Toward Combinatorial Strategies to Improve Proximal Tubule Recovery Following Acute Kidney Injury.

Maintaining kidney health throughout the human lifespan remains a significant global challenge. Worldwide, an estimated 850 million people have some level of kidney disease, with many unaware because of asymptomatic progression. Whether initiated by acute or chronic insults, renal injury and disease can have life-threatening consequences requiring interventions spanning the gamut of supportive care to kidney replacement therapies. Design of precision therapeutics is likely to benefit from understanding the heterogenous cell types and states that arise in the context of kidney injury and disease. Here we review an array of cellular states that have been detected following acute ischemic kidney injury, hypothesized to promote transition to chronic kidney disease. We focused on studies describing the cellular states of the proximal tubule (PT), a segment of the nephron most vulnerable to ischemic injury. PT cells have been shown in preclinical animal studies to have a heterogeneous response to ischemic injury, including repaired and failed-repair cellular states, inter alia. We end by discussing targeting these cellular states and/or pathological processes.