Staging chronic kidney disease and estimating glomerular filtration rate: an opinion paper about the new international recommendations

in Clinical Chemistry & Laboratory Medicine (in press)

Abstract: In January 2013, the international recommendations of the KDIGO (for “ Kidney Disease: Improving Global Outcomes ” ) to define chronic kidney disease (CKD) and classify patients in CKD stages ... [more ▼]

Abstract: In January 2013, the international recommendations of the KDIGO (for “ Kidney Disease: Improving Global Outcomes ” ) to define chronic kidney disease (CKD) and classify patients in CKD stages have been published. In this opinion article, we will review and discuss the most important guidelines proposed about CKD staging and glomerular filtration rate (GFR) estimating. In particular, we question the choice of fixed knot values at 60 mL/min/1.73 m ² to define CKD. We also question the strategies proposed to measure and use cystatin C results. [less ▲]

A randomised, double-blinded, placebo-controlled, parallel study of vitamin D3 supplementation with different schemes based on multiples of 25,000 IU doses

in International Journal of Endocrinology (in press)

Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their ... [more ▼]

Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their country. Unfortunately, even in a given country, there is no consensus on the best way to treat the patients. In Belgium, VTD is mostly prescribed as ampoules containing 25,000 IU of VTD. In this randomised controlled study, we evaluated whether four therapeutic schemes using multiples of 25,000 IU of VTD according to basal vitamin D concentration were able to increase or maintain the 25(OH)D serum level above 30 ng/mL. We randomized 175 subjects who received the drug () or placebo (). Total duration of the study was 12 weeks. Doses ranged from 4167 to 1667 IU/day. Blood sampling was performed at baseline and each 4 visits. In the treated (placebo) subjects, mean 25(OH)D serum concentration was 18.7 (19.1) ng/mL at baseline and 31.5 (20.7) ng/mL at w-12. At the end of the study, 57.1% of the subjects treated with VTD presented 25(OH)D serum concentration ≥30 ng/mL, whereas 94.3% were ≥20 ng/mL. In conclusion, the doses administered were safe and increased or maintained the 25(OH)D concentration ≥20 ng/mL. However, concentrations ≥30 ng/mL were only achieved in 57.1% of the subjects. [less ▲]

Creatinine - or cystatin C - based equations to estimate glomerular filtration in the general population: impact on the epidemiology of chronic kidney disease

in BMC Nephrology (in press)

Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the ... [more ▼]

Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study. Recently, new equations based either on cystatin C (CKD-EPI Cys) or both cystatin and creatinine (CKD-EPI mix) have been proposed by the CKD-EPI consortium. The aim of this study was to measure the difference in the prevalence of stage 3 CKD, defined as an estimated GFR less than 60 mL/min/1.73 m2, in a population using these four equations. METHODS: CKD screening was performed in the Province of Liege, Belgium. On a voluntary basis, people aged over 50 years have been screened. GFR was estimated by the four equations. Stage 3 CKD was defined as a GFR less than 60 mL/min/1.73 m2. RESULTS: The population screened consisted of 4189 people (47% were men, mean age 63 +/- 7y). Their mean serum creatinine and plasma cystatin C levels were 0.88 +/- 0.21 mg/dL and 0.85 +/- 0.17 mg/L, respectively. The prevalence of CKD in this population using the MDRD, the CKD-EPI, the CKD-EPI Cys and the CKD-EPI mix equations was 13%, 9.8%, 4.7% and 5%, respectively. The prevalence of CKD was significantly higher with the creatinine-based (MDRD and the CKD-EPI) equations compared to the new cystatin C-based equations. CONCLUSIONS: Prevalence of CKD varies strongly depending on the method used to estimate GFR. Such discrepancies are of importance and must be confirmed and explained by additional studies, notably by studies using GFR measured with a reference method [less ▲]

Supplementation, optimal status, and analytical determination of vitamin D: Where are we standing in 2012?

in Anti-Cancer Agents in Medicinal Chemistry (in press), 12

There is a growing interest for vitamin D in the medical and scientific community as well as in the public medias as illustrated by a huge number of publications. Most experts claim that vitamin D ... [more ▼]

