Interventional nephrology: current status and clinical impact in Japan.

BACKGROUND: Current status and clinical significance of interventional nephrology has not been reported from Japan. METHODS: Questionnaires were mailed twice to the directors of all 534 Japanese certificated nephrology training institutions in 2014. The main questions were current performance, categorized annual procedure volume and managers of peritoneal dialysis (PD) access, vascular access (VA) surgery, endovascular intervention, and kidney biopsy. Frequencies of nephrologist involvement between high volume center and low volume center and association between the level of nephrologists' involvement to each procedure and annual procedure volume were examined. RESULTS: 332 (62.2%) institutions answered performance of all procedures and 328 (61.4%) institutions answered all procedure volume. Kidney biopsy, VA surgery, endovascular intervention and PD access surgery were performed by any doctors in 94.2, 96.3, 88.4, and 76.2% and each involvement of nephrologist was 93.9, 54.1, 53.1 and 47.6%, respectively. Cochran-Armitage analyses demonstrated significant increases in all 4 procedure volume with greater management by nephrologists (p < 0.01). Nephrologists involvement to VA surgery associated with procedure volume increase in not only VA surgery, but also PD catheter insertion (p < 0.01) and kidney biopsy (p < 0.05). And nephrologists involvement to PD catheter insertion also associated with surgical volume increase in both VA surgery (p < 0.01) and endovascular intervention (p < 0.05). CONCLUSIONS: Main manager of all 4 procedures was nephrologist in Japan. Each procedure volume increased as nephrologists become more involved. Acquisition of one specific procedure by nephrologist associated with increase not only in this specific procedure volume, but also the other procedure volume.

Preventive Strategies for Vascular Calcification in Patients with Chronic Kidney Disease.

BACKGROUND: Vascular calcification is significant because of the close association between the degree of vascular calcification and cardiovascular mortality in chronic kidney disease (CKD) patients. SUMMARY: There are 2 types of vascular calcification in CKD patients. One is endothelial vascular calcification, a common type of vascular calcification. Another is medial vascular calcification, a specific type that is common in CKD patients. The former is mainly associated with atherosclerosis due to hyperlipidemia, especially hypercholesterolemia. The latter CKD-specific type is called Moenckeberg's arteriosclerosis. A known risk factor for this type of vascular calcification is hyperphosphatemia. In this review article, we mainly discuss a preventive strategy for Moenckeberg type vascular calcification in CKD, primarily involving the treatment of hyperphosphatemia. Several possible modalities are considered. However, at present, dietary restriction of phosphate is not recommended so as to avoid malnutrition in CKD patients. The first consideration is the enhancement of phosphate removal by renal replacement therapy in dialysis patients. Various phosphate binder therapies can be beneficial and effective. Surgical and pharmacological parathyroidectomies are also useful for treating secondary hyperparathyroidism. Good quality bone provides a good pool of calcium and phosphate. Thus, bone protection is another option for preventing vascular calcification. Several therapeutic agents have been developed to manage osteoporosis. These trial agents may be reasonably effective in impeding the progression of vascular calcification in CKD patients. Key Messages: We should make full use of several modalities so as to completely prevent vascular calcification.

A Case of Concurrent MPO-/PR3-Negative ANCA-Associated Glomerulonephritis and Membranous Glomerulopathy.

We report a case in which antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis and membranous glomerulopathy (MGN) were detected concurrently. The patient showed rapidly progressive renal deterioration. A renal biopsy showed crescentic glomerulonephritis, together with marked thickening and spike and bubbling formations in the glomerular basement membranes. Indirect immunofluorescence examination of the patient's neutrophils showed a perinuclear pattern. Enzyme-linked immunosorbent assays revealed that the ANCA in this case did not target myeloperoxidase (MPO) or proteinase 3 (PR3) but bactericidal-/permeability-increasing protein, elastase, and lysosome. The relationship between these two etiologically distinct entities, MPO-/PR3-negative ANCA-associated glomerulonephritis and MGN, remains unclear.

Successful treatment of adult IgA nephropathy with nephrotic-level proteinuria by combination therapy including long-term coadministration of mizoribine.

A 41-year-old male patient was admitted to our hospital due to massive proteinuria and hematuria. His 24-hour urinary protein excretion and the number of urinary erythrocytes were 3.91 g/day and 50-99/high-power field, respectively. A renal biopsy showed a severe pathological pattern of immunoglobulin A nephropathy (IgAN) that involved marked endocapillary proliferation and segmental sclerosis (Oxford-MEST score: M0, E1, S1, T0). Because he had nephrotic-level proteinuria with severe pathological findings, which are tonsillectomy and corticosteroid pulse therapy-resistant characteristics, he received mizoribine for a long period as part of the combination therapy using corticosteroid, tonsillectomy, dipyridamole, warfarin and renin-angiotensin-aldosterone system blockers. Twelve months after the beginning of treatment, his urinary findings were normal. In this report, we describe the pathological findings and successful treatment course, and discuss the potential effects of long-term coadministration of mizoribine for adult IgAN treatment.

