Uremic Adults Research Articles

The relationship between glutathione peroxidase and bioimpedance parameters in nondiabetic hemodialysis patients

There is growing evidence from experimental and clinical studies that oxidative stress is involved in the pathogenesis of malnutrition. This cross-sectional study aimed to investigate the relationship between glutathione peroxidase (GPx) levels as a marker of antioxidant status and the nutritional status assessed by bioimpedance analysis (BIA). Ninety-seven nondiabetic stable outpatient uremic adults undergoing chronic hemodialysis (HD) were recruited for this study. Impedance measurements were performed using a multifrequency bioelectrical impedance analyzer after dialysis. GPx levels correlated with intracellular water (ICW) (r = 0.341, P = 0.011), ICW/total body weight (r = 0.320, P = 0.017), lean body mass (r = 0.300, P = 0.026) and total body cell mass (r = 0.339, P = 0.011). When patients were divided into two groups according to mean GPx levels (83.9 U/gr hemoglobin), the patients with higher GPx (GPx > 83.9 U/gr hemoglobin) had higher albumin (P = 0.038), lean body mass (P = 0.026), ICW (P = 0.011), and total body cell mass (P = 0.011) compared with those with lower GPx (GPx ≤ 83.9 U/gr hemoglobin). Furthermore, in the patients with higher GPx, body fat; extracellular water/total body water; illness marker and body fat mass index were lower than other group. In conclusion, our results reveal correlation indicating a relationship between antioxidant status (as measured by GPx) and nutritional status as assessed by BIA in nondiabetic HD patients.

Report: Cutaneous disorders in uremic patients on hemodialysis: an Egyptian case‐controlled study

We studied the prevalence of mucocutaneous disorders in uremic adults and children on hemodialysis (HD) vs. controls, in Egypt. A total of 206 Egyptians with uremia (163 adults and 43 children) undergoing HD, and 199 healthy controls (161 adults and 38 children), were examined for mucocutaneous abnormalities. Specific cutaneous diseases associated with renal insufficiency were found in five adults, including acquired perforating dermatosis and pseudo-porphyria. Non-specific abnormalities included xerosis (54%), pallor (42.2%), nail changes (34.9%), hair changes (34%), pruritus (32%), hyper-pigmentation (22.2%), coated tongue (14.1%), ecchymosis (1.5%), and gingival hypertrophy (1.5%). Disorders found significantly more often in uremics than controls included pallor, nail changes, hair changes, pruritus, hyperpigmentation and coated tongue in adults (P < 0.05), and nail changes, hair changes, and hyper-pigmentation in children (P < 0.05). The prevalence of each mucocutaneous abnormality was similar in uremic adults and children except for pallor [more common in adults (P = 0.001)], and hyper-pigmentation [more common in children (P = 0.003)]. A greater number of hepatitis C virus-positive than -negative adult uremics had hyper-pigmentation (P < 0.05), and more diabetic uremics had pruritus than did non-diabetics (P < 0.05). Mucocutaneous disorders occur in adults and children with uremia, some of which are specific associations with the underlying renal disease. Occurrence of some of the non-specific abnormalities, such as xerosis, ecchymosis, and gingival hypertrophy, may be coincidental or associated with factors other than renal insufficiency.

La Osteodistrofia Renal y la Paratohormona supresora de la remodelación ósea

Hyperparatiroidism plays a central role in renal osteodystrophy (ROD) in patients with chronic renal failure (CRF). The first plasmatic paratohormone (PTH) determinations back in 1960 were based in radioinmunoanalysis (RIA), using one antibody against the carboxiterminal or middle region of the hormone. In 1987, an inmunometric method (IMA) based on two antibodies, denominated or sandwich assay was introduced, and it is used until today in clinical treatment, guideliness, and investigation of ROD. In the late 1990s, authors detected two inmunoreactive peaks using the traditional method; one of them moved with intact PTH 1-84 and the second peak migrated with the fraction 7-84, which suggested that an important inactive segment was included in the IMA quantifications, increasing the real value of PTH, therefore, exposing the patient to high doses of active vitamin D. This method allowed the separation of a biologically active fraction (CAP-PTH) from a bone-metabolism suppressor fraction (CIP-PTH), maybe associated to the lack of correlation between bone histomorphometry and intact PTH 1-84. The increase of the adynamic form of ROD and the presence of vascular calcifications in uremic adults have been related to high dosis of vitamin D, along with calcium and phosphorus therapies, that were orientated by plasmatic PTH levels until nowadays. The current treatment of ROD must be re-evaluated according to new knowledge, and future laboratory research will allow a better control of this CRF complication.

