Anemia, Hyperuricemia, and Mortality Risk in Patients With CKD

Hyperuricemia and anemia not only result from chronic kidney disease (CKD) but, conversely, can play a role in the occurrence and development of CKD. People with CKD (currently about 13% of the world’s population) have a higher risk of all-cause mortality compared with those with normal kidney function. So, identifying factors involved in CKD prognosis is important to developing interventions and reducing the disease burden.

With that in mind, researchers led by Zhaoxuan Lu, MD, sought to examine the part hyperuricemia and anemia play in all-cause mortality with CKD in hopes that the findings may assist in risk stratification management and the formulation of interventions among patients with CKD. Their results appeared in Frontiers in Endocrinology.

The researchers examined data on 4642 adults with CKD from the National Health and Nutrition Examination Surveys (NHANES) database from 2009 to 2018. Of those, 2678 were found to be eligible for the study. The researchers excluded anyone <18 years old (n=558), without available information on serum hemoglobin (Hb) or uric acid (n=8), having an extreme energy intake (n=392), or lost to follow-up (n=6).

All patients met the Kidney Disease Improving Global Outcomes definition of CKD: urinary albumin-to-creatinine ratio >30 mg/g and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². The mean age of participants was 58.98 years; 1855 (53.93%) were female, 802 (16.50%) had anemia, and 1218 (32.71%) had hyperuricemia. Hyperuricemia was defined as a serum uric acid level >7 mg/dL in male patients and >6 mg/dL in females. Anemia was defined as serum Hb level <13 mg/dL in males and <12 mg/dL in female patients, per World Health Organization standards.

The study outcome was all-cause mortality, determined using a probability-matching algorithm by the National Death Index and the public-use NHANES-linked mortality file correlated with the National Center for Health Statistics. The follow-up ended on December 31, 2019, or when patients died. The researchers compared characteristics of patients in the survival group (n=2859) and the all-cause mortality group (n=819). Among the total number of patients, 21 (0.5%) died due to renal disease. Average follow-up time was 63.82 months.

The team used weighted univariate and multivariate COX regression analyses to investigate the associations of hyperuricemia and anemia with all-cause mortality. The evaluation indexes were hazard ratios (HRs) and 95% CI. The researchers evaluated the interaction effect between hyperuricemia and anemia on the risk of all-cause mortality via relative excess risk due to interaction (RERI) and attributable proportion of interaction (AP). They also conducted subgroup analyses of age, gender, cardiovascular disease, hypertension, diabetes mellitus, and cancer to determine the interaction effect.

After adjusting for covariables, anemia (HR, 1.72; 95% CI, 1.42-2.09) and hyperuricemia (HR, 1.21; 95% CI, 1.01-11.45) were associated with a higher risk of all-cause mortality. Patients who had both anemia and hyperuricemia in addition to CKD had a higher risk of all-cause mortality (HR, 2.17; 95% CI, 1.73-2.72). There appeared to be a possible synergetic effect between anemia and hyperuricemia on all-cause mortality, with RERI of 0.630 and AP of 0.291.

Furthermore, Kaplan-Meier curves showed that patients with CKD and anemia or hyperuricemia had a lower likelihood of survival than those without these diseases, and the possible synergetic effect between anemia and hyperuricemia was again observed. The synergetic effect was also seen in subgroups of patients ≥65 years old (AP, 0.330), as well as in those who were male (AP, 0.355), without hypertension (AP, 0.281), with hypertension (AP, 0.736), with diabetes (AP, 0.371), and with cancer (AP, 0.391).

The authors conceded some limitations of the study. Data regarding ferritin were missing, data from the investigation until the end of follow-up were unavailable in NHANES, and results from participants in NHANES may not be applicable to populations outside the United States.

The authors concluded that “anemia and hyperuricemia were both linked to all-cause mortality in patients with CKD, and there was a potential synergetic effect between them on the risk of all-cause mortality.” They believe that further studies are required to clarify the relationship between anemia and hyperuricemia and mortality in CKD.

Source: Frontiers in Endocrinology