Parathyroid hormone levels in pubertal uremic adolescents treated with growth hormone

We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively recorded every 3 months starting 1 year before rhGH administration. The mean (±SD) rhGH treatment observation period was 19.9±5.9 months. The mean age at the start of rhGH treatment was 8.3±3.6 years. Of the 67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment and 12 of these 15 progressed to pubertal stage 3. The relative increase in parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal [1.95, 95% confidence interval (CI) 1.43–2.66] than in prepubertal patients (1.19, 95% CI 1.01–1.40). Increases in PTH levels were significantly different between the two groups (=1.64, 95% CI 1.16–3.19, P=0.007). Multiple regression analysis showed an inverse correlation between PTH and calcium levels and a positive correlation between PTH and pubertal stage 3. There was no correlation with phosphate levels and calcitriol dosage. In conclusion, these results suggest that in uremic adolescents treated with rhGH puberty may influence PTH levels.     

Parathyroid hormone and growth in children with chronic renal failure

BACKGROUND: In pediatric chronic renal failure (CRF) optimal parathyroid hormone (PTH) concentrations that minimize renal osteodystrophy and maximize growth are unknown. The search for optimum concentrations has been complicated as currently used "intact" PTH (iPTH) assays cross-react with long carboxyl-terminal PTH fragments (C-PTH), which antagonize the biologic actions of 1-84 PTH. The purpose of this study was to investigate the relationship between PTH, the 1-84 PTH:C-PTH ratio and growth rate in children with CRF. METHODS: A total of 162 patients, median (range) age 9.9 years (0.3 to 17.1 years), were recruited: 136 with a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2)[96 managed conservatively (CRF group) and 40 transplanted patients], and 26 dialysis patients. Over a median (range) period of 1.1 years (0.5 to 1.7 years), children attended five (three to 15) clinics at which iPTH, cyclase-activating PTH (CAP-PTH), and height were measured. RESULTS: Mean PTH concentrations were within the normal range for both assays for the CRF group and up to twice the upper limit of normal for the dialysis group; CAP-PTH 24.8 pg/mL and 59.9 pg/mL (normal range 5 to 39 pg/mL), iPTH 37.1 pg/mL, and 102.6 pg/mL, respectively (normal range 14 to 66 pg/mL). The patients grew normally (change in height standard deviation score per year (DeltaHtSDS) =-0.01). There was no relationship between PTH concentrations and DeltaHtSDS in any patient group. The 1-84 PTH:C-PTH ratio was lower in dialyzed patients (P= 0.003), with worsening renal function (P= 0.047) and with PTH concentrations outside the normal range (P= 0.01). There was a weak correlation between the 1-84 PTH:C-PTH ratio and the DeltaHtSDS (r= 0.2, P= 0.01). CONCLUSION: Normal range PTH concentrations are appropriate, allowing normal growth in children with CRF managed conservatively. C-PTH may be of clinical significance.     

Parathyroid hormone and its fragments in children with chronic renal failure

Parathyroid hormone (PTH) immunoradiometric assays (IRMA) exhibit cross-reactivity between 1-84 PTH and long carboxyl-terminal-PTH (C-PTH) molecules. C-PTH antagonizes the biological actions of 1-84 PTH and circulates in excess in chronic renal failure (CRF), partially explaining why supra-physiological PTH levels are recommended to maintain bone turnover. Furthermore, the ratio 1-84 PTH/C-PTH may be related to bone turnover. This study characterizes the 1-84 PTH/C-PTH ratio in children with varying severity of CRF and levels of PTH. Two hundred and forty-one children with CRF, managed with the aim of preventing the development of hyperparathyroidism, had PTH measured by intact IRMA and a new more specific Cyclase-Activating-PTH (CAP) IRMA. C-PTH levels were calculated by subtracting CAP-IRMA from intact IRMA. Fifty-three controls with normal renal function were also recruited. Mean intact IRMA correlated with CAP-IRMA (r=0.98), but was higher (P<0.001). The mean 1-84 PTH/C-PTH ratio was lower than controls in dialysis patients (P=0.022) and those with a glomerular filtration rate <30 ml/min per m² (P=0.033). This ratio was comparable to controls when the PTH level was normal, but was lower with PTH levels outside the normal range (P<0.01). These data suggest that CAP-IRMA gives a more accurate assessment of actual PTH levels than intact IRMA in CRF. Maintenance of normal PTH levels throughout the course of CRF permits the maintenance of a normal 1-84 PTH/C-PTH ratio, the clinical significance of which requires further investigation in children.     

