Parathormone and bone-specific alkaline phosphatase for the follow-up of bone turnover in hemodialysis patients : Is it so simple?

in Clinica Chimica Acta (2013), 417

Background: Chronic Kidney Disease (CKD) is associated with mineral and bone disorders (MBD). International guidelines suggest that levels of serum parathormone (PTH) or bone-specific alkaline phosphatase ... [more ▼]

Background: Chronic Kidney Disease (CKD) is associated with mineral and bone disorders (MBD). International guidelines suggest that levels of serum parathormone (PTH) or bone-specific alkaline phosphatase (b-ALP) can be used to evaluate MBD in dialysis patients. The evidence remains moderate and based on transversal studies. <br />Methods: We retrospectively investigated the variations of PTH (ΔPTH) and b-ALP (Δb-ALP) serum concentrations over a short (6-weeks) and a long (one-year) period in a monocentric hemodialysis population. The proportion of patients reaching the critical difference (CD) (50% for PTH and 25% for b-ALP) was calculated. <br />Results: Seventy-seven patientswere included. A significant correlation between PTHand b-ALP levelswas found at baseline (r=0.51). By contrast, no correlation was observed between ΔPTH and Δb-ALP over a 6-week interval (r=0.07). The CD for PTH and b-ALP was reached by 19 and 11 patients, respectively, with 2 patients showing consistent variations of both biomarkers. One year later, measurements were repeated in 48 survivors. <br />No correlation was found between ΔPTH and Δb-ALP (r=0.27). The CD for PTH or b-ALP was reached by 24 patients and 28 patients, respectively, with 6 patients (12.5%) showing opposite results for both biomarkers. <br />Conclusion: This study shows the lack of correlation between ΔPTH and Δb-ALP over time in patients under chronic hemodialysis. [less ▲]

Comparison of acid and enzymatic methods for insulin dosage: Analytical performances and impact on glomerular filtration rate evaluation

in Clinica Chimica Acta (2012), 413(5-6), 556-560

Among issues susceptible to hamper a reliable measurement of inulin clearance, those regarding the dosage of inulin are largely neglected. We have compared the analytical performances of 2 commonly used ... [more ▼]

Among issues susceptible to hamper a reliable measurement of inulin clearance, those regarding the dosage of inulin are largely neglected. We have compared the analytical performances of 2 commonly used methods of inulin dosage (one “acid” and one “enzymatic” method) and studied their potential impact on the glomerular filtration rate (GFR) value given by inulin clearance. Repeatability, uncertainty and the beta-expectation limits were evaluated from pre-determined serum and urine pools of inulin. Agreement between the two methods was analyzed from 99 inulin clearances performed in renal transplant patients. Impact of the method of dosage on GFR evaluation was simulated according to the respective beta-expectations limits of each method. Overall, intra-assay coefficient of variability and relative bias were inferior to 5% and 10% for both methods. Contrary to the acid method, analytical performance of the enzymatic method was not influenced by the presence of glucose. The relative difference in GFR values obtained with the two methods in transplant patients was − 0.4 ± 10%. Simulations suggested that changes in inulin concentration attributable to analytical error could modify the value of GFR from − 12% to + 28%. In conclusion, while analytical performances are globally acceptable for both methods, they are not strictly equivalent. The impact on the determination of GFR, albeit limited, is not negligible and adds to other sources of inaccuracy. International standardization for the dosage of inulin is necessary. [less ▲]

New insights on the stability of the Parathyroid hormone as assayed by an automated 3rd generation PTH assay

in Clinica Chimica Acta (2012), 413(1-2), 353-4

Human anti-animal antibodies interference in the Siemens Immulite chemiluminescent insulin immuno-assay: about one case

in Clinica Chimica Acta (2011), 412(7-8), 668-669

Urinary NGAL measurement : Biological variation and ratio to creatinine

in Clinica Chimica Acta (2011), 412(3-4), 390

False positive PTH results: An easy strategy to test and detect analytical interferences in routine practice

in Clinica Chimica Acta (2008), 387(1-2), 150-152

Background: As other immunoassays, PTH determination is not free from interferences. Indeed, natural antibodies like heterophile antibodies (HAMA) and rheumatoid factor (RF) can induce falsely elevated ... [more ▼]

Background: As other immunoassays, PTH determination is not free from interferences. Indeed, natural antibodies like heterophile antibodies (HAMA) and rheumatoid factor (RF) can induce falsely elevated results, leading to misdiagnosis and expensive unnecessary explorations. However, in routine practice, these interferences are not always obvious to detect. Methods: On 2084 PTH samples, we applied a validation strategy in four steps to screen for HAMA and rheumatoid factor interferences. Results: 36% of our samples presented an elevated PTH. We found a clinically plausible reason for 91% of them. The remaining 63 suspicious samples were treated with HBT and 40% of them were found to be HAMA positive. RF determination was performed on the HAMA-negative samples and RE was positive in 21 of them. They were then treated with RF-Absorbent. Nine of these 21 samples presented RE interference. Conclusion: Applying this strategy in our routine validation, we managed to avoid spuriously elevated PTH results, which could have caused medical errors as well as unnecessary cost-effective extra-investigations. (c) 2007 Elsevier B.V. All rights reserved. [less ▲]

Analytical study of three cystatin C assays and their impact on cystatin C-based GFR-prediction equations.

in Clinica Chimica Acta (2008), 398(1-2), 118-24

BACKGROUND: Cystatin C-based equations are used to estimate GFR. However, three cystatin C immunoassays are on the market. Difference in cystatin C assays could have strong consequences on the accuracy ... [more ▼]

