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Background: After initiating cardioprotective agents, a fall of estimated glomerular filtration rate (eGFR) has been reported in several studies. Our goal was to evaluate the accuracy of change of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR in patients with type 2 diabetes (T2D) after short-term pharmacological intervention with angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, gliptin or sodium-glucose cotransporter-2 inhibitor., Methods: We analyzed 190 patients with T2D in the early stage of the disease, having no overt renal impairment by CKD-EPI equation. In each patient, we measured GFR (mGFR) by applying the constant infusion input clearance technique with sinistrin (Inutest; Fresenius, Linz, Austria) at baseline and after short-term (4-12 weeks) pharmacological intervention with cardioprotective agents (ramipril, telmisartan, linagliptin, metformin, empagliflozin) that potentially lead to an alteration of renal function. Simultaneously, a standardized analysis of serum creatinine was performed and eGFR was estimated by the CKD-EPI equation., Results: Average mGFR was 111 ± 20 ml/min/1.73m 2 , whereas eGFR was lower with 93 ± 13 ml/min/1.73m 2 . The ratio eGFR/mGFR in relation to mGFR was almost curvilinear, showing an underestimation of renal function by eGFR in the upper normal range. At baseline only 80 patients (42%) lay within ± 10% of mGFR and the concordance correlation coefficient (CCC) was extremely low (- 0.07). After short-term pharmacological intervention changes in eGFR and mGFR correlated with each other (r = 0.286, p < 0.001). For example, for a given mGFR of 111 ml/min/1.73m 2 , a change of mGFR by ± 10% corresponded to ± 11 ml/min/1.73m 2 , but the confidence interval of eGFR was 25 ml/min/1.73m 2 . The CCC was low (0.22)., Conclusion: The agreement between eGFR by CKD-EPI and mGFR is modest and the change of renal function after short-term pharmacological intervention is not accurately and precisely reflected by the change of eGFR in patients with T2D in the early stage of their disease., (© 2022. The Author(s).)

Background: Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail., Methods: Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model., Results: Treatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both p adjust  < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (R A ) (p = 0.116), but diminished resistance of efferent arterioles (R E ) (p = 0.001). In M+I group R A was increased (p = 0.006) and R E remained unchanged (p = 0.538). The effects on R A (p adjust  < 0.05) and on R E (p adjust  < 0.05) differed between the groups., Conclusions: In patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing R A and E+L predominantly decreasing R E , which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects., Trial Registration: The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016., (© 2021. The Author(s).)