Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study.

BACKGROUND: Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin (Hb) concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression. METHODS: Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at renal biopsy were identified: age 56 (45-63) years; 62.6% men; Hb 13.3 (12.0-14.5) g/dL; eGFR 76.2 (66.6-88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio 534 (100-1480) mg/g Crea. Serum Hb concentration was divided into quartiles: ≤12, 12.1-13.3, 13.4-14.5 and ≥14.6 g/dL. The association between serum Hb concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum Hb concentration to the known risk factors of DKD was assessed. RESULTS: Serum Hb levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ = -0.52; P < 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second and third quartile (the fourth quartile was reference) were 2.74 [95% confidence interval (CI) 1.26-5.97], 2.33 (95% CI 1.07-5.75) and 1.46 (95% CI 0.71-3.64), respectively. Addition of the serum Hb concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global Chi-statistics increased from 55.1 to 60.8; P < 0.001). CONCLUSIONS: Serum Hb concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease.

Association of coexisting anti-ribosomal P and anti-dsDNA antibodies with histology and renal prognosis in lupus nephritis patients.

OBJECTIVES: Anti-ribosomal P protein autoantibodies (anti-P) specifically develop in patients with systemic lupus erythematosus. Associations of anti-P with lupus nephritis (LN) histological subclass and renal outcome remain inconclusive. We sought to determine the association of anti-P and anti-double-stranded DNA antibody (anti-dsDNA) with renal histology and prognosis in LN patients. METHODS: Thirty-four patients with LN, having undergone kidney biopsy, were included. The 2018 revised ISN/RPS classification system was used for pathophysiological evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for > 3 months. RESULTS: Six patients (17.6%) were positive for anti-P and 26 (76.5%) for anti-dsDNA. Among the six patients with anti-P, one did not have anti-dsDNA, but did have anti-Sm antibody, and showed a histological subtype of class V. This patient maintained good renal function for over 14 years. The remaining five patients, who had both anti-P and anti-dsDNA, exhibited proliferative nephritis and were associated with prolonged hypocomplementemia, and the incidence of CKD did not differ from patients without anti-P. CONCLUSION: Although this study included a small number of patients, the results indicated that histology class and renal prognosis associated with anti-P depend on the coexistence of anti-dsDNA. Further studies with a large number of patients are required to confirm this conclusion.

Lower trabecular bone score is associated with an increased incidence of localized femoral periosteal thickening.

INTRODUCTION: Femoral localized periosteal thickening (LPT, also termed "beaking") of the lateral cortex often precedes an atypical femoral fracture (AFF). Bisphosphonate (BP) use, glucocorticoid use, and Asian race are major risk factors for developing such fractures. The aim of this study was to determine whether the trabecular bone score (TBS) reflecting the lumbar trabecular microarchitecture was related to LPT in glucocorticoid-treated Japanese patients with autoimmune diseases. MATERIALS AND METHODS: We retrospectively investigated 111 women with autoimmune diseases treated with prednisolone (PSL) who had undergone both femoral X-ray and dual-energy X-ray absorptiometry of the L1 - L4 lumbar vertebrae and for whom TBS could be evaluated for two or more of these. RESULTS: Femoral LPT was evident in the X-rays of 18 of 111 patients (16.2%). Higher body mass index (BMI), longer duration of PSL use and longer duration of BP use were significant in patients with LPT compared to those without. The TBS was significantly lower in patients with LPT than in those without (1.314 ± 0.092 vs. 1.365 ± 0.100, p = 0.044); however, the lumbar bone mineral density did not differ significantly (0.892 ± 0.141 vs. 0.897 ± 0.154 g/cm2, p = 0.897). TBS was significantly associated with LPT (odds ratio, 0.004; 95% CI, 0 - 0.96; p = 0.048), but not in the multivariate analysis including BMI, duration of PSL use and duration of BP use. CONCLUSIONS: The TBS was lower in glucocorticoid-treated Japanese women with autoimmune diseases with LPT than in those without LPT, and deteriorated trabecular microarchitecture influenced by longer use of BP and glucocorticoid might be associated with the development of LPT.