There is a growing interest for vitamin D in the medical and scientific community as well as in the public medias as illustrated by a huge number of publications. Most experts claim that vitamin D deficiency/insufficiency is widespread with potential important public health consequences. It may seem surprising for many persons that a deficiency in a vitamin may be so frequent in countries where food is so diversified and easily available. In fact, vitamin D is not a vitamin stricto sensu as it is mainly synthesized in the skin under the action of UVB rays, while its food sources are scarce. Furthermore, UVB rays are absent during a marked part of the year at latitudes greater than 35-40°, while pollution and cloud cover reduce the number of UVB reaching the earth, and many factors such as age, skin pigmentation, covering clothes, sun creams reduce the capacity of the skin to synthesize vitamin D3. Vitamin D must be hydroxylated to form 1,25dihydroxyvitamin D (1,25OH2D), the active metabolite. As 1,25OH2D is released into the bloodstream and binds to a receptor present in several distant tissues, it may be considered as a hormone, vitamin D being thus a pre-prohormone. In the present article, we review briefly the metabolism and various effects of vitamin D as well as the vitamin D assays and vitamin D treatments. We define vitamin D deficiency/insufficiency considering [less ▲]

MDRD Versus CKD_EPI equation to estimate glomerular filtration rate in kidney transplant recipients

in Transplantation (2013), 95(10),

Background. The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by ... [more ▼]

Background. The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed. Methods. We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients. Bias, precision, and accuracy within 30% of true GFR were determined. GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of 51Cr-EDTA (n=337). Results. Mean measured GFR (mGFR) was 50T19 mL/min/1.73 m2. On the whole cohort, bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine. This superiority translates into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation is confirmed both in the subgroups of patients with mGFR G60 mL/min/1.73 m2 and between 60 and 90 mL/min/1.73 m2. For mGFR 990 mL/min/1.73 m2, there were no significant differences between the two equations in terms of performance. Conclusions. The CKD-EPI creatinine equation does not offer a better GFR prediction in renal transplant patients compared with the MDRD Study equation, even in the earlier CKD stages. [less ▲]

Comparison of the Heart-type fatty acid-binding protein (H-FABP) with the high sensitive cardiac troponin T in healthy runners

in Biochimica Clinica (2013, May), 37(SS), 544

Background: Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein involved in the intracellular uptake and buffering of long chain fatty in the myocardium. It is an early marker ... [more ▼]

Background: Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein involved in the intracellular uptake and buffering of long chain fatty in the myocardium. It is an early marker for acute coronary syndrome. Troponin T (TnT) is a component of the contractile apparatus of the striated musculature. Cardiac TnT is a cardio-specific, highly sensitive marker for myocardial damage. The aim of our study was to compare the results obtained with the H-FABP and the highly sensitive cardiac troponins (hsTnT) and to test their cardiospecificity in healthy runners. Methods: Twenty three runners (marathon) were enrolled. We drowned samples at three times: just before (T0), just after (T1), and three hours after the end of the race (T3). H-FABP was determined with a Randox immunoturbidimetric assay and hs-TnT with a Roche electrochemiluminescence immunoassay, both on Cobas 6000. A linear regression was calculated to observe if there is any correlation between the two biomarkers. Values above the 95th percentile for H-FABP (2.5ng/mL) and the 99th percentile for hsTnT (14ng/L) were considered as positive. Results: At T0, none of the subjects were positive for hsTnT but 35% were positive for H-FABP; at T1, 83% for hsTnT and 100% for H-FABP; at T3, 83% for hsTnT and 96% for H-FABP. At T0, the regression equation was H-FABP T0 = 3.9454 – 0.1001 x hsTnT T0; at T1: H-FABP T1 = 51.838 – 1.7026 x hsTnT T1; at T3: H-FABP T3 = 47.977 – 1.6193 x hsTnT T3. No correlation was observed between the two biomarkers at the different time. Conclusions: We observed a significant increase of H-FABP and hsTnT in runners. These markers are independent to each other. These values could biologically correspond to a heart ischemia. However, we suggested that exercise-induced cardiac hsTnT and H-FABP release is not a marker of exercise-induced pathology but likely a physiologic response to effort or an exercise-induced cardiac remodelling. [less ▲]