Can the controversy of the role of aluminum in Alzheimer's disease be resolved? What are the suggested approaches to this controversy and methodological issues to be considered?

Aluminum (Al) is unquestionably neurotoxic in both experimental animals and certain human diseases. Minute quantities injected intracerebrally into rabbits will induce severe neurological symptoms and neuropathological features of neurodegeneration. Hyper-aluminemia often develops in patients with renal failure being treated with intermittent hemodialysis on a chronic basis, and in severe cases results in an encephalopathy. Uremic adults and premature infants not on dialysis treatment also can develop encephalopathy due to Al toxicity, as is the case when large amounts of alum are used as a urinary bladder irrigant. There are many other examples of Al-induced neurotoxicity; however, the question as to whether Al presents a health hazard to humans as a contributing factor to Alzheimer's disease is still the subject of debate. Several lines of evidence are presented that have formed the basis of the debate concerning the possible pathogenic role for Al in Alzheimer's disease. Important evidence for an Al-Alzheimer's causal relationship is the observation by laser microprobe mass analysis (LMMS) of the presence of Al in neurofibrillary tangles, although there are conflicting data on the extent of the Al deposition. The relatively poor sensitivity of some of the analytical instruments available for these challenging in situ microanalyses could explain the discrepant results, although LMMS and perhaps secondary ion mass spectrometry (SIMS) appear to be sufficiently sensitive. Harmonization of the techniques is an essential next step. There is new evidence that exposure to Al from drinking water might result in cognitive impairment and an increased incidence of Alzheimer's disease. However, these epidemiological studies have inherent problems that must be scrutinized to determine if an association really does exist. An understanding of a possible enhanced bioavailability of Al in this type of exposure, versus other exposures such as antacid intake or industrial exposure, needs to be considered and explored. There has been one promising clinical trial of the treatment of Alzheimer's disease patients with the Al chelator desferrioxamine (DFO). Further studies are needed, and if confirmation is forthcoming then such data could also support an Al-Alzheimer's disease link as well as suggesting that DFO offers potential as a therapeutic agent. The possibility that iron might be the offending agent needs to be considered since DFO is a very strong iron chelator. The significance of Al-induced neurofibrillary degeneration in experimental animals should be assessed especially in light of new data showing that this model exhibits abnormally phosphorylated tau protein structures in the neuronal perikarya. Thus the key questions that must be answered before it can be asserted that Al possesses causal relationship to Alzheimer's disease, are as follows and are addressed in this present discussion: (1) Are there elevations of the concentration of Al in the brains of Alzheimer's disease patients? (2) Is there a relationship between environmental exposure to Al, particularly in drinking water, and an increased risk of Alzheimer's disease? (3) Is treatment with DFO a potentially useful therapeutic approach and to what extent might beneficial effects of DFO implicate Al in the etiology of Alzheimer's disease? (4) Are there similarities between the experimental animal studies and Alzheimer's disease particularly in the development of abnormal forms of tau seen in neurofibrillary tangles? (5) Does Al promote the deposition of the A beta peptide in Alzheimer's disease? (6) Does hyperaluminemia associated with long-term hemodialysis treatment induce neurofibrillary degeneration? If the answer to each of these six questions is yes, then does this assert that Al possesses a causal relationship to Alzheimer's disease? On the other hand, must all six be met to be able to make this assertion?