[Association between Immunotherapy with Immune Checkpoint Inhibitors(Anti-PD-1 Antibodies)and Intestinal Microbiota].

Immune checkpoint inhibitors(ICIs)are playing an increasingly important role in the treatment of cancer. In the field of lung cancer, ICIs are widely administered from primary therapy to maintenance therapy after chemoradiation for non-small cell lung cancer. However, excluding tumor proportion score(TPS)for PD-L1, no other biomarker has been reported to be clinically useful. While many biomarkers are being searched for, analysis of intestinal microbiota is attracting attention as a parameter that may reflect immune status. Research on the relationship between ICIs and gut microbiota has expanded worldwide after 2 reports in Science in 2015. In a study in which the gut microbiota of ICI-treated patients was transplanted into germ-free mice, enhanced antitumor effects were observed in the group that received gut microbiota from the response group, suggesting the possibility of stool transplantation. At the same time, when Akkermansia muciniphila, which is one of the mucin-degrading bacteria, was ingested by mice transplanted with non-responsive gut microbiota, a portion of tumor-infiltrating T cells increased on tumor localization, indicating the effect of changes in gut microbiota. In addition, there is a possibility that the anti-tumor effect may be enhanced by the effect of metabolites on immune cells in the blood rather than the gut microbiota itself, and the analysis of metabolites produced by bacteria is attracting attention. In our department, we have analyzed the intestinal microbiota of 25 non-small cell lung cancer patients treated with anti- PD-1 antibody. Although we have achieved diversity and identification of specific bacterial species, analysis of bacterial metabolites will be important in the future when considering the impact of the intestinal microbiota on immune cells. The gut microbiota is not only a biomarker for the treatment of ICIs, but also has the potential to create an immune state that facilitates the effects of ICI by changing the gut environment and metabolites.

High bisphosphonate treatment rates and the prevalence of atypical femoral fractures in patients with systematic lupus erythematosus: a single-center retrospective study performed in Japan.

Treatment of systemic lupus erythematosus (SLE) often continues with moderate-to-low doses of glucocorticoids for the long term. Bisphosphonates aid in the prevention and management of glucocorticoid-induced osteoporosis (GIOP). However, long-term use of bisphosphonates increases the relative risk of atypical femoral fracture (AFF) and the incidence is typically 16 or 113 per 100,000 person-years in patients treated with bisphosphonates for 5 or 10 years, respectively. Here, we explored bisphosphonate prescription rate and prevalence of AFF in patients with SLE. In total, 270 patients with SLE were enrolled. The Japanese Society for Bone and Mineral Research Guideline 2014 for GIOP management and treatment was used. We also explored AFF history through medical records. Most (n = 251) patients were recommended to treat by the GIOP guideline (scores ≥ 3); bisphosphonates, denosumab, teriparatide, or active vitamin D was prescribed for 85.7%. Bisphosphonates were currently used by 66.1% of the patients, and 65% had used them for ≥ 5 years. Of all patients, 76.7% had a history of bisphosphonate use, 5 of 270 (1.9%) had histories of AFF. Four of five patients with AFF had taken bisphosphonates for ≥ 3.5 years, in addition to moderate doses (≥ 10 mg/day) of glucocorticoids. For the SLE patients with a history of bisphosphonate use, the incidence of AFF was calculated to be 278 per 100,000 person-years. Our single-center study found that bisphosphonates were commonly used long term by Japanese patients with SLE. As AFF is not rare, AFF should be cared in patients with SLE.

Higher estimated net endogenous acid production with lower intake of fruits and vegetables based on a dietary survey is associated with the progression of chronic kidney disease.

