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We have read with great interest the results of the cross-over randomized controlled trial (RCT) by Hasni et al. assessing the effect of pioglitazone on arterial stiffness indices and cardio-metabolic risk parameters in subjects with systemic lupus erythematosus (SLE).1 Renal involvement is of utmost importance for the prognosis of SLE, with a significant proportion of affected patients developing lupus nephritis within the first years after diagnosis.2
As demonstrated in the supplementary material of the article by Hasni et al.,1 treatment with pioglitazone resulted in a significant increase in blood urea nitrogen (BUN) (p = 0.005) and serum creatinine levels (p = 0.03), although the result seems to be of no clinical significance. It would be really interesting to know if the researchers also assessed the effect of pioglitazone on albuminuria levels in the enrolled participants. Among patients with diabetes mellitus thiazolidinediones have been shown to produce a significant reduction in urinary albumin to creatinine ratio (UACR), even among those with normo-albuminuria at baseline.3 Albuminuria should be taken into account, since it represents an additional prognostic marker for cardiovascular disease development, besides the established, traditional, cardiovascular risk factors.4 In addition, albuminuria is significantly associated with arterial stiffness indices, even in the general population setting, posing a potential causal link.5
Therefore, if avai...
Therefore, if available, such data would be really interesting and of additional value, since pioglitazone appears to be a drug with beneficial effect on cardio-metabolic profile of patients with SLE.
1. Hasni S, Temesgen-Oyelakin Y, Davis M, et al. Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus [published online ahead of print, 2022 Aug 1]. Ann Rheum Dis. 2022;annrheumdis-2022-222658. doi:10.1136/ard-2022-222658
2. Mahajan A, Amelio J, Gairy K, et al. Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression. Lupus. 2020;29(9):1011-1020. doi:10.1177/0961203320932219
3. Sarafidis PA, Stafylas PC, Georgianos PI, Saratzis AN, Lasaridis AN. Effect of thiazolidinediones on albuminuria and proteinuria in diabetes: a meta-analysis. Am J Kidney Dis. 2010;55(5):835-847. doi:10.1053/j.ajkd.2009.11.013
4. Matsushita K, Coresh J, Sang Y, et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3(7):514-525. doi:10.1016/S2213-8587(15)00040-6
5. Wang T, Fan F, Gong Y, et al. Comparison of brachial-ankle pulse wave velocity and carotid-femoral pulse wave velocity in association with albuminuria in a community of Beijing: a cross-sectional study [published online ahead of print, 2022 Apr 26]. J Hum Hypertens. 2022;10.1038/s41371-022-00697-7. doi:10.1038/s41371-022-00697-7