Background Low-intensity shockwave therapy (LI-SWT) is suggested as a therapy for promoting tissue regeneration. In pigs, it was recently found that LI-SWT improved renal function after ischaemic injury. Our objectives were to study glomerular filtration rate (GFR) and albuminuria in diabetic nephropathy (DN) after treatment with LI-SWT. The present pilot study reports on the clinical safety of LI-SWT in DN. Methods A total of 14 patients with diabetes mellitus and Stage 3 chronic kidney disease were recruited for this prospective, one-arm Phase 1 study. The patients were treated with six sessions of LI-SWT during a 3-week period. At each session, 3000 shockwaves were applied to each kidney with 0.265 mJ/mm2, extended focal size and 4 Hz. Follow-up visits were performed at 1, 3 and 6 months. Results In general, the treatment was well tolerated. Transient macroscopic haematuria was observed in three patients immediately after LI-SWT. The majority of patients experienced lower back tenderness lasting up to 2 days after treatment. There was no need for analgesic treatment. LI-SWT showed no negative effect on GFR and albuminuria. At baseline, median (interquartile range) GFR was 33.5 mL/min/1.73 m2 (27.8–43.8) compared with 36.0 mL/min/1.73 m2 (27.5–52.0) at 6 months follow-up. In parallel, median albuminuria was 256 mg/24 h (79–619) at baseline and tended to decrease to 137 mg/24 h (41–404) 6 months after LI-SWT. There was no statistical difference between baseline and follow-up results. Conclusions LI-SWT is a safe treatment for DN. Inclusion of more patients is needed to determine whether LI-SWT can improve renal functional outcomes. [ABSTRACT FROM AUTHOR]