Determination of urinary metanephrine, normetanephrine and methoxymetanephrine by liquid chromatography-electrospray tandem mass spectrometry.

in Biochimica Clinica (2013, May), 37(SS), 316

Background: The aim of this work was to develop and validate a method for the determination of metanephrine (M), normetanephrine (NM) and methoxymetanephrine (METHO) in urine by liquid chromatography ... [more ▼]

Background: The aim of this work was to develop and validate a method for the determination of metanephrine (M), normetanephrine (NM) and methoxymetanephrine (METHO) in urine by liquid chromatography-tandem mass spectrometry (LCMS-MS) on the Triple Quad TQ 5500 from AB SCIEX. In fact, the determination of M and NM concentrations is used in clinical diagnosis of pheochromocytoma, a rare but potentially fatal tumor arising primarily from the chromaffin cells of the adrenal medulla. Methods: The samples were made of 24 hours acidified urines after centrifugation. Sample preparation was performed by hydrolysing and purifying by extraction column. After that, labeled M, NM and METHO were added as internal standard. Samples were analysed by liquid chromatography-electrospray tandem mass spectrometry. We determined the repeatability, reproducibility, accuracy profile and recovery on pooling urines samples from 9 volunteers analysed in triple run. Results: The results of the precision evaluation are shown in table. The repeatability did not exceed 8.4 % for M, 6.8% for NM and 10.8% for METHO. The concentration range was 71-781 µg/24h, 71-853 µg/24h and 20-854µg/24h for the M, NM and METHO respectively. The total precision did not exceed 12.5%, 11.8% and 8.8% for M, NM and METHO. The limit of quantification (LOQ) were 33.77µg/24h, 14.49µg/24H and 19.81 µg/24H for M, NM and METHO respectively. The accuracy varied from 99.69 to 100.2% for a range of 71 to 781 µg/24h, from 93.32 to 100.2% for a range of 71-853 µg/24h and from 99.85 to 100.6% for the range 20-854µg/24h for M, NM and METHO respectively. The recovery were 99.96% (95% CI for the mean: 96.5-103.4), 99.75% (96.5-102.9) and 100.08 (95.97-104.2) for the M, NM and METHO respectively. Conclusions: We have successfully developed and validated an LCMS-MS method to determine urinary M, NM and METHO on the TQ 5500 from AB SCIEX. It represents a convincing alternative to the HPLC method for a faster and reliable measurement of urinary M, NM and METHO. [less ▲]

Creatinine- or cystatin C-based equations to estimate glomerular filtration rate in the general population: impact on the epidemiology of chronic kidney disease

in Nephrology Dialysis Transplantation (2013, May), 28(S1),

Enzymatic but not compensated Jaffe methods reach the desirable specifications of NKDEP at normal levels of creatinine. Results of the French multicentric evaluation

in Clinica Chimica Acta (2013), 419

The French Society of Clinical Biochemistry conducted this study to compare the accuracy and performances of the best creatinine enzymatic assays and the compensated Jaffe methods from the same ... [more ▼]

The French Society of Clinical Biochemistry conducted this study to compare the accuracy and performances of the best creatinine enzymatic assays and the compensated Jaffe methods from the same manufacturers. Creatinine was measured in 3 serum pools with creatinine levels of 35.9 ± 0.9 μmol/L, 74.4 ± 1.4 μmol/L, and 97.9 ± 1.7 μmol/L (IDMS determination). The performances of the assays (total error that includes the contribution of bias and imprecision) were evaluated using Monte-Carlo simulations and compared against desirable NKDEP criteria. The enzymatic assays always fell within the desirable total Error of 7.6%. By contrast, this requirement was never obtained for the compensated Jaffe methods at the critical level of 74.4 ± 1.4 μmol/L. Only the compensated Jaffe creatinine on Olympus analyzer reached this specification at 35.9 ± 0.9 and 97.9 ± 1.7 μmol/L levels. This study demonstrates that, despite substantial improvement regarding traceability to the IDMS reference method and precision, compensated Jaffe creatinine methods, by contrast to enzymatic ones, do not reach the desirable specifications of NKDEP at normal levels of creatinine. [less ▲]

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 ▲]