Stéphane Roueff

mild hypothyroidism were also found.After 3 days of water deprivation, the sodium con-A 30-year-old woman presented in active labour at the centration was normal. No pituitary abnormality was38th week of gestation. Two years previously, a found with magnetic resonance imaging.Caesarean section was performed due to pelvic–fetal With hormonal substitution, 30 mg/day hydrocortis-disproportion. The patient had spontaneous vaginal one and 100 mg/day l-thyroxine, no relapse of inappro-delivery, followed by severe blood loss because of priate secretion of antidiuretic hormone has occurreduterine scar disjunction. Hysterectomy was performed 18 months after delivery. Subsequent magnetic reson-to control blood loss: transient disseminated intravas- ance imaging showed pituitary atrophy.cular coagulation occurred.The patient had normal biochemical data for 6 days

BACKGROUND: Urinary biomarkers may improve the prediction of chronic kidney disease (CKD) progression. Yet, data reporting the applicability of most commercial biomarker assays to the detection of their target analyte in urine together with an evaluation of their predictive performance are scarce. METHODS: CrEDTA clearance-based measured glomerular filtration rate (mGFR) decline (>10% per year) in a subsample of 229 CKD patients (mean age, 61 years; 66% men; baseline mGFR, 38 mL/min) from the NephroTest prospective cohort. FINDINGS: Among the 30 assays, directed against 24 candidate biomarkers, encompassing different pathophysiological mechanisms of CKD progression, 16 assays fulfilled the FDA-approved criteria. LASSO logistic regressions identified a combination of five biomarkers including CCL2, EGF, KIM1, NGAL, and TGF-α that improved the prediction of fast mGFR decline compared to the kidney failure risk equation variables alone: age, gender, mGFR, and albuminuria. Mean area under the curves (AUC) estimated from 100 re-samples was higher in the model with than without these biomarkers, 0.722 (95% confidence interval 0.652-0.795) vs. 0.682 (0.614-0.748), respectively. Fully-adjusted odds-ratios (95% confidence interval) for fast progression were 1.87 (1.22, 2.98), 1.86 (1.23, 2.89), 0.43 (0.25, 0.70), 1.10 (0.71, 1.83), 0.55 (0.33, 0.89), and 2.99 (1.89, 5.01) for albumin, CCL2, EGF, KIM1, NGAL, and TGF-α, respectively. INTERPRETATION: This study provides a rigorous validation of multiple assays for relevant urinary biomarkers of CKD progression which combination may improve the prediction of CKD progression. FUNDING: This work was supported by Institut National de la Santé et de la Recherche Médicale, Université de Paris, Assistance Publique Hôpitaux de Paris, Agence Nationale de la Recherche, MSDAVENIR, Pharma Research and Early Development Roche Laboratories (Basel, Switzerland), and Institut Roche de Recherche et Médecine Translationnelle (Paris, France).

Background Hypertension is highly prevalent during chronic kidney disease ( CKD ) and, in turn, worsens CKD prognosis. We aimed to describe the determinants of uncontrolled and resistant hypertension during CKD . Methods and Results We analyzed baseline data from patients with CKD stage 1 to 5 (NephroTest cohort) who underwent thorough renal explorations, including measurements of glomerular filtration rate (clearance of 51 Cr‐EDTA) and of extracellular water (volume of distribution of the tracer). Hypertension was defined as blood pressure ( BP ; average of 3 office measurements) ≥140/90 mm Hg or the use of antihypertensive drugs. In 2015 patients (mean age, 58.7±15.3 years; 67% men; mean glomerular filtration rate, 42±15 mL/min per 1.73 m 2 ), prevalence of hypertension was 88%. Among hypertensive patients, 44% and 32% had uncontrolled (≥140/90 mm Hg) and resistant (uncontrolled BP despite 3 drugs, including a diuretic, or ≥4 drugs, including a diuretic, regardless of BP level) hypertension, respectively. In multivariable analysis, extracellular water, older age, higher albuminuria, diabetic nephropathy, and the absence of aldosterone blockers were independently associated with uncontrolled BP . Extracellular water, older age, lower glomerular filtration rate, higher albuminuria and body mass index, male sex, African origin, diabetes mellitus, and diabetic and glomerular nephropathies were associated with resistant hypertension. Conclusions In this large population of patients with CKD , a lower glomerular filtration rate, a higher body mass index, diabetic status, and African origin were associated with hypertension severity but not with BP control. Higher extracellular water, older age, and higher albuminuria were independent determinants of both resistant and uncontrolled hypertension during CKD . Our results advocate for the large use of diuretics in this population.