BACKGROUND: Cystatin C-based equations are used to estimate GFR. However, three cystatin C immunoassays are on the market. Difference in cystatin C assays could have strong consequences on the accuracy and precision of cystatin C-based equations. We have performed an analytical study of these three assays and studied potential differences between assays on the precision of cystatin C-based equations. METHODS: We have studied imprecision, recovery, linearity and interferences of the three immunoassays (nephelometric assay from Siemens and turbidimetric assays from Dako and Gentian). The impact of differences in cystatin C assays has been studied for the equations published by Levey (Siemens assay) and Grubb (Dako assay). RESULTS: Analytical performance of the Dako assay is slightly less high. For cystatin C values below 2.5 mg/L, no statistical difference is found between results given by the Dako and the Gentian assays. So, both assays can be used in the Grubb equation. Cystatin C results are different with the Siemens assay. The Levey equation, built with the Siemens assay, can only be used with cystatin C values measured with this assay. Using the Dako or Gentian assay results in the Levey equation can lead to differences in estimating GFR up to 6 mL/min/1.73 m2. Differences can reach 9.5 mL/min/1.73 m2 if the Siemens assay is used in the Grubb equation. CONCLUSION: The Siemens and Gentian assays seem analytically more valid than the Dako assay for cystatin C determination. Differences in cystatin C assays can lead to significant differences in cystatin C-based equations. However, these differences seem less important than the differences observed with creatinine and creatinine-based equations. [less ▲]

Evaluation of different bone markers in hemodialyzed patients

in Clinica Chimica Acta (2006), 371(1-2), 107-111

Background: Routinely, nephrologists rely on different biochemical markers like intact PTH (iPTH), bone-specific alkaline phosphatase (BALP), plasmatic calcium and phosphate. The aim of the present study ... [more ▼]

Background: Routinely, nephrologists rely on different biochemical markers like intact PTH (iPTH), bone-specific alkaline phosphatase (BALP), plasmatic calcium and phosphate. The aim of the present study was to evaluate different other bone markers like N-terminal propeptide of type I procollagen (PINP), active isoform 5b of the tartrate-resistant acid phosphatase (TRAP 5b) and beta-crossLaps (R) (CTXS) as well as full-length PTH (wPTH), presumed non-(1-84) PTH, and their ratio in the diagnosis of renal osteodystrophy with high and low turnover. We also determined 25 hydroxyvitamin D (25VTD), 1-25 dihydroxyvitamin D and homocystein (HCY). Methods: We performed those parameters on 73 patients with end-stage renal disease according to the manufacturers' instructions. Results: There were very strong correlations between the bone markers concentrations, particularly between BALP and PINP (r=0.953). We did not observe any correlation between the ratio whole PTH/non-(1-84) PTH and any of the usual bone markers. This ratio was significantly (p < 0.05) higher in low and high bone turnover patients than in normal patients according to the K/DOQI. We found a correlation between low levels of 25VTD and high levels of HCY Conclusions: BALP offers the best clinical and analytical profile as the easier marker of choice in hemodiallyzed patients for the diagnosis of bone disease. (c) 2006 Elsevier B.V All rights reserved. [less ▲]

Soluble transferrin receptor for the evaluation of erythropoiesis and iron status.

in Clinica Chimica Acta (2003), 329(1-2), 9-22

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR ... [more ▼]

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR (sTfR) has been identified in animal and human serum. Soluble TfR is a truncated monomer of tissue receptor, lacking its first 100 amino acids, which circulates in the form of a complex of transferrin and its receptor. The erythroblasts rather than reticulocytes are the main source of serum sTfR. Serum sTfR levels average 5.0+/-1.0 mg/l in normal subjects but the various commercial assays give disparate values because of the lack of an international standard. The most important determinant of sTfR levels appears to be marrow erythropoietic activity which can cause variations up to 8 times below and up to 20 times above average normal values. Soluble TfR levels are decreased in situations characterized by diminished erythropoietic activity, and are increased when erythropoiesis is stimulated by hemolysis or ineffective erythropoiesis. Measurements of sTfR are very helpful to investigate the pathophysiology of anemia, quantitatively evaluating the absolute rate of erythropoiesis and the adequacy of marrow proliferative capacity for any given degree of anemia, and to monitor the erythropoietic response to various forms of therapy, in particular allowing to predict response early when changes in hemoglobin are not yet apparent. Iron status also influences sTfR levels, which are considerably elevated in iron deficiency anemia but remain normal in the anemia of inflammation, and thus may be of considerable help in the differential diagnosis of microcytic anemia. This is particularly useful to identify concomitant iron deficiency in a patient with inflammation because ferritin values are then generally normal. Elevated sTfR levels are also the characteristic feature of functional iron deficiency, a situation defined by tissue iron deficiency despite adequate iron stores. The sTfR/ferritin ratio can thus describe iron availability over a wide range of iron stores. With the exception of chronic lymphocytic leukemia (CLL) and high-grade non-Hodgkin's lymphoma and possibly hepatocellular carcinoma, sTfR levels are not increased in patients with malignancies. We conclude that soluble TfR represents a valuable quantitative assay of marrow erythropoietic activity as well as a marker of tissue iron deficiency. [less ▲]

Combined diagnostic value of biochemical markers in acute pancreatitis.

in Clinica Chimica Acta (1990), 189(2), 191-8