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

Figures & data

Table 1 Comparisons of BP Target Ranges and Recommendations for Drug Treatment in KDIGO CKD 2012, JSN CKD 2018, ESC/ESH 2018, and ACC/AHA 2017

Guidelines	Comorbidity	BP Target Ranges (mmHg)	Recommendations for Drug Treatment
KDIGO CKD 2012	Diabetes proteinuria (-) Diabetes proteinuria (+) CKD proteinuria (-) CKD proteinuria (+)	≤140/90 ≤130/80 ≤140/90 ≤130/80	ACEI, ARB, CCB, D ACEI, ARB ACEI, ARB, CCB, D ACEI, ARB
JSN CKD 2018	Diabetes CKD proteinuria (-) CKD proteinuria (+)	<130/80 <140/90 <130/80	ACEI, ARB ACEI, ARB, CCB, D ACEI, ARB
ESC/ESH 2018	Diabetes CKD	<130/80 <140/90	ACEI, ARB + CCB (or D) ACEI, ARB + CCB (or D)
ACC/AHA 2017	Diabetes proteinuria (-) Diabetes proteinuria (+) CKD proteinuria (-) CKD proteinuria (+)	<130/80 <130/80 <130/80 <130/80	ACEI, ARB, CCB, D ACEI, ARB ACEI, ARB, CCB, D ACEI, ARB

Notes: This table are shown for younger, middle-aged patients and not for the elderly.

Abbreviations: KDIGO CKD 2012, KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease; JSN CKD 2018, Evidence-based Clinical Practice Guidelines for Chronic Kidney Disease 2018, Japanese Society of Nephrology; ESC/ESH 2018, 2018 ESC/ESH Guidelines for the management of arterial hypertension; ACC/AHA 2017, 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.

Figure 1 Mechanisms of hypertension induced by renal parenchymal damage.

Table 2 BP Treatment Target Ranges of JSN CKD 2018

		<75 Years	≥75 Years
Diabetes (-)	Proteinuria (-)	<140/90	<150/90
	Proteinuria (+)	<130/80	<150/90
Diabetes (+)		<130/80	<150/90

Notes: For younger and middle-aged population under the age of 75, blood pressure targets have been determined by the presence or absence of diabetes and proteinuria, regardless of the CKD stage. Mild proteinuria (0.15 g/gCr) or higher was determined to be proteinuria (+). For aged 75 years or above, blood pressure target lower than 140/90 mmHg is recommended if there are no adverse events such as orthostatic hypertension or AKI.

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.

Table 3 Randomized Clinical Trials of Sodium-Glucose Cotransporter-2 Inhibitors

Drug	EMPA-REG Outcome	CANVAS Program	DECLARE-TIMI 58	CREDENCE
	Empagliflozin	Canagliflozin	Dapagliflozin	Canagliflozin
Median follow-up time, year	3.1	2.4	4.2	2.6
Trial participants	7020	10,142	17,160	4401
Patients with established atherosclerotic cardiovascular disease (ratio: %)	7020 (100%)	6656 (65.6%)	6974 (40.6%)	2220 (50.4%)
Patients with a history of heart failure (ratio: %)	706 (10.1%)	1461 (14.4%)	1724 (10.0%)	652 (14.8%)
Patients with eGFR<60 mL/min per 1.73 m^2 (ratio: %)	1819 (25.9%)	2039 (20.1%)	1265 (7.4%)	2592 (58.9%)

Abbreviations: EMPA-REG OUTCOME, empagliflozin cardiovascular outcome event trial in type-2 diabetes mellitus patients – removing excess glucose; CANVAS, SGLT2 inhibitors could improve renal prognosis in patients with atherosclerotic disease. Second, in the subsequent canagliflozin cardiovascular assessment study; DECLARE-TIMI 58, dapagliflozin effect on cardiovascular events – thrombolysis in myocardial infarction 58; CREDENCE, canagliflozin and renal events in diabetes with established nephropathy clinical evaluation.