Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

Elevated levels of serum sulfite in patients with chronic renal failure

Sulfite, a well known air pollutant, is toxic for humans, especially those with sulfite hypersensitivity. Sulfite is also generated endogenously, during normal metabolism of sulfur-containing amino acids. Mammalian tissues contain the enzyme sulfite oxidase, which detoxifies both endogenous and exogenous sulfite by oxidation to sulfate. Deficiency of sulfite oxidase in humans is fatal, demonstrating its physiologic importance. Nevertheless, information about serum and tissue levels of sulfite in normal and pathologic conditions is limited. Using a sensitive HPLC assay, it is shown here that sera from patients with chronic renal failure (CRF) contain significantly higher amounts of sulfite than those from healthy subjects. Mean +/- SD of serum sulfite in healthy subjects (n = 20) was 1.55 +/- 0.54 microM, whereas those in patients under maintenance hemodialysis (HD patients; n = 44) and CRF patients before introducing dialysis therapy (pre-HD patients; n = 33) were 3. 23 +/- 1.02 microM (P < 0.01) and 3.80 +/- 3.32 microM (P < 0.01), respectively. Among pre-HD patients, serum sulfite was positively correlated with serum creatinine (r = 0.714, P < 0.0001), and negatively with serum albumin (r = -0.407, P = 0.0188), hematocrit (r = -0.524, P = 0.0017), and total cholesterol (r = -0.375, P = 0. 0318). There was no significant association between sulfite and patient age, gender, or leukocyte counts. Multiple regression analysis revealed serum creatinine as the sole independent predictor of serum sulfite levels. Each HD treatment was associated with approximately 27% reduction in serum sulfite levels, suggesting the presence of a dialyzable form in serum. Thus, these results indicate that reduced glomerular filtration is a factor that determines serum sulfite levels. Chronic elevation in serum sulfite levels might contribute to tissue or organ dysfunction in patients with CRF.     

Clinical significance of serum and urinary neopterins in patients with chronic renal disease

To determine the clinical significance of serum and urinary neopterins in patients with chronic renal disease, we measured these values using IMMUtest Neopterin RIA kits. Serum neopterin levels in patients with chronic glomerulonephritis (CGN) (10.2 +/- 8.1 nmol/l) and in those with chronic renal failure (CRF) (109 +/- 90) were significantly increased compared with the control subjects (C) (4.2 +/- 2.4) (p less than 0.001). The levels of serum neopterins in patients on chronic hemodialysis (HD) (212 +/- 106) were increased almost twofold compared with CRF (p less than 0.001). In CGN and CRF, a strong positive correlation was demonstrated between serum neopterin levels and serum creatinine concentrations (r = 0.95, p less than 0.001). In HD patients, neopterin levels and serum were not correlated with the length of time on dialysis. The urinary neopterin excretion ratios (urinary neopterin/urinary creatinine level) in CRF (227 +/- 114 mumols/molCr) were significantly increased compared with C (116 +/- 43) (p less than 0.01). A significantly negative correlation was observed between the urinary neopterin levels and the creatinine clearance in CGN and CRF (p less than 0.01). These data suggest that, in patients with chronic renal disease, the neopterin levels in serum are closely linked with glomerular filtration rate and yet the urinary neopterin/creatinine ratios may reflect the predominance of increased tubular secretion of neopterin over the renal injury per se.     