BACKGROUND: Dietary acid load has been suggested to mediate the progression of chronic kidney disease (CKD). However, it is unclear what kinds of foods are actually associated with dietary acid load in patients with CKD. The self-administered diet history questionnaire (DHQ), which semi-quantitatively assesses the dietary habits of Japanese individuals through 150 question items, can estimate average daily intake of various foods and nutrients during the previous month. Using the DHQ, we investigated the association of dietary acid load with CKD progression. We also analyzed the kinds of food that significantly affect dietary acid load. METHODS: Subjects were 96 outpatients with CKD (average estimated glomerular filtration rate [eGFR], 53.0 ± 18.1 ml/min/1.73 m2) at Niigata University Hospital, who had completed the DHQ in 2011. We calculated net endogenous acid production (NEAP) from potassium and protein intake evaluated by the DHQ in order to assess dietary acid load. CKD progression was assessed by comparing eGFR between 2008 and 2014. RESULTS: NEAP was not correlated with protein intake (r = 0.088, p = 0.398), but was negatively correlated with potassium intake (r = - 0.748, p < 0.001). Reduction in eGFR from 2008 to 2014 was estimated to be significantly greater in patients with higher NEAP (NEAP > 50.1 mEq/day, n = 45) than in those with lower NEAP (NEAP ≤50.1 mEq/day, n = 50) by 5.9 (95% confidence interval [95%CI], 0.1 to 11.6) ml/min/1.73 m2. According to multiple logistic regression analysis, higher NEAP was significantly associated with lower intake of fruits (odds ratio [OR], 6.454; 95%CI, 2.19 to 19.00), green and yellow vegetables (OR, 5.18; 95%CI, 1.83 to14.66), and other vegetables (OR, 3.87; 95%CI, 1.29 to 11.62). CONCLUSIONS: Elevated NEAP could be a risk factor for CKD progression. Low intake of fruits and vegetables would increase dietary acid load and might affect the progression of renal dysfunction in Japanese CKD patients.

Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes.

Background: The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-term observations are limited. Methods: Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results: During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. Conclusions: This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients.

Nationwide multicenter kidney biopsy study of Japanese patients with hypertensive nephrosclerosis.

BACKGROUND: Nephrosclerosis is an increasingly reason for dialysis in Japan. However, kidney biopsy specimens for hypertensive nephrosclerosis are very limited; thus, the pathologic evaluation of hypertensive nephrosclerosis currently remains unclear. METHODS: Clinical and pathologic data of a total of 184 biopsy-confirmed hypertensive nephrosclerosis patients were collected from 13 centers throughout Japan. Seven pathological findings were assessed in this study. The outcomes of interest for this study were dialysis, composite kidney events, cardiovascular events, and all-cause mortality. RESULTS: The Green and Yellow (G&Y), Orange, and Red groups of the chronic kidney diseases (CKD) heat map contained 36, 57, and 91 cases, respectively. The mean observation period was 7.3 ± 5.2 (median, IQR; 6.1, 2.6-9.7) years. Global glomerulosclerosis (GScle), interstitial fibrosis and tubular atrophy (IFTA), arteriolar hyalinosis in Red exhibited higher scores than those in G&Y and Orange. The incidence rates of the composite kidney end points in 100 person-years for the G&Y, Orange, and Red groups were 1.42, 2.16, and 3.98, respectively. In the univariate Cox analysis for the composite kidney end points, GScle, IFTA and interstitial cell infiltration exhibited statistically significant high hazard ratios (1.18, 1.84, 1.69, respectively). However, after adjustment for clinical and medication data, the Red group in the CKD heat map category was risk factor for the composite kidney end points (HR 9.51). CONCLUSIONS: In summary, although pathologic findings had minor impacts on the prediction of composite outcomes in this study, the clinical stage of the CKD heat map is a good predictor of composite kidney events.

Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy.

BACKGROUND: The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. METHODS: The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy. RESULTS: The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m2/year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. CONCLUSIONS: This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

Decline in estimated glomerular filtration rate is associated with risk of end-stage renal disease in type 2 diabetes with macroalbuminuria: an observational study from JDNCS.

