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Summary Aims We assessed the potential efficacy and safety of propagermanium (PG), an organic compound that inhibits the C–C chemokine receptor type 2, administration in patients with type 2 diabetes and nephropathy. Furthermore, we assessed the feasibility of future studies. Materials and methods We recruited patients from nine medical institutions in Japan for this randomized, open‐label, parallel two‐arm pilot trial. Inclusion criteria were diagnosis of type 2 diabetes, age 30‐75 years, dipstick proteinuria of ≥1+ or urinary albumin‐to‐creatinine ratio (UACR) of ≥30 mg/g and estimated glomerular filtration rate of ≥30 mL/min/1.73 m2. Patients were randomly assigned (1:2) using a minimization algorithm to either continuing usual care or concomitant administration of 30 mg PG per day for 12 months. The primary outcome was the change in UACR from baseline to 12 months. We also collected safety information for all patients who received at least one dose of PG. Results We enrolled 29 patients, 10 were assigned to continue usual care and 19 to receive PG. Changes in UACR by PG in addition to the usual care were 25.0% (95% CI −20.4%, 96.5%, P = .33). No severe adverse events or renal events were observed during the study. Conclusion Although the treatment with PG was generally well tolerated, the dosage of 30 mg/d for 12 months did not reduce albuminuria when used in addition to usual care in patients with type 2 diabetes and nephropathy. Efficacy of PG should be verified in future definitive trials., We assessed the potential efficacy and safety of propagermanium (PG), an organic compound that inhibits the C–C chemokine receptor type 2, administration in patients with type 2 diabetes and nephropathy. Changes in albuminuria by PG in addition to the usual care were 25.0% (95% CI −20.4%, 96.5%, P = .33). No severe adverse events or renal events were observed during the study.

A decreased response to erythropoiesis-stimulating agents (ESAs) leads to refractory anemia and worse prognosis in patients with chronic kidney disease. We examined the association between autoantibodies to the erythropoietin receptor (EPOR) and responsiveness to ESAs in patients on maintenance hemodialysis. A total of 108 Japanese patients on maintenance hemodialysis at three institutions were enrolled. Sera from these patients were screened for anti-EPOR antibodies using an enzyme-linked immunosorbent assay. An ESA resistance index (ERI) was calculated, and patients in the highest ERI quartile were defined as ESA hyporesponsive. Anti-EPOR antibodies were detected in 11 patients (10%). Body mass index and hemoglobin, platelet, magnesium, and ferritin levels decreased with higher ERI levels. On the other hand, C-reactive protein (CRP) levels and the prevalence of anti-EPOR antibodies increased with higher ERI levels. In multivariate analysis, the presence of anti-EPOR antibodies together with CRP was a significant risk factor for ESA hyporesponsiveness. Anti-EPOR antibodies were detected in patients on maintenance hemodialysis, and these autoantibodies were independent factors for hyporesponsiveness to ESAs in these patients.

There is increased interest in surrogate endpoints for clinical trials of chronic kidney disease. 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. Low eGFR (

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.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.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.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.

金沢大学保健管理センター, 金沢大学大学院医学系研究科, 金沢大学附属病院, Background: In hemodialysis patients, adynamic bone disease has been reported to be closely associated with low levels of parathyroid hormone (PTH) due to exposure to high levels of serum calcium following the administration of calcium carbonate (CaCO3) or vitamin D agents. This study was conducted to clarify the therapeutic effect of a non-calcemic phosphate binder, sevelamer hydrochloride (sevelamer), for hypoparathyroidism in hemodialysis patients with or without diabetes mellitus. Methods: Based on entry criteria, 40 Japanese chronic hemodialysis patients (22 males and 18 females with a mean age of 60.6, 14 diabetic patients and 26 non-diabetic patients) were switched from CaCO3 to sevelamer for 48 weeks. Serum calcium, phosphate, intact (i) PTH and PTH-(1-84) were analyzed. Bone remodeling activity was evaluated by determining intact osteocalcine (iOC), bone-specific alkaline phosphatase (BAP). Results: The switch from CaCO3 to sevelamer significantly decreased the serum levels of calcium, resulting in the elevation of iPTH levels from 31±18 pg/mL to 95±96 pg/mL by 48 weeks. In contrast, serum phosphate levels remained similar to those in patients with CaCO3 treatment. Concomitantly, the levels of BAP and iOC were elevated. Further, these beneficial effects on bone turnover were observed in both diabetic and non-diabetic patients. Conclusion: Sevelamer reduced the calcium concentration and thereby increased PTH levels, resulting in the improvement of markers of bone turnover. The administration of sevelamer is of therapeutic benefit for the improvement of bone remodeling activity even in hemodialysis patients with diabetes. © 2007 The Japanese Society of Internal Medicine.