Fibronectin in patients with chronic renal failure undergoing dialysis

Fibronectin (FN) levels were determined in 64 cases with chronic renal failure (CRF), some of whom were undergoing dialysis. FN levels were 14.9 +/- 7.6 mg/dl in CRF (n = 20), 13.4 +/- 4.3 mg/dl in patients on continuous ambulatory peritoneal dialysis (CAPD) (n = 20) and 16.7 +/- 7.2 mg/dl in patients on hemodialysis (HD) (n = 24). All the levels were significantly lower than in normal subjects (23.1 +/- 4.6 mg/dl). Serum FN was compared with some nutritional indices. Positive correlations were found between serum FN and nitrogen balance (BN), serum prealbumin (PreA) and transferrin (Tf) in all the patients. With serum albumin (Alb), however, this correlation was only found in patients undergoing dialysis. Negative correlations were found between serum FN and the ratio of serum urea to serum creatinine (Surea/Scr) in CAPD and HD patients. In 10 CAPD patients, the low serum FN levels went up after increased protein intake. This indicates that it was the result of malnutrition due to decreased protein intake. Serum FN level reflects a negative BN earlier and better than serum PreA, Tf and Alb. It is a sensitive, reliable and simple index for judging the nutritional protein status and the effect of nutritional treatment in patients with CRF undergoing dialysis.     

Hyperhomocysteinemia in chronic renal failure patients: relation to tissue factor and platelet aggregation

BACKGROUND: A moderate increase in plasma total homocysteine (t-hcy) is considered to be an independent risk factor for cardiovascular disease (CVD) in general population. One of the mechanisms by which hyperhomocysteinemia contributes to cardiovascular risk has been explained to be the increased thrombotic potential. Elevated t-hcy levels were also reported in chronic renal failure patients because the renal function is a major determinant of serum t-hcy levels. PATIENTS AND METHODS: We measured serum hcy and ADP-induced platelet aggregation and plasma tissue factor as a major activator of the coagulation cascade in hemodialysis (HD), peritoneal dialysis (PD) and early stage chronic renal failure (early stage CRF) patients who are not receiving dialysis and compared with those of control. In addition, we also determined serum vitamin B12 and folat levels which are the important factors regulating the metabolism of t-hcy. RESULTS: Hcy levels in all patient groups were significantly higher (HD: 20.42 +/- 1.91 micromol/l, PD: 35.47 +/- 6.30, early stage CRF: 24.39 +/- 3.06) than the normal levels (10.74 +/- 0.74) in spite of standard multivitamin supplementation. The highest t-hcy values were found in peritoneal dialysis patients. Vitamin B12 levels in hemodialysis/peritoneal dialysis patients and folat levels in hemodialysis/early stage CRF patients were also significantly above those of control. On the other hand, the significant elevations in plasma tissue factor concentration were found in all patient groups (HD: 331.4 +/- 31.3 pg/ml, PD: 306.0 +/- 30.0, early stage CRF: 277.2 +/- 25.5 and Control: 69.5 +/- 13.5). t-hcy levels were positively correlated with creatinine (r: 0.791 p < 0.002) and tissue factor levels (r: 0.526 p < 0.05) in only early stage CRF group. The association between t-hcy and tissue factor persisted after these two parameters were adjusted for creatinine (r: 0.649 p < 0.05). On the other hand the same correlations were not observed in dialysis patient groups. In spite of the high tissue factor levels, ADP-induced platelet aggregations were found to be lower in all patient groups (HD: 102.6 +/- 6.7, PD: 98.6 +/- 7.6 and Early stage CRF: 84.9 +/- 7.6) than controls (154.9 +/- 13.7). CONCLUSION: These results suggest that hyperhomocysteinemia and increased tissue factor level are present in patients with renal failure, despite supplementation with vitamin B6 and B12 and folat. However, elevated levels of these thrombogenic factors are not linked with platelet aggregation.     

Increased levels of soluble TNF-alpha receptors and cellular adhesion molecules in patients undergoing bioincompatible hemodialysis

