Group Of Chronic Renal Failure Patients Research Articles

Inflammatory status in chronic renal failure: The role of homocysteinemia and pro-inflammatory cytokines

To evaluate determinants of inflammatory markers in chronic renal failure patients according to the level of glomerular filtration rate. One hundred fifty four patients (Age: 44 ± 06 years; male/female: 66/88) with chronic renal failure (CRF) were divided into 6 groups according to the National Kidney Foundation (NKF) classification. They included 28 primary stage renal failure patients (CRF 1), 28 moderate stage renal failure patients (CRF 2), 28 severe stage renal failure patients (CRF 3), 18 end-stage renal failure patients (CRF 4), 40 hemodialysis (HD) patients, and 12 peritoneal dialysis (PD) patients. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and C-reactive protein (CRP) were analyzed by immunosorbent assay kit (ELISA) (Cayman Chemical's ACETM EIA kit). Immunoassay methods were used for total homocysteine (tHcy) (fluorescence polarization immunoanalysis HPLC, PerkinEmer 200 series), transferrin (MININEPHTM human transferin kit: ZK070.R), ferritin (ADVIA Centaur) and fibrinogen analysis (ACL 200). Differences between groups were performed using SPSS 20.0 and data are expressed as the mean ± SD. Results showed that in comparison with CRF 1 group and other groups, TNF-α and IL-6 levels were respectively more elevated in HD (16.38 ± 5.52 pg/mL vs 0.39 ± 0.03 pg/mL, 11.05 ± 3.59 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001) and PD (14.04 ± 3.40 pg/mL vs 0.39 ± 0.03 pg/mL, 10.15 ± 1.66 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001). IL-1β levels were increased in HD (9.63 ± 3.50 pg/mL vs 3.24 ± 0.10 pg/mL, P < 0.001) and CRF 4 (7.76 ± 0.66 pg/mL vs 3.24 ± 0.10 pg/mL, P < 0.001) patients than in CRF 1 and in the other groups. Plasma tHcy levels were higher in HD (32.27 ± 12.08 μmol/L) and PD (28.37 ± 4.98 μmol/L) patients compared to the other groups of CRF (P < 0.001). The serum CRP level was significantly increased in HD (18.17 ± 6.38 mg/L) and PD (17.97 ± 4.85 mg/L) patients compared to the other groups of CRF patients (P < 0.001). The plasma fibrinogen level was more elevated in HD (6.86 ± 1.06 g/L) and CRF 4 (6.05 ± 0.57 g/L) than in the other groups (P < 0.001). Furthermore; the ferritin level was higher in HD (169.90 ± 62.16 ng/mL) and PD (90.08 ± 22.09 ng/mL) patients compared to the other groups of CRF (P < 0.001). The serum transferrin value was significantly decreased especially in PD (1.78 ± 0.21 g/L) compared to the other groups (P < 0.001). We found a negative correlation between glomerular filtration rate (GFR), TNF-α levels (r = -0.75, P < 0.001), and tHcy levels (r = -0.68, P < 0.001). We observed a positive correlation between GFR and transferrin levels (r = 0.60, P < 0.001). CRF was associated with elevated inflammatory markers. The inflammation was observed at the severe stage of CRF and increases with progression of renal failure.

