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Innovative Medicines & Omics Current approach in the management of kidney disease

the effects of NO system activation within the central possible to determine the renal benefit of combined
sympathetic nervous system. 27 ACEI/ARB treatment for patients with proteinuria. Due
to hypotensive symptoms, 784 participants (mostly those
3. Current therapeutic approach of CKD on combination therapy) permanently stopped receiving

3.1. Combining ACEI and ARB therapy randomized therapy throughout the research. Compared
to patients receiving monotherapy, the combination
According to recent studies, since the RAS is clearly treatment group had a considerably higher number of
involved in the development of renal disease, more patients reaching the primary renal outcome of dialysis,
complete RAS blockade may be able to halt its progression. doubling of serum creatinine, or death. Acute renal failure
In contrast to ACEI/ARB monotherapy, short-term was the primary cause of many dialysis episodes, and it was
use of MRAs, such as spironolactone or eplerenone, in more common in individuals with normotension. These
combination with ACEIs/ARBs was not associated with a unsatisfactory but not totally unexpected findings highlight
lower risk of cardiovascular and renal outcomes in patients the safety concerns related to ACEI/ARB treatment.
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with diabetic KD and hypertension. Given the short The abrupt transition to sodium-glucose cotransporter-2
duration of combination therapy and the risk factor of inhibitors and MRAs for reducing albuminuria, followed
hyperkalemia, MRA-integrated ACEI/ARB combination
therapy may face practical therapeutic challenges. 26,28 To by a return to ACEIs and ARBs, resulted in greatly
investigate this, several trials investigating the combination reduced hyperkalemia and potassium levels, as well as a
of an ACEIs and ARBs have been performed. Although dramatically lowered the urinary albumin-to-creatinine
they have distinct mechanisms of action, ACEIs and ARBs ratio when dapagliflozin and eplerenone were taken as
both disrupt the RAS. ACEIs inhibit Angiotensin-I from adjuvants to ACEIs or ARBs. These recent trials imply that
dapagliflozin with eplerenone is a desirable combination
converting to Angiotensin II, whereas ARBs prevent
Angiotensin II from binding to Angiotensin II Type 1 to help individuals with CKD reduce the course of their
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receptors. Analyses of ACEIs and other ARBs have illness. RAS blocker medications increased the risk of
revealed that they are equally effective in reducing blood hyperkalemia, hypotension, and cough, but they also
pressure. By maintaining peritubular capillary perfusion improved the outcomes for patients with non-dialysis
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through efferent arteriolar vasodilation and boosting the CKD. ACEIs were more likely than ARBs and other
renal medullary plasma flow by decreasing the filtration antihypertensive drugs to be the most effective therapy
fraction, ACEIs/ARBs could mitigate tubular damage for renal events, cardiovascular outcomes, and causes of
following AKI insults. Angiotensin II blockade has been mortality in patients with diabetic KD, and non-dialysis
demonstrated to lessen the development of acute tubular CKD. ARBs outperformed ACEIs in preventing the risk of
necrosis or damage as well as tubular ischemia. In addition, cardiovascular and renal events, but they were less effective
ACEIs/ARBs are advised to slow the course of kidney than ACEIs in lowering all-cause mortality. 35-37
deterioration in diabetic nephropathy. In addition, ACEIs/ 3.2. RAS and renin inhibition
ARBs lower CVD-related mortality, such as myocardial
infarction and congestive heart failure. The use of ACEIs/ ACEIs and ARBs are RAS inhibitors that slow the
ARBs is generally supported by evidence, as they protect progression of mild to severe CKD. According to some
the kidneys and heart and lower all-cause mortality. Our research, discontinuing RAS inhibitors in individuals with
present meta-analysis findings support their timely use severe chronic renal disease may result in an increase in
following AKI and consistent with previous reports. estimated glomerular filtration rate or a slowing of its
Profibrotic pathways may directly damage essential organs decline. Evidence does not support the combination
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if the RAAS is activated, and AKI has a major effect on therapy of aliskiren and losartan among non-diabetic
the functioning of injury/repair pathways in distant CKD patients generally, and aliskiren does not provide
organs. Following AKI and CKD, we hypothesize that extra renoprotection over a 144-week period in individuals
using ACEIs/ARBs may enhance organ function and avoid with non-diabetic KD. However, KD responders could
maladaptive repair. 30-32 The Ongoing Telmisartan Alone potentially benefit from direct renin inhibition, making
and in Combination with Ramipril Global Endpoint Trial it a more targeted treatment option for specific subgroups
(ONTARGET), which included 25,920 individuals with of CKD patients, based on some positive short-term
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vascular diseases and a higher risk of diabetes, evaluated outcomes. In particular, proinflammatory chemicals
the benefits of ACEI ramipril, ARB telmisartan, and and stress hormones seem to increase the synthesis of
their combination. The majority of patients included in kynurenine and its downstream metabolites, which
ONTARGET did not exhibit microalbuminuria and/ may affect insulin action and favor the onset of diabetes
or macroalbuminuria at baseline. Therefore, it was not mellitus and its complications, including nephropathy.

Volume 2 Issue 1 (2025) 40 doi: 10.36922/imo.4969