BACKGROUND: The study aimed to differentiate the effects of hemodialysis (HD) and chronic renal failure (CRF) on the levels of circulating tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha receptors p55 and p75, soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), soluble endothelial-leukocyte adhesion molecule-1 (sE-selectin) and sP-selectin in 18 patients on regular HD treatment with cuprophane membrane in relation to 15 non-dialyzed CRF patients and 15 healthy controls. METHODS: The serum concentrations were determined with standard ELISA assays. RESULTS: Blood serum p75 and p55 were approximately tenfold increased in CRF (36.7 +/- 6.2 and 27.1 +/- 5.6 ng/ml) and HD patients (45.6 +/- 18.4 and 28.7 +/- 5.9 ng/ml) before the HD session (HD 0), during (HD 20) the session (45.7 +/- 18.4 and 28.5 +/- 7.3 ng/ml) and after (HD 240) the HD session (52.1 +/- 17.4 and 30.9 +/- 8.2 ng/ml) in comparison to control values (5.6 +/- 1.3 and 2.4 +/- 0.8 ng/ml, respectively) (p < 0.01). The highest increment of p75 at the end of HD session (HD 240) was also significantly higher than at preceding time points (HD 0 and 20) (p < 0.05). However, the remaining study parameters did not change during an HD session. Also, there were no relevant changes in TNF-alpha levels if (HD 0) 22.7 +/- 21.5 ng/ml and (HD 240) 21.1 +/- 18.9 ng/ml were compared. Chronic HD status was related to the increase of sVCAM-1 and sICAM-1 levels. Prior to HD, T0 sVCAM-1 and sICAM-1 concentrations were 2,180.4 +/- 761.8 and 567.3 +/- 218.8 ng/ml, during HD (T20): 2,172.7 +/- 759.2 and 602.3 +/- 379.9 ng/ml, and after HD (T240): 2,401.6 +/- 756.4 and 648.3 +/- 183.5 ng/ml, respectively (p < 0.05 vs. controls and CRF patients). sVCAM-1 and sICAM-1 serum levels (1,262.2 +/- 472.9 and 165.6 +/- 50.4 ng/ml) were similar in CRF patients and healthy controls (854.4 +/- 241.5 and 217.6 +/- 74.2 ng/ml, respectively). Even though serum sE- and sP-selectin in CRF patients did not differ from the control (39.8 +/- 21.3 vs. 42.1 +/- 18.9 ng/ml and 187.9 +/- 66.9 vs. 198.8 +/- 62.2 ng/ml, respectively), their levels were increased in HD patients up to 111.9 +/- 54.6 and 453.2 +/- 231.1 ng/ml in patients prior to HD, 118.7 +/- 66.2 and 350.8 +/- 114.8 ng/ml during the HD session and then 132.3 +/- 61.1 and 368.3 +/- 126.6 ng/ml, respectively, after its completion (p < 0.05 in comparison with CRF patients and controls). CONCLUSIONS: The increased circulating TNF-alpha receptors appear more associated with the uremic milieu than HD-related systemic inflammation, whereas increased soluble cellular adhesion molecules in patients undergoing bioincompatible HD may be related to the enhanced systemic inflammation specifically due to maintenance HD.     

High fluoride exposure in hemodialysis patients

The observation of higher plasma flouride levels in our hemodialysis (HD) patients than our continuous ambulatory peritoneal dialysis (CAPD) patients (4.0 +/- 0.5 mumol/L [n = 17] v 2.5 +/- 0.3 mumol/L [n = 17], P less than 0.005) prompted an evaluation of fluoride metabolism during HD. We found that serum fluoride was completely ultrafiltrable across cuprophane membranes (99% +/- 4%) and that HD produced acute changes in plasma fluoride levels that correlated well with the fluoride gradient between plasma and dialysis fluid at the start of dialysis. Our HD fluids contained significantly higher fluoride concentrations than were present in commercially prepared peritoneal dialysis fluid. Our fluids are prepared from fluoridated tap water that is purified by reverse osmosis (RO). We conclude that the different concentrations of fluoride in our dialysis fluids account for the differences in the plasma flouride concentrations between our dialysis groups. Since many HD units rely on RO systems to purify fluoridated tap water, it is likely that many HD patients are being exposed inadvertently to increased concentrations of fluoride.     