Endogenous erythropoietin levels and anemia in long-term renal transplant recipients

BACKGROUND/AIM: Although anemia is a common complication after renal transplantation (RT), data concerning endogenous erythropoietin (EPO) levels in long-term RT recipients are rare. The goal of this study was to evaluate the prevalence of anemia within 6 months to 5 years after RT and to assess the relationship between the serum concentrations of endogenous EPO, graft function and grade of improvement of anemia. METHODS: 140 patients who had undergone RT were included in the group: 89 males (63.6%) and 51 females (36.4%), with an average age 46.8 +/- 12.8 years. The serum concentrations of EPO and creatinine (Cr) were tested in all the individuals and the values of the red blood component of blood count, serum ferritin (SF), plasma iron concentration, plasma total iron-binding capacity (TIBC), transferrin saturation (TS), folic acid and vitamin B(12) levels in the serum were determined. A statistical analysis of the results was performed using the correlation analysis, Mann-Whitney U test and Duncan's multiple range test. RESULTS: Normal blood count values were found in 91 patients (65%), and a mild grade of anemia with a mean hemoglobin (Hb) 114.4 +/- 11.9 g/l was observed in 45 patients (32.1%), and 4 patients (2.9%) fulfilled the diagnostic criteria for post-transplantation erythrocytosis. Individuals with normal Hb values had a mean EPO serum concentration of 39.3 +/- 12.3 mU/ml (median 37.2) and the mean Cr was 133.8 +/- 36.9 micromol/l (median 122). Patients with anemia (Hb <120 g/l in females, Hb <130 g/l in males) had a mean EPO value of 47.0 +/- 26.6 mU/ml (median 36.0) and a mean Cr of 203.8 +/- 108.9 micromol/l (median 181). The difference in the Cr values was statistically significant (p < 0.0001), while the difference between the EPO concentrations was not significant. No relation of EPO serum concentration with regard to graft function was found in the analysis. A lack of storage iron (SF <10 microg/l in females, SF <22 microg/l in males) was found in 16 patients (11.4%), and a lack of functional iron (TS <20%) was found in 27 patients (19.3%). CONCLUSIONS: Theprevalence of anemia in patients after transplantation was 32.1%. The most common cause of anemia is insufficient graft function development. The achieved values of the red component of blood count have no relation to the endogenous EPO serum concentrations.     

Intact parathyroid hormone levels in renal transplant patients with normal transplant function

Bleskestad IH, Bergrem H, Leivestad T, Gøransson LG. Intact parathyroid hormone levels in renal transplant patients with normal transplant function.
Clin Transplant 2011: 25: E566–E570. © 2011 John Wiley & Sons A/S. Abstract: Introduction: Chronic kidney disease mineral and bone disorder (CKD‐MBD) is common in patients who have undergone kidney transplantation. There is limited information on the extent to which patients with normal renal function after transplantation have persistent disturbances in their mineral metabolism. Aim: The aim of the study is to investigate the prevalence of elevated intact parathyroid hormone (iPTH) levels at least one yr after transplantation in patients living with a first renal transplant with normal transplant function. Methods: A retrospective, observational study of 607 patients was collected from the Norwegian Renal Registry. Of these, iPTH was recorded for 360 patients. Results: One hundred and eighty‐eight patients (52%) had elevated iPTH levels. Twenty‐six patients (7%) had iPTH levels >2.5 times the upper limit of normal (ULN). Patients with a pre‐emptive transplant were significantly younger than the patients who had received treatment with dialysis (p < 0.0001). The prevalence of iPTH > ULN was significantly higher in patients with a pre‐emptive transplant (p = 0.037). Conclusions: In post‐transplant patients with normal transplant function, our data indicate that more than 50% have elevated levels of iPTH more than one yr after transplantation. If elevated iPTH level is associated with mortality in this patient population, it may have major impact on clinical treatment guidelines.     

