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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., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background and Objectives: Anemia in patients with CKD is highly related to impaired erythropoietin (EPO) response, the timing and determinants of which remain unknown., Design, Setting, Participants, & Measurements: This study measured EPO levels and studied their relation to GFR measured by 51Cr-EDTA renal clearance (mGFR) in 336 all-stage CKD patients not receiving any erythropoiesis-stimulating agent., Results: In patients with anemia defined by World Health Organization criteria (hemoglobin [Hb] <13 g/dl in men and 12 g/dl in women), EPO response to Hb level varied by mGFR level. EPO and Hb levels were negatively correlated (r=-0.22, P=0.04) when mGFR was >30 ml/min per 1.73 m(2), whereas they were not correlated when mGFR was <30 (r=0.09, P=0.3; P for interaction=0.01). In patients with anemia, the ratio of observed EPO to the level predicted by the equation for their Hb level decreased from 0.72 (interquartile range, 0.57-0.95) for mGFR ≥60 ml/min per 1.73 m(2) to 0.36 (interquartile range, 0.16-0.69) for mGFR <15. Obesity, diabetes with nephropathy other than diabetic glomerulopathy, absolute iron deficiency, and high C-reactive protein concentrations were associated with increased EPO levels, independent of Hb and mGFR., Conclusions: Anemia in CKD is marked by an early relative EPO deficiency, but several factors besides Hb may persistently stimulate EPO synthesis. Although EPO deficiency is likely the main determinant of anemia in patients with advanced CKD, the presence of anemia in those with mGFR >30 ml/min per 1.73 m(2) calls for other explanatory factors.

Background: Vitamin D (25 hydroxyvitamin D [25(OH)D]) deficiency is common in patients with chronic kidney disease (CKD). Neither the relation of this deficiency to the decrease in glomerular filtration rate (GFR) nor the effects on CKD mineral and bone disorders (MBD) are clearly established., Study Design: Cross-sectional analysis of baseline data from a prospective cohort, the NephroTest Study., Setting & Participants: 1,026 adult patients with all-stage CKD not on dialysis therapy or receiving vitamin D supplementation., Predictors: For part 1, measured GFR (mGFR) using (51)Cr-EDTA renal clearance; for part 2, 25(OH)D deficiency at <15 ng/mL., Outcomes & Measurements: For part 1, 25(OH)D deficiency and several circulating MBD markers; for part 2, circulating MBD markers., Results: For part 1, the prevalence of 25(OH)D deficiency was associated inversely with mGFR, ranging from 28%-51% for mGFR ≥60-<15 mL/min/1.73 m(2). It was higher in patients of African origin; those with obesity, diabetes, hypertension, macroalbuminuria, and hypoalbuminemia; and during winter. After adjusting for these factors, ORs for 25(OH)D deficiency increased from 1.4 (95% CI, 0.9-2.3) to 1.4 (95% CI, 0.9-2.1), 1.7 (95% CI, 1.1-2.7), and 1.9 (95% CI, 1.1-3.6) as mGFR decreased from 45-59 to 30-44, 15-29, and <15 (reference, ≥60) mL/min/1.73 m(2) (P for trend = 0.02). For part 2, 25(OH)D deficiency was associated with higher age-, sex-, and mGFR-adjusted ORs of ionized calcium level <1.10 mmol/L (2.6; 95% CI, 1.2-5.9), 1,25 dihydroxyvitamin D concentration <16.7 pg/mL (1.8; 95% CI, 1.3-2.4), hyperparathyroidism (1.8; 95% CI, 1.3-2.4), and serum C-terminal cross-linked collagen type I telopeptides concentration >1,000 pg/mL (1.6; 95% CI, 1.0-2.6). It was not associated with hyperphosphatemia (phosphate >1.38 mmol/L)., Limitations: Cross-sectional analysis of the data prevents causal inferences., Conclusions: 25(OH)D deficiency is related independently to impaired mGFR. Both mGFR decrease and 25(OH)D deficiency are associated with abnormal levels of circulating MBD biomarkers., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

