Yasuhiko Tomino

The Prevalence and Management of Diabetic Nephropathy in Asia

Background: Diabetic nephropathy (DN), especially type 2 diabetes, is now increasing rapidly worldwide, also in Asian countries, and is one of the major long-term vascular complications. The pathogenesis of DN involves both genetic and environmental factors. Around 30-40% of type 2 diabetic patients develop DN despite strict blood glucose and/or blood pressure control. Although it is considered that the genetic background may influence the initiation and progression of DN, the candidate genes are still obscure. Summary: To search for genes that are involved in the susceptibility of DN, a candidate gene approach was taken in the beginning before the development of genome-wide association studies. Although a candidate gene approach can detect rare genetic variants, in advance we need known or presumed pathophysiological knowledge of the specific gene. Investigations using spontaneous animal models are important to determine the pathogenesis and treatment of DN patients. There are many spontaneous animal models, such as the NOD and Akita mice for type 1 diabetes and the Ob/Ob, db/db, Tsumura Suzuki Obese Diabetics, and KK-Ay mice for type 2 diabetes. Furthermore, the toxicity of persistent hyperglycemia, the activation of reactive oxygen species, systemic and/or glomerular hypertension, microinflammation, dyslipidemia, and other factors are considered to play important roles. Diabetic patients with normoalbuminuria and normal renal function showed typical histological patterns of DN. The discovery of a specific and reliable diagnostic and prognostic biomarker other than albuminuria is urgently needed and indispensable. Since large clinical trials of oral hypoglycemic drugs in renal failure are lacking, these recommendations will need to be regularly updated after results of larger randomized trials with longer follow-up durations are available. Key Messages: It is necessary to summarize the basic and clinical features of DN patients in Asia and to use these for the treatment of such patients. Facts from East and West: The prevalence of DN is increasing in Asia and Western countries alike. The deletion (D) allele of the angiotensin-converting enzyme gene is associated with progression to end-stage renal disease in Asian patients with DN, but this association is uncertain in Europeans. An association between DN and polymorphism of the gene coding for acetyl coenzyme A carboxylase β has been reported in Asian and Western populations. Both in Japan and the US, criteria for diagnosis are a 5-year history of diabetes and persistent albuminuria. Renal biopsy should be done in patients with severe hematuria, cellular casts and - in the US - hepatitis and HIV to rule out other pathologies. Diabetic retinopathy is considered a key criterion in Japan, but the absence of it does not rule out DN in the US. Enlargement of the kidney is observed as a diagnostic criterion in Japan. The differential use of renal biopsy as diagnostic tool might account for a different prevalence between Asian countries. Some Japanese diabetic patients showed typical histological alterations for DN with a normal ACR and GFR. The clinical classification is similar between Japan and the US including five stages based on ACR and GFR. The Japanese guidelines do not include blood pressure values for the classification of DN. Guidelines for DN treatment are evolving quickly both in Asia and Western countries based on the numerous clinical trials performed worldwide. Targeting the angiotensin system for its hemodynamic and nonhemodynamic effects is a common approach. DPP-4 inhibitors are widely used in Japan and might have a higher glucose-lowering effect in Asian patients due to their specific diet. A randomized, double-blind placebo-controlled study has been launched to assess the efficacy of the Chinese herbal tea extract Shenyan Kangfu in DN.

Chronological Change of the Serum IgA/C3 Ratio Indicates the Efficacy ofTonsillectomy for IgA Nephropathy

Background/aims: Although the serum IgA/C3 ratio is a good biomarker to predict the diagnosis, histological findings, and prognosis of IgA nephropathy (IgAN), the chronological change of the IgA/C3 ratio has not been discussed. The present study evaluates the chronological change of the IgA/C3 ratio. Methods: The serum IgA/C3 ratio of 43 IgAN patients was measured at the time of biopsy and on the nearest consultation day in an outpatient clinic since April 30th, 2014. The change rate of the serum IgA/C3 ratio (âx8a?IgA/C3/ year) was calculated. The correlation between âx8a?IgA/C3/year and other parameters, including the change rate of serum creatinine (âx8a?Cr/year), clinical and histological grades, and the risk stratification for end-stage kidney disease (ESKD) in IgAN patients determined by Japanese Society of Nephrology (JSN). Results: The patients with tonsillectomy had a smaller âx8a?IgA/C3/year than those without tonsillectomy. âx8a?IgA/C3/ year was positively correlated with âx8a?Cr/year. âx8a?IgA/C3/year decreased along with the severity of histological grade, clinical grade, and ESKD risk. The patients with a combination of tonsillectomy and steroid pulse therapy show a strong down-regulation of âx8a?IgA/C3/year and conserved their renal function. A multiple regression analysis revealed that significant enhancers for âx8a?IgA/C3/year are tonsillectomy and ESKD risk grade 3, and that those for âx8a?Cr/year are tonsillectomy, steroid therapy, and the clinical grade. Conclusion: The serum IgA/C3 ratio does not only show the activity of IgAN, but also the chronological change of the IgA/C3 ratio indicates the efficacy of tonsillectomy for IgAN patients.