Preclinical gout is common in the patient with stage 3-5 chronic kidney disease. Relevance of musculoskeletal ultrasound

Background: One in 10 patients with hyperuricemia may develop gout over time, with urate deposition sometimes asymptomatic. Recent reviews and guidelines support ultrasound (US) to assess asymptomatic hyperuricemic (AH) patients to detect gout lesions, showing double contour (DC) and tophus the highest specificities and positive predictive values. Hyperuricemia and gout are common in chronic kidney disease (CKD), especially with glomerular filtration rate (GFR) <60, and both are associated with worse prognosis, although treatment of AH in CKD is not yet recommended in all guidelines. US gout lesions have been found more frequently in AH (up to 35%) than in normouricemic (NU) patients, but evidence is scarce in CKD.

Objectives: To assess the prevalence of urate deposit in stages 3-5 CKD detected by US, and to investigate if there are differences between AH and NU patients.

Methods: Multicenter cross-sectional study, recruiting patients aged ≥18 years with AH and stages 3-5 CKD in 4 hospitals. A comparator group of NU patients with stage 3-5 CKD was included.

Exclusion criteria: previous diagnosis of gout, tophi. Hyperuricemia was defined as serum uric acid (sUA) >7 mg/dl, documented at least twice during the last 12 months. A standardized US exam of the knees and bilateral first metatarsophalangeal joints was performed to assess patients for DC/tophus as defined by OMERACT. Demographic, clinical and laboratory data were recorded. A descriptive analysis was performed using SPSS. Pre-clinical gout (PCG: DC and/or tophus) was considered as outcome variable. Chi-square and Fisher's exact test were used for qualitative variables, and Mann-Whitney U test for quantitative variables; significant threshold p < 0.05.

Results: Fifty-three patients with stages 3-5 CKD (59.6% stage 3, 19.1% stage 4, 21.3% stage 5) were recruited, 38 AH (71.7%) and 15 NU. A higher prevalence of US findings was observed in HU patients compared to NU patients (DC 23.7% vs 13.3%, tophus 31.6% vs 26.7%, PCG 39.5% vs 33.3%), although the differences were not statistically significant. NU patients had CKD of longer duration than HU patients [11 (7.2-13.5) vs 6 (2-9.2) years; p = 0.02], with no differences in sex, age, comorbidities, or urate-lowering therapy (ULT) (66.7% vs 44.7%; p = 0.05) and other treatments. Seventy percent of NU patients with TRU had AH before starting treatment. In patients with tophi, we observed a trend towards shorter duration of CKD and shorter duration of treatment with ULT compared to those without tophi [3.5 (2-6.7) vs 7 (3-12) years; p = 0.05] and [22 (12-44) vs 39 (29-73) months; p = 0.08], respectively. This trend was also observed in PCG, but not in DC, first US sign to disappear after initiation of ULT. Ninety percent of patients (100% in non-dialyzed patients) with PCG had a median uricemia ≥5 mg/dl in the past 12 months.

Conclusion: We found a significant prevalence of asymptomatic urate deposition in patients with stage 3-5 CKD, mostly in subjects with median uricemia ≥5 mg/dl in the last 12 months. Early diagnosis of PCG by musculoskeletal US in CKD may allow earlier introduction and optimization of ULT. This will probably contribute to slowing down the progression of this pathology, which makes it essential to promote collaboration between Nephrology and Rheumatology.