In CKD, large arteries remodel and become increasingly stiff. The greater pulsatile pressure reaching the glomerulus as a result of increased aortic stiffness could induce renal damage, suggesting that the stiffening and remodeling of large arteries could affect the progression of CKD. We measured carotid-femoral pulse wave velocity, aortic pressure and carotid remodeling and stiffness parameters in 180 patients with CKD (mean measured GFR, 32 ml/min per 1.73 m(2)) and followed them prospectively for a mean of 3.1 years. During follow-up, carotid stiffness significantly increased (+0.28 ± 0.05 m/s; P<0.0001) but aortic stiffness did not. Carotid intima-media thickness decreased significantly during follow-up and the internal diameter of the carotid increased, producing increased circumferential wall stress (+2.08 ± 0.43 kPa/yr; P<0.0001). In a linear mixed model, circumferential wall stress significantly associated with faster GFR decline after adjustment for risk factors of cardiovascular disease and progression of CKD. In a multivariable Cox model, carotid circumferential wall stress and pulse pressure independently associated with higher risk for ESRD. None of the arterial stiffness parameters associated with progression of CKD. In conclusion, maladaptive remodeling of the carotid artery and increased pulse pressure independently associate with faster decline of renal function and progression to ESRD., (Copyright © 2011 by the American Society of Nephrology)

Background: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates measured glomerular filtration rate (GFR) at levels>60 mL/min/1.73 m2, with variable accuracy among subgroups; consequently, estimated GFR (eGFR)>or=60 mL/min/1.73 m2 is not reported by clinical laboratories. Here, performance of a more accurate GFR-estimating equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, is reported by level of GFR and clinical characteristics., Study Design: Test of diagnostic accuracy., Setting & Participants: Pooled data set of 3,896 people from 16 studies with measured GFR (not used for the development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid-organ transplant, and body mass index., Index Tests: eGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine., Reference Test: Measured GFR using urinary or plasma clearance of exogenous filtration markers., Results: Mean measured GFR was 68+/-36 (SD) mL/min/1.73 m2. For eGFR<30 mL/min/1.73 m2, both equations have similar bias (median difference compared with measured GFR). For eGFR of 30-59 mL/min/1.73 m2, bias was decreased from 4.9 to 2.1 mL/min/1.73 m2 (57% improvement). For eGFR of 60-89 mL/min/1.73 m2, bias was decreased from 11.9 to 4.2 mL/min/1.73 m2 (61% improvement). For eGFR of 90-119 mL/min/1.73 m2, bias was decreased from 10.0 to 1.9 mL/min/1.73 m2 (75% improvement). Similar or improved performance was noted for most subgroups with eGFR<90 mL/min/1.73 m2, other than body mass index<20 kg/m2, with greater variation noted for some subgroups with eGFR>or=90 mL/min/1.73 m2., Limitations: Limited number of elderly people and racial and ethnic minorities with measured GFR., Conclusions: The CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR>or=60 mL/min/1.73 m2 can be reported using the CKD-EPI equation., (Copyright (c) 2010 National Kidney Foundation, Inc. All rights reserved.)

Background: Damages to large arteries are related to bone disease in end-stage renal disease and contribute to cardiovascular mortality. An outward remodeling and stiffening of carotid artery already exist at an earlier stage of chronic kidney disease (CKD). We made the hypothesis that bone disease could be associated with the carotid outward remodeling in parallel with the decline of renal function in this population., Methods: One hundred and seven patients (60.4 +/- 14.6 years) with CKD (mean glomerular filtration rate = 34 +/- 17 mL/min/1.73 m(2)) were included in this cross-sectional study. Common carotid artery diameter, intima-media thickness and carotid stiffness were determined with an echotracking system. Bone evaluation was performed by bone densitometry and the measurement of a bone-remodeling marker, bone-specific alkaline phosphatase (BSALP)., Results: After adjustment for age, sex, mean blood pressure, carotid pulse pressure and glomerular filtration rate, bone mineral densities measured at the radius, hip and lumbar spine were significantly and negatively correlated with carotid internal diameter (P = 0.0001, P = 0.0003, P = 0.01, respectively). This association exists only in patients with glomerular filtration rate < or =38 mL/min/ 1.73 m(2). BSALP was independently and positively correlated with carotid internal diameter and explained 13% of the variance., Conclusions: Bone mineral density and serum marker of bone remodeling are independently correlated with arterial remodeling in CKD patients suggesting a crosstalk between kidney, arterial wall and bone.