Increased sweat sulfate concentrations in chronic renal failure

Inorganic sulfate concentrations are markedly elevated in patients with chronic renal failure (CRF). During hemodialysis, sulfate is removed and circulating levels drop significantly, while chloride concentrations remain relatively constant. We measured sulfate and chloride in sweat from CRF patients collected by pilocarpine iontophoresis. Sweat sulfate concentrations in uremic patients were significantly increased (404 +/- 43 vs. 105 +/- 6 microM in 22 controls). The correlation between plasma and sweat SO4 concentrations in CRF patients was significant (r = 0.77, P less than 0.01). However, the fractional excretion of sulfate in sweat (the sweat/serum ratio) was close to that of chloride (0.26 +/- 0.01 vs. 0.19 +/- 0.02) and was essentially the same before and after dialysis (0.20 +/- 0.01 vs 0.23 +/- 0.01) despite the significant absolute change in the extracellular SO4 concentration (from 2,018 +/- 153 to 709 +/- 21 microM) and no change in chloride concentrations. In patients with CRF, we conclude that the handling of inorganic sulfate by the sweat gland is not significantly different from that for chloride. Hemodialysis reduces absolute sulfate excretion markedly and thus may reduce the likelihood of forming calcium sulfate complexes in the sweat secretions. This could be a significant factor in the dialysis-related pruritus that has been ascribed to excess calcium deposition in the skin.     

Significant elevations in serum mannose-binding lectin levels in patients with chronic renal failure

BACKGROUND/AIMS: Mannose-binding lectin (MBL), a liver-derived C-type serum lectin, activates the complement cascade through the lectin pathway. Since the complement system contributes to the host defense against infections and mediates inflammatory processes including atherosclerosis, and since chronic renal failure (CRF) patients are prone to the development of infectious complications and cardiovascular disease, we focused on serum MBL levels in CRF patients who were either uremic, or who were receiving hemodialysis treatment. METHODS: MBL levels were measured in the sera of subjects with CRF before they began dialysis treatment (pre-HD patients; n = 23) and in the sera of subjects who were receiving maintenance hemodialysis (HD patients; n = 178), by ELISA using polyclonal anti-rabbit IgG and a monoclonal antibody directed against MBL (3E7). METHODS: Mean levels (+/- SD) of serum MBL were significantly higher in pre-HD subjects (4.343 +/- 2.533 microg/ml, p < 0.05) and in HD subjects (8.897 +/- 4.920 microg/ml, p < 0.05), than in healthy controls (1.452 +/- 0.692 microg/ml). Levels were also significantly higher in HD subjects than in pre-HD subjects (p < 0.05). CONCLUSIONS: Elevated serum MBL levels in patients with CRF might have significantly influence pathologic conditions such as alterations of the immune system and acceleration of atherogenesis.     

Serum VCAM-1, ICAM-1, and L-selectin levels in children and young adults with chronic renal failure

Children and young adults with chronic renal failure (CRF) present with an impaired immune response. Our aim was to analyze whether leukocyte migration, determined by adhesion molecules, is disturbed in the course of CRF, hemodialysis (HD), and peritoneal dialysis (PD). Soluble (s) VCAM-1, ICAM-1, and L-selectin serum levels were evaluated by ELISA in 15 patients with CRF, 22 patients on cuprophane membrane HD, 24 patients on PD, and in 15 controls. The sVCAM-1 levels in all groups were significantly elevated compared with controls. The levels in HD patients were higher than in CRF patients (P <0.05), while levels in PD patients were higher than in CRF and HD (P <0.001 and P <0.01, respectively). The sICAM-1 concentrations in CRF and PD patients were significantly elevated compared with controls (P <0.001 and P <0.0001, respectively); in PD patients sICAM-1 levels were higher than in HD patients (P <0.001), but there were no differences between other groups. sL-selectin levels were decreased in all groups compared with controls. The levels in HD patients were the lowest and the differences, compared with CRF and PD patients, were significant (P <0.05 and P <0.01, respectively). Children and young adults with CRF and on maintenance dialysis have altered concentrations of soluble adhesion molecules, resulting from either inadequate clearance or disturbed synthesis and release. The differences in sVCAM-1 levels between CRF and both groups of patients on dialysis, as well as the differences in sL-selectin concentrations between HD and CRF patients, indicate that these disturbances are aggravated by maintenance dialysis, particularly HD.     

