Salt restriction boosts losartan benefits in type 2 diabetes
medwireNews: Finding from the PROCEED trial show that dietary salt restriction helps to reduce albuminuria in patients with type 2 diabetes taking losartan, the investigators report in The Lancet Diabetes & Endocrinology.
The patients in the study all had macroalbuminuria despite treatment with a renin–angiotensin system inhibitor. All participants switched to losartan 100 mg/day; the 57 who were randomly assigned to a low-sodium diet achieved a median 36.6% reduction in albuminuria between baseline and the end of month 3, with substantial reductions seen from month 1.
Of note, patients in the low-sodium group had been allocated to achieve urine sodium excretion of less than 100 mEq per day (2.4 g of salt per day), but in fact achieved only 170 mEq per day on average, from a baseline of approximately 200 mEq.
“Whether prescription of a very restricted sodium diet is required to achieve moderate sodium restriction, or whether prescription of a moderate sodium restriction might attain the double aim of facilitating compliance and achieving a degree of sodium restriction that has a renoprotective effect, remains unclear,” write Beatriz Fernandez-Fernandez and Alberto Ortiz, both from Universidad Autonoma de Madrid in Spain, in an accompanying commentary.
Patients in the low-salt group were also randomly assigned to take the vitamin D receptor activator paricalcitol 2 µg/day or placebo, but this had no additional effect on albuminuria, report Giuseppe Remuzzi (Istituto di Ricovero e Cura a Carattere Scientifico—Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy) and study co-authors.
However, it was a different story in a further 58 patients who were randomly assigned to a high-salt diet (4.8 g salt/day). Within this group, patients taking placebo had no significant change in albuminuria by the end of month 3, but those taking paricalcitol had a significant 14.7% reduction.
The commentators say that the PROCEED findings “send a clear message in favour of moderate salt restriction for reduction of albuminuria, and a mixed message for paricalcitol treatment.”
Taking the results of the VITAL trial into account, they believe that “any potential renal benefit of paricalcitol is limited to the high dose of 2 μg per day in patients unable or unwilling to decrease salt intake.”
They also raise the issue of safety, with cardiovascular events reported for the 2 µg dose in VITAL, and also in PROCEED (one ischemic heart disease, one stroke), compared with none among patients taking the 1 µg dose (in VITAL) or placebo. And in PROCEED there were also increased rates of hypercalcemia and hyperphosphatemia (5% and 4% vs 0% on placebo) and of hypercalciuria (12% vs 1%).
“This safety signal for paricalcitol is counterintuitive, in view of putative renal and cardiovascular benefits suggested by preclinical data and findings from observational studies,” say Fernandez-Fernandez and Ortiz. “If the association is confirmed, the potential mechanisms remain unclear.”
In the meantime, they say that the 2 µg dose should be used only in a clinical trial setting.
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