Factors related to long-term renal transplant function in children

Short-term renal allograft survival in children has improved. It is therefore important to determine the factors leading to long-term graft function. To this end, we evaluated patients in the NAPTRCS registry who were <12 years old when they received their renal transplant between 1987 and 1993. Children with 10 years of post-transplant follow-up were compared to those in whom the transplant failed within 10 years. Children with a failed transplant within 10 years of the surgery tended to be older, female, and non-Caucasian; they also manifested obstructive uropathy less often and had focal segmental glomerulosclerosis more often, and they received more deceased donor kidneys. Children with a failed renal transplant had fewer HLA donor and recipient matches, received pre-transplant dialysis compared to a preemptive transplant, required dialysis in the first week post-transplant, and required more antihypertensives the first month post-transplant. Allograft function was examined at 10 years. Patients with continued allograft function and a serum creatinine 相似文献   

Hepatitis C infection in children and adolescents on haemodialysis and after renal transplant

Serum antibodies to hepatitis C virus (HCV) were measured in children and adolescents on haemodialysis (HD,n=20) and after renal transplant (RT,n=33). Seropositivity was observed in 3 HD patients (15%) and in 7 RT patients (21.2%) with an enzyme-linked immunosorbent assay (2nd generation) and a recombinant immunoblotting assay (2nd generation). HCV RNA was detected by the polymerase chain reaction in the 10 patients with anti-HCV antibodies. Anti-HCV positivity was significantly correlated (P<0.05) with the number of blood transfusions and the time on HD. Transaminase levels were not useful for screening. This study confirms that there is a high risk of HCV infection in children and adolescents on HD or after RT. Moreover, HCV infection is closely related to the number of blood transfusions as well as the time on HD.     

Parathyroid hormone levels, hyperparathyroidism and acute pancreatitis

Since 1971, in Glasgow Royal Infirmary 880 patients with acute pancreatitis (AP) have been prospectively studied. Only two (0.23 per cent) have been found with associated hyperparathyroidism (HPT), one of whom also had gallstones. During the period of study daily serum calcium levels were measured routinely in all patients with AP and, in addition, a consecutive series of 200 patients had daily mineral metabolism screening of blood and urine in an attempt to identify patients with hypercalcaemia as an aetiological factor. A separate group of 90 patients had sequential daily serum calcium and parathyroid hormone assays (PTH) performed for the first five days of their hospital admission and one of the patients described in this paper came from this group. She is the first patient, to our knowledge, documented in this manner. The overall pattern of the PTH and calcium response from all these patients is also recorded according to the severity of the AP. Hyperparathyroidism is uncommonly associated with AP and when it is other aetiological factors must be excluded.     

Effect of tangerine juice on cyclosporine levels in renal transplant children

The aim of our study was to investigate the effect of tangerine juice on the pharmacokinetics of cyclosporine A (CsA), in children who had received a renal transplant. This placebo-controlled study was done on ten kidney transplant recipients with stable cyclosporine trough levels who received either tangerine (Unshio Satsuma) juice or water. Patients were given their morning doses of CsA and then 250 ml water or the juice, and 12 h, investigations of the pharmacokinetics (PK) were performed. The main outcome measures were peak concentration and time to peak and area under the concentration–time curve. Administration of CsA with tangerine juice compared with water did not increase significantly the area under the whole-blood concentration versus time curve from 0–12 h (AUC_0–12) of CsA, (tangerine juice 2,797 ± 1,361 (P = 0.5); water 3,053 ± 1,532). Co-administration of tangerine juice with CsA compared with water had no significant effects on the AUC_0–12, peak concentration (C_max) or time to C_max (t_max) of the CsA in pediatric renal transplantation.     

