According to the GBD Chronic Kidney Disease Collaboration (2020), chronic kidney disease (CKD) accounted for the deaths of 1.2 million people across the globe with a prevalence of 697.5 million or 9.1%! This makes the disease a cause of morbidity and mortality across the globe. More than 2.5 million people receive renal replacement therapy and this figure is pitched to double by 2030. A sad fact is that 2.3–7.1 million adults died due to a lack of access to this therapy.
The development of dialysis and drugs that target the rennin-angiotensin- aldosterone system has brought in some hope. Yet, there is potential to improve the quality of life in such patients using the field of stem cell-based regenerative therapies. Let us see few examples of how human MSCs (mesenchymal stem cells) have been used with promising results to treat kidney diseases:
Early work in 2008 by Gooch and colleagues (NCT00733876) and Tögel & Westenfelder (2012) showed that the administration of allogeneic MSCs from the bone marrow in patients with acute kidney injury was safe, protected from deterioration of renal functions and lowered the stay in the hospital.
15 patients with refractory systemic lupus erythematosus (SLE) received allogeneic bone-marrow- derived-MSCs and were followed up for more than 12 months. While the clinical symptoms were improved, the condition of proteinuria or increased levels of protein in the urine was also lowered. No adverse side effects were reported and the stabilization of renal function in patients shows the beneficial effects of MSC therapy for such kidney disorders.
Packham and team administered one dose of allogeneic bone-marrow -derived mesenchymal precursor cells (MPC) in patients with type 2 diabetes and advanced diabetic nephropathy in a multicenter, randomized, double-blind trial. The estimated glomerular filtration rate (eGFR) was stabilized in patients who received the stem cells against controls at the end of week 12 showing the safety and promise of stem cells in treating the chronic condition.
The main effects of MSCs in healing the kidney diseases are due to the secretion of paracrine factors that are anti-oxidative, anti-apoptotic, immunomodulatory, and pro-angiogenic. They also create a pro-regenerative environment and preliminary reports show that MSCs can lower the immune responses to kidney transplants (Rota et al, 2019).
The first aspects of any treatment are safety and efficacy; both these aspects are met by MSCs as evidenced by clinical trials conducted so far. The use of MSCs has an edge as it repairs the damaged kidney cells rather than depending on only suppression of symptoms. The wand of stem cells is ready to be waved to create magic!
GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. DOI: https://doi.org/10.1016/S0140-6736(20)30045-3
Rota, C., Morigi, M., & Imberti, B. (2019). Stem Cell Therapies in Kidney Diseases: Progress and Challenges. International journal of molecular sciences, 20(11), 2790.
Tögel F.E., Westenfelder C. Kidney protection and regeneration following acute injury: Progress through stem cell therapy. Am. J. Kidney Dis. 2012; 60:1012–1022.
Gooch A., Doty J., Flores J., Swenson L., Toegel F.E., Reiss G.R., Lange C., Zander A.R., Hu Z., Poole S., et al. Initial report on a phase I clinical trial: Prevention and treatment of post-operative Acute Kidney Injury with allogeneic Mesenchymal Stem Cells in patients who require on-pump cardiac surgery. Cell. Ther. Transpl. 2008; 1:31–35.
Liang J., Zhang H., Hua B., Wang H., Lu L., Shi S., Hou Y., Zeng X., Gilkeson G.S., Sun L. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: A pilot clinical study. Ann. Rheum. Dis. 2010; 69:1423–1429.
Packham, D. K., Fraser, I. R., Kerr, P. G., & Segal, K. R. (2016). Allogeneic Mesenchymal Precursor Cells (MPC) in Diabetic Nephropathy: A Randomized, Placebo-controlled, Dose Escalation Study. EBioMedicine, 12, 263–269.