Iron Status in Chronic Renal Failure with Anemia

Background: Chronic renal failure (CRF) is a major public health hazard. Anemia is an accompaniment and independent risk factor for the development of cardiac dysfunction and responsible for 40% to 50% deaths in CRF patients. For this reason, effective erythropoiesis to correct anemia by erythropoietin therapy and mainte­nance of target iron level is very much important. Subjects and Methods: The present study has been designed to observe iron status in different stages of CRF patients suffering from anemia. For this purpose, 65 male CRF patients with anemia and 25 healthy male (control) subjects, in the age group of 30–50 years were selected randomly from BSMMU outpatient department. Iron level, hemoglobin and creati­nine clearance were estimated by usual laboratory technique. Data were analyzed statistically by ANOVA and Pearson’s correlation coefficient test. Among 65 CRF patients, 15 were mild, 25 were moderate and 25 were reported severe renal failure with anemia. Results: The mean serum iron, transferrin saturation and ferritin were significantly ( P < 0.001) lower in moderate but severe in CRF patients with anemia compared to those of healthy subjects and these values were also significantly ( P < 0.001) lower in severe CRF than those of mild and moderate groups of patients. On the other hand, total iron binding capacity was significantly ( P < 0.001) higher only in severe group of CRF patients compared to healthy, mild and moderate group of CRF patients. In addition, 72% severe group of CRF patients had serum ferritin and 28% had transferrin saturation below the target level (≥100 ng/ml serum ferritin & ≥20% transferrin saturation). Decreasing iron status which is more marked in severe CRF patients are suggestive of iron deficiency and iron status below the target level in severe CRF patients indicate inadequate iron store. Also, a significantly ( P < 0.001) decreasing hemoglobin concentration is observed in severe CRF case compared to those of mild and moderate CRF patients with anemia. Conclusion: From the present study it may be concluded that changes in iron status occur in CRF patients with anemia and these changes vary along with severity of CRF. DOI: http://dx.doi.org/10.11566/cmoshmcj.v12i1.21 Chatt Maa Shi Hosp Med Coll J 2013; 12(1): 12-17

Recombinant Human Erythropoietin Treatment of Chronic Renal Failure Patients Normalizes Altered Phenotype and Proliferation of CD4‐positive T Lymphocytes

Patients with chronic renal failure (CRF) receive recombinant human erythropoietin (rhEPO) for the correction of anemia. However, rhEPO also has an immunomodulatory effect. Detailed changes of phenotype and function of CD4(+) T lymphocytes in CRF patients receiving rhEPO have not been reported yet; their study may bring insight into understanding of this immunomodulatory action of rhEPO. Two groups of CRF patients were included into the study: those treated; and those not receiving rhEPO. The expression of activation markers on CD4(+) lymphocytes was measured with flow cytometry, both ex vivo and in vitro. The kinetics of CD4(+) T lymphocytes proliferation was calculated using a dividing cells tracing method and numerical approach. Significantly higher percentages of CD4(+)CD95(+), CD4(+)HLA-DR(+) cells, and lower percentages of CD4(+)CD69(+) and CD4(+)CD28(+) cells were observed in both rhEPO-treated and untreated patients when compared with healthy controls. Changes in the proportions of CD4(+)CD28(+) and CD4(+)HLA-DR(+) subpopulations were dependent on the type of rhEPO, being more pronounced for rhEPObeta. CD4(+) lymphocytes from untreated patients exhibited decreased expression of CD28 and CD69 after stimulation in vitro, whereas the expression of these antigens on lymphocytes of rhEPO-treated patients was similar to that observed in healthy controls. Fewer CD4(+)CD28(+) T lymphocytes of untreated patients proliferated in vitro; these cells had longer G0-->G1 time, which negatively correlated with surface expression of CD28. Our study confirms that rhEPO treatment normalizes activation parameters of CD4(+) T lymphocytes and their proliferative capacity, which could explain earlier described immunomodulatory effects of rhEPO in patients suffering from CRF.

Precisão dos testes sorológico e molecular para diagnóstico do HBV e HCV em pacientes com Insuficiência Renal Crônica em hemodiálise, em Porto Velho, Brasil

&lt;div&gt;Pacientes em tratamento com hemodiálise para a Insuficiência Renal Crônica (IRC) estão entre os grupos com maior prevalência da infecção pelo vírus da hepatite B e C, devido às transfusões de sangue e transmissão nosocomial. Um grupo de pacientes com IRC residentes em Porto Velho foi testado com marcadores sorológicos para hepatite B e C utilizando o teste ELISA e técnicas de biologia molecular (PCR). Os parâmetros para a validação dos resultados sorológicos foram medidos com base nos resultados da PCR. Dos 128 pacientes em hemodiálise durante o estudo, 12 (9,4%) eram HBsAg positivos, 69 (53,9%) eram anti-HBc positivos, 93 (72,7%) eram anti-HBs positivos, e 22 (17,2%) eram anti- HCV positivos. Os resultados dos testes com PCR foram de 12 (9,4%) HBV-DNA positivos e 16 (12,5%) HCV-RNA positivos. A precisão, sensibilidade e especificidade do ELISA para o HBsAg foram de 90,6%, 50% e 94,8%, e os mesmos parâmetros foram de 92,2%, 87,5% e 92,9% para anti-HCV. Com base nos resultados, apenas o valor preditivo negativo para anti-HCV (98,2%) mostrou-se confiável em pacientes renais crônicos em hemodiálise. Além disto, testes sorológicos e/ou moleculares representam a metodologia indicada para o diagnóstico da infecção pelo HBV e HCV nestes pacientes.&lt;/div&gt;

