Treating Hypertension in Diabetic Patients With Advanced Chronic Kidney Disease: What Should We Have in Mind?

To the Editor:

We have read with interest the study by Weinrauch and colleagues,1 which investigated the prevalence of multidrug antihypertensive therapy in diabetic patients with and without impaired renal function. In a retrospective cohort of 10,151 diabetic outpatients collected during a 5‐year period in the Joslin Diabetes Center, Weinrauch and coworkers showed that the mean number of prescribed antihypertensive drugs increased from 1.5 agents daily in those with an estimated glomerular filtration rate (eGFR) >90 mL/min/1.73 m² to 3.1 antihypertensive agents daily in those with eGFR <30 mL/min/1.73 m².1 The prevalence of multidrug antihypertensive therapy (defined as the use of at least three antihypertensive agents, one of which had to be a diuretic) was 17% in those with an eGFR of >90 mL/min/1.73 m² and increased to 67% in those with eGFR <30 mL/min/1.73 m². The proportion of patients treated with multidrug antihypertensive regimens was shown to increase with advancing stage of chronic kidney disease (CKD), even when the alternative definition of use of at least four antihypertensive drugs, including a diuretic, was applied.1

These findings are clinically relevant because the study emphasizes the necessity for multidrug therapy in a high proportion of hypertensive patients with advanced CKD, incorporating real‐world data from a huge sample of US diabetic outpatients. However, the estimates of the prevalence of multidrug antihypertensive therapy provided in this analysis should not be interpreted as a proxy for the prevalence of resistant hypertension, as falsely suggested in the paper.1 Undoubtedly, hypertension is often difficult to control in patients with advanced CKD. However, the term “resistant hypertension” reflects a particular category of hypertensive patients and the diagnosis of this clinical entity should follow the currently available definitions. One patient is considered to have resistant hypertension when the blood pressure (BP) remains uncontrolled despite the concomitant use of three or more antihypertensive drugs at maximally tolerated doses, including a diuretic, or when four or more antihypertensive agents are used regardless of BP levels.2, 3 Even if we consider that those patients who met the second definition of multidrug antihypertensive therapy used in this study truly had resistant hypertension, there may be several others with resistant hypertension who remained misclassified without properly performed BP recordings to assess BP control status. Even in that case, we need to know whether these patients had controlled or uncontrolled resistant hypertension, because uncontrolled resistant hypertension has been associated with worse clinical outcomes.4

Apart from the issue of multidrug antihypertensive regimens, several other modifications may be necessary when treating hypertension in diabetic patients with advanced CKD. The authors nicely present in Table I of their paper the categories of antidiabetic compounds prescribed to the study participants according to stage of CKD.1 In a similar manner, it would be valuable to know the most commonly prescribed antihypertensive drug classes in diabetic patients with varying levels of renal function. For example, hydrochlorothiazide and thiazide‐like diuretics are generally inactive in patients with eGFR <30 mL/min/1.73 m² and should be replaced by the more potent loop diuretics.5 Further, although agents that block the renin‐angiotensin‐aldosterone system (RAAS) are recommended as first‐line antihypertensive therapy in patients with diabetes, particularly when albuminuria is present,6 it is not so rare in daily clinical practice to discontinue RAAS inhibitor use in patients with eGFR as low as 20 to 25 mL/min/1.73 m²; this commonly occurs because of fear of acute renal injury and hyperkalemia that may result in the need for earlier initiation of hemodialysis in such patients. We encourage the authors to provide this valuable information either in their response to this letter or in a separate paper. We believe that these data would be informative for clinicians who manage hypertension in patients with advanced CKD.

Disclosures

The authors have no conflicts of interest to disclose.