Kidney Decline Rate Predicts Death Risk

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Kidney Decline Rate Predicts Death Risk
By Michael Smith, North American Correspondent, MedPage Today
Published: October 15, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
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Action Points 

    * Explain to interested patients that a faster rate of decline in renal function was associated with an increased risk of all-cause mortality.


    * Note that the study was retrospective, conducted at a VA facility, and included only patients with rheumatoid arthritis and stage 3 chronic kidney disease.

In patients with chronic kidney disease, a higher rate of decline in renal function is associated with an increased risk of death, researchers reported.

In a retrospective cohort study, rheumatoid arthritis patients whose kidneys failed rapidly had a 54% increase in the risk of dying compared with those whose kidney function had the slowest rate of decline, according to Ziyad Al-Aly, MD, of the St. Louis Veterans Affairs Medical Center in St. Louis, Mo., and colleagues.

The finding suggests that not all patients with early stage 3 kidney disease have the same prognosis, Al-Aly and colleagues reported online in the Journal of the American Society of Nephrology.

Indeed, two patients with the same level of kidney function may have quite different mortality risks, depending on how long it took their kidneys to fail, they reported. "The take-home message from the study is that it matters how you got here," Al-Aly said in a statement.

Several investigators have linked rapid kidney failure with increased mortality, but not in patients with stage 3 chronic kidney disease, the researchers noted. Indeed, one recent study -- among people with normal kidney function -- found that those with the highest rate of decline had a significantly increased risk of coronary heart disease and death, compared with people whose kidney function fell at a lower rate.

The current study, Al-Aly and colleagues reported, extends those findings to a cohort of 4,171 patients with rheumatoid arthritis and early stage 3 chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) of 45 to 60 milliliters per minute.

The participants were studied for a median of 2.6 years to determine their rate of decline in eGFR, and then followed for another 5.7 years to characterize predictors of disease progression and the effect of rate of kidney function decline on mortality.

Overall, Al-Aly and colleagues found, 1,604 patients (or 38%) had stable kidney function and 426 (10%), 1,147 (28%), and 994 (24%) had mild, moderate, and severe progression, respectively, where mild, moderate, and severe were defined as a yearly eGFR decline of zero to 1, 1 to 4, and more than 4 milliliters per minute.

A mild decline, the researchers noted, is "commensurate with age-related functional decline, not disease" while stable function is probably linked to a decrease in creatinine as a result of muscle loss related to other conditions, including comorbid illness, malnutrition, or poor overall health.

Analysis showed that peripheral artery disease was a significant predictor of moderate and severe progression, with odds ratios of 1.512 and 1.55, respectively. Black race, hypertension, diabetes, and cardiovascular disease also predicted severe progression, with odds ratios of 1.853, 1.614, 1.387, and 1.392, respectively.

During the follow-up, the researchers reported, 1,947 patients died, representing 47% of the cohort. That included 672 deaths among those with stable disease, and 174, 524, and 577 deaths among those with mild, moderate, and severe progression, respectively.

Compared with those with mild progression, analysis showed:

    * Patients with stable disease had a trend toward increased mortality, with a hazard ratio of 1.149 and a 95% confidence interval from 0.988 to 1.24.
    * Patients who had moderate progression also showed a trend toward increased risk for death, with a hazard ratio of 1.100 and a 95% confidence interval from 0.975 to 1.304.
    * And patients who had severe progression had significantly increased risk for death from any cause, with a hazard ratio of 1.539 and a 95% confidence interval from 1.298 to 1.824.

The researchers noted that the mechanisms underlying the increased risk remain unclear.

Al-Aly and colleagues cautioned that the study included patients with rheumatoid arthritis and stage 3 disease, so the results may not apply to the whole population of patients with chronic kidney disease.

As well, they noted, the study design may have led to sampling bias. And the study population was largely male, so the results may not apply to women, they noted.

Nevertheless, the study "could have some immediate and far-reaching practical implications," according to Csaba Kovesdy, MD, of the Salem Veterans Affairs Medical Center in Salem, Va.

In an accompanying editorial, Kovesdy noted that the expansion of electronic medical records means many practitioners can now track serial measurements of serum creatinine for their kidney patients, which could make it easier for them to identify those at increased risk for progression.

Among other benefits, Kovesdy argued, this would prevent the "unnecessary anguish" for some patients who "face hypothetically ominous outcomes" as a result of being classified as having stage 3 disease.

The study "should stimulate further research on how best to implement this slope concept in clinical practice and to determine which therapeutic interventions it should trigger," Kovesdy concluded.

The study had support from the Department of Veterans Affairs. The researchers made no disclosures of potential conflicts.

Kovesdy made no disclosures.

Primary source: Journal of the American Society of Nephrology
Source reference:
Al-Aly Z, et al "Rate of kidney function decline associates with mortality" J Am Soc Nephrol 2010; DOI: 10.1681/ASN.2009121210.

Additional source: Journal of the American Society of Nephrology
Source reference:
Kovesdy CP "Rate of kidney function decline associates with increased risk of death" J Am Soc Nephrol 2010; 21: 1816-1817.

http://www.medpagetoday.com/Nephrology/GeneralNephrology/22768