Among others, they include higher serum uric acid levels and self-reported nocturia.

Researchers have identified four new independent risk factors for the development of end-stage renal disease (ESRD). These are higher serum uric acid levels, lower hemoglobin levels, family history of kidney disease, and self-reported history of nocturia.

Chi-yuan Hsu, MD, MSc, of the University of California at San Francisco, and colleagues studied 177,570 members of the Kaiser Permanente of Northern California health system who volunteered for health checkups between June 1, 1964, and August 31, 1971. The researchers identified patients who initiated ESRD treatment using the U.S. Renal Data System.

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A total of 842 cases of ESRD occurred during more than 5.2 million person-years of follow-up. Subjects in the highest quartile of serum uric acid level had a twofold increased risk of ESRD compared with those in the lowest quartile, the investigators reported in Archives of Internal Medicine (2009;169:342-350). Individuals in the lowest quartile of hemoglobin level were at 33% higher risk compared with subjects in the highest quartile.

A self-reported history of nocturia and a family history of kidney disease were associated with 36% and 40% increased risk of ESRD, respectively.

The study also confirmed the importance of other established risk factors for ESRD, such as proteinuria, excess weight, hypertension, and African American race. Patients with proteinuria, as indicated by urine dipstick measurements, had a 2.37-7.90 times increased ESRD risk (depending on degree of proteinuria), compared with those who had no proteinuria.

Compared with normal-weight individuals, those with excessive weight had a 1.65-4.39 times increased risk of ESRD. Patients with stage 2 hypertension were at nearly three times higher risk than normotensive individuals. ESRD was three times more likely to develop in African Americans than in whites.

With respect to the nocturia finding, the investigators suggested that nocturia “may reflect subtle early renal disease not captured by serum creatinine level or urine dipstick analysis.” They also stated that they cannot exclude the possibility that nocturia reflects undiagnosed diabetes mellitus.

“An alternative hypothesis,” they wrote, “is that nocturia reflects a high volume of ingested fluid that is detrimental (especially among patients with existing kidney disease), as high urine volume increases intratubular volume and pressure and these stretch forces induce fibrosis.”

Dr. Hsu’s group noted that the “identification of novel modifiable risk factors, such as hyperuricemia, opens the door to potentially new interventions beyond blood pressure control and blockade of the renin-angiotensin-aldosterone system to reduce the risk of ESRD.”