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. 2024 Aug 30;25(17):9468.
doi: 10.3390/ijms25179468.

Renoprotective Effects of Daprodustat in Patients with Chronic Kidney Disease and Renal Anemia

Yoshitaka Shimada  1 , Yuichiro Izumi  2 , Yukiko Yasuoka  3 , Tomomi Oshima  3 , Yasushi Nagaba  1 , Masayoshi Nanami  4 , Jeff M Sands  5 , Noriko Takahashi  3 , Katsumasa Kawahara  3 , Hiroshi Nonoguchi  1   6
Affiliations

Renoprotective Effects of Daprodustat in Patients with Chronic Kidney Disease and Renal Anemia

Yoshitaka Shimada et al. Int J Mol Sci. .

Abstract

Many large-scale studies revealed that exogenous erythropoietin, erythropoiesis-stimulating agents, have no renoprotective effects. We reported the renoprotective effects of endogenous erythropoietin production on renal function in ischemic reperfusion injury (IRI) of the kidney using the prolyl hydroxylase domain (PHD) inhibitor, Roxadustat. The purpose of this study was to investigate the effects of daprodustat on the progression of chronic renal failure. We retrospectively investigated the effects of daprodustat on the progression of chronic renal failure and renal anemia in patients with stages 3a-5 chronic kidney diseases (estimated glomerular filtration rate, eGFR < 60 mL/min/1.73 m2). The results show that daprodustat largely slowed the reduction in eGFR. The recovery of renal function was observed in some patients. Daprodustat is useful not only for renal anemia but also for the preservation of renal function. The renoprotective effect of daprodustat was small in patients with serum creatinine larger than 3-4 mg/dL because of low residual renal function. The appearance of renal anemia would be a sign of the time to start using daprodustat.

Keywords: PHD inhibitor; deglycosylation; distal tubules; erythropoietin; hypoxia; proximal tubules; renal erythropoietin-producing interstitial cells.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The changes in the eGFR slope in three patients before and after (pre and post, respectively) the administration of daprodustat. The line was drawn using least square method (Excel 2019).
Figure 1
Figure 1
The changes in the eGFR slope in three patients before and after (pre and post, respectively) the administration of daprodustat. The line was drawn using least square method (Excel 2019).
Figure 2
Figure 2
The change in the slope of the decline of eGFR (mL/min/1.73 m2/month) by daprodustat. Daprodustat significantly reduced the decline of eGFR slope. Box and bar show mean + SD.
Figure 3
Figure 3
Relationship between eGFR levels at the start point and changes in eGFR. Renoprotective effects of daprodustat (reduction of the loss of eGFR) was not evident in patients with eGFR levels at the start point less than 10 mL/min/1.73 m2. ΔeGFR, the changes in the slopes of the decline of eGFR.
Figure 4
Figure 4
Relationship between serum creatinine levels and changes in eGFR. Renoprotective effect of daprodustat (reduction in the slopes of the decrease in eGFR) was small in patients with serum creatinine levels more than 4 mg/dL. Renoprotective effect was seen mainly in patients with serum creatinine levels less than 3 mg/dL.
Figure 5
Figure 5
Relationship between plasma hemoglobin levels and the changes in eGFR. Renoprotective effects of daprodustat did not correlate with plasma hemoglobin levels.
Figure 6
Figure 6
Relationship between the changes in hemoglobin levels (ΔHb) and the changes in eGFR. Renoprotective effects of daprodustat did not correlate with plasma hemoglobin levels.
Figure 7
Figure 7
Interaction between the changes in slope of eGFR and the changes in urinary protein excretion (ΔU-TP). The reduction in the decrease in the slope of eGFR was correlated with the change in urinary protein excretion as shown by the multiple regression analysis.
See this image and copyright information in PMC

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