Data_Sheet_1_Aging and hypertension in kidney function decline: A 10 year population-based study.DOCX

BackgroundAging is associated with a physiological decline in kidney function (KFD). In this study, we aimed to describe the impact of age on the rate of KFD and its interplay with risk factors for chronic kidney disease (CKD), considering mainly hypertension (HT), in the general population.Materials and methodsParticipants of European descent, aged 35–75, were recruited from a populational cohort in Lausanne, Switzerland. Participants with a 10 year follow-up were selected. KFD was defined as the difference in estimated glomerular filtration rate (eGFR) between baseline and follow-up, divided by the observation period. Multivariate linear regressions were used with KFD as the outcome and age as the main predictor. HT was tested as a modifying factor.ResultsWe included 4,163 participants with mean age 52.2 ± 10.4, 44.7% men, 31.9% HT, and 5.0% diabetics. Mean baseline eGFR was 85.9 ± 14.6 ml/min/1.73 m2. Mean KFD was –0.49 ± 1.08 ml/min/1.73 m2 per year with 70% of participants decreasing their eGFR during follow-up. The relationship between age and KFD was non-linear and age was divided in tertiles. Old participants had faster rates of KFD as compared to young and middle-age participants (p ConclusionA physiological KFD is present over time in the general population. Age contributes non-linearly to the rate of this decline with older subjects declining the fastest. The presence of HT is a major contributing factor in this setting as KFD worsened with age only in hypertensive participants. Thus, HT represents an important pathological factor aggravating the age-related physiological decline in eGFR in the general population.</p

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<p>Background: Corticosteroids are associated with reduced bone mineral density (BMD), as well as water and salt retention, leading to hypertension. They are substrates for P-glycoprotein, a protein coded by the highly polymorphic ABCB1 gene. We hypothesized that one ABCB1 polymorphism, rs1045642, is associated with blood pressure and BMD parameters at 1-year post kidney transplantation (KT).</p><p>Methods: Rs1045642 was genotyped using pyrosequencing in 40 KT recipients. Both dominant (CC vs. CT + TT) and codominant (CC vs. CT vs. TT) genetic models (analysis of variance from linear regressions) were adjusted for confounding variables (age, sex, type of nephropathy, glomerular filtration rate, and corticosteroid use at 1 year).</p><p>Results: Rs1045642 genotypes were significantly associated with systolic (SBP) and diastolic (DBP) blood pressure 1-year post-transplantation, independent of the genetic model used (adjusted codominant model: SBP p-value = 0.015, DBP p-value = 0.038; adjusted dominant model: SBP p-value = 0.003, DBP p-value = 0.011). A non-statistically significant trend was observed for an association between rs1045642 and BMD change at 1-year post-KT.</p><p>Conclusions: Rs1045642 is significantly associated with higher BP 1 year after KT. Further investigations are necessary to confirm the role of rs1045642 in corticosteroid-related adverse effects.</p

ROC curves of ln FGF23, ln PTH, T₅₀, proteinuria and eGFR in predicting fibrosis ≤20%.

<p>ROC curve analysis of ln FGF23 (Fig 2A), ln PTH (Fig 2B), T₅₀ (Fig 2C), proteinuria (Fig 2D), eGFR (Fig 2E) for the prediction of fibrosis ≤20%. (2F): ROC cuvre analysis of ln FGF23, ln PTH and T₅₀ combined for the prediction of fibrosis ≤20%. As T₅₀ and eGFR are markers that are negatively associated with fibrosis, we used the opposite values of those markers. AUC: Area Under the Curve; eGFR: estimated Glomerular Filtration Rate; FGF23: Fibroblast growth factor 23; Ln: log-transformed; PTH: parathyroid hormone; ROC: Receiver Operating Characteristic; T₅₀: Calcification propensity.</p

Table1_Association of serum copeptin and urinary uromodulin with kidney function, blood pressure and albuminuria at 6 weeks post-partum in pre-eclampsia.docx

