Healthy Bone Marrow Cells Reduce Progression of Kidney Failure Better Than CKD Bone Marrow Cells in Rats With Established Chronic Kidney Disease

Chronic kidney disease (CKD) is a major health care problem. New interventions to slow or prevent disease progression are urgently needed. We studied functional and structural effects of infusion of healthy and CKD bone marrow cells (BMCs) in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX) in Lewis rats, and disease progression was accelerated with L-NNA and 6% NaCl diet. Six weeks after SNX, CKD rats received healthy eGFP(+) BMCs, CKD eGFP(+) BMCs, or vehicle by single renal artery injection. Healthy BMCs were functionally effective 6 weeks after administration: glomerular filtration rate (GFR; inulin clearance) (0.48 +/- 0.16 vs. 0.26 +/- 0.14 ml/min/100 g) and effective renal plasma flow (RPF; PAH clearance) (1.6 +/- 0.40 vs. 1.0 +/- 0.62 ml/min/100 g) were higher in healthy BMC- versus vehicle-treated rats (both p<0.05). Systolic blood pressure (SBP) and proteinuria were lower 5 weeks after treatment with healthy BMCs versus vehicle (SBP, 151 +/- 13 vs. 186 +/- 25 mmHg; proteinuria, 33 +/- 20 vs. 59 +/- 39 mg/day, both p<0.05). Glomerular capillary density was increased, and less sclerosis was detected after healthy BMCs (both p<0.05). Tubulointerstitial inflammation was also decreased after healthy BMCs. eGFP(+) cells were present in the glomeruli and peritubular capillaries of the remnant kidney in all BMC-treated rats. CKD BMCs also reduced SBP, proteinuria, glomerulosclerosis, and tubular atrophy versus vehicle in CKD rats. However, CKD BMC therapy was not functionally effective versus vehicle [GFR: 0.28 +/- 0.09 vs. 0.26 +/- 0.16 ml/min/100 g (NS), RPF: 1.15 +/- 0.36 vs. 0.78 +/- 0.44 nil/min/100 g (NS)], and failed to decrease tubulointerstitial inflammation and fibrosis. Single intrarenal injection of healthy BMCs in rats with established CKD slowed progression of the disease, associated with increased glomerular capillary density and less sclerosis, whereas injection of CKD BMCs was less effective.