Serum uric acid is associated with high blood pressure in pediatric hemodialysis patients

Serum uric acid (UA) is positively associated with hypertension (HTN). HTN is common in pediatric patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We assessed the relationship between UA and BP in 63 pediatric dialysis patients by measuring pre-treatment UA levels and BP in HD patients and in-center UA levels and blood pressure (BP) in PD patients. UA levels were similar in both groups [6.8 ± 0.2 (HD) vs. 6.5 ± 0.3 (PD), p = 0.6]. Pre-treatment systolic BP percentile was associated with a high UA level [91.9 ± 2.3 (>6.0 mg/dL) vs. 79.3 ± 5.8 mm Hg (≤6.0 mg/dL), p = 0.01] in HD patients only. There was a negative relationship between UA and dialysis vintage (r = −0.31, p = 0.01). In both groups, there was no relationship between UA and Kt/V. In HD patients, fluid overload was unrelated to UA level [4.2 ± 0.6% (≤6.0 mg/dL) vs. 4.3 ± 0.3% (>6.0 mg/dL), p = 0.9]. Moreover, pre-HD treatment systolic BP percentile correlated with UA (beta 0.36, p = 0.02) independent of volume. UA levels were higher in patients receiving anti-hypertensive medications [6.3 ± 0.2 (No Meds] vs 7.0 ± 0.2 (BP Meds) mg/dL,  p= 0.01]. Finally, there was no relationship between serum UA and normalized protein catabolic rate (r = 0.14; p = 0.4). In summary, serum UA impacts BP in pediatric HD patients, independent of volume, nutritional and weight status.     

Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients

Increased mortality of adult chronic hemodialysis (HD) patients is associated with coronary calcifications (CC), increased serum phosphorus (P), use of calcium (Ca)-containing P-binders, and vitamin D deficiency. Serum concentration of fibroblast growth factor 23 (FGF 23) is markedly elevated in adults receiving dialysis and is independently associated with increased mortality. Although coronary calcifications have been described in pediatric and adult HD patients, no significant association between serum FGF 23 and CC has been reported. In our study, 5/16 patients had CC. Patients with CC were older, had longer dialysis vintage and higher serum P. Serum Ca, total PTH, elemental Ca intake, and calcitriol doses were not different for CC patients. Serum FGF 23 levels were markedly elevated in all patients (mean 4,024, range 874–8,253), but significantly higher in patients with CC (4,247 ± 10,35 vs 2,427 ± 11,92, p = 0.01) and positively correlated with Agatston calcification score (r = 0.69, p = 0.003) and serum P (r = 0.49, p = 0.05). Using multivariate analysis, serum FGF 23 and serum P remained the most significant factors associated with Agatston score. This study confirms the occurrence of CC in pediatric HD patients and is the first to show a significant association between CC and elevated serum FGF 23 in children.     

Serum zinc and copper levels in children with chronic renal failure

We evaluated changes in serum zinc (Zn) and copper (Cu) levels in two groups of children with chronic renal failure (CRF) – children with CRF who were on regular hemodialysis (Group 1, n=40) and children with CRF who were on conservative management (Group 2, n=31) – and in one group of healthy children (Group 3, n=30). All of the participants in the study were between 5–18 years old, and the composition of the three groups was almost identical with respect to age and sex. The length of time the children in Group 1 had been on hemodialysis varied between 3 and 52 months (mean: 20.97±14.8 months). To evaluate the impact of the duration of dialysis on serum levels of Zn, we further sub-divided Group 1 patients into two subgroups: Subgroup A patients (n=20) had been on hemodialysis therapy for less than 18 months (mean: 8.85±4.83 months); Subgroup B patients (n=20) had been on hemodialysis therapy for longer than 18 months (mean: 33.1±10.86 months). The PIXE (proton-induced X-ray emission) was used for measuring the trace elements. Results: The mean serum level of Zn was lower in the Group 1 (hemodialysis group) children than in the children of Group 2 (on conservative management) and group 3 (healthy children) (p<0.001), but the difference was not significant between Groups 2 and 3. No significant differences in serum levels of Cu were found among the three groups. The serum level of Zn was lower in Subgroup B than in Subgroup A (p<0.001). The correlation test showed that there was an inverse linear relation between the length of time the child was on the hemodialysis regimen and serum Zn levels. Conclusion: Chronic hemodialysis may lead to abnormalities in the serum levels of some trace elements in children with CRF that increase in severity with increasing duration of hemodialysis. Deficiencies of these trace elements – zinc in particular – may contribute to various conditions and symptoms in children undergoing chronic hemodialysis.     