Left ventricular diastolic dysfunction in patients with chronic renal failure: impact of diabetes mellitus

Left ventricular (LV) hypertrophy and LV diastolic dysfunction are cardiac changes commonly observed in patients with chronic renal failure (CRF) as well as hypertension. Although the impairment of LV diastolic function in patients with diabetes mellitus has been shown, little is known about the specific effect of diabetes on LV diastolic function in patients with CRF. The present study was designed to investigate the impact of diabetic nephropathy on LV diastolic dysfunction, independent of LV hypertrophy, in CRF patients. In 67 patients with non-dialysis CRF as a result of chronic glomerulonephritis (n = 33) or diabetic nephropathy (n = 34), and 134 hypertensive patients with normal renal function, two-dimensional and Doppler echocardiographic examinations were performed, and LV dimension, mass, systolic function, and diastolic function were evaluated. LV mass was increased and LV diastolic dysfunction was advanced in subjects with CRF compared with hypertensive controls. In the comparison of echocardiographic parameters between the two groups of CRF patients, i.e. chronic glomerulonephritis and diabetic nephropathy groups, all indices of LV diastolic function were more deteriorated in the diabetic nephropathy group than in the chronic glomerulonephritis group, although LV structure including hypertrophy and systolic function did not differ between the groups. In a multiple regression analysis, the presence of diabetes (i.e. diabetic nephropathy group) was a significant predictor of LV diastolic dysfunction in CRF subjects, independent of other influencing factors such as age, blood pressure, renal function, anaemia and LV hypertrophy. The present findings suggest that LV diastolic dysfunction, independent of LV hypertrophy, is specifically and markedly progressed in patients with CRF as a result of diabetic nephropathy.

Erythrocyte Susceptibility to Oxidative Stress in Chronic Renal Failure Patients Under Different Substitutive Treatments

An increased oxidative stress is now considered one of the major risk factors in chronic renal failure (CRF) patients that may be exacerbated by dialysis. It has been postulated that this increased oxidative stress might cause an augmented red blood cell (RBC) membrane lipid peroxidation with the consequent alteration in membrane deformability. The aim of this study was to evaluate RBC susceptibility to an in vitro induced oxidative stress and RBC antioxidant potential in different groups of CRF patients undergoing different substitutive treatment modalities. Fifteen end-stage CRF patients were evaluated in conservative treatment, 23 hemodialysis (HD) patients, 15 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 kidney transplanted patients, and 16 controls. Their RBCs were incubated with the oxidative stress-inducing agent tert-butylhydroperoxide both in the presence and in the absence of the catalase inhibitor sodium azide, and the level of malondialdehyde (MDA) (a product of lipid peroxidation), was measured at 0, 5, 10, 15, and 30 min of incubation. In addition, the RBC content of reduced glutathione (GSH) was measured by HPLC. As opposed to the controls, RBCs from end-stage CRF patients exhibited an increased sensitivity to oxidative stress induced in vitro, both in the absence and presence of a catalase inhibitor, as demonstrated by a significantly higher level of MDA production at all the incubation times (P < 0.05). Different substitutive treatments had different impacts on this phenomenon; CAPD and kidney transplantation were able to normalize this alteration while HD was not. GSH appeared to be related to the increase in RBC susceptibility to oxidative stress; its content being significantly elevated in end-stage CRF and HD patients as compared with CAPD and transplanted patients and controls (P < 0.05). No significant changes were observed in the RBC glutathione content during the HD session. The increase of GSH in RBCs of end-stage CRF and HD patients seems to indicate the existence of an adaptive mechanism under increased oxidative stress occurring in vivo. Unlike HD, the beneficial effect of CAPD on the anemia of dialysis patients might partly be due to a condition of lower oxidative stress that might in addition counterbalance the cardiovascular negative effects of dislipidemia of CAPD patients.

