FGF23-klotho axis, bone fractures, and arterial stiffness in dialysis: a case-control study.

We performed a case-control study on 130 age- and sex-matched hemodialysis patients. In multivariate analysis, we observed that FGF23 levels were associated with fracture incidence and that soluble α-klotho levels were associated with the aortic-brachial arterial stiffness ratio. INTRODUCTION: New bone markers such as sclerostin, Dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23), and α-klotho have been identified as potential key players in bone and vascular abnormalities of chronic kidney disease. Therefore, we aimed to assess whether these markers are associated with fractures, bone metabolism, and vascular stiffness in dialysis patients. METHODS: In a prospective hemodialysis cohort, where plasma samples and vascular assessment were performed at baseline, we matched patients who experienced a fracture during follow-up with sex- and age-matched non-fractured patients on a 1:4 ratio. Sclerostin, DKK1, α-klotho, FGF23, and markers of bone formation (alkaline phosphatase and procollagen type 1-N terminal propeptide [P1NP]) and bone resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) were measured in baseline plasma samples. Aortic-brachial pulse wave velocity ratio, a blood pressure independent measure of arterial stiffness, was used to assess vascular stiffness at baseline. RESULTS: We included 130 hemodialysis patients (26 fractured, 104 non-fractured) with a median follow-up of 42 months and a median age of 72 years. In multivariate Cox regression models, high FGF23 levels were associated with increased fracture incidence (adjusted HR = 2.97; 95% CI 1.18, 7.43). α-Klotho levels were associated with bone formation but not resorption markers. In both univariate and multivariable adjusted models, α-klotho levels were inversely associated with the aortic-brachial pulse wave velocity ratio (ß = - 0.070; 95% CI - 0.133, - 0.006). CONCLUSIONS: These results suggest a role for FGF23/klotho axis on bone and vascular metabolism in dialysis populations.

2013 Banff Criteria for Chronic Active Antibody-Mediated Rejection: Assessment in a Real-Life Setting.

Significant changes in the criteria for chronic active antibody-mediated rejection (CAABMR) were made in the Banff 2013 classification. These modifications expanded the number of patients diagnosed with CAABMR, with undetermined clinical significance. We compared the 2007 and 2013 criteria for the composite end point of death-censored graft failure or doubling of serum creatinine in 123 patients meeting the criterion related to the morphologic evidence of chronic tissue injury. In all, 18% and 36% of the patients met the 2007 and 2013 criteria, respectively. For the criterion related to antibody interaction with endothelium, only 25% were positive based on the 2007 definition compared with 82% using the 2013 definition. Cox modeling revealed that a 2013 but not a 2007 diagnosis was associated with the composite end point (adjusted hazard ratio 2.5 [95% confidence interval (CI) 1.2-5.2] vs. 1.6 [95% CI 0.7-3.8], respectively). The 2013 criterion based on both the C4d score and the glomerulitis plus peritubular capillaritis score (g+ptc) was more strongly associated with the end point than the 2007 criterion based only on C4d; however, when dissected by component, only the C4d component was significant. The association with clinical outcomes improved with the 2013 criteria. This is related to the new C4d threshold but not to the g+ptc ≥2 component.

What added value does ambulatory blood pressure monitoring brings to the management of post renal transplantation hypertension?

OBJECTIVE: To evaluate BP control, white coat hypertension (WCH) and abnormal circadian variability in a significant outpatient sample of renal transplant (RTx) subjects, normotensive at the last regular visit. METHODS: ABPM (Spacelab 90217) was performed every 15 min between 07:00-23:00 h and every 30 min between 23:01-06.59 h. in all patients (N = 68, 39M, S-Cr. = 153 +/- 49 mumol/l) normotensive at their last regular office BP (O-BP) measurement and with available BP records for the 12 months preceding RTx and 6 months preceding ABPM. RESULTS: BP values were frequently abnormal in this RTx cohort considered to have a satisfactory BP control. O-BP (measured with a Hawksley random-0 sphygmomanometer on the day of ABPM) was 135.5/80.6 mmHg, 47.1% of the patients with abnormal BP values. By comparison, ABPM showed a lower prevalence of uncontrolled BP: 44.1% for 24 h.-BP and only 35.3% for the daytime awake period, with values of 134.5/80.4 and 135.3/81 mmHg respectively (P = NS from O-BP). The prevalence of WCH was 12%. 24-h SBP is related to O-SBP (r = 0.71, P < 0.01) and Bland-Altman analysis demonstrates that > 95.6% of all differences between systolic ABPM and O-BP values are within +/- 2SD of the identity line. However, although 24-h DBP is equally related to O-DBP (r = 0.64, P < 0.01), on Bland-Altman analysis, 8.8% of the differences between diastolic ABPM and O-BP values are outside +/- 2SD of the identity line. Thus, systolic but not diastolic O-BP correlates with, and can be substituted to ABPM derived values. Non-dipping was frequent, regardless of the definition of normal nocturnal BP fall (10 mmHg or 10% of the daytime SBP): 82.4%, 89.7%. Even if normality was strictly defined as a night/day ratio < 0.90 for SBP and < 0.92 for DBP, non-dipping prevalence was high 73.5%, with more than one-third of the RTx patients having nocturnal hypertension (ratio > 1). CONCLUSIONS: BP control is not optimal in one-third of a typical RTx population. Furthermore, nocturnal hypertension is a frequent and underestimated phenomenon in this population. There is a good agreement between ABPM derived and casual systolic values. Office measurements, due to WCH, are under-evaluating the quality and efficacy of the antihypertensive regimens.