Serum Lipid Profile and Plasma Fatty Acids Levels in Hemodialysis Pediatric Patients-Possible Deficiency of Essential Fatty Acids

Polyunsaturated fatty acids (PUFA) are reported to be associated with atherosclerotic and inflammatory diseases because they are the major components of the cytoplasmic membrane and are the precursor fatty acids for prostaglandins and leukotrienes. Aim of this study was to identify PUFA profile (PUFAp) in children with end stage renal disease (ESRD) on hemodialysis (HD). And study its relationship with known cardiovascular and arteriosclerotic risk factors. We examined 44 pediatric HD patients (mean age 11 ± 3.36 years). Plasma lipid profile, plasma fatty acid pattern, serum albumin and hemoglobin were studied in these children. Triglyceride levels were increased in the plasma of ESRD patients compared to the healthy subjects. Plasma PUFA decreased whereas behanic acid (saturated fatty acid) increased in ESRD patients. A lower level of eicosapentaenoic acid was revealed in HD patients with cardiomyopathy (HD-CAD) than those without cardiovascular disease(HD-norm) (0.20 ± 0.01 μ/mL vs. 0.88 ± 0.12 μ/mL, P = 0.01). An inverse correlation was found between the linoleic acid level and serum TG level in children on HD (r = −0.54, P = 0.03). A positive correlation was found between plasma arachidonic acid level and serum albumin (r = 0.86, P = 0.003). A significant positive correlation was revealed between plasma eicosapentaenoic acid concentration and serum hemoglobin level (r = −0.64, P = 0.04). Saturated acid was negatively correlated with serum albumin (r = −0.70, P = 0.03). Children under regular hemodialysis evidence significant abnormalities in serum fatty acid levels together with triglyceride abnormalities, a finding that might be relevant to the risk of cardiovascular disease in this setting.     

Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in children with chronic renal failure: relationship to growth and glomerular filtration rate

Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor (IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined 89 children [age 11.5 (2.8–19.0) years] with CRF [glomerular filtration rate 26.6 (7.0–67.4) ml/min per 1.73 m²], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold increased in CRF (prepubertal 1080±268 ng/ml; pubertal 989±299 ng/ml) compared to healthy prepubertal controls (265±73 ng/ml). In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361±120 ng/ml vs 282±75 ng/ml in controls) nor pubertal CRF children (478±165 ng/ml vs 491±80 ng/ml in controls). Immunoblot analysis showed the presence of intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR (r=–0.39, P<0.001). In prepuber- tal children, IGFBP-4 levels were inversely correlated with standardized height (r=–0.40; P<0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45, P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P<0.001), IGF-II (r=0.42, P<0.001) and IGFBP-3 (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=–0.41, P<0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either by enhancing IGF activity through better presentation of IGF to its receptor or by an IGF-independent effect through activation of a specific, recently described putative IGFBP-5-receptor. Received: 24 September 1999 / Revised: 6 January 2000 / Accepted: 13 January 2000 / Accepted: 13 January 2000     

Association of macroalbuminuria with oxidized LDL and TGF-β in type 2 diabetic patients: a case–control study