BACKGROUND: There is increased interest in surrogate endpoints for clinical trials of chronic kidney disease. METHODS: In this nationwide observational study of 456 patients with type 2 diabetes and clinically suspected diabetic nephropathy followed for a median of 4.2 years, we evaluated the association between estimated glomerular filtration rate (eGFR) and albuminuria at baseline or during follow-up and risk of ESRD. RESULTS: Low eGFR (<60 mL/min/1.73 m2) and macroalbuminuria at enrollment were independently associated with risk of ESRD. In patients with macroalbuminuria, both ≤-50% change and -50 to -30% change in eGFR over 1 and 2 years were predictive of ESRD. The higher cut point (≥50% decline in eGFR) was more strongly predictive but less common. Remission of macroalbuminuria to normo-/microalbuminuria at 1 and 2 years was associated with a lower incidence of ESRD than no remission; however, it was not a determinant for ESRD independently of initial eGFR and initial protein-to-creatinine ratio. CONCLUSION: These results suggest that a ≥30% decline in eGFR over 1 or 2 years adds prognostic information about risk for ESRD in patients with type 2 diabetes and macroalbuminuria, supporting the consideration of percentage decline in eGFR as a surrogate endpoint among macroalbuminuric cases in type 2 diabetes. On the other hand, our study suggests that additional analyses on the relationship between remission of macroalbuminuria and risk of ESRD are needed in type 2 diabetes.

Identification of hispidin as a bioluminescent active compound and its recycling biosynthesis in the luminous fungal fruiting body.

We previously showed that luminous fungi share a common mechanism in bioluminescence, and identified hispidin as a luciferin precursor in Neonothopanus nambi mycelium. Here we showed the presence of hispidin as a bioluminescent active compound at 25-1000 pmol g-1 in the fruiting bodies of Mycena chlorophos, Omphalotus japonicus, and Neonothopanus gardneri. These results suggest that luminous mushrooms contain hispidin as a luciferin precursor. We also found that non-luminous "young" fruiting bodies exhibited luminescence by hispidin treatment. Furthermore, we observed a gradual luminescence enhancement of the cell-free fruiting body extract by the addition of hispidin biosynthetic components, namely caffeic acid, ATP and malonyl-CoA. These findings suggest that continuous weak glow of luminous mushrooms is regulated by slow recycling biosynthesis of hispidin.

A new classification of Diabetic Nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy.

The Joint Committee on Diabetic Nephropathy has revised its Classification of Diabetic Nephropathy (Classification of Diabetic Nephropathy 2014) in line with the widespread use of key concepts such as the estimated glomerular filtration rate (eGFR) and chronic kidney disease. In revising the Classification, the Committee carefully evaluated, as relevant to current revision, the report of a study conducted by the Research Group of Diabetic Nephropathy, Ministry of Health, Labour and Welfare of Japan. Major revisions to the Classification are summarized as follows: (1) eGFR is substituted for GFR in the Classification; (2) the subdivisions A and B in stage 3 (overt nephropathy) have been reintegrated; (3) stage 4 (kidney failure) has been redefined as a GFR less than 30 mL/min/1.73 m(2), regardless of the extent of albuminuria; and (4) stress has been placed on the differential diagnosis of diabetic nephropathy versus non-diabetic kidney disease as being crucial in all stages of diabetic nephropathy.

Clinical impact of albuminuria and glomerular filtration rate on renal and cardiovascular events, and all-cause mortality in Japanese patients with type 2 diabetes.

BACKGROUND: The number of patients suffering from diabetic nephropathy resulting in end-stage kidney disease is increasing worldwide. In clinical settings, there are limited data regarding the impact of the urinary albumin-to-creatinine ratio (UACR) and reduced estimated glomerular filtration rate (eGFR) on renal and cardiovascular outcomes and all-cause mortality. METHODS: We performed a historical cohort study of 4328 Japanese participants with type 2 diabetes from 10 centers. Risks for renal events (requirement for dialysis or transplantation, or half reduction in eGFR), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), and all-cause mortality were assessed according to UACR and eGFR levels. RESULTS: During follow-up (median 7.0 years, interquartile range 3.0-8.0 years), 419 renal events, 605 cardiovascular events and 236 deaths occurred. The UACR levels increased the risk and the adjusted hazard ratios for these three events. In addition to the effects of UACR levels, eGFR stages significantly increased the adjusted hazard ratios for renal events and all-cause mortality, especially in patients with macroalbuminuria. Diabetic nephropathy score, based on the prognostic factors, well predicted incidence rates per 1000 patient/year for each event. CONCLUSIONS: Increased UACR levels were closely related to the increase in risks for renal, cardiovascular events and all-cause mortality in Japanese patients with type 2 diabetes, whereas the association between high levels of UACR and reduced eGFR was a strong predictor for renal events.

