RESEARCH

INTRODUCTION

When treating patients, it is necessary to have the ability to see both the details and the whole picture with two eyes, as if you were looking at a tree and also seeing the forest. To cultivate this ability, we believe it is important to experience research, both basic and clinical, in which we conduct our hypothesis testing.
As shown in the figure below, we are focusing on various kidney diseases (diabetic nephropathy, acute kidney injury, nephrotic syndrome, lupus nephritis, hereditary kidney disease; renal coloboma syndrome), organ fibrosis, which is a common pathway of organ failure, and elucidation of kidney disease and systemic organ networks (infectious diseases, amino acids). We are also focusing on organ fibrosis, a common pathway of organ failure, and elucidation of kidney disease and systemic organ networks (infection, amino acids).

Diabetic nephropathy

We have conducted the following study as an official research team of the Japanese Society of Nephrology during the fiscal year of 2009-2017 (Primary investigator: Prof. Takashi Wada). 　1) Revised the classification of diabetic nephropathy. 　2) Made a manual for pathological diagnosis of diabetic nephropathy and hypertensive nephrosclerosis. 3) Made a guide for pathological diagnosis of diabetic nephropathy based on the classification. To improve the prognosis of diabetic nephropathy and diabetic kidney disease, we have been maintaining the Japan Diabetic Nephropathy Cohort Study (JDNCS) as a secondary study of J-RBR/J-KDR (*). We are conducting studies integrating clinical, pathological, biomarkers, and genome information. * J-RBR = Japan Renal Biopsy Registry, J-KDR = Japan Kidney Disease Registry

Acute kidney injury

AKI is a risk factor for all-cause mortality. We are researching focus on AKI recurrence. Recently, we reported that patients experiencing recurrent AKI before 21 days from the first AKI showed a poor prognosis (BMJ Open. 2019 Jun 16; 9 (6): e023259). In addition, as a basic research, we are examining the association with PAX2 gene involved in the development of kidney. PAX2 is a transcription factor necessary for kidney development. It has been reported that homozygous mutation of PAX2 is embryonic lethal. PAX2 mutation causes renal coloboma syndrome. There are still unknown points in this disease, and we aim to further elucidate the clinical condition through the association with AKI.

Nephrotic syndrome

Nephrotic syndrome is a kidney disorder that glomerular filtration is impaired, resulting in severe proteinuria, hypoalbuminemia and edema. The type of disease is classified by pathological diagnosis. In our department, we have examined more than 10,000 kidney tissue specimens for over 50 years. In addition to a long-term clinical course, we evaluate the renal pathology and examine the therapeutic effect and prognosis. In particular, we focus on long-term clinicopathological features of membranous nephropathy and therapeutic effects of LDL apheresis on refractory nephrotic syndrome including focal segmental glomerulosclerosis.

Lupus nephritis

Our department conducts clinical and basic research on systemic erythematosus (SLE). We have analyzed the clinical features of the patients with SLE and lupus nephritis. We participate in the PLEASURE-J study, which is the nationwide clinical research of SLE. We also have performed basic research with lupus model mice. Especially we are focusing on the relations of immune cells and autoimmune kidney injury. Moreover, we have explored the relationship between lysophospholipids and lupus nephritis.

hereditary renal disease: renal coloboma syndrome

Renal coloboma syndrome (RCS) which is known as genetic kidney disease is characterized by kidney hypoplasia or dysplasia and abnormality of the optic nerve. Approximately 400 cases have been reported in the world. In our laboratory, we have accumulated the more than 30 cases by focusing on clinical phenotype. PAX2 gene is one of the main genetic abnormalities of RCS. The phenotype of RCS patients with PAX2 gene mutation were more severe than that without PAX2 gene mutation. We reported that KIF26B is a novel causative gene of RCS. Furthermore, we established RCS derived iPS cells. We are analyzing the role of PAX2 genes in human kidney development and pathophysiology of RCS.

Organ fibrosis

Organ fibrosis is one of common pathways for organ fibrosis. Renal fibrosis is also a common pathway to result in renal fibrosis with any etiologies. We have been investigating mechanisms to develop fibrosis focusing on cells and humoral mediators. We have identified new type of bone marrow-derived cells to induce fibrosis, therefore we have been checking their impact for organ fibrosis. In addition, we have been the role of signal transductions associated with lipid mediator and pro-fibrotic molecules, such as lysophosphatidic acid and transforming growth factor-beta. Our goal is to establish the ways available in clinical settings including diagnostic tools and therapeutic targets.

Infectious disease

Infectious disease may cause the subsequent peripheral organ damages, including kidney injury. Although the host factor, such as immune compromised status, contributes to the pathogenesis of infection, it is not clear whether bacterial factor has impacts on peripheral organ damages. We have been investigating the pathophysiology of infectious disease, especially kidney injury with a focus on bacterial gene information.

Amino acid

Proteins, which are constituents of all organs, are made from amino acids. Amino acids have two optical isomers. D-amino acids (D-form) and L-amino acids (L-form). Amino acids identified in D- and L-forms are called chiral amino acids. The amino acids necessary for human life activities have long been considered to be L-forms, but in recent years it has become clear that D-forms also play important roles. We are trying to elucidate the biological network mechanism of the kidney and systemic organs through this chiral amino acid, especially D-amino acid. We are researching the clinical application of novel kidney disease biomarkers and therapeutic agents using D-amino acids in the future.