Uric Acid Control in Advanced Chronic Kidney Disease in a Southeastern US Urban Cohort

Tibor Fülöp, MD, PhD; Christian A. Koch, MD, PhD, MACE; Lindsey T. Norris, MD; BetzaidaRodríguez, MD; Tibor Szarvas, PhD; Zsolt Lengvárszky, PhD; Éva Csongrádi, MD, PhD; Mehul P. Dixit, MD


South Med J. 2018;111(9):549-555. 

In This Article

Abstract and Introduction


Objectives: Uric acid (UA) control may be insufficient in chronic kidney disease (CKD) patients in the current era. It is unclear, however, whether this is the result of environmental effects, patient anthropometrics or insufficient dosing of medical therapy (allopurinol).

Methods: We have collected data on multiple clinical and laboratory parameters of 114 CKD clinic patients attending the nephrology clinic of the University of Mississippi Medical Center with an estimated glomerular filtration rate <45 mL · min−1 · 1.73 m2. We assessed the correlates of UA levels and the allopurinol doses along with achieved serum UA and urine pH.

Results: The cohort consisted of middle-aged to elderly patients with a mean (± standard deviation) age of 62.1 (11.6) years; 45.6% were female, 68.4% were African American and 47.4% had a history of gout. The mean UA level was 7.7 (2.49) mg/dL (range 3.1–16), allopurinol dose was 192 (99) mg/day (range 50–450) and estimated glomerular filtration rate was 23.8 (11.3) mL · min−1 · 1.73 m2. While the overall serum bicarbonate level was 25 (3.2) mEq/L, urine pH was <6 in 60.5% of the cohort. Significant univariate correlates of the administered doses of allopurinol were weight (r 0.317, P = 0.001), body mass index (BMI; r 0.313, P = 0.001), and female sex (r −0.198; P= 0.035). Achieved UA levels correlated directly with BMI (r 0.201, r = 0.036) but inversely with the allopurinol dose (r −0.196; P = 0.036). During logistic regression analysis with stepwise selection, only weight (β 0.313, P = 0.001) and sex (β −0.190, P = 0.039) proved to be predictive of the allopurinol dose; as for the achieved UA level, only BMI (β 0.271, P = 0.006) and the allopurinol dose (β −0.258; P = 0.009) had a significant effect.

Conclusions: In patients with advanced CKD, conventional dosing recommendations for allopurinol are unlikely to suffice in reaching target serum UA goals. In our cohort, larger-than-usual allopurinol doses were well tolerated.


The presence of elevated uric acid (UA) concentrations in the serum is a very common biochemical abnormality in patients with chronic kidney disease (CKD).[1] In fact, a progressive rise of UA commensurate with a gradual decline of the glomerular filtration rate (GFR) is the rule in progressive CKD.[1,2] Additional risk factors for elevated UA levels include male sex, African continental ancestry, obesity, certain medications,[1] and sleep-disordered breathing,[3] while clinical gout may also co-occur with a progressive rise of UA.[4] Moreover, elevated UA may be a potential independent risk factor of renal failure itself,[5,6] and most clinicians agree that elevated UA concentrations >10 mg/dL should be medically treated even in the absence of gouty arthropathy.

The optimal management of elevated UA is, nonetheless, controversial to some degree. Current guidelines for UA dosing are based on small case series dating back to the 1970s, an era preceding the progressive increase in body mass index (BMI), exposure to excessive fructose intake and an overall Westernization of the US population. Currently, the mainstay of medical therapy is the administration of allopurinol adjusted for renal failure—i.e., a standard dose of 300 mg/day; a reduced dose of 200 mg/day for patients with a GFR of 10 to 30 mL· min−1 · 1.73 m2 and a further reduction of the dose to 100 mg (or 25%–30% of the original dose) for patients with a GFR ≤10 mL· min−1 · 1.73 m2.[7] Certain cohort characteristics (excess weight, obesity, race, relative physical inactivity and poor dietary choices) create a virtual setup for failure of the medical therapy and therefore hinder sufficient UA control. As expected, CKD is highly prevalent in the local community in and around Jackson, Mississippi, in keeping with the large burden of CKD among African American individuals.[8]

Under such circumstances, one may need to revise the concept of appropriate allopurinol dosing. Alternative agents such as febuxostat are more expensive, while others (eg, probenecid) are ineffective in renal failure. Our hypothesis was that in our economically challenged, mostly African American inner-city patients, UA control would be insufficient with the currently utilized allopurinol dosages in the presence of significant CKD.