Naonori Kumagai

We report a case of tubulointerstitial nephritis with uveitis (TINU) diagnosed from isolated glucosuria detected during school urinary screening. The patient was a 12-year-old girl in whom glucosuria was detected during school urinary screening using a dipstick; however, urinary protein and occult blood were negative. There were no preceding symptoms of infection or medication. The patient visited the Fujita Health University Okazaki Medical Center two weeks after the school urinary screening for further examination. No edema or skin rash was observed. A urine test showed urinary glucose was positive and urinary β2-microglobulin was high; other values were almost normal. Mild renal dysfunction was observed. There was no hyperglycemia or high HbA1c level; therefore, diabetes mellitus was ruled out. Various autoantibody tests were negative, and the angiotensinogen-converting enzyme level was within the normal range. The patient was clinically diagnosed with idiopathic tubulointerstitial nephritis without a renal biopsy. Renal dysfunction tended to improve gradually after the first visit. Three months after the first visit, conjunctival congestion appeared in the right eye, and the patient was diagnosed with uveitis and eventually with TINU. When performing detailed examinations for urinary glucose, it is necessary to differentiate kidney disease as well as diabetes mellitus. Moreover, it is necessary to recognize that even if the urine dipstick test is negative for protein, it may be positive for low-molecular-weight protein.

To maintain the oxygen supply, the production of red blood cells (erythrocytes) is promoted under low-oxygen conditions (hypoxia). Oxygen is carried by hemoglobin in erythrocytes, in which the majority of the essential element iron in the body is contained. Because iron metabolism is strictly controlled in a semi-closed recycling system to protect cells from oxidative stress caused by iron, hypoxia-inducible erythropoiesis is closely coordinated by regulatory systems that mobilize stored iron for hemoglobin synthesis. The erythroid growth factor erythropoietin (EPO) is mainly secreted by interstitial fibroblasts in the renal cortex, which are known as renal EPO-producing (REP) cells, and promotes erythropoiesis and iron mobilization. Intriguingly, EPO production is strongly induced by hypoxia through iron-dependent pathways in REP cells. Here, we summarize recent studies on the network mechanisms linking hypoxia-inducible EPO production, erythropoiesis and iron metabolism. Additionally, we introduce disease mechanisms related to disorders in the network mediated by REP cell functions. Furthermore, we propose future studies regarding the application of renal cells derived from the urine of kidney disease patients to investigate the molecular pathology of chronic kidney disease and develop precise and personalized medicine for kidney disease.