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The purpose of the review is to summarize the current pharmacological management of chronic kidney disease (CKD) in pediatric patients and critically present emerging evidence for the use of mineralocorticoid receptor antagonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Globally, CKD is the 19th leading cause of years of life lost and the current total number of children and adolescents affected with CKD Stages II-V is predicted to exceed 2 million in a global population of 2 billion children. The severity of kidney disease is strongly correlated with the extent of proteinuria. Agents that target the renin-angiotensin-aldosterone-system reduce proteinuria in mild to moderate CKD, slowing disease progression. Recent clinical trials evaluating mineralocorticoid receptor antagonists, such as finerenone and SGLT2 inhibitors, demonstrate similar results. However, additional pediatric clinical trials are necessary to determine their complete therapeutic potential. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 (SGLT2) inhibitor is an antidiabetic agent with cardiac and renal protective properties. Its renal protective property is a result of the inhibition of tubular sodium reabsorption and reduction in the intraglomerular pressure. The use of SGLT2 inhibitor in chronic kidney disease (CKD) independent of diabetic status is emerging. However, the real-world data of SGLT2 inhibitor utilisation in CKD is limited. We conducted a descriptive study of patients with CKD, who were prescribed with SGLT2 inhibitor in our Nephrology Clinic. A total of 156 patients were initiated on SGLT2 inhibitor from 2017 to 2022. Among them, 58.3% were male, with a mean age of 61 ± 13 years, and 86.5% had diabetes mellitus, with estimated mean glomerular filtration rate (eGFR) of 46.41 ± 21.14 ml/min/1.73m², and proteinuria of 2.22 ± 2.62 g/day. A total of 85.9% of patients were on renin-angiotensin-system (RAS) blockers, whereby those who were not prescribed with RAS were mostly CKD stage 4. Among the non-diabetic patients, 81% had glomerulonephritis, half of which was IgA nephropathy, and 42.9% were on immunosuppressants. There was a significant retardation of eGFR decline over a six-month-duration after the initiation of SGLT2 inhibitor from -3.46 ± 6.56 ml/ min/1.73m² to -0.77 ± 7.97 ml/min/1.73m± (p=0.001). The retardation of eGFR decline was more pronounced in more advanced CKD stages. However, the proteinuria reduction was insignificant over a six-month-duration (-0.03 ± 2.31 g/day). There were no adverse events reported. In conclusion, SGLT2 inhibitor retarded the eGFR decline with minimal proteinuria reduction in short-term. Nonetheless, long-term efficacy and safety data of SGLT2 inhibitor in local populations requires further evaluation. [ABSTRACT FROM AUTHOR]

The purpose of this manuscript is to review the effects of sodium-glucose cotransport protein 2 inhibitors (SGLT2is) in patients with chronic kidney disease according to basic mechanisms, current recommendations, and future perspectives. Based on growing evidence from randomized, controlled trials, SGLT2is have proven their benefit on cardiac and renal adverse complications, and their indications expanded into the following five categories: glycemic control, reduction in atherosclerotic cardiovascular disease (ASCVD), heart failure, diabetic kidney disease, and nondiabetic kidney disease. Although kidney disease accelerates the progression of atherosclerosis, myocardial disease, and heart failure, so far, no specific drugs were available to protect renal function. Recently, two randomized trials, the DAPA-CKD and EMPA-Kidney, demonstrated the clinical benefit of the SGLT2is dapagliflozin and empagliflozin in improving the outcome in patients with chronic kidney disease. For the consistently positive results in cardiorenal protection, the SGLT2i represents an effective treatment to reduce the progression of kidney disease or death from cardiovascular causes in patients with and without diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objectives To assess mortality and cardiovascular and renal outcomes among patients with chronic kidney disease (CKD) (primary objective), with a particular focus on heart failure (HF) risk following diagnosis of CKD (secondary objective) in Spain. Methods We conducted an observational study comprising cross-sectional and longitudinal retrospective analyses using secondary data from electronic health records. For the primary objective, adults with prevalent CKD [estimated glomerular filtration rate (eGFR) <60 or ≥60 mL/min/1.73 m2 with a urine albumin:creatinine ratio (UACR) ≥30 mg/g at the index date (1 January 2017)] were included. For the secondary objective, adults with incident CKD in 2017 were enrolled. Results In the prevalent population, 46 786 patients with CKD without HF [75.8 ± 14.4 years, eGFR 51.4 ± 10.1 mL/min/1.73 m2; 75.1% on renin–angiotensin system inhibitors (RASis)] and 8391 with CKD and HF (79.4 ± 10.9 years, eGFR 46.4 ± 9.8 mL/min/1.73 m2) were included. In the prevalent population, the risk of all-cause death {hazard ratio [HR] 1.107 [95% confidence interval (CI) 1.064–1.153]}, HF hospitalization [HR 1.439 (95% CI 1.387–1.493)] and UACR progression [HR 1.323 (95% CI 1.182–1.481)] was greater in those patients with CKD and HF versus CKD only. For the incident population, 1594 patients with CKD without HF and 727 with CKD and HF were included. Within 24 months from the CKD diagnosis (with/without HF at baseline), 6.5% of patients developed their first HF hospitalization. Although 60.7% were taking RASis, only 3.4% were at maximal doses and among diabetics, 1.3% were taking sodium-glucose cotransporter-2 inhibitors. Conclusions The presence of HF among CKD patients markedly increases the risk of outcomes. CKD patients have a high risk of HF, which could be partially related to insufficient treatment. [ABSTRACT FROM AUTHOR]