The pathogenesis of diabetic nephropathy, mainly characterized by macroalbuminuria, is still poorly understood, but it is reported that transforming growth factor-β (TGF-β) plays a key role. In vitro evidence suggests that administration of oxidized LDL (ox-LDL) can lead to upregulation of TGF-β by human glomerular mesangial cells. This study aimed to evaluate the association between macroalbuminuria, ox-LDL, and TGF-β in diabetic patients. A total of 77 type 2 diabetic patients with macroalbuminuria (albumin excretion rate: AER ≥ 300 mg/24 h) and 66 patients with normoalbuminuria (AER ≤ 30 mg/24 h) were recruited. Fasting blood samples were obtained and serum levels of ox-LDL and TGF-β were determined. Ox-LDL and TGF-β were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria (98.93 ± 3.99 vs. 72.45 ± 2.48 U/l; P < 0.001 and 6.46 ± 0.74 vs. 2.49 ± 0.39 ng/ml; P < 0.001, respectively). In patients with macroalbuminuria, there was a significant correlation between Ox-LDL and TGF-β (r = 0.376; P < 0.01). AER was significantly correlated to ox-LDL (r = 0.302; P < 0.05) and TGF-β (r = 0.306; P < 0.05) in macroalbuminuric patients. This association remained significant after adjustment for potential confounders. Adjustment for TGF-β (ox-LDL), attenuated the association of ox-LDL (TGF-β) with AER. In conclusion, this study demonstrated the association of TGF-β and ox-LDL with albuminuria in macroalbuminuric type 2 diabetic patients, and suggested that this relationship is highly mediated through the correlation between TGF-β and ox-LDL.     

Subtotal Parathyroidectomy in Renal Failure: Still Needed after All These Years

There are scant data on the frequency of parathyroidectomy (PTX) for end-stage renal disease (ESRD). Medical therapy for ESRD and secondary hyperparathyroidism has evolved to include better dialytic urea removal and the use of calcitriol. The aim of this study was to determine whether medical therapy has changed the frequency or indications for PTX in the management of renal failure. Hospital and clinic records were analyzed to gather information on all patients undergoing PTX for secondary hyperparathyroidism (2HPT) (n= 48) and tertiary hyperparathyroidism (3HPT) (n= 26) from 1986 through 1998 at our institution. Prospective computer databases were queried for information concerning both chronic dialysis and renal transplant patients at our center. The patients were divided based on date of operation before or after 1991, a divider that separated the patients into groups before or after the widespread adoption of intravenous calcitriol treatment during hemodialysis at our institution. Over the 12 year period, the proportion of our chronic dialysis patients undergoing PTX did not change significantly, ranging from 0% to 2.5% per year. Comparing all patients undergoing PTX for 2HPT during 1986–1991 versus 1992–1998, there was no significant difference in time on dialysis [7.0 ± 4.2 (n= 11) vs. 7.5 ± 4.6 (n= 36) years, mean ± SD]. The later group had higher intact parathyroid hormone (iPTH) levels [765 ± 415 (n= 6) vs. 1377 ± 636 (n= 28) pg/ml; p= 0.03], lower serum calcium [11.2 ± 1.0 (n= 12) vs. 9.9 ± 1.5 (n= 34) mg/dl; p= 0.006], and higher serum phosphate [5.7 ± 1.6 (n= 12) vs. 7.2 ± 2.3 (n= 31) mg/dl; p= 0.042]. Among the population of patients with transplants undergoing PTX for 3HPT, the average percent per year undergoing PTX ranged from 0% to 4.2% and did not change during the study period. Comparing the 1986–1991 group to the 1992–1998 group, the time from transplantation to PTX did not change during the study period (3.3 ± 2.3 vs. 2.9 ± 3.0 years; p= 0.391), and there were no significant differences between preoperative calcium levels or iPTH levels. Despite advances in dialysis technique and pharmacologic therapy, there has been no change in the proportion of dialysis patients requiring PTX for 2HPT or 3HPT. There was also no change in the time on dialysis for patients with 2HPT or the time from transplant to PTX for patients with 3HPT. Analysis of preoperative biochemical markers as evidence of disease severity suggests there was no change in indications for PTX during our study. From this information we conclude that parathyroid pathophysiology is incompletely understood and medical therapy is not optimal, resulting in a continuing need for PTX in some patients.     