Vitamin D deficiency and parathyroid hormone levels following renal transplantation in children

The objectives were to determine the prevalence of vitamin D deficiency [25(OH)D < 10 ng/ml] in pediatric renal transplant (RTx) recipients, compared with controls and identify correlates of changes in 25(OH)D and intact parathyroid hormone (iPTH) levels following transplantation. Serum 25(OH)D, 1,25(OH)₂D, and iPTH were measured once in 275 healthy controls and at transplantation, and 3 and 12 months posttransplantation in 58 RTx recipients. Multivariate logistic regression models determined the odds ratio (OR) of vitamin D deficiency in RTx recipients vs. controls adjusted for age, sex, race, and season. Generalized estimating equations were used to assess changes following transplantation. At transplantation, 22% of nonblack and 27% of black RTx recipients were vitamin D deficient. The adjusted OR of vitamin D deficiency was greater in RTx recipients (p < 0.001) compared with controls; however, the transplant association was greater in nonblack vs. black individuals (interaction p = 0.02). Overall, 25(OH)D levels did not change significantly following transplantation. Younger age (p < 0.01), nonblack race (p < 0.001), visits in nonwinter months (p < 0.001), and supplementation with ≥400 IU/day ergo/cholecalciferol (p < 0.001) were associated with increases (or lesser declines) in 25(OH)D following transplantation. Increases in 25(OH)D levels (p < 0.001) and vitamin D supplementation (p < 0.01) were associated with greater reductions in iPTH levels following transplantation, independent of 1,25(OH)₂D levels.     

Renin-angiotensin-aldosterone system in long-term renal transplant patients

Seventeen anephric patients who constituted the subjects of this study received renal allografts between the years 1969 to 1973. The renin-angiotensin-aldosterone mechanism was evaluated in relation to either a normotensive or hypertensive clinical state in these subjects. Group I (Controls) were normotensive and on a normal diet; Group II were normotensive, on sodium restriction for five days, followed by saline infusion on the seventh day; and Group III were hypertensive, on similar sodium restriction for five days, followed by saline infusion on the seventh day. Glomerular filtration rates and levels of plasma renin and aldosterone, and the secretion rate of the latter were obtained on appropriate days. These studies confirm that an intact renin-angiotensin-aldosterone relationship exists in human renal transplant patients. The presence of high aldosterone secretion rate without hypertension is a new but unexplained finding. The lack of correlation of high aldosterone secretion rates in our normotensive and hypertensive patients suggests that aldosterone does not play a detectable or significant role in the pathogenesis of chronic or sustained transplant hypertension.     

Effective long-term immunosuppression maintained by low cyclosporine levels in primary cadaveric renal transplant recipients

Nephrotoxicity and cost are the major problems in the use of cyclosporine (CsA) in renal transplantation. Thus, maintenance of CsA levels at the lower limits of the therapeutic range is desirable. The lowest CsA level effective in preventing rejection while avoiding nephrotoxicity has not been defined. We report on 44 primary cadaveric renal transplant recipients treated with a protocol that involved a progressive reduction in the trough CsA levels. CsA was initiated at an oral dose of 15 mg/kg, and this dose was adjusted to achieve serum trough levels, as measured by radioimmunoassay, of 150-200 ng/ml during the first month, 100-150 ng/ml during the second month, 75-100 ng/ml during the third month, and 50-75 ng/ml thereafter. Patient and graft survival at 18 months were 94% and 83.6%, respectively. The mean daily CsA doses were 6.7 +/- 3.1 mg/kg at 6 months, 5.5 +/- 3.2 mg/kg at 12 months, and 4.7 +/- 2.4 mg/kg at 18 months. Corresponding trough serum CsA levels were 94 +/- 59 ng/ml, 64 +/- 22 ng/ml, and 44 +/- 21 ng/ml at 6, 12, and 18 months, respectively. Mean serum creatinine concentrations were 1.8 +/- 0.6 mg/dl at 6 months, 1.7 +/- 0.5 mg/dl at 12 months, and 1.6 +/- 0.5 mg/dl at 18 months. The mean serum creatinine concentration at 18 months was not significantly different from that of 18 conventionally treated primary cadaveric renal transplant recipients (1.6 +/- 0.5 vs. 1.4 +/- 0.4 mg/dl, P = .31). A total of 67% of patients did not have any rejection episodes under this protocol, while 71% of patients never developed CsA nephrotoxicity. No patient was taken off CsA for progressive nephrotoxicity. We conclude that trough serum CsA levels of 50-75 ng/ml, as measured by radioimmunoassay, are sufficient to maintain effective immunosuppression in the long-term management of primary cadaveric renal transplant recipients. These values are much lower than previously recommended, and this approach ameliorates chronic CsA nephrotoxicity.     

