ULT for CKD Patients With Asymptomatic Hyperuricemia

The worldwide prevalence of hyperuricemia and gout has grown. A cross-sectional survey of 3547 patients with chronic kidney disease (CKD) found the prevalence of hyperuricemia in patients with CKD stages 3, 4, and 5 in China to be 42.6%, 59.1%, and 61.2%, respectively. Hyperuricemia is associated with faster progression of CKD and an increased risk of poor renal prognosis and cardiovascular events in patients with CKD. It is also linked with a high risk of gout flare, which brings its own complications.

Results of studies on the effect of uric acid-lowering therapy (ULT) on renal and cardiovascular outcomes are controversial, and recommendations for ULT in CKD patients with asymptomatic hyperuricemia vary among different countries. Whether ULT should be used in CKD patients with asymptomatic hyperuricemia to prevent the progression of CKD remains uncertain. To provide clarity, Yuxin Luo, MD, and others embarked on a systematic review to examine the effects of ULT on renal outcomes in this patient population. Their results were published in BMC Nephrology.

The research team conducted searches of PubMed, EMBASE, China National Knowledge Internet, and the Cochrane Library through January 2024 to find randomized, controlled trials (RCTs) assessing the effects of ULT, including febuxostat or allopurinol or other uric acid-lowering drugs

versus a control group in patients with CKD. They included studies with: (1) adult CKD patients with hyperuricemia (serum uric acid [SUA] ≥7 mg/dl [420 μmol/L] in men or ≥6 mg/dl [360 μmol/L] in women) or at least mean baseline SUA ≥6 mg/dl (360 μmol/L) and no prior gout flares; (2) well-documented inclusion and exclusion criteria; (3) adequately documented dosage and duration of the intervention and control groups; (4) RCTs; and (5) changes in SUA, changes in serum creatinine (Scr), changes in estimated glomerular filtration rate (eGFR), acute kidney injury (AKI), or events of doubling of Scr without the requirement of dialysis used as outcome measures to assess the efficacy of agents for hyperuricemia in patients with CKD.

The initial searches generated 3400 studies; in total, 17 eligible studies with 2032 participants were included in the meta-analysis. Given the considerable heterogeneity in SUA level, only trials with

SUA ≥7 mg/dl (420 μmol/L) in men or SUA ≥6 mg/dl (360 μmol/L) in women—or at least mean baseline SUA ≥6 mg/dl (360 μmol/L) with no prior gout flares—were included in the analysis.

Primary outcomes included the change in eGFR and Scr from baseline until the study’s end. Compared with placebo or no treatment, the researchers found that use of ULT preserved the loss of eGFR (weighted mean difference [WMD] and 95% CI, 2.07 [0.15-3.98] mL/min/1.73m²) in the long-term subgroup. Meanwhile, the short-term subgroup also demonstrated that ULT preserved the loss of eGFR (WMD, 5.74 [2.09-9.39] mL/min/1.73m²). When compared with placebo or no treatment, ULT also reduced the increase in Scr in the short-term (WMD, −44.48 [−84.03 to −4.92] μmol/L) subgroup and long-term (WMD −46.13 [−65.64 to −26.62] μmol/L) subgroup.

Secondary outcomes included AKI and doubling of Scr without the requirement of dialysis (a deterioration of renal function, indicating an increase in Scr values exceeding 100% from baseline, without requiring dialysis). ULT was associated with a lower incidence of the events of doubling of Scr without dialysis (relative risk, 0.32 [0.21-0.49]; P<.001). However, there was no difference for lower incidence of AKI (P=.943).

The researchers acknowledged a few limitations of the study. They lacked some raw data on the standard deviation of GFR and Scr changes before and after ULT. In addition, the study is based on the analysis of existing clinical research data, and there is considerable heterogeneity between the various RCTs. The lack of a clear, unified definition for the starting level of uric acid reduction and target control may have affected study results. Finally, the team used Egger’s regression test to assess the relationship between ULT and change in uric acid, which could have introduced publication bias from the included literature.

In summary, the authors wrote, “Our study suggests that [ULT] is beneficial in slowing CKD progression in patients with asymptomatic hyperuricemia, both in short-term and long-term follow-ups, and this is consistent across different races and different levels of baseline eGFR. Meanwhile, among patients aged less than 60 years, the protective impact of ULT on renal outcomes is notably enhanced. Nevertheless, it does not show a significant difference in the incidence of AKI. These findings underscore the importance of considering ULT in clinical strategies for CKD patients with asymptomatic hyperuricemia.”

Source: BMC Nephrology