BackgroundPreeclampsia (PE) is associated with subsequent higher risk of cardiovascular and kidney disease. Serum copeptin, as a proxy for vasopressin, and urinary uromodulin, were associated with PE physiopathology and kidney functional mass respectively. We describe concentrations of these proteins in the post-partum period and characterize their association with persistent hypertension (HTN) or albuminuria.MethodsPatients with PE and healthy controls with uncomplicated pregnancy were prospectively included at two teaching hospitals in Switzerland. Clinical parameters along with serum copeptin and urinary uromodulin were measured at 6 weeks post-partum. PE patients were further characterized based on presence of HTN (defined as either systolic BP (SBP) ≥140 mmHg or diastolic (BP) ≥90 mmHg) or albuminuria [defined as urinary albumin to creatinine ratio (ACR) ≥3 mg/mmol].ResultsWe included 226 patients with 35 controls, 120 (62.8%) PE with persistent HTN/albuminuria and 71 (37.1%) PE without persistent HTN/albuminuria. Median serum copeptin concentration was 4.27 (2.9–6.2) pmol/L without differences between study groups (p > 0.05). Higher copeptin levels were associated with higher SBP in controls (p = 0.039), but not in PE (p > 0.05). Median urinary uromodulin concentration was 17.5 (7.8–28.7) mg/g with lower levels in PE patients as compared to healthy controls (p  0.05). Higher uromodulin levels were associated with lower albuminuria in PE as well as control patients (p = 0.040).ConclusionSerum copeptin levels at 6 weeks post-partum are similar between PE patients and healthy controls and cannot distinguish between PE with or without residual kidney damage. This would argue against a significant pathophysiological role of the vasopressin pathway in mediating organ damage in the post-partum period. On the opposite, post-partum urinary uromodulin levels are markedly lower in PE patients as compared to healthy controls, potentially reflecting an increased susceptibility to vascular and kidney damage that could associate with adverse long-term cardiovascular and kidney outcomes.</p

Additional file 1: of Risk factors for community-acquired acute kidney injury in patients with and without chronic kidney injury and impact of its initial management on prognosis: a prospective observational study

Classification of ARBs, ACEIs and diuretics doses. (DOCX 13 kb

ROC curves of ln FGF23, ln PTH, T₅₀, proteinuria and eGFR in predicting fibrosis ≤20%.

<p>ROC curve analysis of ln FGF23 (Fig 2A), ln PTH (Fig 2B), T₅₀ (Fig 2C), proteinuria (Fig 2D), eGFR (Fig 2E) for the prediction of fibrosis ≤20%. (2F): ROC cuvre analysis of ln FGF23, ln PTH and T₅₀ combined for the prediction of fibrosis ≤20%. As T₅₀ and eGFR are markers that are negatively associated with fibrosis, we used the opposite values of those markers. AUC: Area Under the Curve; eGFR: estimated Glomerular Filtration Rate; FGF23: Fibroblast growth factor 23; Ln: log-transformed; PTH: parathyroid hormone; ROC: Receiver Operating Characteristic; T₅₀: Calcification propensity.</p

Phosphocalcic biomarkers and T₅₀ associate with chronic vascular lesions as assessed by banff (ah+aah+cv) in renal allograft recipients.

<p>Scatter plot graphs of (A) calcium, (B) phosphate, (C) vitamin D, (D) ln PTH, (E) ln FGF23, (F) Klotho, (G) T_50, (H) eGFR versus vascular lesions. Each symbol represents one patient. The continuous line indicates least-square linear regression. Ah: arteriolar hyaline thickening; aah: circumferential hyaline arteriolar thickening; cv: vascular fibrous intimal thickening; eGFR: estimated Glomerular Filtration Rate; Ln: log-transformed; PTH: parathyroid hormone; T₅₀: Calcification propensity.</p

Associations of T₅₀ with vascular lesions in kidney allograft recipients (n = 129), univariate and multivariate linear regression analysis.

<p>Associations of T₅₀ with vascular lesions in kidney allograft recipients (n = 129), univariate and multivariate linear regression analysis.</p

Correlations between phosphocalcic biomarkers, T₅₀ and interstitial fibrosis in renal allograft recipients (n = 129).

<p>Scatter plot graphs of (A) calcium, (B) phosphate, (C) vitamin D, (D) ln PTH, (E) ln FGF23, (F) Klotho, (G) T₅₀, (H) eGFR versus interstitial fibrosis. Each symbol represents one patient. The continuous line indicates least-square linear regression. eGFR: estimated Glomerular Filtration Rate; FGF23: Fibroblast growth factor 23; PTH: parathyroid hormone; T₅₀: Calcification propensity; Ln: log-transformed. </p

Clinical settings of AKI patients and healthy control pools included in the screening experiment.

<p>N/A: Not Applicable</p><p>* Data expressed as mean ± standard deviation</p><p>Clinical settings of AKI patients and healthy control pools included in the screening experiment.</p