Preliminary evidence of renal function improvement in chronic progressive kidney disease using autologous CD34+ cell therapy: A clinical trial

Abstract

Background: To date, no specific treatment has been established to reverse progressive chronic kidney disease (CKD).

Aim: To evaluate the safety and efficacy of autologous CD34⁺ cell transplantation in CKD patients who exhibited a progressive decline in renal function.

Methods: The estimated glomerular filtration rate (eGFR) at the beginning of the study was 15.0-28.0 mL/minute/1.73 m². After five days of treatment with the granulocyte colony-stimulating factor, mononuclear cells were harvested and CD34⁺ cells were magnetically collected. CD34⁺ cells were directly injected into the bilateral renal arteries twice (at 0 and 3 months), and their safety and efficacy were evaluated for 6 months.

Results: Four patients were enrolled and completed the study. Three of four patients showed improvement in eGFR slope (eGFR slope > 0 mL/minute/1.73 m²), with the monthly slope of eGFR (delta eGFR) changing from -1.36 ± 1.1 (pretreatment) to +0.22 ± 0.71 (at 6 months) mL/minute/1.73 m²/month (P = 0.135) after cell therapy. Additionally, intrarenal resistive index (P = 0.004) and shear wave velocity (P = 0.04) were significantly improved after cell therapy. One patient experienced transient fever after cell therapy, and experienced bone pain during granulocyte colony-stimulating factor administration. However, no severe adverse events were reported.

Conclusion: In conclusion, our findings suggest that repetitive peripheral blood-derived autologous CD34⁺ cell transplantation into the renal arteries is safe, feasible, and may be effective for patients with progressive CKD. However, a large-scale clinical trial is warranted to validate the efficacy of repetitive regenerative cell therapy using autologous CD34⁺ cells in patients with progressive CKD.

Keywords: CD34+ cell; Chronic kidney disease; Clinical trial; Granulocyte colony-stimulating factor; Regenerative therapy.

Figure 1

The change of estimated glomerular filtration rate before and after cell therapy. The estimated glomerular filtration rate (eGFR) slope reversed from negative to positive inclination in case 2, 3, and 4 after 1^st cell therapy. The improved eGFR after 1^st cell therapy was almost maintained after 2^nd cell therapy for three months. eGFR slope slightly improved after 1^st cell therapy in case 1 (patient with the lowest eGFR, highest amount of proteinuria, and lowest purity of administered CD34⁺ cells among four patients). However, it did not change to positive inclination. eGFR: Estimated glomerular filtration rate.

Figure 2

Monthly change of estimated glomerular filtration rate at pretreatment and 6 months after cell therapy. Delta estimated glomerular filtration rate/month improved from negative to positive values in case 2, 3, and 4 after cell therapy. Delta estimated glomerular filtration rate/month in case 1 slightly improved. However, it was still negative value. eGFR: Estimated glomerular filtration rate.

Figure 3

Ultrasonographic findings before and after cell therapy. A: Resistive index at pretreatment and 6 months after cell therapy; B: Shear wave velocity at pretreatment and 6 months after cell therapy. Both intra-renal resistive index and shear wave velocity significantly improved at 6 months after 1^st cell therapy compared to pretreatment values. ^aP < 0.05, ^bP < 0.01.