From Patient to Dish and Back Again

Chronic kidney disease affects significant parts of the general population, and novel treatment strategies are warranted. In this issue, Lazzeri et al.1 explore the use of exfoliated cells in the urine of children affected by proteinuric kidney diseases for diagnostic and therapeutic purposes (from patient-to-dish-to-patient). The authors investigate whether the isolated cells represent putative renal progenitor cells (RPCs) and test whether they are similar to a previously isolated putative progenitor population. They find that both cell populations ameliorate doxorubicin-induced nephritis in severe combined immunodeficiency mice. The controversial identity of the isolated cells and their potential use for diagnostic purposes or stem cells therapy are discussed. Chronic kidney disease affects an estimated 5% of the general population. It represents a major risk factor for cardiovascular disease and increased mortality at least as potent as smoking or arterial hypertension. Glomerular diseases are still the most common causes of ESRD. It is time to translate recent advances in our understanding of glomerular diseases into novel improved diagnostic and therapeutic strategies. Several approaches can be used. One is to search for unique intrinsic cells depending on specific signaling pathways, which can be manipulated by specific pharmacologic interventions in situ/in vivo. Alternatively, renal cell populations can be isolated to then be used for diagnostic purposes. Moreover, isolated cells can be expanded in culture and/or manipulated to then be returned back into the diseased organism (i.e., from patient to dish to patient). In this issue of JASN, this latter strategy was explored by Lazzeri et al.1 The authors established cultures of rare exfoliated cells from the urine of children affected by different proteinuric disorders of the kidney. The authors noted that cultured cells expressed a certain combination of markers (CD133+, CD24+, CD106+ [VCAM–1], and uroplakin III negative). In addition, cells coexpressing this combination of markers showed a higher proliferative index and expressed RNA transcripts similar to previously isolated cultures of adult parietal epithelial multipotent progenitor cells (APEMPs). The authors propose that the cultured cells represent the previously postulated fixed intrinsic population of progenitor cells (urinary renal progenitor cells [u-RPCs]).2 To substantiate this, the authors repeated an experiment where doxorubicin-induced renal disease in immunodeficient severe combined immunodeficiency mice was treated by intravenous injection of human APEMPs, u-RPCs, or cultured cells expressing other markers.2 Only the APEMPs and u-RPCs engrafted into the kidney and ameliorated proteinuria. In addition, the u-RPCs engrafted to regenerate podocytes and proximal tubule cells. Finally, the authors explored the tool of cultured u-RPCs for personalized investigations of genetic kidney disorders. They found that u-RPCs from patients with homozygous podocin mutations expressed lower levels of podocin. In a patient with a mutated LMX1B gene, authors found that filamentous actin distribution was altered in cultured u-RPCs. The authors concluded that u-RPCs represent an innovative tool to investigate genetic kidney disorders in more detail.