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Hypertension in Diabetes: Considering Therapies which Optimise Kidney Protection

Written By : Dr Sujoy Ghosh |Medically Reviewed By : Dr. Kamal Kant Kohli Published On 2020-11-20T11:25:38+05:30  |  Updated On 20 Nov 2020 2:31 PM IST
Hypertension in Diabetes: Considering Therapies which Optimise  Kidney Protection
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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.

The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Cilnidipine, click here

References

Adapted from:
1 Wenzel RR. Renal protection in hypertensive patients: selection of antihypertensive therapy. Drugs. 2005;65 Suppl 2:29-39. doi: 10.2165/00003495-200565002-00005. PMID: 16398060.
2 Sowers JR, Haffner S. Treatment of CV and renal risk factors in the diabetic hypertensive. Hypertension 2002;40:781-8
3 Gress TW, Nieto FJ, Shahar E, Wofford MR, Brancati FL. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med 2000;342:905-12.
4 Singh RB, Beegom R, Rastogi V, Rastogi SS, Madhu V. Clinical characteristics and hypertension among known patients of noninsulin dependent diabetes mellitus in North and South Indians. J Diab Assoc India 1996;36:45-50.
5 Mark E. Molitch, Ralph A. Defronzo, Marion J. Franz, William F. Keane, Carl Erik Mogensen. American Diabetes Association. Diabetic nephropathy. Diabetes Care 2002;25:S85-9. PR
6 Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703-13
7 Bakris GL, Smith A. Effects of sodium intake on albumin excretion in patients with diabetic nephropathy treated with long-acting calcium antagonists. Ann Intern Med 1996;125:201-4.
8 Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Eng J Med 2001;345:851-60.
9 Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, Wainford RD, Williams B, Schutte AE. 2020 International Society of Hypertension global hypertension practice guidelines. J Hypertens. 2020 Jun;38(6):982-1004. doi:10.1097/HJH.0000000000002453. PMID: 32371787.
10 Huggett RJ, Scott EM, Gilbey SG, Stoker JB, Mackintosh AF, Mary DA. Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in hypertension. Circulation 2003;108:3097-101
11 Fujita T, Ando K, Nishimura H, Ideura T, Yasuda G, Isshiki M, et al. Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease. Kidney Int 2007;72:1543-9.
12 Singh VK, Mishra A, Gupta KK, Misra R, Patel ML, Shilpa. Reduction of microalbuminuria in type-2 diabetes mellitus with angiotensin-converting enzyme inhibitor alone and with cilnidipine. Indian J Nephrol. 2015 Nov-Dec;25(6):334-9. doi: 10.4103/0971-4065.151764. PMID: 26664207; PMCID: PMC4663769.
13 Gadge P, Gadge R, Paralkar N, Jain P, Tanna V. Effect of telmisartan on blood pressure in patients of type 2 diabetes with or without complications. Perspect Clin Res 2018;9:155-60.
14 Ganesh J, Viswanathan V. Management of diabetic hypertensives. Indian J Endocrinol Metab. 2011 Oct;15 Suppl 4(Suppl4):S374-9. doi: 10.4103/2230-8210.86982. PMID: 22145142; PMCID: PMC3230084.
15 Williams B et al, 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018 Oct;36(10):1953-2041. doi: 10.1097/HJH.0000000000001940. Erratum in: J Hypertens. 2019 Jan;37(1):226. PMID: 30234752.
hypertensionkidneyend-stage renal diseasecardiovascularrenin-angiotensin systemcalcium channel blockersdiabetes
Dr Sujoy Ghosh
Dr Sujoy Ghosh

    Dr Sujoy Ghosh, DM ( Endocrinology), F.R.C.P. (London, Glasgow, Edinburgh), F.A.C.E., is a noted endocrinologist in West Bengal and is currently associated as a Professor of Endocrinology at IPGME&R Kolkata. He is an avid writer and is currently serving as Editor in chief: Oxford handbook series (South East Asia Edition) as well as Executive Editor: Thyroid Research & Practice and the Indian Journal of Endocrinology & Metabolism.

    Dr. Kamal Kant Kohli
    Dr. Kamal Kant Kohli

    Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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