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Advances in renal regenerative medicine are crucial to address the increased rate of kidney disease. Clinicians and researchers are investigating new renal therapeutics aimed at promoting endogenous repair and/or at designing new technologies for organ and tissue regeneration. This review explores the potential promises and limitations of recent renal regenerative medicine approaches. Current research directions include efforts to delay and deter acute and chronic kidney disease progression by exploiting the immune-modulatory and tissue regenerative properties of pharmacology agents, stem cells, and extracellular vesicles. Furthermore, advancement of novel technologies in the field of xenotransplantation, and transplantable devices are showing progress towards the design of de novo replacement organs. With integrated collaborations of multiple disciplinaries, improvements in novel technologies, and understanding of kidney disease progression, the field of renal regenerative medicine is progressing forward with promising therapeutic potential.

Purpose Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES. Methods We conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping. Results In 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype–phenotype correlation. Conclusion We conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.