Diabetic nephropathy is one of the most frequent complications in type 1 and type 2 diabetes and the leading cause of chronic kidney disease (CKD) in patients starting renal replacement therapy in developed countries. Early detection along with multifactorial treatments, such as blood glucose control with sodium glucose cotransporter 2 inhibitors and blood pressure control with renin-angiotensin system blockers, are of particular importance to prevent disease progression and reduce mortality. In clinical settings, diabetic nephropathy is typically diagnosed by detecting microalbuminuria, the earliest indicator of this disease, in patients with diabetes for whom other causes of albuminuria are absent. However, recent renal biopsy based studies have demonstrated that albuminuria is neither a specific nor a sensitive biomarker for the development of diabetic nephropathy.
The classical diabetic nephropathy is characterized by the progressive increase of albuminuria from normoalbuminuria to microalbuminuria and macroalbuminuria, declining glomerular filtration rate (GFR), and eventual end-stage renal disease. However, the clinical course of diabetic nephropathy has changed profoundly in recent years, due to the diversification of diabetes, therapeutic successes, as well as an aging population. Indeed, CKD attributable to diabetes which runs an atypical clinical course (i.e., so-called non-albuminuric renal function decline) has increased over the past decades.
The paradigm shift from albuminuria-based to GFR-based kidney disease results in a new concept of diabetic kidney disease (DKD). This review article describes the concept of DKD, and differences between classical diabetic nephropathy and DKD.
The prevalence of patients with type 2 diabetes mellitus (T2DM) continues to increase. One primary concern in the patients with T2DM is the development of various complications, including retinopathy, nephropathy, neuropathy, myocardial infarction, and stroke; their prevention is the main treatment goal in T2DM. Furthermore, the frequencies of dementia, sarcopenia, and cancer are also higher in elderly patients with T2DM. Numerous clinical trials reveal that improving glycemic control can mitigate complications. In addition, hypoglycemia is associated with increased rates of dementia and cardiovascular death.
Over the last several decades, the treatment strategies for T2DM have changed with the improved understanding of the underlying pathophysiology and the development of many glucose-lowering drugs. Sulfonylureas and glinides promote the secretion of insulin, α-glucosidase inhibitors suppress the absorption of glucose from the intestinal tract, biguanides suppress the hepatic production of glucose, and thiazolidinediones improve the action of insulin in the liver and muscles. Additionally, dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists promote the secretion of insulin in a glucose-dependent manner, whereas sodium glucose cotransporter 2 inhibitors reduce glucose reabsorption in the proximal renal tubules and urinary glucose excretion. Sulfonylureas are prone to precipitate hypoglycemia in patients with renal dysfunction. It is important for patients to understand the symptoms of hypoglycemia for appropriate resolution.
Appropriate selection of glucose-lowering drugs based on the condition of the individual patient is necessary for better control of the onset and the progression of complications and to achieve better glycemic control without causing hypoglycemia.
Recently, low-carbohydrate diet (LCD) is becoming popular among diabetes patients due to its efficacy in glycemic and body weight control. While LCD might lead to excess intake of protein and lipid, a low-protein diet (LPD) has been recommended to preserve renal function in advanced renal stages. Thus, diabetes patients on LCD are forced to change their diet therapies in accordance with deterioration of renal function. Additionally, the reno-protective effect of LPD on DKD is controversial because several clinical trials regarding efficacy of LPD failed to show conclusive results. This might be associated with the difﬁculty to adhere to a daily LPD and the insufﬁciency of clinical data regarding the optimal amount of restricted protein intake. Exercise therapy as well as diet is important for better glycemic control. Mild exercise therapy such as walking in patients with DKD has been recommended. However, intensity of exercise needs to be determined considering the severity of other micro and macrovascular complications.
Diabetic vascular complications include not only kidney disease but also retinopathy, neuropathy, stroke, angina pectoris, myocardial infarction, and foot gangrene. The definition of diabetic kidney disease (DKD) includes, in addition to classical diabetic nephropathy, atypical diabetes-related nephropathy in which renal function declines without albuminuria. Therefore, it is necessary to regularly assess the estimated glomerular filtration rate together with the level of albuminuria for early detection and treatment of DKD. In addition to lifestyle modifications and diet therapy, comprehensive treatment for hypertension, hyperglycemia, and hyperlipidemia, as well as multidisciplinary team medical care are important to achieve the goal of preventing DKD aggravation.