Impact of residual renal function in children on hemodialysis

Residual renal function (RRF) contributes to dialysis adequacy as well as lower mortality and morbidity in dialysis patients. Even very small changes in glomerular filtration rate (GFR) account for considerable improvements in complications of dialysis. The purpose of this cross-sectional study is to determine the possible contribution of RRF to hemodialysis clearance and to compare the biochemical markers of this patient group with anuric patients. Ten patients with RRF on chronic hemodialysis for more than 6 months were enrolled in the study. Duration of dialysis was not different between the two patient populations. Average GFR was 3.4±2.6 ml/min in the group with RRF. Cholesterol, albumin, and triglyceride levels were not different between the groups. Residual renal urea clearance enhanced mean Kt/V of patients from 1.29 to 1.52. However erythropoietin and renin levels were higher in the group with RRF (P=0.019, P=0.044, respectively). There was a positive correlation between erythropoietin, renin levels, and average GFR of all patients (r=0.69, P=0.002, r=0.60, P=0.014). We conclude that RRF plays a greater role in pediatric patients on hemodialysis than previously recognized, and knowledge about patients’ RRF should assist in improved overall management. Received: 31 January 2001 / Revised: 27 June 2001 / Accepted: 28 June 2001     

May an Altered Hypothalamo–Pituitary–Adrenal Axis Contribute to Cortical Bone Damage in Primary Hyperparathyroidism?

Cortisol secretion has been reported to be increased in primary hyperparathyroidism (PHPT). Our aim was to evaluate circulating and urinary cortisol levels and the relationships with biochemical and bone parameters in patients with PHPT at the time of diagnosis. We studied 180 consecutive patients with PHPT (mean age ± SD 60.0 ± 13.2 years; F/M 140/40, BMI 25.8 ± 4.8 kg/m²) and 56 subjects with incidentally discovered adrenal adenoma who served as controls (age 56.2 ± 12.8 years, F/M 40/16, BMI 25.7 ± 3.9 kg/m²). Serum morning and midnight cortisol and urinary free cortisol were measured in both groups. In PHPT patients bone mineral density was measured at the lumbar spine, femur, and forearm. Serum morning cortisol and urinary cortisol were similar in PHPT patients and controls, whereas midnight cortisol was higher in PHPT patients (5.3 ± 4.7 vs. 2.9 ± 0.9 μg/dL, P = 0.001). In this group, midnight cortisol correlated positively with age (r = 0.27, P = 0.008) and negatively with forearm (r = −0.36, P = 0.003) and total-femur T score (r = −0.30, P = 0.02). Multivariate regression analysis, including age, calcium, parathyroid hormone (PTH), and midnight cortisol as independent variables and forearm T score as dependent variable, indicated that age (β = –0.29, P < 0.0001), PTH (β = –0.33, P < 0.0001), and midnight cortisol (β = –0.14, P < 0.04) were independently associated with forearm T score. Our findings show increased midnight cortisol levels in patients with PHPT, indicating a subtle alteration of the hypothalamo–pituitary–adrenal axis dynamics that is unrelated to the degree of disease activity; further data are needed to demonstrate the supplementary effect of this subtle alteration to bone damage in this condition.     

Relation of stiffness parameter β to carotid arteriosclerosis and silent cerebral infarction in patients on chronic hemodialysis

Objective   Aortic stiffness measured by pulse wave velocity (PWV) predicts all-cause and cardiovascular mortality in hemodialysis (HD) patients. However, there is a lack of information on stiffness parameter β, another index of arterial stiffness, in HD patients. The aim of the present study was to investigate the clinical usefulness of stiffness parameter β in HD patients. Materials and methods   We compared the relation of stiffness parameter β to carotid intima-media thickness (IMT) and plaque score estimated by carotid ultrasound and investigated the relationship between stiffness parameter β and silent cerebral infarction (SCI) in 64 HD patients. Results   Stiffness parameter β was positively correlated with mean IMT (r = 0.318, P = 0.0113) and plaque score (r = 0.672, P < 0.0001). Stepwise regression analysis revealed that pulse pressure and age were found to be independent determinants of stiffness parameter β (partial correlation coefficients: β = 0.501 and P < 0.0001 for pulse pressure, β = 0.488 and P < 0.0001 for age). In addition, stiffness parameter β in patients with SCI (12.2 ± 3.9) was significantly higher than those (8.0 ± 2.4) in patients without SCI. However, there was no significant difference in mean IMT and plaque score in both groups. Conclusion   These results suggest that arteriosclerosis assessed by stiffness parameter β is associated with atherosclerotic changes of carotid arteries and with the presence of SCI in HD patients.     