Growth Hormone and Malnutrition in Dialysis Patients

ObjectiveTo review the normal function of the growth hormone (GH) insulin-like growth factor (IGF) axis, how it is altered in end-stage renal failure, how this may contribute to malnutrition in dialysis patients, and how therapy with recombinant human growth hormone (rHuGH) and recombinant human IGF-I (rHuIGF-1)might be used to treat malnutrition in these patients.Data SourcesStudies in the literature dealing with the GH-IGF endocrine axis and its role in uremic malnutrition.Study SelectionEight studies in which uremic adults were treated with either rHuGH or rHuIGF-I.Data ExtractionData were abstracted from all of these studies.ResultsThe review shows that there are marked abnormalities of the GH-IGF axis in uremic patients and that these lead to a state of GH resistance, which can be overcome by pharmacological doses of rHuGH. A small number of clinical studies in uremic adults suggests that both rHuGH and rHuIGF-I have dramatic beneficial effects on nutritional status in these patients.ConclusionsrHuGH and rHuIGF-I have both been shown to have a beneficial effect on nutritional status in shortterm studies on small numbers of patients. Further studies need to be done for longer periods in larger groups of patients. Areas for additional research are suggested.

Growth Hormone and Malnutrition in Dialysis Patients

To review the normal function of the growth hormone (GH) insulin-like growth factor (IGF) axis, how it is altered in end-stage renal failure, how this may contribute to malnutrition in dialysis patients, and how therapy with recombinant human growth hormone (rHuGH) and recombinant human IGF-I (rHuIGF-1) might be used to treat malnutrition in these patients. Studies in the literature dealing with the GH-IGF endocrine axis and its role in uremic malnutrition. Eight studies in which uremic adults were treated with either rHuGH or rHuIGF-I. Data were abstracted from all of these studies. The review shows that there are marked abnormalities of the GH-IGF axis in uremic patients and that these lead to a state of GH resistance, which can be overcome by pharmacological doses of rHuGH. A small number of clinical studies in uremic adults suggests that both rHuGH and rHuIGF-I have dramatic beneficial effects on nutritional status in these patients. rHuGH and rHuIGF-I have both been shown to have a beneficial effect on nutritional status in short-term studies on small numbers of patients. Further studies need to be done for longer periods in larger groups of patients. Areas for additional research are suggested.

Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor I (IGF-I) and IGF-II in acid-chromatographed uremic serum.

Somatomedin levels measured by radioreceptor assay (RRA) or RIA on acid-ethanol-extracted or unextracted serum from patients with uremia are quite variable relative to normal values. We have investigated whether compounds accumulating in uremic serum were interfering with these RRA and RIA measurements. Insulin-like growth factor I (IGF-I) and IGF-II were separated from carrier proteins by either Sephadex G-50 acid chromatography or acid-ethanol extraction. IGF-I was measured by RIA, and IGF-II was determined by rat placental membrane RRA. IGF-I levels in the acid-ethanol extracts of serum from eight uremic adults were only 50% of the levels found in seven normal subjects, and IGF-II levels in these uremic patients were 350% of normal values. However, these significant differences were not found when comparable serum samples were acid chromatographed rather than acid-ethanol extracted; instead, IGF-I levels were 343 +/- 168 (mean +/- SD) ng/ml in uremic patients and 325 +/- 54 ng/ml in normal subjects, while IGF-II levels were 780 +/- 215 ng/ml in uremic patients and 588 +/- 46 ng/ml in normal subjects. To determine whether compounds that interfere with somatomedin assays were present in the acid-ethanol extracts of uremic serum, we acid chromatographed these extracts and found that a compound eluting in the carrier protein fraction of the uremic extract artifactually decreased IGF-I levels measured by RIA and increased IGF-II levels measured by RRA. We also found that unsaturated carrier protein binding of IGF-I and IGF-II was significantly increased in the carrier protein fraction of uremic acid-ethanol extracts at the dilutions used for somatomedin assays. We conclude that acid chromatography of unextracted or acid-ethanol-extracted uremic serum is necessary to remove a compound, probably unsaturated carrier protein, which interferes with RIA of IGF-I and RRA of IGF-II. Once this compound is removed, serum IGF-I levels (RIA) in uremic patients are not different from normal, and serum IGF-II levels (RRA) are not lower than normal.

