We appreciate the insightful comments of Ben-Dov and Bursztyn and Portaluppi regarding our recent investigation of the association of nondipping with a subsequent decline in glomerular filtration rate (GFR).
Ben-Dov and Bursztyn provide evidence to suggest that nondipping may be a subtle manifestation of early nephropathy and may be amenable to reversal by agents that address “salt-sensitive” states, namely diuretics, as opposed to inhibitors of the renin-angiotensin-aldosterone (RAAS) system as we suggested. This is a possibility that we cannot dispute. Creatinine-based GFR formulas are imperfect and we lacked urine microalbumin measurements in most of our patients, so it is plausible that nondipping may have resulted from occult baseline nephropathy in some of our patients. Furthermore, given recent data suggesting that much of the renoprotection conferred by blockade of the RAAS comes from BP reduction rather than pathway-specific glomerular protection,1 diuretics may be an effective first-line treatment in hypertensive nondippers based on their established efficacy for treating hypertension in general. However, we do not agree with the notion that nondipping itself contributes to a decline in GFR or that the BP pattern itself is a therapeutic target.2 Instead, we suggest that nondipping is a marker of disrupted vascular homeostasis, likely due in large part to disrupted autonomic regulation, and that correction of the BP pattern itself need not be a goal of treatment. Mechanistically, the association of nondipping with insulin resistance,3 the ability of RAAS blockade to increase insulin sensitivity,4,5 and the sympatholytic effect of RAAS blockade in patients with nephropathy6 all support our recommendation for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in the treatment of hypertensive nondippers who respond suboptimally to lifestyle modifications.
Davidson MB, Brotman DJ. Loss of Nocturnal Blood Pressure Fall in Patients With Renal Impairment—Reply. Arch Intern Med. 2006;166(19):2159. doi:10.1001/archinte.166.19.2159