Homocysteine and carotid atherosclerosis in chronic renal failure—the confounding effect of renal function

Since total homocysteine (tHcy) level is markedly elevated in patients with chronic renal failure (CRF), it has been presented as a potential factor contributing to the high risk of cardiovascular disease (CVD) in CRF. Our aim was to examine the significance of elevated tHcy level and other cardiovascular risk factors for carotid atherosclerosis in patients with CRF. In this cross-sectional study, 135 study patients with CRF (52±11 years) included 58 patients with moderate to severe predialysis CRF, 36 dialysis patients and 41 renal transplant recipients. In addition, 58 control subjects were examined. The association of tHcy level and classic risk factors for atherosclerosis with common carotid artery intima-media thickness (IMT) or carotid artery plaque score was examined. We found no association between tHcy and carotid IMT or a high carotid plaque score in the CRF patient groups. No consistent association was found between elevated tHcy and coronary artery disease, cerebrovascular disease or peripheral arterial disease. Renal function, described as creatinine clearance, was the strongest determinant for tHcy level. Significant predictors of carotid atherosclerosis were age, duration of hypertension and elevated low-density lipoprotein cholesterol level. In conclusion, the present study shows no apparent association between tHcy level and atheromatous carotid findings in patients with CRF. However, because of the changing renal function in the course of renal disease, the strong confounding effect of renal function may not be adequately controlled for the analysis of the significance of elevated tHcy level for CVD in patients with CRF.

Carotid atherosclerosis in chronic renal failure—the central role of increased plaque burden

Studies on carotid artery atherosclerosis have been performed in order to understand the high risk for cardiovascular disease in chronic renal failure (CRF). The purpose of this study was to evaluate the extent and nature of carotid artery atherosclerosis in patients with CRF. Of the 135 patients with CRF (52±11 years), 58 had moderate to severe predialysis CRF (PR), 36 were on dialysis treatment (DI), and 41 were renal transplant recipients (TR). In addition, 58 control subjects (CO) were examined. Common carotid artery intima-media thickness (IMT), plaque prevalence, plaque score, and stiffness index beta were determined. Furthermore, plaque calcification and internal carotid artery stenoses were classified. Plaque prevalence (PR 64%, DI 61%, TR 51%, CO 28%; P<0.001) and plaque score (PR 3.3±4.3, DI 3.0±3.4, TR 2.5±3.2, CO 0.8±1.7 mm; P<0.001) were significantly greater in the CRF patient groups compared to the controls, whereas no difference in IMT was noted between the study groups. The prevalences of plaque calcification and internal carotid artery stenoses were higher among the CRF patient groups. In addition, the stiffness index beta was higher in the CRF patient groups. The present study shows that the characteristic alterations of the carotid arteries in CRF include increased plaque burden, calcification and increased arterial stiffness.

Poincaré plot indexes of heart rate variability capture dynamic adaptations after haemodialysis in chronic renal failure patients.

The hypothesis that the Poincaré plot indexes of heart rate variability (HRV) detect dynamic changes after haemodialysis (HD) over the HRV in haemodynamically stable chronic renal failure (CRF) patients was examined. Minor axis (SD1), major axis (SD2) and the SD1/SD2 ratio were compared against standard HRV indexes in time and frequency domain, in a group of healthy subjects and in a group of CRF patients before and after HD. These indexes were estimated from Poincaré plots reconstructed with lags of one, two and four heartbeats. The surrogate data analysis technique was applied in order to discern if only random components or linear features of HRV contribute to its dynamics. None of the standard linear HRV indexes changed after HD. The Poincaré plot indexes measured from CRF patients were smaller than the ones measured from healthy subjects. In CRF patients the SD1/SD2 ratio decreased after HD, when a lag of four heartbeats was used (0.68 +/- 0.19 before HD versus 0.55 +/- 0.12 after HD, P<0.05). The presence of deterministic components in HRV were confirmed for all measures of the SD1/SD2 ratio. Moreover, a loss of non-linear components after HD was detected by the surrogate analysis over the SD1/SD2 ratio with a lag of four heartbeats. In conclusion, the SD1/SD2 ratio measured at lag of 4 heartbeats capture dynamic changes after HD upon the HRV of CRF patients that are not solely related to linear autocorrelations of HRV. This suggests that the SD1/SD2 ratio reflects non-linear information of HRV.