With chronic kidney disease (CKD) being a global arising health problem, strategies for delaying kidney disease progression and reducing the high cardiovascular risk inherent to CKD, are the main objectives of the actual management of patients with kidney diseases. In these patients, the control of arterial hypertension is essential, as high blood pressure (BP) is a strong determinant of worst cardiovascular and renal outcomes. Achieving target blood pressures recommended by international guidelines is mandatory and often demands a multiple levels management, including several pharmacological and lifestyle measures. Even in the presence of adequate BP control, the residual cardiovascular risk remains high. In this respect, the recent demonstration that novel agents such as sodium glucose transporter 2 (SGLT2) inhibitors or the new non-steroidal mineralocorticoid antagonist finerenone can retard the progression of kidney diseases and reduce cardiovascular mortality on top of standard of care treatment with renin-angiotensin system inhibitors represent enormous progresses. These studies also demonstrate that cardiovascular and renal protection can be obtained beyond blood pressure control. Other promising novelties are still to come such as renal denervation and endothelin receptor antagonists in the setting of diabetic and non-diabetic kidney diseases. In the present review, we shall discuss the classic and the new aspects for the management of hypertension in CKD, integrating the new data from recent clinical studies. [ABSTRACT FROM AUTHOR]

The therapeutic options for preventing or slowing the progression of chronic kidney disease (CKD) have been thus far limited. While angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are, without a doubt, safe and effective drugs, a significant proportion of patients with CKD still progress to end‐stage kidney disease. After decades of negative trials, nephrologists have finally found cause for optimism with the introduction of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors and non‐steroidal mineralocorticoid receptor antagonists (MRAs). Recent trials such as EMPA‐REG OUTCOME and CREDENCE have provided evidence of the renal benefits of SGLT2 inhibitors, which have now found widespread acceptance as first‐line agents for diabetic CKD, in addition to ACEi/ARBs. Considering results from the DAPA‐CKD study, it is expected that their use will soon be expanded to other causes of albuminuric CKD as well, although confirmation from further trials, such as the EMPA‐KIDNEY study is awaited. Likewise, although the role of mineralocorticoid receptor overactivation in CKD progression has been known for decades, it is only now with the FIDELIO‐DKD study that we have evidence of benefits of MRAs on hard renal endpoints, specifically in patients with diabetic CKD. While further research is ongoing, given the evidence of synergism between the three drug classes, it is foreseeable that a combination of two or more of these drugs may soon become the standard of care for CKD, regardless of underlying aetiology. This review describes pathophysiologic mechanisms, current evidence and future perspectives on the use of SGLT2 inhibitors and novel MRAs in CKD. SUMMARY AT A GLANCE: This is a comprehensive review of two important agents that have emerged in recent years, namely the SGLT‐2 inhibitor and the non‐steroidal MRA, in the management of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

When renal function declines, blood pressure rises, which in turn causes the kidneys to deteriorate. In order to stop this vicious cycle, it is necessary to lower the blood pressure to a "moderate" level in patients who have chronic kidney disease (CKD)-associated hypertension. Such optimization is problematic, since tight control of blood pressure might worsen the prognosis in elderly patients with CKD, especially those with advanced arteriosclerosis. Although renin-angiotensin system (RAS) inhibitors, angiotensinogen converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are first-line drugs for hypertensive patients with diabetes, they should be used with caution depending on the patients' conditions. Recently, there has been a focus on the preventive effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, anti-diabetic drugs that have been shown to have an impact, on heart and kidney complications. SGLT2 inhibitors increase the amount of sodium chloride delivered to the macular densa of the distal tubules and correct glomerular hyperfiltration by contraction of afferent arterioles via the tubule-glomerular feedback system. It might be one of the reasons why SGLT2 inhibitors show the renal- and cardio-protective effects; however, the mechanism behind their function remains to be elucidated. [ABSTRACT FROM AUTHOR]