J-shaped mortality relationship for uric acid in CKD.
BACKGROUND
Hyperuricemia is a common feature in patients with chronic kidney disease (CKD). Hyperuricemia has been associated with increased cardiovascular mortality in the general population, but less is known about this association in patients with CKD.


METHODS
To explore possible associations of serum uric acid with all-cause mortality and comorbidity in patients with CKD, we studied 294 incident patients with CKD stage 5 (185 men; age, 53 +/- 12 years) starting renal replacement therapy with a median glomerular filtration rate of 6.4 mL/min/1.73 m(2) (0.11 mL/s/1.73 m(2); range, 0.8 to 14.3 mL/min/1.73 m(2) [0.01 to 0.24 mL/s/1.73 m(2)]). Survival was determined from the day of examination and during a mean follow-up period of 27 months (range, 3 to 72 months); 94 patients died. Patients were divided into 3 groups based on serum uric acid levels (low quintile, 3 middle quintiles, and high quintile).


RESULTS
In a nonadjusted analysis, patients in the high quintile, followed by patients in the low quintile, had greater all-cause mortality compared with patients in the 3 middle quintiles (log-rank test chi-square, 6.8; P = 0.03). After adjusting for age, sex, glomerular filtration rate, cholesterol level, phosphate level, C-reactive protein level, cardiovascular disease, diabetes mellitus, diuretics, and allopurinol treatment, the association showed a "J-shaped" association with hazard ratios of 1.96 (confidence interval, 1.10 to 3.48; P = 0.02) for the high quintile and 1.42 (confidence interval, 0.76 to 2.66; P = not significant) for the low quintile. Moreover, uric acid levels correlated positively with levels of triglycerides, phosphate, C-reactive protein, and intracellular adhesion molecule 1 and negatively with levels of calcium, high-density lipoprotein cholesterol, and apolipoprotein A.


CONCLUSIONS
Serum uric acid levels showed a J-shaped association with all-cause mortality, with the lowest risk in the 3 middle quintiles. Moreover, uric acid level was associated with calcium/phosphate metabolism, dyslipidemia, and inflammation.
Suliman
Mohamed E
ME
Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Johnson
Richard J
RJ
García-López
Elvia
E
Qureshi
A Rashid
AR
Molinaei
Hadi
H
Carrero
Juan Jesús
JJ
Heimbürger
Olof
O
Bárány
Peter
P
Axelsson
Jonas
J
Lindholm
Bengt
B
Stenvinkel
Peter
P
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use; D000963:Antimetabolites / Q000627:therapeutic use; D002423:Cause of Death; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D003928:Diabetic Nephropathies / Q000097:blood / Q000401:mortality; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000097:blood / Q000401:mortality; D006801:Humans; D033461:Hyperuricemia / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D010710:Phosphates / Q000097:blood; D007690:Polycystic Kidney Diseases / Q000097:blood / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D017582:Renal Replacement Therapy; D016019:Survival Analysis; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000097:blood*
D000963:Antimetabolites; D004232:Diuretics; D010710:Phosphates; D014280:Triglycerides; D014527:Uric Acid; D000493:Allopurinol