Lipoprotein particle abnormalities and the impaired lipolysis in renal insufficiency

Increased concentrations of very low- (VLDL) and intermediate-density (IDL) lipoproteins in chronic renal failure (CRF) are thought to result from a defect(s) in degradation of plasma triglyceride (TG)-rich lipoproteins. The purpose of this study was to identify lipoprotein abnormalities associated with the reduced lipolytic rate constant, k1, of combined VLDL and IDL substrate from renal patients and asymptomatic controls. The VLDL + IDL were isolated from 18 predialytic patients (CRF-I), 8 patients on hemodialysis (CRF-II) and 10 asymptomatic controls. The lipolytic rate constant (k1) of VLDL + IDL was measured by an assay using bovine milk lipoprotein lipase and determination of TG before and after incubation by gas chromatography (GC). Neutral lipids were measured by GC and apolipoproteins by electroimmunoassays; the apolipoprotein-defined TG-rich lipoproteins including Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E were determined by immunoaffinity chromatography. The k1 values of VLDL + IDL were significantly (P < 0.001) lower in CRF-I and CRF-II patients (0.0341 and 0.0352 min-1, respectively) than controls (0.0515 min-1). The levels of apolipoproteins B, C-III and E, and TG-rich Lp-B:C, Lp-B:C:E and Lp-A-II:B:C:D:E particles normalized to 100 mg TG per VLDL + IDL were significantly higher in both groups of CRF patients than in controls. All three TG-rich lipoproteins were characterized by significantly increased percent contents of free (FC) and esterified (CE) cholesterol and a decreased percentage of TG. The k1 values of the combined CRF-I and CRF-II patient groups showed significant negative correlations (P < 0.001) with FC (r=-0.81) and CE (r=-0.63) and a positive correlation with TG (r=0.72). Among lipoprotein particles, only Lp-A-II:B:C:D:E levels showed a significant negative correlation with k1 values (r=-0.47, P < 0.03). This study shows that the abnormal neutral lipid composition of all three TG-rich lipoprotein particles and increased concentrations of Lp-A-II:B:C:D:E particles represent the main factors affecting the in vitro lipolytic rates of VLDL + IDL substrate in both the CRF patients before dialysis and patients on hemodialysis.

Polymorphonuclear leucocyte rheology and cytosolic Ca2+ content after activation in chronic renal failure

SUMMARY: We evaluated polymorphonuclear leucocyte (PMN) flow properties in patients with clinically stable chronic renal failure (CRF) and in control subjects at baseline and after activation with 4‐phorbol 12‐myristate 13‐acetate (PMA) and N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP). Initial relative flow rate (IRFR) and clogging particles (CPs) were obtained using the St. George's Filtrometer, and PMN membrane fluidity was assessed by marking PMNs with 1‐(4‐(trimethylamino)phenyl)‐6‐phenyl‐1,3,5‐hexatriene (TMA‐DPH). PMN cytosolic Ca2+ concentration was determined by marking PMNs with Fura 2‐AM. At baseline, CRF patients showed a significant increase only in PMN cytosolic Ca2+ content. After activation with PMA and fMLP, a decrease in IRFR and an increase in CP were observed in both control subjects and CRF patients, although the variation in IRFR present in the group of CRF patients was greater than in the control group. After activation with PMA and fMLP, we found a decrease in PMN membrane fluidity only in CRF patients, but no variation in PMN cytosolic Ca2+ concentration in either group was observed. These results provide evidence for PMN dysfunction in chronic renal failure.

Circulating levels of human insulin-like growth factor binding protein-6 (IGFBP-6) in health and disease as determined by radioimmunoassay.

