Practical Strategy for Treating Chronic Kidney Disease (CKD)-Associated with Hypertension

Abstract

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.

Keywords: CKD; RAS inhibitors; SGLT2 inhibitors; atherosclerosis; chronic kidney disease; hypertension; intensive blood pressure control; renin-angiotensin system inhibitors; sodium-glucose cotransporter 2 inhibitors.

Figure 1

Mechanisms of hypertension induced by renal parenchymal damage.

Figure 2

Hypothetical mean arterial blood pressure (BP) and intra-glomerular BP curves when using RAS inhibitors. In the absence of arteriosclerosis, if the mean systemic arterial pressure drops from (A) 160 mmHg to (B) 80 mmHg, the decrease in glomerular pressure is small (white arrow). However, if the atherosclerotic change is severe, there would be an insufficient increase in glomerular pressure due to dilation of efferent arterioles induced by RAS inhibitors, and the mean arterial pressure decreases rapidly (a’ to b’), causing glomerular pressure to drop sharply (black arrow).

Figure 3

Meta-analysis results of the composite renal endpoints of EMPA-REG outcome, CANVAS, DECLARE-TIMI 58 and CREDENCE. The composite renal endpoints were significantly suppressed by SGLT2 inhibitors, regardless of baseline renal function. These meta-analyses were performed using RevMan 5 software (Cochrane, London, UK). The analyses were performed regardless of renal function (A) and limited to eGFR ≤60 mil/min/1.73 m² (B). The results show that renal composite endpoints are significantly suppressed, regardless of baseline renal function or if eGFR is limited <60 mL/min/1.73 m². Abbreviation: SGLT2i, SGLT2 inhibitors.