Nafamostat mesilate as an anticoagulant during continuous veno-venous hemodialysis: a three-year retrospective cohort study.

INTRODUCTION: Although nafamostat mesilate, a synthetic serine protease inhibitor, has been commonly used in Japan as an anticoagulant during continuous renal replacement therapy (CRRT), its clinical utility has not been well determined. The aim of this study was to evaluate the efficacy (filter survival) and safety (bleeding complications) of nafamostat mesilate in CRRT for acute kidney injury (AKI) among critically ill patients. METHODS: We retrospectively studied consecutive patients with AKI treated with continuous veno-venous hemodialysis and nafamostat mesilate from April 2005 to March 2008. Demographic, clinical and laboratory data were extracted from the clinical chart. RESULTS: Fifty-eight patients were enrolled in this study (45 males with an average age of 66±15 years). The median filter survival was 21.8 h (range: 2.8-55.5 h), and the mean was 20.8±8.4 h. Only 38 out of 181 filters (21%) were interrupted because of filter failure within 24 hours and 89 filters (49%) were electively renewed within 24 hours. Activated partial thromboplastin time was elevated especially during the first 24 hours (46.7±13.1 s at baseline versus 73.9±24.3 s at day 1; ANOVA p<0.01). Hematocrit level was kept around 30% and did not change significantly (ANOVA p=0.69). No patients experienced major bleeding while treated with CRRT. CONCLUSIONS: Nafamostat mesilate provided sufficient filter survival without causing major bleeding complications despite the prolongation of APTT.

Comparison between the pathology of encapsulating sclerosis and simple sclerosis of the peritoneal membrane in chronic peritoneal dialysis.

Reports analyzing the histopathological differences between encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis (non-EPS) and those comparing the pathology of early and late EPS are limited. We present pathological comparisons between EPS and non-EPS, also between the early and late EPS stages. We compared peritoneal membrane (PM) samples (Group B) of 12 EPS patients (Group A) and 23 non-EPS cases regarding; mesothelial loss, submesothelial compact zone degenerated layer and compact zone thicknesses, densities of total and diseased vessels, fibrin stain, new membrane formation and degenerative changes. Group A was subdivided into 7 early (group A1) and 8 late (group A2) EPS cases; we compared both subgroups in the same manner and finally compared groups A1, A2, and B. No differences were found between groups A and B in the incidences of mesothelial detachment, new membrane formation and compact zone degenerative changes between the two groups. Furthermore, there were no differences in compact zone thickness, and vascular densities in the compact zone of respective vascular grade. Whereas, fibrin deposition and thickness of the submesothelial degenerated layer were significantly higher in group A than group B (P = 0.01 and 0.05, respectively), and the thickness of the compact zone was less in group A1 than in group A2 (P = 0.03). Positive fibrin stains and thick degenerative compact zone layers are important pathological findings in EPS. Angiogenesis, vasculopathy, new membrane formation, fibrosis and degenerative changes of the compact zone are not unique characteristics for EPS. Larger size studies are recommended to verify this issue.

A rumor transmission model with various contact interactions.

We consider a rumor transmission model with various contact interactions and explore what effect such interactions have on the spread of a rumor, in particular whether they can explain the rumor recursion. Through mathematical analysis and computer simulations, we conjecture that rumor recursion remains a major challenge to mathematical models of rumors beyond our model proposed here.

[Mechanism, imaging technique and therapy for vascular calcification in patients of chronic kidney disease].

Vascular calcification has been reported to influence mortality and complications of cardiovascular diseases in patients with chronic kidney disease. Once vascular calcification was thought to the result from passive precipitation of calcium and phosphate, it now appears that end result of phenotypic change of vascular smooth muscle cells (VSMC) into osteoblast-like cells. A variety of imaging technique are available to visualize vascular calcification, including X-ray, vascular ultrasound, electron beam computed tomography (EBCT) and multidetector-row computed tomography (MDCT) . Especially, MDCT with contrast medium that can detect not only coronary calcification but also stenosis is useful and noninvasive methods for screening of coronary artery disease. Through greater understanding of both the mechanism and clinical consequence of vascular calcification, future therapeutic strategies may be more effectively designed and applied.