[Classification of Diabetic Nephropathy 2014].

The Committee on Diabetic Nephropathy revised the classification of diabetic nephropathy in view of the current status of eGFR and CKD in Japan. To make revisions for the classification of diabetic nephropathy 2014, the Committee carefully evaluated the report of the Research Group on Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. The major revisions made were as follows: 1. eGFR can be used for the evaluation of GFR; 2. In stage 3 (overt nephropathy), A and B were combined; 3. Stage 4 (renal failure) was defined as GFR less than 30 mL/min/1.73 m2, regardless of albuminuria; and 4. The importance of differential diagnosis was stressed in all stages.

Association between the initial physical activity and functional recovery after 1†month of inpatient rehabilitation for subacute stroke: stratified analysis by nutritional status.

Objectively measured physical activity volume serves as a predictive factor for functional recovery in patients with stroke. Malnutrition, a frequent complication of stroke, may influence the relationship between physical activity and functional recovery. This study aimed to examine the association between physical activity volume and functional recovery in patients with stroke, stratified by their nutritional status. This multicenter prospective observational study included 209 patients with stroke admitted to two Japanese convalescent rehabilitation hospitals. Participants were categorized based on the geriatric nutritional risk index (GNRI) at admission [≥92, high GNRI group ( n  = 133); <92, low GNRI group ( n  = 76)]. Physical activity levels were measured as the duration of total physical activity (TPA), which is the sum of light-intensity physical activity and moderate-to-vigorous physical activity, using a triaxial accelerometer during the first 7 days after admission. Outcome measures are represented as the relative gain of the motor score on functional independence measure (M-FIM effectiveness) during the first month after admission. The multiple regression analysis, adjusting for age, sex, comorbidity, onset to admission intervals, motor paralysis, initial M-FIM, and cognitive FIM, showed that the duration of TPA in the first 7 days was significantly associated with the M-FIM effectiveness over the first month in both low GNRI [ B  = 0.12, 95% confidential intervals (CI) = 0.01; 0.24, P  = 0.049] and high GNRI group ( B  = 0.11, 95% CI = 0.01; 0.21, P  = 0.027). This study demonstrates a positive predictive association between early TPA level and functional recovery in stroke patients, irrespective of their nutritional status.

Changes in daily intake of nutrients and foods including confectionery after the initiation of empagliflozin in Japanese patients with type 2 diabetes: a pilot study.

INTRODUCTION: It is unclear how dietary intake changes after sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is started in patients with type 2 diabetes. METHODS: We performed a non-controlled, open-label study that enrolled 51 patients with type 2 diabetes. The patients were newly administered empagliflozin, and their dietary habits were examined using a self-administered diet history questionnaire at the beginning of the study and after 24 weeks. We investigated the association of changes in HbA1c and body weight with changes in energy, nutrient, and food group intakes. RESULTS: At 24 weeks after the start of the study, HbA1c improved significantly and body weight decreased. In the food group, only the intake of confectionery increased, and there were no significant differences in the association between changes in HbA1c and body weight and changes in energy, nutrient, and food group intakes after 24 weeks. However, a significant negative correlation was found between change in HbA1c after 4 weeks and change in energy intake after 24 weeks, and principal component analysis showed an association between change in HbA1c levels after 4 weeks and change in energy intake and some food group intakes including confectionery after 24 weeks. CONCLUSION: In this study, after 24 weeks of treatment with empagliflozin, only intake of confectionery increased. Early assessment by dietitians after initiation of SGLT2i treatment might be important because our data suggested that the reduction in blood glucose levels after the start of empagliflozin was associated with a subsequent increase in energy intake. TRIAL REGISTRATION: University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on September 5, 2016 (registration ID, UMIN000002309|| http://www.umin.ac.jp/ctr/ ).

Japan Diabetic Nephropathy Cohort Study: study design, methods, and implementation.

