Aoumeur Hadj-Aissa

The Relation between Renal Function and Serum Sclerostin in Adult Patients with CKD

BACKGROUND AND OBJECTIVES Sclerostin, a bone antianabolic peptide involved in osteoporosis, is elevated in patients undergoing maintenance dialysis. However, there are no data for patients with early CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Between January and July 2010, serum sclerostin and GFR (calculated by inulin clearance) were measured in 90 patients with CKD. Fasting blood samples were also drawn for determination of calcium, phosphorus, parathyroid hormone, bone alkaline phosphatase, and 25-OH vitamin D. RESULTS Median GFR was 66.5 (interquartile range, 40.0-88.3) ml/min per 1.73 m(2). Median sclerostin level was 53.5 (interquartile range, 37.5-77.2) pmol/L, was higher in patients with a GFR <60 ml/min per 1.73 m(2), and was highest in those with ESRD. Sclerostin levels were significantly more elevated in men than women (P<0.05). An inverse relationship was found between sclerostin and GFR (r=-0.58; P<0.001), and a positive correlation was seen with age (r=0.34; P<0.01) and serum phosphate (r=0.26; P=0.02). In multiple regression analyses, GFR, sex, and serum phosphate were the only variables associated with serum sclerostin (P<0.001). Age lost its relationship with sclerostin level. CONCLUSIONS This is the first study reporting higher serum sclerostin levels starting at CKD stage III. GFR, sex, and serum phosphate were the only measures associated with sclerostin level, suggesting that the effect of age reported in the literature might instead be attributable to the altered renal function in the elderly. Correcting the serum phosphorus level may be associated with lower sclerostin levels.

Which Creatinine and Cystatin C Equations Can Be Reliably Used in Children

BACKGROUND AND OBJECTIVES Estimation of GFR in children is challenging; reference methods are cumbersome, and formulas have limitations. The aims of this study were to evaluate (1) the new creatinine-based formula recently proposed by Schwartz using a kinetic colorimetric compensated Jaffe technique; (2) some cystatin C-derived formulas (Hoek, Le Bricon, Larsson, Rule, Filler, and Zappitelli) using a nephelemetric technique; and (3) combined formulas using both cystatin and creatinine (Zappitelli and Bouvet). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS These formulas were evaluated in a cross-sectional cohort of 252 children with moderate CKD or normal GFR, in comparison with the reference standard (inulin clearance, iGFR). Mean age, body weight, height, creatinine, and cystatin C were 10.7 ± 4.0 years, 35 ± 15 kg, 137 ± 20 cm, 55 ± 30 μmol/L, and 0.91 ± 0.35 mg/L, respectively. RESULTS Mean ± SD iGFR was 101 ± 32 ml/min per 1.73 m². When evaluating agreement between these formulas and iGFR (e.g. correlation, Bland Altman plots, bias, and accuracies), there was a good correlation between iGFR and all Le Bricon, Larsson, Rule, and Zappitelli (both) and locally adapted Schwartz and 2009 Schwartz formulas; by contrast, Filler and original 1976 Schwartz formulas overestimated iGFR, whereas Hoek and Bouvet formulas underestimated iGFR. CONCLUSION Different cystatin C-derived formulas (at least Larsson and Le Bricon) for estimating GFR as well as the Zappitelli combined formula are accurate in addition to the new Schwartz bedside formula in a general pediatric population.

Performance of the Chronic Kidney Disease Epidemiology Collaboration Equation to Estimate Glomerular Filtration Rate in Diabetic Patients

OBJECTIVE The best method to estimate glomerular filtration rate (GFR) in diabetic patients is still largely debated. We compared the performance of creatinine-based formulas in a European diabetic population. RESEARCH DESIGN AND METHODS We compared the performance of Cockcroft and Gault, simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equations in 246 diabetic patients by calculating the mean bias and the interquartile range (IQR) of the bias, 10% (P10) and 30% (P30) accuracies, and Bland-Altman plots. GFR was measured by inulin clearance. RESULTS For the whole population, the IQR was slightly lower for CKD-EPI, but the mean bias was lower and P10 and P30 were higher for MDRD. Similar results were observed in specific subgroups, including patients with mild renal insufficiency, obese patients, or type 2 diabetic patients. CONCLUSIONS In our population, the CKD-EPI formula does not exhibit better performance than the simplified MDRD formula for estimating GFR.

