Fibroblast growth factor 23 is associated with proteinuria and smoking in chronic kidney disease: An analysis of the MASTERPLAN cohort

Contains fulltext : 107913.pdf (postprint version ) (Open Access)BACKGROUND: Fibroblast growth factor 23 (FGF23) has emerged as a risk factor for cardiovascular disease and mortality throughout all stages of chronic kidney disease (CKD), independent from established risk factors and markers of mineral homeostasis. The relation of FGF23 with other renal and non-renal cardiovascular risk factors is not well established. METHODS: Using stored samples, plasma FGF23 was determined in 604 patients with moderate to severe kidney disease that participated in the MASTERPLAN study (ISRCTN73187232). The association of FGF23 with demographic and clinical parameters was evaluated using multivariable regression models. RESULTS: Mean age in the study population was 60 years and eGFR was 37 (+/- 14) ml/min/1.73 m(2). Median proteinuria was 0.3 g/24 hours [IQR 0.1-0.9]. FGF23 level was 116 RU/ml [67-203] median and IQR. Using multivariable analysis the natural logarithm of FGF23 was positively associated with history of cardiovascular disease (B = 0.224 RU/ml; p = 0.002), presence of diabetes (B = 0.159 RU/ml; p = 0.035), smoking (B = 0.313 RU/ml; p < 0.001), phosphate level (B = 0.297 per mmol/l; p = 0.0024), lnPTH (B = 0.244 per pmol/l; p < 0.001) and proteinuria (B = 0.064 per gram/24 hrs; p = 0.002) and negatively associated with eGFR (B = -0.022 per ml/min/1.73 m(2); p < 0.001). CONCLUSIONS: Our study demonstrates that in patients with CKD, FGF23 is related to proteinuria and smoking. We confirm the relation between FGF23 and other cardiovascular risk factors

A meta-analysis of GFR slope as a surrogate endpoint for kidney failure

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min−1 per 1.73 m2 or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R2) = 0.97 (95% Bayesian credible interval (BCI) 0.82–1.00)) and moderately associated with those on chronic slope (R2 = 0.55 (95% BCI 0.25–0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression

Renal artery and parenchymal changes after renal denervation: assessment by magnetic resonance angiography

Relatively little is known about the incidence of long-term renal damage after renal denervation (RDN), a potential new treatment for hypertension. In this study the incidence of renal artery and parenchymal changes, assessed with contrast-enhanced magnetic resonance angiography (MRA) after RDN, is investigated.status: publishe

Variable IgE cross-reactivity between peanut 2S-albumins: The case for measuring IgE to both Ara h 2 and Ara h 6.

BACKGROUND:2S-albumins Ara h 2 and Ara h 6 are the most potent peanut allergens and levels of specific immunoglobulin E (IgE) towards these proteins are good predictors of clinical reactivity. Because of structural homologies, Ara h 6 is generally considered to cross-react extensively with Ara h 2.OBJECTIVE:We aimed to quantify the IgE cross-reactivity between Ara h 2 and Ara h 6.METHODS:Peanut 2S-albumins were purified from raw peanuts. The IgE cross-reactivity between Ara h 2 and Ara h 6 was evaluated with 32 sera from French and US peanut-allergic patients by measuring the residual IgE-binding to one 2S-albumin after depletion of IgE antibodies recognizing the other 2S-albumin. The IgE cross-reactivity between Ara h 2 and Ara h 6 was further investigated by competitive inhibition of IgE-binding and by a model of mast cell degranulation.RESULTS:A highly variable level of IgE cross-reactivity was revealed among the patients. The mean fraction of cross-reactive IgE antibodies represented only 17.1% of 2S-albumins-specific IgE antibodies and was lower than the mean fraction of IgE specific to Ara h 2 (57.4%) or to Ara h 6 (25.5%). The higher level of Ara h 2-specific IgE was principally due to the IgE-binding capacity of an insertion containing the repeated immunodominant linear epitope DPYSPOH S. The impact of IgE cross-reactivity on diagnostic testing was illustrated with a serum displaying an Ara h 6-specific IgE response of 26 UI/mL that was not associated with the capacity of Ara h 6 to trigger mast cell degranulation.CONCLUSIONS & CLINICAL RELEVANCE:Immunoglobulin E antibodies specific to peanut 2S-albumins are mainly non-cross-reactive, but low-affinity cross-reactivity can affect diagnostic accuracy. Testing IgE-binding to a mixture of 2S-albumins rather than to each separately may enhance diagnostic performance