Background The utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of ...newly developed CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use with standardized SCysC level to reassess the performance of SCysC as a filtration marker in kidney transplant recipients. Study Design Study of diagnostic test accuracy. Setting & Participants 670 kidney transplant recipients from 3 centers undergoing glomerular filtration rate (GFR) measurements from December 2006 to November 2012. Index Test Estimated GFR (eGFR) using the 2012 SCysC-based and serum creatinine (SCr)/SCysC-based CKD-EPI equations (eGFRcys and eGFRcr-cys , respectively) and the 2009 SCr-based CKD-EPI equation (eGFRcr ), with SCysC and SCr measured at a single laboratory between April 2011 and June 2011. Reference Test Measured GFR (mGFR) using urinary clearance of inulin. Results Bias (the difference between mGFR and eGFR) was significantly smaller for eGFRcys and eGFRcr-cys versus eGFRcr (−2.82 and −0.54 vs +4.4 mL/min/1.73 m2 , respectively; P < 0.001). Precision (standard deviation of the mean bias) also was better for eGFRcys and eGFRcr-cys versus eGFRcr (12 and 11 vs 13 mL/min/1.73 m2 P < 0.001 for both comparisons). Accuracy (percentage of GFR estimates within 30% of mGFR) was greater for eGFRcys and eGFRcr-cys versus eGFRcr (81% and 86% vs 75%, respectively P = 0.004 and P < 0.001). Net reclassification index with respect to mGFR of 30 mL/min/1.73 m2 for eGFRcr-cys and eGFRcys versus eGFRcr was 18.8% 95% CI, 8.6%-28.9% and 22.5% 95% CI, 10.2%-34.9%. Limitations Patients were exclusively of European descent; association with transplant outcome was not evaluated. Conclusions Our data validate the use of both the newly developed SCysC-based and SCr/SCysC-based CKD-EPI equations (2012) in kidney transplant recipients. Both equations perform better than the SCr-based CKD-EPI equation (2009).
Klotho is an "aging-suppressor" gene and encodes a single-pass transmembrane protein predominantly expressed in renal tubules. Whether chronic kidney disease (CKD) affects serum Klotho is poorly ...documented. We aimed to measure the relationship of serum α-Klotho with renal function, acid-base status, bone biomarkers, and proteinuria in CKD patients.
We measured serum α-Klotho, serum FGF23, and glomerular filtration rate by inulin clearance in 60 CKD patients between January and July 2011. We also measured serum creatinine, bicarbonate, calcium, phosphorus, parathyroid hormone, C-reactive protein, and 25-OH vitamin D. Proteinuria was obtained from a 24-h urine collection.
The median serum α-Klotho was 478 (348-658) pg/mL. We found an inverse relationship between serum α-Klotho and serum creatinine (r = -0.36, P = .007), proteinuria (r = -0.36, P = .013), and a positive relationship with serum bicarbonate (r = 0.33, P = .011). There was no further significant relation between serum α-Klotho and inulin clearance or serum FGF23. Multiple regression analysis including serum bicarbonate, serum creatinine, and proteinuria indicated that only serum bicarbonate was associated with serum α-Klotho (P = .003).
This study shows that in CKD, serum α-Klotho is related to serum bicarbonate and proteinuria and not to renal function. Further research is required to determine whether correcting these 2 amenable conditions would improve serum α-Klotho.
Background In patients with atrial fibrillation (AF), adherence to guidelines for antithrombotic treatment is poorly followed, and undertreatment (or nonadherence with guidelines) is associated with ...a worse prognosis. The study objective was to evaluate whether this was also the case in a large contemporary series of unselected patients with AF in real-world clinical practice. Methods All patients with AF or atrial flutter seen in our institution between 2000 and 2007 were identified in a database and followed up for mortality and stroke. Antithrombotic guideline adherence was assessed according to the 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines. Results We reviewed outcomes in 3,646 consecutive patients with AF or atrial flutter (aged 71 ± 14 years; mean CHADS2 congestive heart failure, hypertension, aged ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack score, 1.5 ± 1.1). Antithrombotic treatment was in agreement with the guidelines in 53% of patients, whereas 31% were classified as undertreated and 16% as overtreated. Among other parameters, nonpermanent AF and atrial flutter were independently associated with an increased risk of undertreatment. After a follow-up of 953 ± 767 days (median, 771 days; interquartile range, 1,286 days), guideline adherence was associated with a lower risk of adverse events (death from all causes or stroke) compared with undertreatment (relative risk, 0.47; 95% CI, 0.40-0.55; P < .0001). Overtreatment was associated with a lower risk of adverse events compared with the guideline-adherent population (relative risk, 0.40; 95% CI, 0.28-0.58; P < .0001). Factors independently associated with increased risk of mortality or stroke were antithrombotic undertreatment, older age, heart failure, renal failure, diabetes, male sex, and previous history of stroke. Conclusions Guideline nonadherence and undertreatment with antithrombotic agents in unselected real-world patients with AF or atrial flutter are independently associated with a high risk of stroke and mortality.
Summary Background Charcot–Marie–Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy that affects roughly one in 5000 births. No specific therapy currently exists for this ...degenerative disorder, which is characterised by distal progressive muscle atrophy and sensory loss, although ascorbic acid has been shown to reduce demyelination and improve muscle function in a transgenic mouse model of CMT1A. We tested the safety and efficacy of ascorbic acid in adults with CMT1A. Methods This 12-month, randomised, double-blind, placebo-controlled study was undertaken between September, 2005, and October, 2008. Patients diagnosed with CMT1A according to clinical examination and confirmation by genotyping were randomly assigned in a 1:1:1 ratio to receive 1 g ascorbic acid per day, 3 g ascorbic acid per day, or placebo. Treatment allocation was based on a computer-generated list of random numbers in blocks of 12, with stratification according to study site and sex; all investigators and participants were unaware of treatment allocation. The primary outcome was the Charcot–Marie–Tooth disease neuropathy score (CMTNS) at 12 months. Analysis was by intention to treat. This study is registered with the Orphanet Database , number ORPHA60779. Findings The median change in CMTNS from baseline to 12 months was 0·5 points (95% CI −0·3 to 1·4) for the placebo group (n=62), 0·7 points (0·0 to 1·4) for the 1 g ascorbic acid group (n=56), and −0·4 points (−1·2 to 0·4) for the 3 g ascorbic acid group (n=61). We did not find any significant difference in these changes between the groups (p=0·14). The occurrence of adverse events did not differ between the groups (p=0·74). Interpretation Ascorbic acid at both doses was safe and well tolerated in adults with CMT1A over 12 months. However, there were no significant differences between the groups and the efficacy of ascorbic acid was not shown. Funding French Ministry of Health (National PHRC 2004) and Association Française Contre les Myopathies.
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