Skeletal Status in Children,Adolescents and Young Adults with End-Stage Renal Failure Treated with Hemo- or Peritoneal Dialysis

The skeletal status in 30 children, adolescents and young adults (18 females, 12 males) with end-stage renal failure (ESRF) aged 9-23 years (mean 15.8 ± 3.6 years) was evaluated using measurements of bone mineral density (BMD, g/cm²) at the spine and total body (TB) (Lunar DPX-L, USA), quantitative ultrasound (QUS) of the hand phalanges (DBM Sonic 1200, IGEA, Italy) and laboratory investigations (parathyroid hormone, serum total and ionized calcium, serum phosphate). Eleven subjects were treated with hemodialysis and 19 with peritoneal dialysis. The mean value of the amplitude-dependent speed of sound (Ad-SoS, m/s) measured by QUS was significantly decreased in comparison with the value obtained in a group of 686 age-matched controls (1942 ± 74 m/s vs 2050 ± 77 m/s, p<0.0001). BMD measurements were also decreased in comparison with mean values for the healthy population (Z-scores for spine −1.47, and for TB −1.53). Duration of dialysis correlated significantly with spine-BMD, TB-BMD and Ad-SoS (r=−0.37, r = −0.45, r=−0.55, respectively, p<0.05), while duration of ESRF did not have such an influence. Laboratory investigations did not correlate with skeletal parameters. Ad-SoS correlated significantly with spine-BMD (r= 0.45, p<0.05) and TB-BMD (r= 0.56, p<0.01). Both QUS and BMD values correlated significantly with Tanner stages (r ranged from 0.59 to 0.69, p<0.001) and did not increase with age except for correlation between age and TB-BMD. In conclusion, skeletal status in the population studied is strongly affected by ESRF. Both QUS and BMD measurements show an ability to express skeletal changes in a similar manner, though the QUS parameter seems to be more sensitive at revealing changes due to renal failure. Received: 12 July 2001 / Accepted: 8 November 2001     

Plasma levels of fibroblast growth factor-23 and mineral metabolism in diabetic and non-diabetic patients on chronic hemodialysis

Objective  Fibroblast growth factor (FGF) 23 is a circulating factor that regulates phosphate (P) metabolism. Since higher P levels are associated with vascular calcification, we examined the role of serum FGF-23 levels in P metabolism and vascular calcification in hemodialysis (HD) patients with and without diabetes mellitus (DM). Materials and methods  Chronic HD patients with DM (n = 39) and without DM (n = 50) were enrolled. Serum samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Abdominal computed tomography (CT) scan was performed, and the aortic calcification index (ACI) was determined by one examiner, blinded to the patient characteristics. Measurements of bone mineral density (BMD) were performed at the time of ACI estimation. Results  Log plasma FGF-23 levels were higher in non-DM (3.74 ± 0.71 pg/ml) than in DM (3.35 ± 0.74 pg/ml) patients. The log FGF-23 correlated positively with serum creatinine (r = 0.424, P < 0.0001), albumin (r = 0.225, P = 0.0337), Ca (r = 0.392, P = 0.0001), P (r = 0.735, P < 0.0001), and Ca × P product (r = 0.780, P < 0.0001). There were negative correlations between log FGF-23 and age (r = −0.208, P = 0.0497), glucose (r = −0.231, P = 0.0294), and CRP (r = −0.222, P = 0.0359). Multiple regression analyses were performed to explore the correlations between plasma FGF-23 and other factors associated with vascular calcification in all HD patients. Independent variables were selected based on the results of univariate analyses. The significant factors associated with FGF-23 in HD patients were age, serum levels of creatinine, albumin, glucose, Ca, P, and Ca × P product. Plasma FGF levels did not correlate significantly with either ACI or BMD in these patients. Conclusion  Our findings indicate that the plasma FGF-23 level is associated with calcium-phosphate metabolism disorders, but not with aortic calcification, in both non-DM and DM patients on chronic HD. In addition, plasma FGF-23 is associated with serum levels of creatinine and albumin. Therefore, the plasma FGF-23 level may provide a reliable marker for Ca and P imbalance and nutritional status in HD patients.     