Creatinine‐ versus cystatine C‐based equations in assessing the renal function of candidates for liver transplantation with cirrhosis

Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre‐OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR‐predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD‐EPI‐Pcr, CKD‐EPI‐CystC, and CKD‐EPI‐Pcr‐CystC) and the more classical ones (4‐ and 6‐variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR‐predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score ≤ or >15 and KDOQI stages, respectively). In the whole population, CystC‐based equations showed a better performance than Pcr‐based ones (lower bias and higher 10% and 30% accuracies). CKD‐EPI‐CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR <60 mL/min/1.73 m2). Conclusion: Pcr‐based GFR predicting equations are not reliable in pre‐OLT patients even when an IDMS‐traceable enzymatic Pcr assay is used. Whenever a CystC‐assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC‐based equations, especially CKD‐EPI‐CystC, may be recommended to evaluate renal function and for KDOQI staging. (Hepatology 2014;59:1522‐1531)

Performance of creatinine-based equations compared in older patients.

BACKGROUND The current equations for estimating glomerular filtration rate (GFR) have limited precision in older people. The Berlin Initiative Study (BIS-1) equation has recently been developed to improve the precision and accuracy of GFR estimation in older people, over the previous simplified Modification of Diet in Renal Disease (MDRD) Study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. METHODS The study included 224 white patients aged >70 years who had simultaneous measurements of plasma creatinine and renal clearance of inulin. Creatinine assays used an enzymatic method with calibrators defined by isotope dilution mass spectrometry. The performance of BIS-1, MDRD and CKD-EPI equations in estimating GFR were compared. RESULTS BIS-1 was the most accurate: the percentage of GFR estimates that fell within the range of measured GFR ± 30% (P30) was 75.56% vs. 70.67% with MDRD and 72% with CKD-EPI. BIS-1 had the lowest median bias: (interquartile range) (4.1 (11.4) vs 5.8 (12.7) and 5.4 (12.8) respectively) the highest precision (the SD of the estimated GFR minus measured GFR differences was 9.21 vs 12.78 and 10.83 mL/min/1.73 m² respectively) and the highest concordance correlation coefficient (CCC) (0.82 vs. 0.74 and 0.79 respectively, p<0.05). However, in chronic kidney disease (CKD) stages 4 and 5, the CKD-EPI equation had the highest P30, the lowest median bias and the highest CCC: it was more accurate than the BIS-1 equation. CONCLUSION Among the 3 creatinine-based equations compared, BIS-1 was the most reliable for assessing renal function in older white patients, especially in those with CKD stages 1 to 3.

A new equation to estimate the glomerular filtration rate in children, adolescents and young adults

BACKGROUND A new estimated glomerular filtration rate (eGFR) equation, designed for isotope dilution mass spectrometry-standardized serum creatinine (Scr), is presented for use in children, adolescent boys and girls and young adults. METHODS The new equation, eGFR = 107.3/(Scr/Q), is based on the concept of normalized Scr: Q is the normalization value and is considered as the Scr concentration for the average healthy child, adolescent or young adult of a specific height (L) and is modeled as a height-dependent polynomial of the fourth degree. RESULTS The well-known Schwartz equation [eGFR = kL/Scr, k = 0.413 (Schwartz) or k = 0.373 (Schwartz-Lyon)] for children between 1 and 14 years can be seen as a special case of the new equation for which the Q-polynomial is simplified to a linear equation: Q = 0.0035 × L (cm). The new eGFR equation has been validated in a data set of n = 750 children, adolescents and young adults aged 10-25, against the true GFR (inulin method), and outperforms the selected (but most used) creatinine-based eGFR equations for children, mainly in the healthy GFR region. CONCLUSIONS The new Q(height)-eGFR equation serves as an excellent screening tool for kidney disease in 1-25-year-old children, adolescents and young adults.

GFR Estimation in Adolescents and Young Adults

The performance of creatinine-based equations to obtain the estimated GFR in adolescents and young adults is poorly understood. We assessed creatinine-based GFR estimating equations in a cross-section of 751 adolescents and young adults (1054 measurements), using inulin clearance (measured GFR [mGFR]) as the reference method. We evaluated the following: Cockcroft-Gault, four-variable Modified Diet in Renal Disease, and the Chronic Kidney Disease Epidemiology Collaboration equations for adult participants, as well as the Schwartz 2009 and Schwartz-Lyon equations for pediatric age groups. Participants ranged in age from 10 to 26 years (mean 16.8 years); we divided the population into four groups according to age (10-12 years, 13-17 years, 18-21 years, and 21-25 years). Evaluation of the agreement between these formulas and mGFR (e.g., correlation, Bland-Altman plots, bias, and accuracy) showed that there was a good correlation between mGFR and both pediatric formulas in all age groups, whereas the adult formulas substantially overestimated mGFR. In conclusion, we recommend the use of pediatric equations to estimate GFR from childhood to early adulthood.