Increased plasma malondialdehyde levels in glomerular disease as determined by a fully validated HPLC method.

BACKGROUND: Reactive oxygen species and particularly free radical induced lipid peroxidative tissue damage have been implicated in the pathogenesis of various renal diseases. Lipid peroxidation is assessed indirectly by the measurement of secondary products, such as malondialdehyde (MDA), using the widely employed thiobarbituric acid reactive substances (TBARS) method. However, this method lacks sensitivity and specificity. We have therefore developed and validated an HPLC (high-performance liquid chromatography) method for measurement of MDA and applied this to a variety of plasma samples in renal patients. METHODS: The optimized method involves antioxidant treatment of the plasma sample, followed by a protein precipitation step using trichloroacetic acid, acid hydrolysis and formation of an MDA thiobarbituric acid complex. The MDA-(TBA)2 adduct is separated from other interfering compounds by C18 reverse-phase HPLC techniques, with visible detection at 532 nm. RESULTS: The assay was linear over the ranges 0.25-1.0 microM MDA and the detection limit was 0.06 microM MDA. Within-run precision was <4.5% and between-run precision was <10.0%. MDA plasma concentrations (mean+/-SD) were higher in ESRF diabetic patients (0.32 +/- 0.14 microM, n=20), non-diabetic ESRF patients (0.32 +/- 0.09 microM, n=20), and CRF patients (0.14 +/- 0.06 microM, n=40) compared to healthy controls (0.11 +/- 0.03 microM, n=40), (P < 0.001, P < 0.001 and P = 0.008). Levels were similar in healthy controls with normal renal function and transplanted patients (0.12 +/- 0.03 microM MDA, n=40), (P=NS). No correlation was observed between MDA and creatinine levels (r2 = 0.05, n=80), which suggests that MDA does not correlate with the degree of renal impairment. We matched CRF patients with glomerular and non-glomerular causes of renal failure for creatinine levels and found that MDA levels were higher in patients with glomerulonephritis (0.16 +/- 0.06 microM) than in those with CRF from non-glomerular causes (0.12 +/- 0.04 microM, P = 0.002). CONCLUSIONS: We have introduced a reliable and sensitive HPLC technique to enhance the specificity of MDA-(TBA)2 measurement, with a significant improvement in HPLC column life. Using this method, picomole quantities of MDA can be detected in plasma. We have shown that MDA levels are significantly raised in patients with CRF due to glomerulonephritis, regardless of serum creatinine, which suggests that there is oxidative injury independent of any possible MDA retention due to renal impairment.     

Differential diagnosis of bacterial infection and inflammatory response in kidney diseases using procalcitonin

BACKGROUND: Early diagnosis of bacterial infection in renal patients remains difficult. Common laboratory parameters, such as white blood cell (WBC) count, erythrocyte sedimentation rate, and C-reactive protein (CRP) may be affected by the underlying disease, uremia or its extracorporeal treatment, or by immunosuppressive drugs. Procalcitonin (PCT) may be useful for the detection of systemic bacterial infections in patients with end-stage renal disease (ESRD) undergoing renal replacement therapy, but elevated PCT concentrations have also been found in a significant number of uremic patients without signs of infection. METHODS: We tested whether measurements of PCT levels help distinguish the chronic inflammation in renal diseases from invasive bacterial infections. Serum levels of PCT were compared with the corresponding serum C-reactive protein (CRP) concentrations and WBC counts in 197 patients with different stages of renal disease: Group I) 32 patients with chronic renal failure (serum creatinine 2-6 mg/dL); group II) 31 patients with a functioning renal transplant receiving standard immunosuppressive regimens; group III) 76 clinically stable patients with ESRD undergoing hemodialysis (HD); group IV) 23 patients with chronic renal failure (CRF) due to systemic autoimmune disease; group V) 35 patients with proven systemic bacterial infection and CRF. RESULTS: PCT levels were within the normal range (< 0.5 ng/mL) in patients with CRF and renal transplant patients without any clinical evidence of bacterial infection, regardless of the degree of renal failure and the underlying disorders. In 22 out of 76 stable HD patients, PCT levels were above the upper limit of normal, but 97% of these values were below the proposed cut-off for chronic HD patients of < 1.5 ng/mL. CRP levels were elevated in 17 of 32 patients with CRF (mean +/- SD: 0.57 +/- 0.49 mg/dL), in 10 of 31 renal transplant patients (0.41 +/- 0.55 mg/dL), in 16 of 23 patients with autoimmune disorders (2.78 +/- 3.21 mg/dL) and in 42 of 76 patients treated by HD (0.64 +/- 0.58 mg/dL). In patients with CRF and systemic bacterial infections, both PCT and CRP were markedly elevated (PCT 61.50 +/- 115.4 ng/mL, CRP 14.50 +/- 10.36 mg/dL), but in contrast to PCT, CRP values overlapped in infected and non-infected patients. CONCLUSIONS: Our data indicate that PCT levels are not significantly affected by loss of renal function, immunosuppressive agents or autoimmune disorders. Thus, significantly elevated PCT concentrations offer good sensitivity and specificity for the early diagnosis of systemic bacterial infection in patients with CRF or patients with ESRD treated by HD. CRP concentrations may be useful indicators for inflammation in patients with renal diseases, but have low specificity for the diagnosis of bacterial infection.     