Insulin-like growth factor binding protein-6 (IGFBP-6) is a relatively unknown member of a family of six specific structurally related IGF binding proteins which are involved in the modulation of the biological effects of the IGFs. A distinctive property of IGFBP-6 is its preferential affinity for IGF-II relative to IGF-I. In order to obtain more insight into the clinical significance and regulation of circulating levels of IGFBP-6 we developed a specific radioimmunoassay (RIA) for this protein. Selected human biological fluids and plasma from 847 normal subjects were analysed. In addition, plasma samples from patients with different disorders (i.e. GH-deficiency, acromegaly, cancer, corticosteroid-treated children suffering from different kinds of severe illness and chronic renal failure) were investigated. The IGFBP-6 assay is competitive, utilizing a rabbit polyclonal antibody raised against a synthetic peptide comprising amino acids 90-118 of the hIGFBP-6 sequence and an additional tyrosine residue. It is calibrated against recombinant human (rh)IGFBP-6. The 125I tracer is prepared by iodination of the synthetic peptide. There is no significant cross-reactivity with other IGFBPs and no interference with the IGFs. Extensive normative range values for IGFBP-6 were determined using 847 plasma samples from normal males and females, ranging from 0 to 75 years of age. IGFBP-6 levels increased gradually (about two-fold) with age. In childhood the plasma levels of IGFBP-6 in females tended to be slightly higher than those for males. For the adult population the reverse was observed. Overall, the mean +/- SD value for males was higher than that for females (149 +/- 57 vs. 139 +/- 45 micrograms/l, P < 0.004). GH status did not appear to influence IGFBP-6 level since normal levels were found for both untreated acromegalic patients and GH-deficient subjects. GH treatment of the latter group of patients did not alter IGFBP-6 in plasma. Pharmacological doses of glucocorticosteroids affected circulating IGFBP-6 levels only slightly. IGFBP-6 levels in plasma samples derived both from children with acute lymphoblastic leukaemia and from patients with various types of solid neoplasms were generally within the normal range. In contrast, plasma samples from four of six patients with non-islet cell tumour induced hypoglycaemia (NICTH) showed elevated concentrations of IGFBP-6 (SDS > 2.9). An excess of IGFBP-6 was also found in plasma of both dialysed and non-dialysed prepubertal growth retarded children with chronic renal failure (CRF) (mean SDS: 23.0 and 9.3, respectively). IGFBP-6 levels were inversely correlated with glomerular filtration rate. In a group of CRF patients who underwent renal transplantation circulating IGFBP-6 levels were markedly lower (mean SDS: 4.6). The presence of IGFBP-6 could also be demonstrated in several other human biological fluids. Low amounts were detected in saliva (3-12 micrograms/l) and breast milk (6-45 micrograms/l) while the levels in amniotic fluid and follicular fluid were comparable with those determined in normal plasma. The IGFBP-6 content of cerebrospinal fluid (CSF) ranged between 25 and 87 micrograms/l, which is rather high in relation to the relatively low concentration of total protein in this body fluid. Measurements of IGFBP-6 have been shown so far to be of relatively minor clinical relevance. The exceptions are chronic renal failure patients and subjects with large tumours and non-islet cell tumour induced hypoglycaemia who may exhibit elevated circulating levels of this IGFBP. The physiological significance of this observation remains to be elucidated. The possibility of quantifying IGFBP-6 by specific RIA will facilitate further in vitro and in vivo studies of its regulation and function in man.

Somatostatin release in response to glucose is impaired in chronic renal failure

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.

Free thyroxine concentrations in serum measured by equilibrium dialysis in chronic renal failure

