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Uric acid (UA) is the end product of purine metabolism; The association between UA and kidney disease is very close. The majority of UA in the blood is filtered by the kidney, and 90% of it undergoes proximal tubular reabsorption. Numerous observational studies have pointed out an association between hyperuricemia and the development of chronic kidney disease (CKD). On the other hand, the increase in UA levels is correlated with other cardiovascular risk factors. Diabetic Kidney Disease (DKD) continues to be a chronic and devastating complication of diabetes is the leading cause of CKD in patients with type 2 diabetes (T2D).
Between January 2017 to December 2020, 480 patients with T2D treated in first and second level medical units of the IMSS in the State of Michoacán, Mexico, were enrolled in the study. CKD was classified according to the Glomerular Filtration Rate (GFR) estimated with the Chronic Kidney Disease-epidemiology Collaboration (CKD-EPI) equation and/or albuminuria values. General and cardiovascular death were recorded and analyzed. Patients with CKD in stage G2 + microalbuminuria, G3a and G3b and hyperuricemia were treated with enalapril 10 mg and allopurinol 300 mg every 24 hours, orally for 6 months plus lifestyle changes (low-purine diet); additionally, the plasmatic values of interleukin-6 (IL-6), interleukin-10 (IL-10) and the tumor necrosis factor-α (TNF-α) were measured. The analysis was done with two-way ANOVA, followed by Tukey’s post-hoc, or Student's t for paired samples; The risk was estimated with logistic regression and Kaplan-Meyer to evaluate survival. A value of p<0.05 was considered statistically significant. The analysis was done with the SPSS v.23 statistical package for Windows.
The CKD found by eGFR was G1 47 (9.8%), G2 172 (35.8%), G3a 42 (8.8%), G3b 34 (7.1), G4 40 (8.3% and G5 145 (30.2%). Age, systolic blood pressure (SBP), diastolic blood pressure (DBP), years of T2D Dx, plasma hemoglobin (Hb) concentrations and serum uric acid levels were different (p<0.0001). Mortality was extraordinarily high in the population with hyperuricemia OR= 3.573, 95% CI 2.084-6.124, p<0.0001, adjusted for age, SBP, DBP, years of TD2 Dx, plasma Hb levels and dialysis treatment; Kaplan Meyer analysis and Log-Rank = 24.727, p<0.0001 made evident the risk of death determined especially in patients with CKD Stage 5. Treatment with ACE inhibitors + uricosurics had a nephroprotective effect in patients with G2, G3a and G3b CKD stages. In the subgroup of patients treated with enalapril and allopurinol, a reduction was observed in the plasma values of IL-6 (10.26±2.10 vs 5.76±1.85 pg/mL, p<0.0001) and TNF-α (9.30±2.08 vs 5.64±1.64 pg/mL, p<0.0001) and an increase in IL-10 (4.87±1.64 to 9.00±3.05 pg/mL p<0.0001).
Hyperuricemia was associated with the development of CKD and with general and cardiovascular mortality in this population. Treatment with ACEIs and uricosurics had a nephroprotective effect attributed to a reduction in intrarenal pressure due to the ACEI and an anti-inflammatory effect of the uricosuric acid. It is important to diagnose ERD early, identify risk factors and implement effective non-pharmacological and pharmacological strategies that prevent or at least delay the development of ERD.