Renin-Angiotensin-Aldosterone System Blockade Effects on the Kidney in the Elderly

Abstract

The proportion of the population that is elderly (age >65 years) is growing across the world. The increasing longevity of humans results in a higher number of elderly patients' presenting with multiple chronic diseases such as hypertension, diabetes, and chronic kidney disease (CKD). These problems increase morbidity and mortality in the elderly. Overactivity of the renin-angiotensin-aldosterone system (RAAS) is associated with the development of hypertension, cardiovascular events, and CKD, so targeting the RAAS is a logical therapeutic approach. Elderly patients present special concerns regarding the benefits versus risks of using RAAS blockers. Plasma renin activity declines with age, which has been attributed to the effect of age-associated nephrosclerosis. Plasma aldosterone is also reduced with age, resulting in a greater risk for hyperkalemia in older individuals, especially when coupled with the age-associated decline in GFR. Moreover, the elderly have a higher frequency of concurrent conditions and are on many medications, which may further increase the risk for adverse effects of RAAS blocking agents. Unfortunately, there is a paucity of literature that is specifically aimed at studying elderly using the RAAS blockers. We present in our in-depth review data regarding benefits and limitations of the use of the RAAS blockades on the various sites along the RAAS pathway for elderly patients. Specific attention was given to the role of combination RAAS blockade therapy and higher monotherapy dosing in the treatment of hypertension in the elderly.

Maxacalcitol ameliorates tubulointerstitial fibrosis in obstructed kidneys by recruiting PPM1A/VDR complex to pSmad3

“…It has been well established that the activation of RAS is hazardous, leading to the progression of CKD. [36][37][38] Therefore, numerous RAS inhibitors, such as direct renin inhibitor, angiotensin-converting enzyme inhibitors, angiotensin II receptor type 1 blockers, and/or aldosterone blockers, have been administered to patients with CKD. [36][37][38] The importance of RAS inhibitors in the treatment of CKD is without doubt, but the high prevalence of CKD in an era of RAS inhibitors indicates that it is necessary to develop new renoprotective strategies with therapeutic mechanisms independent of RAS inhibition.…”

“…[36][37][38] Therefore, numerous RAS inhibitors, such as direct renin inhibitor, angiotensin-converting enzyme inhibitors, angiotensin II receptor type 1 blockers, and/or aldosterone blockers, have been administered to patients with CKD. [36][37][38] The importance of RAS inhibitors in the treatment of CKD is without doubt, but the high prevalence of CKD in an era of RAS inhibitors indicates that it is necessary to develop new renoprotective strategies with therapeutic mechanisms independent of RAS inhibition. [39][40][41] If the main renoprotective mechanism of active vitamin D was renin suppression, therapeutic potential of active vitamin D would be severely limited, because direct renin inhibitor (aliskiren) is currently available.…”

Doença renal crônica e tratamento em idosos: uma revisão integrativa

“…Population aging and an increasing incidence of diabetes, arterial hypertension and other illnesses and non-communicable diseases have contributed to a global increase in the prevalence of CKD and end-stage renal disease (ESRD), 2,3 leading to its recognition as a public health problem. 4,5 While it is debatable whether a decrease in GFR or an increase in the albumin/ creatinine ratio amongst the elderly is indicative of the disease or simply part of the "normal ageing process", it is worth remembering that ageing is associated with a build-up of comorbidities and increased medication use, which may lead to a reduction in incidence of GFR and albuminuria.…”

Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease

“…It is well established that RAAS blockage presents a particular risk-benefit analysis in regards to renal impairment [137], and that such risks are amplified in the setting of salt-restriction/dehydration [138–140], in the elderly [141], or in patients with diabetes, heart or renal disease [142]. Because Ang II has divergent activities on promoting hypertension and disease as well as maintaining essential renal homeostatic mechanisms, the conflicting results obtained to-date underscore the need to better understand the role of intrarenal RAAS.…”