Pentraxin 3 is elevated in haemodialysis patients and is associated with cardiovascular disease.

BACKGROUND: Pentraxins are mediators of inflammation as well as markers of the acute-phase reaction. While elevation of C-reactive protein (CRP) in patients with renal failure and its association with cardiovascular disease is well described, there are no data on pentraxin 3 (PTX3) in this population. METHODS: Plasma was obtained from 44 chronic haemodialysis (HD) patients, 35 peritoneal dialysis (PD) patients, 39 patients with chronic renal failure (CRF) not on dialysis therapy and 14 age-matched normal subjects. PTX3 production in whole blood was also investigated in samples taken before and during HD. RESULTS: PTX3 plasma levels were significantly higher in HD patients (5.8 +/- 0.6 ng/ml) compared with the other three groups. There were no significant differences between PD patients (1.5 +/- 0.4 ng/ml), CRF patients (1.5 +/- 0.4 ng/ml) and normal subjects (0.76 +/- 0.2 ng/ml). In dialysis patients, PTX3 levels correlated significantly with time on renal replacement therapy (RRT) and with weekly erythropoietin dose. PTX3 levels were significantly higher in patients with coronary artery disease and peripheral artery disease compared with those without. During a single HD session, PTX3 production was higher in whole blood samples taken after 3 h HD compared with samples taken before HD. CONCLUSIONS: PTX3 levels are markedly elevated in HD patients. The increase in PTX3 production in whole blood after HD indicates that the HD procedure itself contributes to elevated PTX3 levels in HD patients. The association between PTX3 and cardiovascular morbidity suggests a possible connection of PTX3 with atherosclerosis and cardiovascular disease in HD patients.     

Prevalence of malnutrition in Nigerians with chronic renal failure

In developed countries, malnutrition is common in patients with chronic renal failure (CRF) and has adverse effects on patient morbidity and mortality. The prevalence of malnutrition before the initiation of dialysis is poorly characterized in CRF patients in developing countries. We studied the prevalence of malnutrition among Nigerians with CRF before commencement of dialysis. Body mass index (BMI) and serum protein levels were measured in 74 dialysis na?ve Nigerians with CRF and 48 controls. Patients with nephrotic syndrome, steroid use and failure of organs other than the kidneys were excluded. The mean BMI was significantly lower in the patients compared to the controls (22.4 +/- 14.9 kg/M2 Vs. 25.2 +/- 2.7 kg/M2; p = 0.0001). Low BMI (less than 20 Kg/M2) was present in 16 (21.6%) of the patients compared with one of the controls. The mean serum total protein and albumin were also significantly lower in the patients compared to controls (61.9 +/- 14.4 g/L Vs. 73.8 +/- 6.8 g/L; p < 0.0001, and 31.5 +/- 9.3 g/L Vs. 39.6 +/- 4.4 g/L; p < 0.0001 respectively). Protein malnutrition (serum albumin < 29 g/L) was present in 32 (43.2%) of patients with CRF and one (2.1%) of the control subjects. Malnutrition is common in Nigerian CRF patients before the commencement of dialysis. In these patients, emphasis should be placed on prevention and/or correction of malnutrition because of its documented adverse effects on the outcomes of maintenance dialysis.     

