Pathogenesis and Treatment of Chronic Kidney Disease: A Review of Our Recent Basic and Clinical Data

Abstract

Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. At end of 2013, over 300,000 Japanese patients had maintenance dialysis therapy (JSDT). In Japan, the major causes of end stage kidney disease (ESKD) are chronic glomerulonephritis (particularly IgA nephropathy), type 2 diabetic nephropathy, and hypertensive nephrosclerosis. Hypertension is a major factor driving the progression of CKD to ESKD. Since many features of the pathogenesis of IgA nephropathy are still obscure, specific treatment is not yet available. However, efforts by investigators around the world have gradually clarified different aspects of the pathogenesis and treatment of IgA nephropathy. Today, around half of all diabetic patients in Japan receive medical treatment. Type 2 diabetic nephropathy is one of the major long-term microvascular complications occurring in nearly 40% of Japanese diabetic patients. The pathogenesis of diabetic nephropathy involves both genetic and environmental factors. However, the candidate genes related to the initiation and progression of the disorder are still obscure in patients with diabetic nephropathy. Regarding environmental factors, the toxicity of persistent hyperglycemia, reactive oxygen species, systemic and/or glomerular hypertension, dyslipidemia and complement are considered to play an important role. The first part of this review covers the pathogenesis of IgA nephropathy and type 2 diabetic nephropathy, and combines the clinicopathological findings in patients with our research on the ddY and KKA-y mouse models (spontaneous animal models for IgA nephropathy and diabetic nephropathy, respectively). In Japan, the major renal replacement therapies (RRT) are peritoneal dialysis (PD) and hemodialysis (HD). The second part of this review focuses on PD and HD. Based on our research findings from patients and as well as from animal models, we discuss strategies for the management of patients on PD and HD. i 2015 S. Karger AG, Basel

Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy

“…IgAN is recognized as the most common form of primary glomerulonephritis in developed countries, and remains an important cause of end-stage renal disease [24,25]. However, the mechanism of IgAN is still unknown.…”

Association of <b><i>Interleukin-10</i></b> Polymorphisms (rs1800872, rs1800871, and rs1800896) with Predisposition to IgA Nephropathy in a Chinese Han Population: A Case-Control Study

“…A retrospective study in Czech IgAN patients show that GFR, hypertension and proteinuria are vital factors associated with the prognosis of IgAN [7]. A review by Tomino also states complement activation, podocyte injury and mast cell infiltration may affect diseases activity, development and progression in patients with IgAN [8]. Additionally, Wang et al indicates that thapsigargin may be candidate drugs in treatment of IgAN [9].…”

Analysis of the Relationship Between Renal Remodeling and Vascular Adhesion-1 Protein (Vap-1) in Chronic Primary Glomerulonephritis

“…Объяснением полученных данных, вероятно, явля-ется установленная высокая частота встречаемости увеличенных концентраций белка сосудистой адге-зии-1 у пациентов с IgA-нефропатии, протекающей в большинстве случаев с нефритическим синдромом. Морфологические изменения IgA-нефропатии свя-заны с активным иммунокомплексным воспалением, затрагивающим, главным образом, мезангиальную область (расширение мезангиума, пролиферация и гиперклеточность), с отложением воспалительных, гранулярных депозитов [10]. Данные изменения укладываются в патологические процессы, происхо-дящие при повышении концентрации VAP-1.…”