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Background Sodium-23 magnetic resonance imaging (.sup.23Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na.sup.+]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na.sup.+] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na.sup.+] compared to healthy controls. Methods This was a case-control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg .sup.23Na MRI for tissue [Na.sup.+] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na.sup.+] was compared against healthy controls by computing individual Z-scores. An absolute Z-score > 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na.sup.+] and kidney function. Results A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na.sup.+] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na.sup.+] Z-scores. Reduced whole-leg [Na.sup.+] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal-distal renal tubular acidosis). All tissue [Na.sup.+] measures were significantly associated with proteinuria and hypoalbuminemia. Conclusions Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na.sup.+] compared with healthy controls. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Fabio R. Salerno [sup.1] [sup.2] , Alireza Akbari [sup.2] [sup.3] , Sandrine Lemoine [sup.2] [sup.4] , Timothy J. Scholl [sup.1] [sup.3] [sup.5] , Christopher W. McIntyre [sup.1] [sup.2] [sup.6] [...]

Abstract Background Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. Methods We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyl)theophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean ± standard deviation) between the groups by a variance analysis and post hoc test. Results Desflurane 6% (84 ± 6% of baseline) enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 ± 8% of baseline, P < 0.0001). N-mercaptopropionylglycine (54 ± 3% of baseline), 8-(p-Sulfophenyl)theophylline (62 ± 9% of baseline), HOE140 (58 ± 6% of baseline) abolished desflurane-induced postconditioning. Adenosine (80 ± 9% of baseline) and bradykinin (83 ± 4% of baseline) induced postconditioning (P < 0.0001 vs control), N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 ± 8 and 58 ± 5% of baseline, respectively). Conclusions In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin administered at the beginning of reoxygenation, was mediated, at least in part, through ROS production.

Context Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). Objective To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. Design Open-label, phase 2 study. Participants Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12 and C2, n = 16). Intervention Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at a 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed, and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). Main outcomes Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (serum carboxy-terminal telopeptide of type I collagen and procollagen 1 intact N-terminal propeptide), bone mineral density (BMD), and adverse events (AEs). Results After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased, and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. Conclusion Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range while normalizing uCa excretion and producing a balanced resumption of bone turnover. [ABSTRACT FROM AUTHOR]

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23–23.33, to OR = 28.87, 95% CI 4.77–167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02–1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery. [ABSTRACT FROM AUTHOR]

Introduction In nephropathic cystinosis (NC), adherence to cysteamine remains challenging; poor adherence is worsening the disease progression with a decline of kidney function and increase of extrarenal morbidities. Our objective was to describe adherence to cysteamine in NC patients, using electronic monitoring systems. Methods Patients with confirmed NC, aged > 4 years and receiving oral cysteamine (short acting or delayed release formulation as standard of care) from 3 French reference centers, were included. Adherence to treatment was primarily assessed as the percentage of days with a good adherence score, adherence score rating from 0 (poor) to 2 (good). A descriptive analysis was performed after 1-year follow-up. Results Seventeen patients (10 girls, median age: 13.9 (5.4-33.0) years) were included. Median age at diagnosis was 17.0 (3.0-76.9) months and age at start of cysteamine was 21.0 (15.5-116.3) months. Median daily dose of cysteamine was 1.05 (0.55-1.63) g/m.sup.2/day. Over the year, the median percentage of days with a good adherence score was 80 (1-99)% decreasing to 68 (1-99)% in patients > 11 years old. The median of average number of hours covered by treatment in a day was 22.5 (6.1-23.9) versus 14.9 (9.2-20.5) hours for delayed release versus short acting cysteamine. Conclusion Our data are the first describing a rather good adherence to cysteamine, decreasing in adolescents and adults. We described a potential interest of the delayed release formulation. Our data highlight the need for a multidisciplinary approach including therapeutic education and individualized approaches in NC patients transitioning to adulthood. Graphical abstract, Author(s): Segolene Gaillard [sup.1] [sup.2] , Laurent Roche [sup.2] [sup.4] , Sandrine Lemoine [sup.3] , Georges Deschênes [sup.5] , Denis Morin [sup.6] , Christine Vianey-Saban [sup.7] , Cécile Acquaviva-Bourdain [sup.7] [...]

Context X-linked hypophosphatemia (XLH) is a rare genetic disorder that results in increased plasma levels of fibroblast growth factor 23 (FGF23). Several studies have demonstrated a direct association between FGF23 and cardiovascular mortality in cohorts of patients with chronic renal failure. However, in patients with XLH, studies on the cardiovascular impact of the disease are rare, with contradictory results. Objective The aim was to assess whether the disease led to an increased cardiovascular risk. Methods We conducted a single-center retrospective observational study on a local cohort of adult patients with XLH. The primary endpoint was a composite endpoint of the frequency of left ventricular hypertrophy (LVH) or presence of high blood pressure. Our secondary objectives were to assess echocardiographic, pulse wave velocity, and central blood pressure data as other markers of CV health. Independently of this cohort, tissue sodium content with magnetic resonance imaging was studied in 2 patients with XLH before and after burosumab. Results Twenty-two patients were included. Median serum phosphate was 0.57 (0.47-0.72) mmol/L and FGF23 94 pg/L (58-2226). Median blood pressure was 124 (115-130)/68 (65-80) mm Hg, with only 9% of patients being hypertensive. A majority of patients (69%) had no LVH, only 1 had a left ventricular mass >100 g/m² and 25% of patients had left ventricular remodeling. Pulse wave velocity was normal in all patients. No differences in skin and muscle sodium content were observed before and after burosumab in the 2 patients who underwent sodium magnetic resonance imaging. Conclusion We found no elevated risk of developing hypertension or LVH in patients with XLH. [ABSTRACT FROM AUTHOR]

Background: Shrunken pore syndrome (SPS) is defined as cystatin C‐based‐eGFR (eGFRcys)/creatinine‐based‐eGFR (eGFRcreat) <0.6 or 0.7 and is associated with an increased cardiovascular risk. SPS has been described in children, but no link to increased morbi‐mortality was demonstrated. Objectives: Study the prevalence of SPS in a pediatric population using several glomerular filtration rate (GFR) estimating formulas and measured GFR and evaluate the potential link with cardiovascular risk. Methods: In 307 renal risk pediatric patients, we studied prevalence of SPS either with CKiDU25creat and cyst or with FAScreat and cyst and EKFCcreat. The characteristics of patients with SPS (defined with Full‐age spectrum equation (FAS) and/or European Kidney Function Consortium equation (EKFC)) were compared. Results and conclusion: The prevalence of SPS varies widely depending on the threshold and the formulas used. Higher C‐reactive protein (CRP) and phosphate levels and smaller size are observed in children with SPS defined with FAS and/or EKFC and might be associated with long‐term increased cardiovascular risk. Further studies in wider general pediatric populations are warranted. [ABSTRACT FROM AUTHOR]