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The kidneys’ cellular structure is complex, with inherent bioactivity, and possible restorative capacity Current dogma specifies that new nephrons cannot be formed after 34-36 weeks of gestation; however, recent cell-based therapies (CBT) have shown promise for kidney regeneration and disease modulation. Especially for kidney transplantation induction therapy and diabetic nephropathy, the evidence for CBT is growing. Despite the expected low safety risks and individuality of autologous and allogeneic cell types, a comprehensive review of their safety in humans with kidney diseases is lacking. The objective of this review was to assess the current safety profiles of early phase investigative clinical trials utilizing CBT to treat kidney-related conditions.
Inclusion criteria were single-arm and randomized controlled trials (RCTs) reporting safety outcomes of CBTs on patients with kidney-related conditions. We applied the patient/population/problem, intervention, comparison, and outcome method, and searched all trials published on PubMed, EMBASE, Google Scholar, SciELO, Redalyc, Google Académico, and the clinical trials.gov website. Two co-investigators identified and extracted data independently, and a third co-investigator settled disagreements. All safety analyses were searched for system organ class (SOC) and preferred term (PT) determination and severity grades. Treatment Emergent Adverse Events (TEAEs) and serious adverse events (SAEs) related to procedures and CBT were reported
Eighteen single-arm and eight randomized controlled studies were identified, representing 749 participants. Kidney conditions exposed to cell-based therapies included chronic kidney disease, end stage kidney disease, dialysis, kidney transplantation, acute kidney injury with chronic kidney disease, and systemic lupus erythematosus (SLE). The most frequent conditions were kidney transplantation (n=244) and uncontrolled SLE (n=242). Most cell trials utilize autologous and allogeneic cell types, and the most frequent method of delivery was intravenous. Other methods of delivery, such as locoregional in the kidney cortex and intra-arterial injections are under investigation. The most common SOC classes were infections, blood and lymphatic, kidney and urinary and nervous system disorders. A detailed sub-analysis of four randomized controlled trials revealed no significant difference regarding any of the adverse events (Table 1) with minimal procedure related complications.
There are few cell-based investigative trials underway for kidney-related conditions despite the large global prevalence of chronic kidney disease. Acceptable safety data was found with no deaths or major organ injuries attributed to the cell-based technology interventions, and in principle autologous and allogeneic CBT for kidney conditions appears to be safe. More prospective randomized clinical trials and standardized safety reporting are needed to validate these observations.