Tubular injury and interstitial fibrosis are the hallmarks of chronic kidney disease. While recent studies have verified that proximal tubular injury triggers interstitial fibrosis, the impact of fibrosis on tubular injury and regeneration remains poorly understood. We generated a novel mouse model expressing diphtheria toxin receptor on renal fibroblasts to allow for the selective disruption of renal fibroblast function. Administration of diphtheria toxin induced upregulation of the tubular injury marker Ngal and caused tubular proliferation in healthy kidneys, whereas administration of diphtheria toxin attenuated tubular regeneration in fibrotic kidneys. Microarray analysis revealed down-regulation of the retinol biosynthesis pathway in diphtheria toxin-treated kidneys. Healthy proximal tubules expressed retinaldehyde dehydrogenase 2 (RALDH2), a rate-limiting enzyme in retinoic acid biosynthesis. After injury, proximal tubules lost RALDH2 expression, whereas renal fibroblasts acquired strong expression of RALDH2 during the transition to myofibroblasts in several models of kidney injury. The retinoic acid receptor (RAR) RARg was expressed in proximal tubules both with and without injury, and aBcrystallin, the product of an RAR target gene, was strongly expressed in proximal tubules after injury. Furthermore, BMS493, an inverse agonist of RARs, significantly attenuated tubular proliferation in vitro. In human biopsy tissue from patients with IgA nephropathy, detection of RALDH2 in the interstitium correlated with older age and lower kidney function. These results suggest a role of retinoic acid signaling and cross-talk between fibroblasts and tubular epithelial cells during tubular injury and regeneration, and may suggest a beneficial effect of fibrosis in the early response to injury.Kidney International (2019) 95, 526-539; https://doi.

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Onco-nephrology is a new and evolving subspecialized area in nephrology that deals with kidney diseases in cancer patients. As many newer cancer therapies emerge in the field of oncology, cancer patients are surviving longer than ever before. However, the benefits of the remarkable advances in cancer management have not been fully appreciated. Not only is cancer often associated with abnormalities that affect the kidney, but cancer therapy often leads to both acute and chronic kidney diseases. The development of cancer-associated kidney complications is associated with poor prognosis, whereas prompt recognition and treatment initiation are associated with improved outcomes in this population. Therefore, both nephrologists and oncologists should be familiar with the diagnosis and management of cancer-associated kidney complications. Another unique aspect of onco-nephrology is that significant improvements in predialysis and dialysis care in recent years have led to prolonged survival and a higher incidence of patients with chronic kidney disease suffering from cancer. Therefore, research is urgently needed to establish treatment for patients with chronic kidney disease. This update addresses the pathophysiology and treatment of various cancer-associated kidney complications, and highlights cancer treatment for patients with chronic kidney disease.

Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

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