BACKGROUND: Diabetic nephropathy, leading to end-stage renal disease, has a considerable impact on public health and the social economy. However, there are few national registries of diabetic nephropathy in Japan. The aims of this prospective cohort study are to obtain clinical data and urine samples for revising the clinical staging of diabetic nephropathy, and developing new diagnostic markers for early diabetic nephropathy. METHODS: The Japanese Society of Nephrology established a nationwide, web-based, and prospective registry system. On the system, there are two basic registries; the Japan Renal Biopsy Registry (JRBR), and the Japan Kidney Disease Registry (JKDR). In addition to the two basic registries, we established a new prospective registry to the system; the Japan Diabetic Nephropathy Cohort Study (JDNCS), which collected physical and laboratory data. RESULTS: We analyzed the data of 321 participants (106 female, 215 male; average age 65 years) in the JDNCS. Systolic and diastolic blood pressure was 130.1 and 72.3 mmHg, respectively. Median estimated glomerular filtration rate (eGFR) was 33.3 ml/min/1.73 m(2). Proteinuria was 1.8 g/gCr, and serum levels of albumin were 3.6 g/dl. The majority of the JDNCS patients presented with preserved eGFR and low albuminuria or low eGFR and advanced proteinuria. In the JRBR and JKDR registries, 484 and 125 participants, respectively, were enrolled as having diabetes mellitus. In comparison with the JRBR and JKDR registries, the JDNCS was characterized by diabetic patients presenting with low proteinuria with moderately preserved eGFR. CONCLUSIONS: There are few national registries of diabetic nephropathy to evaluate prognosis in Japan. Future analysis of the JDNCS will provide clinical insights into the epidemiology and renal and cardiovascular outcomes of type 2 diabetic patients in Japan.

A case of idiopathic nodular glomerulosclerosis successfully treated by intensive blockade of the renin-angiotensin-aldosterone system.

Idiopathic nodular glomerulosclerosis has a poor renal prognosis and is characterized by diffuse nodular glomerulosclerotic lesions in the absence of diabetic mellitus. Here, we report the case of a 69-year-old woman with no smoking history who developed renal dysfunction and proteinuria in the absence of overt diabetes or obesity. A biopsy specimen showed nodular mesangial sclerosis with arteriolar hyalinosis and severe large-vessel arteriosclerosis, leading to a diagnosis of idiopathic nodular glomerulosclerosis. Addition of esaxerenone to her existing renin-angiotensin-aldosterone inhibitor therapy led to a rapid decrease in the proteinuria levels and the maintenance of renal function without any complications for more than a year. The results suggest that intensive renin-angiotensin-aldosterone blockade might be an effective treatment for idiopathic nodular glomerulosclerosis.

Relationship between physical activity levels and changes in skeletal muscle characteristics in patients with stroke.

PURPOSE: This study aimed to investigate the relationship between physical activity (PA) levels and short-term changes in skeletal muscle characteristics in patients with subacute hemiparetic stroke. MATERIALS AND METHODS: This prospective observational study included 76 patients with stroke who received inpatient care in a convalescent rehabilitation ward. The PA level was measured as the duration of daily total PA (≥ 1.5 metabolic equivalents) using a triaxial accelerometer for 7 days after admission. The outcomes were changes in the quadriceps muscle quality and quantity on the affected and unaffected sides, as assessed by ultrasonography at admission and 1 month after admission. RESULTS: Multiple regression analysis indicated that the duration of total PA was significantly associated with a percentage change in quadriceps muscle quality (p = 0.011) and quantity (p = 0.012) on the affected side. However, no significant relationship was observed between the muscle quality and quantity on the unaffected side. CONCLUSIONS: The results revealed that PA was associated with changes in the quadriceps muscle quality and quantity on the affected side in patients with subacute hemiparetic stroke. These findings highlight the importance of promoting PA in stroke rehabilitation to improve muscle properties and functional outcomes.

Improving skeletal muscle quality and quantity is an important goal in post-stroke rehabilitation.We investigated physical activity and post-stroke changes in muscle properties.Physical activity is related to changes in muscle quantity and quality on the affected side.Promoting physical activity is essential for improving muscle quantity and quality on the affected side.