Urinary Protein Marks Renal Risk in Hypertension

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Elevated urinary albumin may be a trouble sign for the kidneys and heart in hypertensive patients without diabetes, researchers found.

Microalbuminuria in a prospective cohort study in this population predicted 12.75-fold elevated risk of chronic renal insufficiency (P<0.0001) over about a decade even after adjustment for baseline estimated glomerular filtration rate (eGFR), body mass index, glucose levels, and other variables.

For combined cardiac, cerebrovascular, and renal events, microalbuminuria predicted an adjusted 2.58-fold risk (P=0.0056), Roberto Pontremoli, MD, PhD, of the University of Genoa, Italy, and colleagues reported online in the Clinical Journal of the American Society of Nephrology.

Microalbuminuria conferred “far greater” risk than expected from being 10 years older, from a 10-ml/min decrease in eGFR, or from 10- and 5-mm Hg higher systolic and diastolic blood pressure, respectively, they said.

The researchers recommended more widespread evaluation of the urinary albumin-to-creatinine ratio in hypertension.

“Patients with microalbuminuria should be aggressively targeted for renal and cardiovascular risk factor reduction,” they wrote in the paper, “although further research is warranted to determine whether specific treatment would help to improve outcomes, as already reported for patients with diabetes.”

Their study—Microalbuminuria: A Genoa Investigation on Complications (MAGIC)—included 917 patients with untreated primary hypertension but no diabetes or overt macroalbuminuria at baseline.

Chronic renal insufficiency, defined by hospitalization with a diagnosis of chronic kidney disease, showed a “clear dose-response relationship” with the urinary albumin-to-creatinine ratio measured at baseline.

This relationship was apparent even at albumin levels considered in the normal range, Pontremoli’s group noted.

However, the renal risk jumped substantially once urinary albumin levels reached beyond the microalbuminuria threshold of an albumin-to-creatinine ratio over 22 mg/g in men and 31 mg/g in women, they said.

Microalbuminuria was present at baseline in 36% of those who went on to develop chronic renal insufficiency over the 11.8 years of follow-up, but only 7% of those who didn’t (P<0.001).

Patients with microalbuminuria compared with those with normoalbuminuria showed:

* 6.41-fold higher incidence of chronic renal insufficiency (12% versus 2%, P<0.001).
* 2.34-fold higher incidence of fatal and nonfatal cerebrovascular and cardiovascular events (15% versus 7%, P=0.029).
* 3.52-times higher incidence of the combined endpoint of chronic renal insufficiency, cerebrovascular events, and cardiovascular events (23% versus 8%, P<0.0001).

Urinary albumin remained a significant predictor in a sensitivity analysis limited to patients with preserved kidney function (at least 50 ml/min basal eGFR).

One explanation might be the cluster of traditional risk factors often found with this forerunner of progressive renal damage, Pontremoli's group suggested.

But adjustment for gender, age, eGFR, blood pressure values, body mass index, duration of disease, smoking, serum glucose, uric acid, and LDL cholesterol actually strengthened the association with chronic renal insufficiency and had little impact on the combined renal and vascular endpoints.

On the other hand, the association with cardiovascular and cerebrovascular events lost significance with these adjustments for important variables. The researchers said this could be due to the relatively small number of events, or to treatment of hypertension and other cardiovascular risk factors during follow-up.

They cautioned that their study could not prove a cause-and-effect relationship and that it did not address the risks associated with microalbuminuria on the basis of the type of treatment or achieved blood pressure level.

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Primary source: Clinical Journal of the American Society of Nephrology
Source reference:
Viazzi F, et al “Microalbuminuria is a predictor of chronic renal insufficiency in patients without diabetes and with hypertension: The MAGIC Study” Clin J Am Soc Nephrol 2010; DOI: 10.2215/CJN.07271009.

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By Crystal Phend, Senior Staff Writer, MedPage Today

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