The oxalate level in ultrafiltrate fluid collected from a dialyzer is useful for estimating the plasma oxalate level in hemodialysis patients

Background Patients on chronic hemodialysis are likely to develop secondary hyperoxalemia. It is, however, difficult to measure plasma oxalate levels. To measure plasma oxalate levels, rapid plasma separation, deproteinization, and acidification are essential in preventing the formation of oxalate and the deposition of calcium oxalate within the test tube. The present study was undertaken to examine whether the oxalate level in dialyzer ultrafiltrate is potentially useful for estimating plasma oxalate levels. Methods In nine patients on chronic hemodialysis, the plasma, after deproteinization with a filter, and the ultrafiltrate from the dialyzer before hemodialysis were acidified to a pH level of less than 3, followed by the measurement of oxalate levels by ion chromatography. Also, oxalate levels were compared between acidified and non-acidified ultrafiltrates from the dialyzer. In the second part of the study, seven patients on chronic hemodialysis receiving erythropoietin therapy, in whom the ferritin level was more than 300 ng/ml and transferrin saturation was less than 25%, were intravenously administered ascorbic acid, 100 mg, three times a week, after each dialysis session to facilitate the utilization of stored iron. This treatment was continued until the serum ferritin level decreased to a level below 300 ng/ml (for 3 months, at a maximum). The oxalate level in the dialyzer ultrafiltrate after this treatment was compared with that before treatment. Results The mean ± SE oxalate level in the dialyzer ultrafiltrate was 45 ± 6 μmol/l, essentially equal to the plasma oxalate level (46 ± 7 μmol/l). The plasma oxalate level had a significant positive correlation with the dialyzer ultrafiltrate oxalate level (plasma oxalate level = 0.99 × dialyzer ultrafiltrate oxalate level + 1.5; r = 0.95; P < 0.0001). The oxalate level in the acidified ultrafiltrate (45 ± 6 μmol/l) did not differ significantly from that in the non-acidified ultrafiltrate (45 ± 6 μmol/l). The mean ± SE duration of ascorbic acid administration was 64 ± 13 days. The hemoglobin level remained unchanged at 9.6 ± 0.4 g/dl, whereas the serum iron level increased significantly, from 34 ± 2 μg/dl to 43 ± 4 μg/dl (P < 0.05), and serum ferritin levels decreased significantly, from 645 ± 219 ng/ml to 231 ± 30 ng/ml after the treatment (P < 0.05). The oxalate level in the acidified ultrafiltrate showed no significant change after ascorbic acid administration (31 ± 8 μmol/l vs 47 ± 7 μmol/l). Conclusions In patients on chronic hemodialysis, the oxalate level in acidified ultrafiltrate from the dialyzer was found to be useful for estimating the plasma level of non-protein-bound oxalate. When administering ascorbic acid to hemodialysis patients, the plasma oxalate level can be monitored using this method.     

Relation Between Depression,Some Laboratory Parameters,and Quality of Life in Hemodialysis Patients

Depression is common in patients with end-stage renal disease (ESRD) and is associated with increased mortality and morbidity. Several investigators have estimated that depression occurs in about 20% to 30% of dialysis patients. The aim of this study was to investigate the relationship between depression, some laboratory parameters, and quality of life (QOL) in hemodialysis patients. Forty-three hemodialysis patients (mean age 40.5 ± 15.2; M = 28, F = 15) were included in the study. Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and short form with 36 (SF-36) were used for evaluation. Subsequently, patients were divided into two groups according to HAMD scores: group 1, those who had a low HAMD score (between 0 and 7), and group 2, those who had a high HAMD score (over 7). The two groups were compared in terms of anxiety scores, QOL scores, and some laboratory parameters. The group 2 patients (n = 21; M = 13, F = 8) had lower levels of hemoglobin than the group 1 patients (9.5 ± 1.7 vs. 10.7 ± 1.4 g/dL, respectively; p< 0.01). Group 2 patients also had lower SF-36 scores than group 1 patients (91.5 ± 21.3 vs. 74.9 ± 13.6, respectively; p = 0.03). On the contrary, the patients of group 2 had higher HAMA scores than group 1 patients (16.6 ± 6.9 vs. 6.3 ± 3.5, respectively; p< 0.01) and CRP level (10.7 ± 4.6 vs. 4.5 ± 3.8, respectively; p< 0.001). A significant correlation was found between depression scores and C-reactive protein (CRP) (r = 0.57, p< 0.001) and HAMA scores (r = ? 0.43, p< 0.05). In contrast, a negative correlation was found between HAMD scores and albumin (r = ? 0.43, p< 0.05), hemoglobin (r = ? 0.38, p =0.015) and SF-36 scores (r = 0.39, p = 0.032). These findings demonstrate that there is a relationship among high depression score, low levels of hemoglobin and albumin, high CRP level, low SF-36 score, and high anxiety score. Evaluation of psychiatric status should be part of the care provided to hemodialysis patients.     

Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis

We prospectively evaluated the effects of L-carnitine supplementation on plasma free carnitine (FC) levels, serum lipid profile, and erythropoietin (rhEPO) requirement in 24 children treated with peritoneal dialysis (PD; n = 16) or hemodialysis (HD; n = 8). The study was divided into a 3-month observation period, and a 3-month treatment period during which patients received 20 mg/kg per day of L-carnitine given orally. Clinical, biochemical, and hematological data were collected every 3 months. FC levels were measured in plasma and peritoneal dialysate by tandem mass spectrometry. There were no statistically significant changes in lipid levels, hemoglobin, or rhEPO requirements during the course of the study. Fifteen patients (13 PD, 2 HD) had plasma FC levels measured before and after treatment; FC levels increased from 32.1 ± 14.1 μmol/l to 80.9 ± 38.7 μmol/l (P < 0.001). In PD patients, dialysate FC losses increased from 106 ± 78 μmol/day at baseline to 178 ± 119 μmol/day after supplementation. Positive correlations between FC plasma levels and dialysate levels (R = 0.507) or daily excretion (R = 0.603) were found after treatment. In our case series, an oral dose of 20 mg/kg per day of L-carnitine restored FC levels and produced a positive carnitine balance with no significant effects on hematological parameters or lipid profile over a 3-month period. Prolonged treatment duration may be required to obtain significant results.     

Calcium oxalate saturation in dialysis patients with and without primary hyperoxaluria

Calcium oxalate supersaturation of the blood is associated with deposition of crystals in various tissues. We measured the serum levels of oxalate, citrate, calcium, and magnesium to estimate their saturation in 112 hemodialysis patients without primary hyperoxaluria and two boys with primary hyperoxaluria. Serum levels of oxalate and citrate were determined by high-performance capillary electrophoresis, while calcium and magnesium were measured by ICP spectroscopy. The serum levels of oxalate, citrate, calcium, and magnesium were 44.9±16.5, 138.1±54.9 μmol/l, 2.30±0.28, and 1.07±0.18 mmol/l, respectively, while the levels in patients with primary hyperoxaluria were 83.9±34.3, 197.9±63.5 μmol/l, 2.53±0.15, and 1.14±0.34 mmol/l, respectively. Serum calcium oxalate saturation (SS), as calculated by the Equil program, was significantly correlated with the serum oxalate level. Most patients showed metastable supersaturation (1<SS<8.9), which was associated with a serum oxalate level of more than 30 μmol/l. Serum saturation exceeded the formation product (SS=8.9) in some specimens from patients with type 1 primary hyperoxaluria. The serum calcium oxalate saturation [SS(CaOx)] showed a significant positive correlation with the levels of oxalate [Ox], calcium [Ca], and citrate [Cit]: (all mmol/l, r=0.9848, P<0.01). This formula is useful for estimating the saturation. In conclusion, the serum oxalate level is a good indicator of calcium oxalate saturation and should be monitored accurately while keeping it lower in dialysis patients.     