Anemia among long-term renal transplant recipients

BACKGROUND: The effects of anemia on cardiovascular disease among the end-stage renal disease (ESRD) population suggest that it may be one of the major factors explaining this complication among kidney transplant recipients. Systematic investigation into the prevalence of posttransplantation anemia (PTA) is therefore of critical importance. MATERIALS AND METHODS: This cross-sectional study of data from 650 patients followed at a single outpatient transplant clinic utilized the guidelines of the American Society of Transplantation to define anemia as a hemoglobin (Hb) < or =130 g/L in men or < or =120 g/L in women. RESULTS: Among the 39% of patients who were anemic, the prevalence was greater in women than in men. Serum Hb concentrations significantly correlated with the glomerular filtration rate (GFR), serum transferrin, the use of angiotensin converting enzyme inhibitors and mycophenolate mofetil therapy. Upon multivariate analysis, the GFR, serum transferrin, potential nutritional markers, chronic inflammation, and iron deficiency were independently and significantly associated with the presence of anemia. Erythropoietin was administered to 15 (5.7%) anemic patients. CONCLUSIONS: PTA is a prevalent, undertreated condition. Based on our results, we suggest that protein/energy malnutrition and/or chronic inflammation were independently associated with anemia.     

Parathyroid hormone metabolites in renal failure: bioactivity and clinical implications

Non-(1-84) parathyroid hormones (PTHs) are large circulating carboxyl-terminal PTH (C-PTH) fragments with a partially preserved amino-terminal structure. They were discovered during high-performance liquid chromatography (HPLC) analysis of circulating PTH molecular forms detected by an intact PTH (I-PTH) assay. Like other C-PTH fragments, they accumulate in blood in renal failure and account for up to 50% of I-PTH. They are secreted by the parathyroid glands in humans, and are generated by the peripheral metabolism of hPTH(1-84) in rats. The exact structure of non-(1-84)PTH fragments is not known. To study the possible role of non-(1-84) in PTH biology, hPTH(7-84) has been used as a surrogate, being the only large C fragment available on the market. In anesthetized, thyroparathyroidectomized rats, hPTH(7-84) caused hypocalcemia beyond that induced by surgery. It also blocked the calcemic response to hPTH(1-84) or hPTH(1-34). Other smaller C-PTH fragments, such as hPTH(39-84) and hPTH(53-84), were synergistic to hPTH(7-84) effects. hPTH(7-84) did not bind to the PTH/PTHrP receptor, but only to the C-PTH receptor in ROS 17/2.8 clonal cells, and did not stimulate cyclic adenosine monophosphate (cAMP) production by the same cells, suggesting that its hypocalcemic action was mediated via a receptor different from the PTH/PTHrP receptor, and that the calcium concentration resulted from the sum of the positive effect of hPTH(1-84) on the PTH/PTHrP receptor and of the negative effect of hPTH(7-84) and of C-PTH fragments on the C-PTH receptor. These data will change our understanding of circulating calcium regulation, which must now be viewed as the end result of opposite actions on two PTH receptors. PTH immunoheterogeneity, a highly regulated phenomenon, contributes to this dual biological effect, generating an agonist for the two different receptors. Clinically these results could have some implications in our knowledge of the PTH resistance of renal failure, of renal osteodystrophy, and of certain aspects of the uremic syndrome.