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

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

Effects of dialysis and transplantation on red cell Na pump function in renal failure

Ion pumping by the erythrocyte Na, K-ATPase has been measured using ouabain-sensitive 86Rb flux in 11 non-dialysed patients with chronic renal failure (CRF), 13 patients on haemodialysis (HD), 13 patients on peritoneal dialysis (CAPD) and 15 patients with functional transplants (FT). Flux measurements were performed in plasma and simultaneous estimates of specific 3H-ouabain binding were made. The results indicate that, compared to normal controls, Na,K pump flux was reduced by 21% in CRF (p less than 0.01), 30% in HD (p less than 0.01), 15% in CAPD (p less than 0.02), and was normal in FT. Mean specific ouabain binding sites per cell (+/- SEM) were; controls 366 +/- 16; CRF, 290 +/- 16; HD, 344 +/- 17; CAPD, 321 +/- 18; FT, 345 +/- 26. Calculation of mean turnover rate per pump site indicated that patients on HD showed a 30% reduction compared to controls (influx 55 K ions/s versus 79 K ions/s, p less than 0.01). Cross-incubation experiments suggest that the lowered pump flux seen in the CRF and HD groups was due to plasma factors. This work shows that erythrocyte Na,K pump number is reduced in CRF, while patients on maintenance HD have normal pump numbers per erythrocyte but reduced pump turnover.     

Influence of hemodialysis membrane permeability on serum levels of advanced glycation end products (AGEs) and homocysteine metabolites

BACKROUND: Advanced glycation end products (AGEs), total homocysteine (tHcy) and the homocysteine metabolites cystathionine (Cysta) and dimethylglycine (DMG) are increased in serum of patients with end-stage renal disease. The aim of this prospective randomized study was to compare the efficacy of polysulfone high-flux vs. polysulfone low-flux hemodialysis (HD) treatment regarding removal of AGEs, tHcy, Cysta and DMG. PATIENTS AND METHODS: Twenty-nine patients on chronic HD treatment were randomly assigned to 2 groups in a 3-period 2-treatment design with low flux (A)--high flux (B)--low flux (A) for group I and B-A-B for group II, 6 weeks each period. The following parameters were measured in pre- and postdialytic serum samples at baseline and the end of each period: total serum fluorescence, Nepsilon-carboxymethyllysine (CML), free and protein-bound pentosidine, tHcy, Cysta and DMG. RESULTS: There was increased removal of free pentosidine during high-flux HD treatment compared to low-flux HD treatment, attaining significance between the second and third treatment periods (group 1: 86.0 +/- 4.7% vs. 79.2 +/- 8.8%, p = 0.007; group II: 84.0 +/- 6.3% vs. 79.8 +/- 9.8%, p = 0.049 for high vs. low flux). The intradialytic reduction rates for total serum fluorescence, tHcy, Cysta, DMG did not differ between high- and low-flux HD treatment. Protein-bound pentosidine and CML did not decrease during the dialysis sessions, neither with high-flux nor with low-flux HD membrane. Despite a strong decrease during single HD session, the predialytic levels of free pentosidine, tHcy, Cysta and DMG remained unchanged during the study period both for high- and low-flux HD treatment. CONCLUSION: The more pronounced effect of high-flux dialysis on the removal rate of free pentosidine, found in this randomized crossover study, could not translate into a significant difference in predialysis levels after a 6-week treatment period. We could not find any differences between polysulfone high- and low-flux membranes for lowering predialytic serum concentrations of the measured AGEs, which are mainly bound on albumin.     

