of transforming growth factor-beta or antiresorptive therapies may be effective enhancers of antitumor immune responses in bone. SUMMARY: T cells at the site of bone metastases may be functionally suppressed by factors in the bone microenvironment. Instead of acting against tumor cells, they may increase bone resorption, making bone a privileged site for tumor growth.     

New insights into the mechanism of the elevation of plasma brain natriuretic polypeptide levels in patients with left ventricular hypertrophy

BACKGROUND: Messenger RNA of brain natriuretic polypeptide (BNP) is detected in both the atrium and the ventricle in vitro. Clinical usefulness has been shown in assessment of BNP level in patients with left ventricular hypertrophy; however, few studies have reported the role of the atrium and ventricle separately in the secretion of BNP from the hypertrophied heart. OBJECTIVE: To investigate how the atrium and ventricle secrete natriuretic peptides by comparing the regional concentration of atrial natriuretic polypeptide (ANP) or BNP in the hypertrophied heart with clinical parameters. PATIENTS AND METHODS: ANP and BNP were measured in blood samples from the aortic root, the anterior interventricular vein (AIV) and the coronary sinus in 12 control subjects, 10 subjects with hypertensive hypertrophy and eight with non-obstructive hypertrophic cardiomyopathy. The difference in concentration between the aortic root and the AIV and that between the AIV and the coronary sinus was calculated to estimate ventricular and atrial secretion, respectively. RESULTS: Plasma BNP levels correlated significantly with left ventricular mass index, pulmonary artery wedge pressure, stroke volume and left atrial dimension. Stepwise multiple regression analysis identified BNP from the atrium, not the ventricle, as an independent predictor of left ventricular mass. CONCLUSIONS: These data suggest that atrium-derived BNP is a significant predictor of left ventricular mass index in patients with left ventricular hypertrophy. The atrium-derived component contributes significantly to the elevation of plasma BNP level, reflecting atrial pressure and volume loading in left ventricular hypertrophy without systolic dysfunction.     

Functional status and personality in patients on chronic dialysis

This study describes the functional status of 53 dialysis patients; The Sickness Impact Profile test (SIP), the Karnofsky Activity Scale and Karolinska Scales of Personality (KSP) are used. Our results showed that the dialysis patients had a higher (P less than 0.001) total SIP score when compared to normal controls. Thus, the patients had a worse functional status than the controls. The results of the Karnofsky Activity Scale, estimated by a nurse, were in accordance with the results of the SIP score. The KSP-test showed that both men and women had significantly lower scores in the aggression scale than a control group. We conclude that the dialysis situation has a major influence on the quality of life of dialysis patients. Great attention should be paid to the development of supporting programmes for this patient group.     

Comparative effects of thrombopoietic-stimulatory factor and spleen cell-conditioned medium on megakaryocytopoiesis in a short-term bone marrow liquid culture system

The effect of partially purified thrombopoietic stimulatory factor (TSF) on megakaryocytopoiesis was studied using the soft-gel colony-forming assay and a short-term marrow liquid culture system (STLC) and compared to the effects of megakaryocyte colony-stimulating activity present in pokeweed mitogen-stimulated spleen cell-conditioned medium (PWCM). Nonadherent cells from STLC were sampled daily for acetylcholinesterase-positive cells and megakaryocyte progenitor cells (CFU-M). CFU-M were assayed in the soft-gel colony-forming system using PWCM as a source of colony-stimulating activity. Proliferative capacity of CFU-M obtained from liquid culture was determined from megakaryocyte colony size (number of megakaryocytes per colony) following plating of cells in a secondary colony-forming assay. Megakaryocytes were grouped into four maturation classes and megakaryocyte diameter was determined on acetylcholinesterase-stained cytocentrifuged cells using an eye-piece micrometer. TSF produced no CFU-M-derived colonies in the soft-gel colony-forming assay. Addition of TSF to STLC had no effect on the total number of CFU-M, megakaryocyte colony size, or total number of megakaryocytes compared to unstimulated STLC. However, on days 4-9 there was a significant increase in megakaryocyte diameter and the proportion of mature (stage III, IV) megakaryocytes obtained from TSF containing STLC compared to unstimulated STLC. In contrast, 5 days after addition of PWCM to STLC a sixfold increase in the total number of CFU-M per flask and a threefold increase in megakaryocytes was observed compared to unstimulated STLC. However, megakaryocyte colony size and megakaryocyte size were significantly reduced and a greater number of immature (stage I, II) megakaryocytes were present in STLC containing PWCM compared to unstimulated STLC. These results indicate that TSF accelerates the maturation of megakaryocytes in vitro and that a factor or factors present in spleen cell-conditioned medium, in addition to influencing megakaryocyte progenitor cell proliferation, also affect(s) megakaryocyte size.     

Diminished blood selenium levels in renal failure patients on dialysis: correlations with nutritional status

Selenium deficiency has been implicated as contributing to the development of cardiovascular disease, skeletal muscle myopathy, anemia, increased cancer risk, and deranged immune function. Since these problems may also be associated with renal failure, and the kidney plays an important role in selenium homeostasis, we measured selenium and compared it with nutritional status in 24 stable hemodialysis patients, 12 chronic intermittent peritoneal dialysis patients, and 29 healthy controls. Whole blood and plasma selenium was determined by a spectrofluorometric method. For whole blood the mean (+/- SD) selenium levels were 0.11 +/- 0.02 micrograms/ml in controls vs. 0.071 +/- 0.01 micrograms/ml in hemodialysis cases and 0.052 +/- 0.006 micrograms/ml in peritoneal dialysis (p less than 0.005). Significant decreases were seen also for plasma and red blood cell selenium in all groups respectively. Pre- and postdialysis plasma and whole blood selenium levels showed no significant changes in both dialysis groups. However, predialysis residual peritoneal fluid did contain selenium (0.029 +/- 0.005 micrograms/ml). Some evidence of protein-energy undernutrition was noted in both dialysis groups compared with controls. However, no significant differences in nutritional parameters were noted between hemodialysis and peritoneal dialysis patients. When all groups were combined, significant correlations were found between whole blood selenium and serum albumin (r = 0.61; p less than 0.001), triceps skin fold in females (r = 0.62; p less than 0.001), and midarm muscle circumference in males (r = 0.71; p less than 0.001). We conclude that low blood selenium is present in renal failure patients undergoing hemodialysis. This abnormality is even greater in peritoneal dialysis cases.(ABSTRACT TRUNCATED AT 250 WORDS)