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma

Abstract. The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4±2.2 (±SD) years after chemotherapy (total cumulative dose: methotrexate 41±31 g/m2, ifosfamide 39±14 g/m2, cisplatin 674±188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.

Accuracy of GFR Estimation in Obese Patients

BACKGROUND AND OBJECTIVES Adequate estimation of renal function in obese patients is essential for the classification of patients in CKD category as well as the dose adjustment of drugs. However, the body size descriptor for GFR indexation is still debatable, and formulas are not validated in patients with extreme variations of weight. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study included 209 stages 1-5 CKD obese patients referred to the Department of Renal Function Study at the University Hospital in Lyon between 2010 and 2013 because of suspected renal dysfunction. GFR was estimated with the Chronic Kidney Disease and Epidemiology equation (CKD-EPI) and measured with a gold standard method (inulin or iohexol) not indexed (mGFR) or indexed to body surface area determined by the Dubois and Dubois formula with either real (mGFRr) or ideal (mGFRi) body weight. Mean bias (eGFR-mGFR), precision, and accuracy of mGFR were compared with the results obtained for nonobese participants (body mass index between 18.5 and 24.9) who had a GFR measurement during the same period of time. RESULTS Mean mGFRr (51.6 ± 24.2 ml/min per 1.73 m(2)) was significantly lower than mGFR, mGFRi, and eGFRCKD-EPI. eGFRCKD-EPI had less bias with mGFR (0.29; -1.7 to 2.3) and mGFRi (-1.62; -3.1 to 0.45) compared with mGFRr (8.7; 7 to 10). This result was confirmed with better accuracy for the whole cohort (78% for mGFR, 84% for mGFRi, and 72% for mGFRr) and participants with CKD stages 3-5. Moreover, the Bland Altman plot showed better agreement between mGFR and eGFRCKD-EPI. The bias between eGFRCKD-EPI and mGFRr was greater in obese than nonobese participants (8.7 versus 0.58, P<0.001). CONCLUSIONS This study shows that, in obese CKD patients, the performance of eGFRCKD-EPI is good for GFR ≤ 60 ml/min per 1.73 m(2). Indexation of mGFR with body surface area using ideal body weight gives less bias than mGFR scaled with body surface area using real body weight.

Outcome of preemptive renal transplantation and pretransplantation dialysis in children

Abstract.  The present study compares the outcome of 40 children (39%) transplanted without prior dialysis, i.e., preemptive transplantation (PET), with 63 children (61%) transplanted after a variable duration of dialysis, i.e., pretransplantation dialysis (PTD). The two groups were matched for recipient and donor age and for immunological risk factors. There was no statistical difference in the time to first acute rejection episode nor in the number of acute rejection episodes during the 1st year after renal transplantation. In the PET group, 78% of the recipients received blood transfusion versus 92.5% in the PTD group (P<0.05), and the average number of blood units per patient was 3.2 and 7.8, respectively (P<0.05). Arterial hypertension was found in 55% of the patients in the PET group versus 73% in the PTD group (P<0.05). The number of functioning grafts at the end of the study period was 87.5% in the PET group and 73% in the PTD group (NS). The major cause of graft failure was vascular thrombosis in the PET group (3/5) and chronic allograft rejection in the PTD group (10/17). In the PET group, the actuarial graft survival rate was 100%, 84%, 81%, and 76% at 1, 3, 5, and 7 years, which was not statistically different from the PTD group at 1, 3, and 5 years (98%, 91%, and 73%, respectively) but there was a significantly lower graft survival (59%) after 7 years in the PTD (P<0.05). The 7-year actuarial patient survival rate was 97% in the PET group and 90% in the PTD group (NS). In the PTD group, children on dialysis for less than 1 year (group 1, n = 25) were compared with those on dialysis for more than 1 year (group 2, n = 38). Arterial hypertension was noted in 40% of patients from group 1 and 65% from group 2 (P < 0.05) ; there was no significant difference in graft loss rate. In conclusion, these results confirm PET as the preferred approach rather than PTD in children who need renal replacement therapy.