Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Determination of Advanced Glycation End Products in Serum by Fluorescence Spectroscopy and Competitive ELISA

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Changes in the central ANF-system of renovascular hypertensive rats

Changes in the central ANF-system of renovascular hypertensive rats. The central atrial natriuretic peptides (ANF)-system was investigated in volume-dependent one-kidney, one-clip (1K1C) and renin-dependent two-kidney, one-clip (2K1C) renovascular hypertensive rats by radio-immunological measurement of ANF concentration in 18 selected brain areas. Significant changes were found in nine brain areas of 1K1C and in eight brain areas of 2K1C hypertensive rats. Except unidirectional changes in the organum vasculosum laminae terminalis and the supraoptic nucleus, ANF concentration was changed in the opposite direction in all other brain areas, with an activation of the central ANF system in 1K1C and an inhibition in 2K1C hypertension. The localization of the alterations (circumventricular organs, anteroventral third ventricle region, hypothalamo hypophyseal system, brain stem) implies major differences in the central regulation of blood pressure and electrolyte and fluid homeostasis between these two models. The activation of the central ANF system in 1K1C hypertension may be a compensatory mechanism to prevent further increments in blood pressure and plasma volume. In contrast, the depression of the central ANF system in 2K1C hypertension may promote the elevation of the blood pressure

901-111 ACE Inhibition (Quinapril) Modulates Central Vasopressin in the Rat

The beneficial effects of ACE inhibitors (ACEI) in heart failure and hypertension appear to be mediated not only by their influence on circulating ACE or tissue ACE in the heart. Previous studies have also implicated the brain as a possible site of actions for ACEI, e.g. by modifying central cardiovascular mechanisms. Their effects on central vasopressin (AVP), which is an important neurotransmitter in central cardiovascular regulation, are not known.Following chronic administration of Quinapril (6mg/kgBW; 6 weeks, p.o.) ACE activity (in vitro autoradiography using a specific ACE inhibitor [125I]351A) was markedly inhibited in the thalamus (38%), hypothalamus (37%), hypophysis (35%), cerebellum (36%) and plexus choroideus (20%) suggesting Quinapril may cross the blood brain barrier after chronic treatment. To study the influence of ACEI on central vasopressin, we determined the AVP content of 19 microdissected brain areas in rats treated with Quinapril. Regarding the hypothalamic AVP-producing nuclei, increased AVP levels could only been demonstrated in the paraventricular (PVN; Quinapril: 292±197 vs. 2209±568pg/mg protein of controls; p<0.001), but not in the supraoptic (SON) and the suprachiasmatic nucleus (SCN). Interestingly, vasopressin synthesizing cells in the PVN project not only to the posterior pituitary (like SON), but also to the lower brain stem and the spinal cord suggesting an important role of the PVN in the regulation of the cardiovascular system.Also, AVP content was sign, reduced in the median eminence (15643±9240 vs. 28321±4969, p<0.001), where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. Furthermore, sign, changes were registered in the central amygdala, inthesubcommissural organ and dorsal raphe nucleus.ConclusionsAutoradiographic study in vitro indicates that after chronic treatment Quinapril is able to cross the blood brain barrier and suppress central ACE activity. ACE inhibition with Quinapril markedly influences vasopressin in important brain areas which are involved in central cardiovascular regulation. Therefore, central modulatory effects of ACE inhibitor may contribute to their overall therapeutic efficacy

Central inhibition of AT1receptors by eprosartan—in vitro autoradiography in the brain

All components of the renin-angiotensin system have been demonstrated in the brain and AT(1) receptors have been localized in brain areas involved in central cardiovascular regulation. It is currently unclear whether AT(1) receptor antagonists, which are increasingly used in the treatment of arterial hypertension and chronic heart failure, have the potential to mediate action via the central renin-angiotensin system. Therefore, we tested the in vivo access of the non-peptide AT(1) receptor antagonist, eprosartan (30 and 60 mg per kg of body weight (BW) for 4 weeks, i.p. administered by osmotic minipumps), to angiotensin II receptors in the rat brain by in vitro autoradiography with I-125-(Sar(1)-Ile(8)) angiotensin II as a ligand. Eprosartan significantly increased plasma renin activity by four-fold and six-fold at doses of 30 and 60 mg kg(-1), respectively (P < 0.05 vs CTRL). In the brain, eprosartan produced a dose-dependent inhibition of AT receptor binding in the median cerebral artery (850 +/- 249 and 650 +/- 106 vs 1072 +/- 116 dpm mm(-2) of CTRL: P < 0.05). Furthermore, eprosartan inhibited angiotensin II receptor binding in discrete brain areas, which express exclusively, or predominantly, AT(1) receptors both outside and within the blood-brain barrier, such as the paraventricular nucleus (180 +/- 47 and 130 +/- 18 vs 545 +/- 99 dpm mm(-2) of CTRL, P < 0.05), the subfornical organ (106 +/- 26 and 112 +/- 17 vs 619 +/- 256 dpm mm-2 of CTRL; P < 0.05), and the organum vasculosum laminae terminalis (461 +/- 110 and 763 +/- 136 vs 1033 +/- 123 dpm mm(-2) of CTRL; P < 0.05), These results emphasize that eprosartan readily crosses the blood-brain barrier in vivo and selectively inhibits binding to AT(1) receptors in specific brain nuclei. The modulation of central regulatory mechanisms might contribute to AT(1) receptor antagonists overall therapeutic efficacy in cardiovascular disease, (C) 2001 Academic Press