維持血液透析症例における二次性副甲状腺機能亢進症に対する22-oxacalcitrlol (OCT) の投与量および骨代謝に与える影響を, intact-PTH (iPTH) で層別して検討した. 対象は金沢大学およびその関連施設の714症例より無作為に抽出したiPTHが150pg/mL以上, 血清補正Caが11mg/dL未満かつCa×P積が70mg2/dL2以下の59例 (男性40例, 女性19例, 年齢57.4±15.4歳) であり, iPTHにより3層 (I:150pg/mL以上300pg/mL未満, II: 300pg/mL以上500pg/mL未満, III:500pg/mL以上) に分類し, 各層それぞれ経口ビタミンD3 0.25μg/日 (IA), OCT 2.5μg (IB, IIA), 5μg (IIB, IIIA), 10μg (IIIB) 週3回の2群に分類した. 治療開始前, 治療開始4, 12週後および最終観察時 (平均19.7±7.8か月) での治療効果および骨形成マーカーの検討を行った. 血清iPTHは437±31pg/mLより最終観察時には256±28pg/mLへと低下した (p

Glomerular injury caused by injection of heterologous anti-glomerular basement membrane antibodies (anti-GBM Ab) is increased in rats pretreated with small doses of bacterial lipopolysaccharide (LPS). We have investigated the involvement of tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha and IL-1 beta in this phenomenon by passive immunization against these cytokines. Anti-TNF-alpha or anti-IL-1 beta antibodies given 1.5 h before the induction of nephritis significantly decreased injury in this model, whether assessed by the magnitude of albuminuria, the prevalence of glomerular capillary thrombi or the intensity of glomerular neutrophil infiltrate. Albuminuria in anti-GBM Ab alone was 11 +/- 3, LPS/anti-GBM Ab 87 +/- 22, and anti-TNF-alpha antibodies/LPS/anti-GBM Ab 21 +/- 6 mg/24 h (mean +/- s.e.) P < 0.05. Passive immunization with antibodies to IL-1 beta had a similar effect (anti-GBM Ab, 0.6 +/- 0.1, LPS/anti-GBM Ab, 92 +/- 19, anti-IL-1 beta antibodies/LPS/anti-GBM Ab 39 +/- 8 mg/24 h, P < 0.05). The prevalence of glomerular capillary thrombi was also reduced significantly by these treatments; from 22 +/- 5% to 4 +/- 1% in the case of anti-TNF-alpha antibodies and 28 +/- 5% to 13 +/- 4% with anti-IL-1 beta antibodies. Similarly, the glomerular neutrophil infiltrate was also reduced by these treatments; from 42 +/- 3 to 25 +/- 1 in the case of anti-TNF-alpha and 47 +/- 2 to 30 +/- 1 with anti-IL-1 beta antibodies. In contrast, passive immunization against IL-1 alpha had no effect on either albumin excretion (4 +/- 3, 83 +/- 22 and 77 +/- 24 mg/24 h), glomerular capillary thrombi (2 +/- 1; 19 +/- 5 and 16 +/- 3) or glomerular neutrophil infiltrate (22 +/- 3; 47 +/- 5 and 48 +/- 5 from the three groups respectively). These results demonstrate that enhanced antibody mediated injury in the kidney is modulated by TNF-alpha and IL-1 beta but not by IL-1 alpha.