The Association between Serum Adiponectin Levels and Nutritional Status of Hemodialysis Patients

Adiponectin plays an important role in the regulation of body weight, insulin sensitivity, lipid metabolism, and the inflammatory response. Adiponectin is elevated in hemodialysis patients. We investigated the association between altered serum adiponectin levels and the nutritional–inflammation status of hemodialysis patients. Forty-four hemodialysis patients (21 men and 23 women; mean age 53.9 ± 9.2 years) were enrolled and 32 healthy volunteers were included as the control group. Serum adiponectin was measured using a commercial radioimmunoassay kit. Serum albumin, cholesterol, triglyceride, high-sensitivity C-reactive protein, urea, creatinine, transferrin, lean body mass, fat mass, body mass index (BMI), the subjective global assessment (SGA) score, and the malnutrition–inflammation score (MIS) were measured in all patients. Adiponectin levels were significantly elevated in the hemodialysis patients compared with the healthy subjects (24.8 ± 10.4 μg/mL and 6.8 ± 4.2 μg/mL, respectively, p < 0.0001). Serum adiponectin correlated positively with SGA (r = 0.47) and MIS (r = 0.38), and negatively with BMI (r = ?0.34), triglyceride (r = ?0.53), and glucose levels (r = ?0.42). Serum adiponectin levels were significantly higher in malnourished patients than in well-nourished patients when assessed with SGA (20.5 ± 10.4 μg/mL and 29.0 ± 8.7 μg/mL, respectively, p = 0.005). In conclusion, serum adiponectin levels reflect the nutritional–inflammation status of hemodialysis patients. Adiponectin may also be associated with insulin resistance, dyslipidemia, and the inflammatory response in these patients.     

Circulating osteoprotegerin and receptor activator of NF-κB ligand system in patients with β-thalassemia major

Osteoporosis represents an important cause of morbidity in patients with β-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-κB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age ± SEM, 24.26 ± 1.29 years; range, 13–41 years) and females (n = 31; age, 24.59 ± 0.95 years; range, 12–34 years) with β-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 ± 0.12 vs. 3.25 ± 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 ± 0.03 vs. 0.295 ± 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = −0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = −0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in β-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.     

Inverse correlation between serum magnesium and parathyroid hormone in peritoneal dialysis patients: a contributing factor to adynamic bone disease?

Background Secondary hyperparathyroidism (SHPTH) is present in many patients with end-stage renal disease (ESRD) and has been linked to uremic bone disease. Parathyroid hormone (PTH) levels are affected by calcium, vitamin D, and phosphorus. Recent data suggests that serum magnesium may also modulate PTH levels. Objective The aim of this retrospective study was to investigate the impact of different calcium (Ca) and magnesium (Mg) concentrations of dialysis solutions on serum Mg and serum PTH levels in peritoneal dialysis (PD) patients. Patients and methods Two groups of PD patients-group A (n = 17) on “standard” Ca and Mg dialysis solution (SCa–MgD) (Ca: 1.62 mmol/l, Mg: 0.75 mmol/l and Lactate 35 mmol/l), and group B (n = 29) on “low” Ca and Mg dialysis solution (LCa–MgD) (Ca: 1.25 mmol/l, Mg: 0.25 mmol/l and Lactate 40 mmol/l), on PD for more than 6 months, were studied. Calcium carbonate (CaCO₃) was used as the phosphate (P) binder in 87% (40/46) of the patients. Biochemical parameters were evaluated every 1–2 months over 6 months and the mean values were computed. Results No significant differences were found between the two groups in all parameters except for serum Mg and PTH. Serum Mg was higher in SCa–MgD group compared to those in the LCa–MgD group (1.05 ± 0.19 vs 0.90 ± 0.23 mmol/l, respectively) and serum PTH was higher in LCa–MgD group compared to those in SCa–MgD group (72.3 ± 64.2 vs 31.1 ± 39.0 pmol/l, respectively) even though serum Ca was not different. There was a statistically significant inverse correlation between serum Mg and PTH levels (r = −0.357, p < 0.05). Conclusion Serum Mg is lower and serum PTH higher in patients dialyzed with lower Mg concentration dialysis solution compared to those with higher Mg concentration dialysis solution. Our study confirms previous reports that serum Mg may have a suppressive role on PTH synthesis and/or secretion, and thus may play a role in pathogenesis of adynamic bone disease that often develops in patients on chronic PD with high calcium and high magnesium concentrations.