Chronic kidney disease (CKD) guidelines recommend evaluating patients with GFR <60 ml/min per 1.73 m(2) for complications, but little evidence supports the use of a single GFR threshold for all metabolic disorders. We used data from the NephroTest cohort, including 1038 adult patients who had stages 2 through 5 CKD and were not on dialysis, to study the occurrence of metabolic complications. GFR was measured using renal clearance of (51)Cr-EDTA (mGFR) and estimated using two equations derived from the Modification of Diet in Renal Disease study. As mGFR decreased from 60 to 90 to <20 ml/min per 1.73 m(2), the prevalence of hyperparathyroidism increased from 17 to 85%, anemia from 8 to 41%, hyperphosphatemia from 1 to 30%, metabolic acidosis from 2 to 39%, and hyperkalemia from 2 to 42%. Factors most strongly associated with metabolic complications, independent of mGFR, were younger age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and both male gender and the use of inhibitors of the renin-angiotensin system for hyperkalemia. mGFR thresholds for detecting complications with 90% sensitivity were 50, 44, 40, 39, and 37 ml/min per 1.73 m(2) for hyperparathyroidism, anemia, acidosis, hyperkalemia, and hyperphosphatemia, respectively. Analysis using estimated GFR produced similar results. In summary, this study describes the onset of CKD-related complications at different levels of GFR; anemia and hyperparathyroidism occur earlier than acidosis, hyperkalemia, and hyperphosphatemia.

During the last years, GFR estimation has received substantial attention with a focus on comparing results of new formulas with GFR measurements, and standardization of creatinine assays. Calibration of creatinine should improve performances. However, frequently used equations have lower precision in high GFR populations. This is the reason why a continuous effort in improving predicting equations is still needed. The use of calibrated creatinine, the onset of new GFR markers such as cystatin C, and pooling data across many study populations are underway to develop better prediction.

Cystatin C is a low molecular weight-protein, which may replace creatinine for the evaluation of renal function, particularly in the clinical settings where the relationship between creatinine production and muscular mass impairs the clinical performance of creatinine. This paper intends to summarize the current knowledge about the physiology of cystatin C and about its use as a renal marker, alone or within formulas developed to estimate the glomerular filtration rate. Moreover, this paper reviews the recent data about potential other applications of cystatin C, especially in cardiology, in oncology and in clinical pharmacology.

Progressive decline in kidney function is a cardinal manifestation of Fbry disease. Proteinuria is usually the earliest biological marker of renal involvement. Renoprotection should associate both effective Enzyme Replocement Therapy (ERT) and non-specific anti-proteinuric therapy as recommended for all chronic kidney diseases. ERT has demonstrated high efficiency in the early clearing of globotriaosylceromide deposits, however the functional protecting effect on GFR decrease remains to be validated, especially in patients with CKD stage 3 or higher Estimation of GFR should be very cautious using creatinine based formulas, leading to measure GFR whenever possible in order to characterize the progression of CKD in Fabry patients.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in circumferential wall stress, respectively, since no significant difference in IMT was observed. Carotid distensibility and elastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

The article presents a study on Chronic kidney disease (CKD) characterized by arterial stiffness and enlargement to determine the link between between arterial phenotype and mineral metabolism parameters.