Hypertension in Diabetes: Considering Therapies which Optimise Kidney Protection
Hypertension and Diabetes remain the top two causes of End-Stage Renal Disease (ESRD) (1). Hence, it seems clinically appropriate to establish that when Hypertension and Diabetes come together, they possess the greatest dual threat to the kidneys. Hypertension in diabetes management, therefore, requires a more prudent approach for optimal renal outcomes, which independently could improve cardiovascular outcomes. Renin-Angiotensin System (RAS) Blockers in combination with clinically proven nephroprotective Calcium Channel Blockers (CCBs) seem to be valuable fixed-dose combination options for the management of blood pressure control and target organ protection in hypertensive patients with Diabetes.
Hypertension and diabetes are becoming progressively common. Hypertension affects up to 60% of patients with diabetes, depending on obesity, ethnicity, and age (2) . Hypertension is found to be disproportionately higher in patients with Diabetes. Individuals with elevated BP are two and a half times more likely to develop diabetes within 5 years (3), and in India, it is estimated that about 50% of diabetic patients have hypertension (4) . Most patients with both disorders stand a higher risk for premature microvascular and macrovascular complications. The presence of hypertension leads to a 7.2-fold increase in mortality in diabetic patients (5)
The landmark U.K. Prospective Diabetes Study (UKPDS) study indicated that each 10-mm Hg decrease in mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes, 15% for deaths associated with diabetes, 11% for myocardial infarction, and 13% for microvascular complications Hence, aggressive BP control becomes critical in diabetic patients. Studies have shown that early treatment of blood pressure and tight blood pressure control leads to a significant reduction in microvascular complications and macrovascular complications (6).
Management of diabetic hypertensives starts with lifestyle changes - weight reduction; regular exercise; and moderation of sodium, protein, and alcohol; as well as control of hyperglycemia, dyslipidaemia and proteinuria.
Calcium channel blockers have been useful to hypertensive patients with diabetes, particularly as part of combination therapy, to control blood pressure. These classes of agents have shown to reduce CV events in diabetics in several clinical outcome trials (7). In patients with type 2 diabetes, hypertension, macroalbuminuria, and renal insufficiency, Angiotensin Receptor Blockers (ARBs) have preferably shown to delay the progression of nephropathy (8). Because of these features,in the management of hypertension with Diabetes, the 2020 International Society of Hypertension Global Hypertension Practice Guidelines recommend the treatment strategy should include a RAS inhibitor and a CCB and/or thiazide-like diuretic (9) .
Cilnidipine, unique dihydropyridine derivative 4th generation Ca2+ possesses dual L/N-type Ca2+ channel blocking action. It blocks L-type calcium channels in vascular smooth muscle and N-type calcium channels in sympathetic nerve terminals that supply blood vessels. In diabetic patients, there is an augmented sympathetic nervous activity resulting in constricted efferent arterioles and elevated intraglomerular pressure (10) . Cilnidipine is known to dilate both afferent and efferent arterioles by its effect on N-type calcium channels and thus reduces urinary albumin and protein excretion (11) . In a study conducted on Indian Diabetic patients, cilnidipine use resulted in an additive effect in microalbuminuria reduction over and above the well-proven effect of ACE inhibitors (12) . Telmisartan is reported to be effective in lowering blood pressure and improving metabolic parameters in Indian T2DM patients with or without complications (13) .
In the management of hypertension with diabetes, the target blood pressure should be below 130/80 mm Hg (14). Guidelines suggest that combination treatment is recommended for most hypertensive patients as initial therapy. Preferred combinations should comprise a renin-angiotensin system (RAS) blocker - either an ACE inhibitor or an ARB with a CCB or thiazide/thiazide-like diuretic. (15) Cilnidipine and Telmisartan single-pill combination (SPC) could offer preferential advantages through specific and independent nephroprotective benefits, beyond its potent and sustained blood pressure lowering effect; and additionally, provide a favorable improvement in metabolic profile and cardiovascular outcomes as independent agents.
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References
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