Captopril suppression versus salt loading in confirming primary aldosteronism.

This prospective study was designed to compare the captopril suppression test with the salt-loading approach to confirm the diagnosis of primary aldosteronism. A total of 49 patients were referred with a presumed diagnosis of primary aldosteronism. The captopril test was performed in the morning with patients in the seated position after overnight fasting. Blood samples for plasma aldosterone were obtained before captopril administration (25 mg PO) and again 2 hours later. Patients were then subjected to a high salt diet (300 mmol sodium per day for 3 days). On the third day, urinary sodium (24 hours) was measured, and plasma aldosterone levels were measured at 8:00 AM (recumbent) and at noon (standing). Of the 49 patients, 44 had nonsuppressible aldosterone concentrations with all the clinical characteristics of primary aldosteronism: 22 patients had surgically confirmed unique adenoma, and 22 patients had presumed bilateral hyperplasia. There was a significant correlation between plasma aldosterone values of salt-loaded patients (mean of 8:00 AM and noon results) and the values 2 hours after captopril administration (r=0.8, P<0.01). Plasma aldosterone cumulative distribution curves in primary aldosteronism patients (adenoma and hyperplasia) were not significantly different between the 2 suppression tests. Our results showed that the captopril suppression test is as effective as sodium loading in confirming the diagnosis of primary aldosteronism.

Variation of intra-access flow early and late into hemodialysis.

Intra-access flow (Qac), measured by ultrasound dilution, is a reliable method for screening for access dysfunction. Because of a reduced circulating volume and a relative decrease in blood pressure at the end of hemodialysis (HD), we hypothesized that Qac could be significantly reduced when measured late into HD. Fifty patients were prospectively evaluated for variation in Qac early and late into HD. There were 33 native fistulae and 17 synthetic grafts. Six separate measures of Qac were performed for each patient by ultrasound dilution (Transonic HD01 hemodialysis monitor; Transonic Systems, Inc., Ithaca, NY): three within the first 30 minutes and three within the last 30 minutes of HD. Session time was 3.5 or 4 hours, and mean net ultrafiltration was 3.3 +/- 0.9 L/HD. Early and late into HD, mean arterial pressure (MAP) decreased from 100.0 +/- 14.6 to 92.8 +/- 17.8 mm Hg, heart rate from 73 +/- 11 to 79 +/- 15 bpm, and hematocrit increased from 34 +/- 3 to 38 +/- 4%. For the whole group, mean Qac decreased from 1,101.7 +/- 566.7 to 972.5 +/- 515.6 ml/min (p = NS); when Qac was corrected for a MAP of 100 mm Hg, the reduction remained nonsignificant (from 1,101.7 to 1,048.0 ml/min). When considering native and synthetic fistulae separately, the drop in Qac was still nonsignificant (from 1,098.9 +/- 613.4 to 983.2 +/- 593.2 for native fistulae versus 1,107.2 +/- 480.5 to 999.8 +/- 379.8 ml/min for grafts, p = NS). Overall, the percent reduction in Qac early versus late into HD was 11.7%, whereas it reached only 4.9% when access flows corrected for MAP were considered. We conclude that variation in Qac during HD is relatively small, especially when values are corrected for MAP. Therefore, according to our results, Qac measures by using the ultrasound dilution method made at any time during HD should be reliable for most patients.

Chronic interstitial nephritis due to 5-aminosalicylic acid.

Nephrotoxicity has recently been reported with the use of 5-aminosalicylic acid (5-ASA) which has structural similarities to phenacetin and aspirin. The present paper describes 2 cases of interstitial nephritis and 1 case of end-stage failure associated with 5-ASA treatment. The first patient presented with severe renal failure which was partially reversed with 5-ASA discontinuation and steroid therapy. The second had severe renal failure (serum creatinine 469 mmol/l) but renal function stabilized with 5-ASA withdrawal. The third patient had end-stage renal failure and underwent hemodialysis and a successful kidney transplant.