Abnormal erythrocyte pyrimidine nucleotides in uremic subjects.

Uremia causes major increases in the erythrocyte (RBC) purine nucleotides, presumably secondary to phosphate retention, but no previous study has been made of the pyrimidine nucleotides, normally absent from RBC. This investigation was prompted by demonstration of the abnormal presence of RBC pyrimidine nucleotides, primarily cytidine triphosphate (CTP) plus cytidine diphosphate-choline (CDP-C) and cytidine diphosphate-ethanolamine (CDP-E), in two types of congenital hemolytic anemia as well as in lead poisoning. These observations suggested an analogy to the RBC membrane dysfunction of uremia. This is a report of the identification of CDP-C and CDP-E as the predominant abnormal pyrimidine nucleotides in the RBC hemolysates of uremic subjects. High-performance liquid chromatography of hemolysates from uremic adults showed a 50% increase in purine nucleotides and the abnormal presence of pyrimidine nucleotides and diesters at approximately 10% of the concentration of the purine nucleotides. By means of UV spectra and 31P nuclear magnetic resonance, these were identified as CDP-C and CDP-E. The increased purine and abnormal pyrimidine nucleotides of uremic RBC were unrelated to the pre- or posthemodialysis state, allopurinol, levels of blood lead, copper and zinc, or RBC pyrimidine 5'-nucleotidase, the cytosolic enzyme that specifically dephosphorylates the pyrimidine nucleotides. Although the accumulation of CTP, CDP-C and CDP-E may be an epiphenomenon of phosphate retention, it also suggests a common pathway to the accelerated hemolysis of chronic renal insufficiency.

USE OF DEFERROXAMINE (D) IN A PATIENT WITH IRON (Fe) OVERLOAD MAINTAIMED ON CHRONIC HEMOKDIALYSIS (HD)

Anemia is characteristic of chronic renal failure with resultant transfusion dependency, especially in growing children maintained on chronic HD. Most of these patients develop Fe overload. Chelation therapy has been used in uremic adults on HD to treat Fe overload, but its use in children has not been detailed. We report a 15-year-old white male who has been on chronic HD for the past 8 years. He has chronic normocytic, normochromic anemia of uremia. To maintain the hematocrit (Hct) above 20% and hemoglobin (Hgb) above 6 gm%, he has received 400 cc of packed red blood cells every 4-5 weeks for the past 6 years. Because of elevated serum ferritin and concern about Fe overload, chelation therapy with D was begun. A dose of 24 mg/kg is infused I.V. during the first hour of HD three times per week. The patient continues with the same transfusion requirements, and no adverse effects of D have been noted. The data indicate that chelation therapy during hemodialysis can be used to treat Fe overload in children to prevent hemosiderosis.CV: corpuscular volume; CHC: corpuscular hemoglobin concentration

Bone Mineral Content in Chronic Renal Failure during Long‐Term Treatment with 1α‐Hydroxycholecalciferol

ABSTRACT. Bone mineral content of the radius (BMC) has been measured by photonabsorptiometry in 22 adults with chronic renal failure before and after on an average 15.4 months of treatment with 1α‐hydroxycholecaiciferol (1α‐HCC). Identical measurements were performed in a control group comprising 26 uremic adults, who did not receive any vitamin D supplements during the study. The BMC was reduced and not significantly different in the two groups of uremic patients at the initial measurement. During treatment with 1α‐HCC the BMC increased significantly in 3 patients, while the total group showed only a small (mean 0.7%), non‐significant increase. In the control group the BMC decreased significantly in 4 patients, while the total group showed a non‐significant decrease (mean 3.5%). However, a comparison of the BMC changes in the two groups revealed a significant difference (p &lt;0.01). The BMC changes in the 1α‐HCC group were uncorrelated to changes in serum calcium, ionized calcium, phosphate, alkaline phosphatases, immunoreactive parathyroid hormone and intestinal calcium abosrption during therapy. The data indicate that cessation of skeletal demineralization in chronic renal failure may be achieved by 1α‐HCC, but re‐mineralization of the skeleton seems to be attainable only in a minority of adult patients.