Quantitative assessment of the peritoneal vessel density and vasculopathy in CAPD patients.

BACKGROUND: Peritoneal sclerosis (PS) complicates continuous ambulatory peritoneal dialysis (CAPD). Exploring the peritoneal vascular changes, which are characteristic histological findings in long-term PD, may give new insight into the basic pathological process leading to PS. We present a quantitative analysis of peritoneal vascular density as well as vasculopathy grades in relation to PD duration. METHODS: Peritoneal samples from 56 stable CAPD patients were analysed, and cases with membrane failure were excluded. Patients were classified into four groups according to CAPD duration in years: group A (n = 12), 0 year; group B (n = 11), 1-5 years; group C (n = 17), 5-9 years; and group D (n = 16), >9 years. The total density, of microvessels (capillaries, post-capillary venules and venules) and the density of each vasculopathy grade (0 = intact, 1 = mild, 2 = moderate and 3 = severe) in the compact zone were calculated (numbers/mm(2)) in each sample and the percentage ratio of each grade in relation to the total vessel density was also determined. RESULTS: There was no significant difference in the total vessel density (P-value = 0.64). In the grade of vasculopathy (density and percentage ratio), there were significant differences among groups, with grade 0 highest in group A, grade 1 highest in group C and grade 3 highest in group D. CONCLUSION: The results of this study indicate that vascular density does not increase, at least in stable uncomplicated PD, and that intact vessels decrease with time on PD, while the severe grades of vasculopathy predominate especially on a long-term basis.

[The role of phosphatonin in phosphate metabolism].

PTH and active vitamin D are well known as classical phosphate regulating hormones. However, presence of some phosphaturic factors is assumed from investigations about TIO, XLH, ADHR. Those diseases cause hypophsophatemia, hyperphosphaturia, low vitamin D and rickets/ostepmalacia. FGF-23, which has been detected from TIO tumors, can induce hypophosphatemia by direct inhibition on phosphate reabsorption and by suppressing 1,25 (OH)(2)D(3) production through the inhibition of 25-hydroxyvitaminD 1alpha-hydroxylase, in the kidney. We have still other phosphatonin candidates such as MEPE, FRP4, etc. The role of these substances are not clear yet. Future investigations are required to clarify their roles in phosphate metabolism.

Plasma pteridine concentrations in patients with chronic renal failure.

BACKGROUND: Pteridine metabolism is impaired in the uraemic state. This may affect cardiovascular function and contribute to malnutrition. We wished to clarify further the impact of impaired pteridine metabolism. METHODS: Using the HPLC method, the plasma concentrations of endogenous pteridines were determined in 64 patients with chronic renal failure (33 on intermittent haemodialysis (HD) treatment vs 31 not yet on renal replacement therapy), and in 18 healthy controls. The patients were classified into three groups on the basis of creatinine clearance (Ccr): group (a), Ccr >60 ml/min; group (b), Ccr=10-60 ml/min; group (c), all patients receiving HD. RESULTS: Total neopterin (NP) and biopterin (BP) levels and the NP/BP ratio (a biomarker for macrophage activity) were significantly higher, whereas tetrahydrobiopterin (BH(4))/dihydrobiopterin (BH(2)) ratio (a biomarker for nitric oxide synthase and phenylalanine hydroxylase activities) was significantly lower in group (c) (118.9+/-11.7 ng/ml, 18.8+/-1.2 ng/ml, 6.79+/-0.53, and 0.26+/-0.06) than in healthy subjects (5.17+/-0.29 ng/ml, 2.83+/-0.19 ng/ml, 1.92+/-0.13, and 1.15+/-0.11; P<0.01). These significant differences were also observed between control and group (b) (12.4+/-2.20 ng/ml, 4.48+/-0.36 ng/ml, 2.81+/-0.48, and 0.74+/-0.08; P<0.01). In groups (a) and (b), significant negative correlations were found between Ccr and the total NP level (r=-0.663, P<0.01), the total BP level (r=-0.492, P<0.01), the BH(2) level (r=-0.677, P<0.01), and the NP/BP ratio (r=-0.493, P<0.01). Conversely, significant positive correlations were found between Ccr and the BH(4)/BH(2) ratio (r=0.602, P<0.01). CONCLUSION: The reduction of quinoid-type BH(2) to BH(4) is modified in patients with advanced chronic renal failure, before and after the initiation of regular HD treatment. These metabolic alterations may play a role in the impaired macrophage, endothelial constitutive nitric oxide synthase, or phenylalanine hydroxylase (PH) activities observed in such patients.