The serum concentration of free thyroxine (FT4) is often low in patients with chronic renal failure (CRF) with low serum concentrations of triiodothyronine (T3). We evaluated the serum FT4 concentration by using both an equilibrium dialysis RIA kit (D-FT4) and a labeled-antibody kit (M-FT4) in two different groups of CRF patients, undergoing chronic hemodialysis (HD, n = 145) or not (non-HD, n = 30), and in a group of normal healthy subjects (n = 58). Thyroid peroxidase antibodies and thyroglobulin antibodies were not detected in any patient. Serum FT4 concentrations (mean +/- SD, pmol/L) by the D- and M-FT4 assays were, respectively, 21.5 +/- 4.6 and 16.6 +/- 2.0 in the healthy subjects, 17.8 +/- 4.3 and 13.9 +/- 3.6 in the non-HD patients, and 16.9 +/- 4.9 and 10.7 +/- 1.9 in the HD patients. By the D-FT4 assay, results for both CRF groups were significantly different from those for the healthy group (P <0.01), as were the results for each pair of groups by the M-FT4 assay (P <0.01). FT4 values were reported as being within the healthy reference range by D-FT4 in 73 of 113 HD subjects who had low T3 and low M-FT4 values. Serum FT4 concentrations measured by both assay kits showed a significant inverse correlation with the serum concentration of creatinine (P <0.01), but the serum concentrations of sex-hormone-binding globulin did not differ significantly among the three groups. Our results indicate that the low FT4 concentration measured by D-FT4 in patients with CRF, particularly those on HD, probably reflects the actual, mild nonthyroidal illness of renal failure.

Whole body and regional body composition in patients with chronic renal failure

Nutritional state is a powerful prognostic factor in chronic renal failure (CRF). Techniques for the assessment of nutrition have limitations which are often most marked in the presence of renal disease. We have used techniques of body composition analysis to assess the nutritional state of groups of patients with CRF. Body composition was measured in groups of patients with advanced CRF on conservative treatment, peritoneal dialysis, and haemodialysis and the results compared with a healthy control group. The selection criteria for the CRF patients ensured that they were "stable' with no recent intercurrent illness, and dialysis adequacy was satisfactory according to currently accepted targets. Whole body dual energy X-ray absorptiometry (DEXA) found significant reduction in lean tissue in haemodialysis patients and female peritoneal dialysis patients. Regional analysis with DEXA showed reduction in limb (especially arm), lean tissue in CRF patients, with arm lean tissue being reduced in all three CRF groups for females and both dialysis groups for males. Limb/trunk lean tissue ratios were significantly reduced for all CRF groups. Bioelectrical impedance showed reductions of fat-free mass in the same groups who had reduced whole body lean tissue with DEXA, but skinfold anthropometry failed to detect any significant reduction in fat-free mass. We conclude that even in "healthy' groups of CRF patients receiving adequate dialytic and dietary management, lean tissue depletion is a common problem. Regional analysis by DEXA, with measurement of limb lean tissue mass is a more sensitive method for the detection of lean tissue depletion than measurement of whole body lean tissue in patients with CRF.

Melatonin in chronic renal failure.

The melatonin status of patients in end-stage chronic renal failure (CRF) was evaluated by the determination of daytime plasma melatonin levels and by the investigation of the circadian rhythmicity of melatonin secretion. A significant increase in plasma melatonin concentration was found in all CRF patient groups investigated, i.e. CRF patients on conservative treatment (CT; n = 48), CRF patients on maintenance haemodialysis treatment (HD; n = 39) and CRF patients on peritoneal dialysis (PD; n = 32). Successful transplantation led to a marked reduction in plasma melatonin levels. The circadian rhythm of melatonin secretion would appear to be suppressed in CRF as the nocturnal secretory surge was absent in all HD patients and in 80% of the posttransplantation patients studied.

ABNORMAL FACTOR VIII IN CHRONIC RENAL FAILURE

Factor VIII procoagulant activity (VIII-C), related antigen (VIII-AG), and von Willebrand factor (VIII-vWf) were measured in 38 patients with chronic renal failure (CRF), in 19 patients with normal renal function from a general medical ward, and in 17 normal subjects. Wide variation in the levels of factor VIII (FVIII) functions were found in the group of CRF patients. There was no correlation between the levels of the three individual activities of FVIII in renal disease. The levels of the three functions were elevated in the patient controls and no significant differences were found between the two groups of patients, although both groups were significantly different from the normal subjects. Increased electrophoretic mobility (EM) was detected in 22 of the 38 patients with CRF (58%) compared to seven of the 19 patients controls (37%). These studies suggest caution in interpretation of changes in FVIII status in patients with other clinical disorders, such as liver disease.