IgA nephropathy (IgAN) is characterised by the deposition of IgA in the glomerular mesangium and is the most commonly reported primary glomerulonephritis worldwide. Thirty to forty percent of patients with IgAN develop progressive renal function decline, requiring renal replacement therapy within two decades of diagnosis. Development of a curative treatment and strategies for early diagnosis and treatment are necessary. Renal biopsy is the gold standard for the diagnosis and assessment of disease activity. Therefore, reliable biomarkers are needed for the non-invasive diagnosis of this disease and to more fully delineate the risk for progression. For the pathogenesis of IgAN, it is now widely accepted that multi-hit hypothesis, including production of galactose-deficient IgA1 (Gd-IgA1)(1st hit), and IgG autoantibodies that recognize Gd-IgA1 (2nd hit) and their subsequent immune complex formation (3rd hit) and glomerular deposition (4th hit). Although the prognostic values of several biomarkers have been discussed, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of Gd-IgA1 and Gd-IgA1 contained immune complexes. In addition, urinary Gd-IgA1 may represent a disease-specific biomarker of IgAN. We also confirmed a significant correlation between serum levels of these effector molecules and disease activity, suggesting that each can be considered as a practical surrogate marker of therapeutic response. A better understanding of the molecular basis of the pathogenesis of IgAN will likely result in disease-specific serum and urinary biomarkers. Thus, these disease-oriented specific biomarkers may be useful for screening of potential IgAN with isolated hematuria, earlier diagnosis, disease activity, and eventually, response to treatment.
Objective: The purpose of this study was to evaluate the relationship of freestyle swimming performance between adolescence and adult Japanese top-class swimmers.
Methods: The 234 males and 134 females ranked in the top 100 records of 50, 100, 200 and 400 m freestyle short-course performances of over 22 years old during 2016 to 2018 (latest TIME), and their season best performances during 2006 to 2017 were analyzed. All data were collected from the public database “Swimrecord.com” by Japan Swimming Federation. Performance maturity status was determined by the ratio of each age record to the latest TIME and the relationship between the latest TIME and each age record was evaluated. Also, the subjects were divided into the upper or lower group with reference to the latest TIME and the developmental changes of performance were compared between the groups.
Results: The performance maturity status was higher in females than males at each age. The correlation between the latest TIME and each age record became gradually stronger from males aged 17 years and females aged 14 years, but there was no clear correlation in the previous records. There was no difference in developmental changes in performance between the upper and lower groups in both males and females.
Conclusions: The longitudinal analysis of the swimming performance in the growth period reveals that the Japanese top-class swimmers show high performance before 12 years old and that the time to approximate peak performance appeared earlier in females than in males and the relationship is different depending on swimming distance.
Objective: Acupuncture at acupoint Shenmen (HT7) is used for the treatment of neuropsychological disorders, such as anxiety disorders, in oriental medicine. In the present study, to elucidate the influence of HT7-acupuncture on the reduction of fear memory, we examined freezing responses in contextual fear-conditioned mice with or without acupuncture treatment at HT7.
Materials and Methods: Adult male C57BL/6J mice were subjected to electric foot-shock, which represents a common animal model of post-traumatic stress disorder (PTSD), in a foot-shock cage. The mice were then immediately returned to their home cages and randomly divided into two groups, an HT7 and a sham groups. In the HT7 group, 30 seconds of bilateral acupuncture at HT7 was applied for 7 consecutive days. We then placed the mice from both groups either in their home cages or in the foot-shock cage and observed their freezing behavior for 2 minutes.
Results: In the home cage, HT7 and sham mice displayed almost no freezing responses. In the foot-shock cage, in contrast, the sham group showed freezing responses for 51.3±16.7% in 2 minutes, indicating that in these mice, fear memory was strongly maintained even after 1 week. Surprisingly, the freezing responses of the HT7 group mice in the foot-shock cage were significantly lower, at 25.7±14.9% in 2 minutes.
Conclusions: These findings suggest that acupuncture treatment at HT7 might be effective in reducing fear memories in PTSD.