Plasma protein thiol oxidation and carbonyl formation in chronic renal failure

BACKGROUND: Myeloperoxidase-catalyzed oxidative pathways have recently been identified as an important cause of oxidant stress in uremia and hemodialysis (HD), and can lead to plasma protein oxidation. We have examined patterns of plasma protein oxidation in vitro in response to hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). We measured thiol oxidation, amine oxidation, and carbonyl concentrations in patients on chronic maintenance HD compared with patients with chronic renal failure (CRF) and normal volunteers. We have also examined the effect of the dialysis procedure on plasma protein oxidation using biocompatible and bioincompatible membranes. METHODS: Plasma proteins were assayed for the level of free thiol groups using spectrophotometry, protein-associated carbonyl groups by enzyme-linked immunosorbent assay, and oxidation of free amine groups using a fluorescent spectrophotometer. RESULTS: In vitro experiments demonstrate HOCl oxidation of thiol groups and increased carbonyl formation. In vivo, there are significant differences in plasma-free thiol groups between normal volunteers (279 +/- 12 micromol/L), CRF patients (202 +/- 20 micromol/L, P = 0.005) and HD patients (178 +/- 18 micromol/L, P = 0.0001). There are also significant differences in plasma protein carbonyl groups between normal volunteers (0.76 +/- 0.51 micromol/L), CRF patients (13.73 +/- 4.45 micromol/L, P = 0.015), and HD patients (16.95 +/- 2.62 micromol/L, P = 0.0001). There are no significant differences in amine group oxidation. HD with both biocompatible and bioincompatible membranes restored plasma protein thiol groups to normal levels, while minimally affecting plasma protein carbonyl expression. CONCLUSIONS: First, both CRF and HD patients have increased plasma protein oxidation manifested by oxidation of thiol groups and formation of carbonyl groups. Second, HD with biocompatible and bioincompatible membranes restored plasma protein thiol groups to normal levels. Third, these experiments suggest that there is a dialyzable low molecular weight toxin found in uremia that is responsible for plasma protein oxidation.     

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.     

Expression of scavenger receptor CD36 in chronic renal failure patients

BACKGROUND: Patients with chronic renal failure (CRF) are at increased risk of atherosclerosis development. One of the major steps in pathogenesis of atherosclerosis is formation of foam cells. Scavenger receptor CD36 is among the major receptors for oxidized low density lipoproteins (oxLDL) and therefore it plays a crucial role in foam cell formation. The aim of the present study was to investigate the expression of CD36 on blood monocytes of CRF patients. METHODS: Expression of CD36 on blood monocytes of CRF patients treated with hemodialysis (HD), peritoneal dialysis (PD), those not yet on dialysis (predialysis), and controls was assessed with the use of flow cytometry. Additionally, the major lipid peroxidation markers, malondialdehyde (MDA) and 4-hydroxyalkenals (HAE), were measured. Further, impact of treatment with HMG-CoA reductase inhibitors (statins) on CD36 expression in CRF patients was evaluated. RESULTS: Expression of monocyte CD36, measured as mean fluorescence intensity (MFI) was significantly higher in HD and PD patients, when compared to controls without renal insufficiency (respectively: 1011 +/- 288 and 1000 +/- 309 vs. 710 +/- 313; P < 0.01 for both groups). This was not the case in predialysis group (828 +/- 363 vs. 710 +/- 313). Higher concentrations of lipid peroxidation indicators, MDA and HAE were observed in all three subgroups of CRF patients (2.1 +/- 0.51, 2.02 +/- 0.27, and 1.81 +/- 0.53 microm in HD, PD, and predialysis group, respectively, vs. 1.13 +/- 0.59 microm in controls; P < 0.01). Patients treated with statins showed significantly lower CD36 expression than patients without statin therapy. CONCLUSIONS: The present study, for the first time, demonstrates increased expression of CD36 scavenger receptor in CRF patients. This may be a possible risk factor for accelerated atherogenesis observed in this group of patients.