Hiraku Yoshida

Comparison Between the Pathology of Encapsulating Sclerosis and Simple Sclerosis of the Peritoneal Membrane in Chronic Peritoneal Dialysis

Abstract:  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.

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.

Most patients with coronary artery calcification have no coronary artery stenosis and hyperphosphatemia should be important in reevaluating the K/DOQI guidelines.

Address correspondence and reprints requests to Dr. Keitaro Yokoyama, Division of Nephrology and Hypertension, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8471, Japan. Email: keitaro@jikei.ne.jp Dear Editor, The incidence of cardiovascular complications is very high in end-stage renal disease (ESRD) patients, and life expectancy significantly depends on the complications resulting from coronary artery stenosis. According to the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease published in 2003 (1), hyperphosphatemia influences coronary artery calcification (CAC) in ESRD patients and the use of active vitamin D should be limited in patients with hyperphosphatemia. However, hyperphosphatemia is one of several factors, which effect CAC in ESRD patients. Thus we evaluated the relationship between hyperphosphatemia coronary artery stenosis as well as CAC using 16-slice multislice CT (MSCT) with CT angiography (CTA) in ESRD patients. We recruited 31 ESRD patients (18 male and 13 female, mean age 62 ± 12 years, mean duration of dialysis 6.6 ± 6.6 years) and calculated their coronary artery calcification score (CACS) according to the algorithm suggested by Agaston et al. With contrast enhancement, we evaluated their CTA based on the American Heart Association classification for coronary angiography (CAG). In the first, each coronary segment was classified as either interpretable or not interpretable according to the image quality. Second, when the patent lumen of each segment was 25% or less of the luminal diameter, it was screened for the presence of severe stenosis. As above, whether severe stenosis or occlusion was present or absent could be assessed. In 16 slice MSCT, calcified coronary lesions were found in 24 cases (80%), including 13 cases with a severe degree of calcification of CACS (more than 400). However, the serum phosphorus level was > 5.6 mg/dL in 39% of patients in this sample. With regards to the CT value of each coronary segment with contrast enhancement, severe stenosis or occlusion was found in 13% of patients. Univariate analysis suggested a relationship between serum Ca values and CACS. No statistically significant differences were seen with regard to age, dialysis duration, diabetes, serum phosphorus or serum intact-PTH. We could confirm that the calcified coronary lesions were found in 24 cases (80%), however, most of them did not have severe coronary artery stenosis or occlusion and hyperphosphatemia (serum phosphorus > 5.5 mg/dL). Hyperphosphatemia might merely be one of several factors which influence CAC in ESRD patients. Thus, we should clarify the pathophysiology of CAC in ESRD patients besides hyperphosphatemia to reevaluate the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease.

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 Moenckebergs 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.

Chest X-ray may serve as a screening examination for coronary artery calcification in dialysis patients

To the Editor: In a recent issue, Nakano et al.1 demonstrated a positive correlation between declining renal function and degree of intimal neovascularization and intraplaque hemorrhage in coronary arteries of the autopsy samples from the Hisayama Study. Together with their previously published finding of the association between more advanced coronary atherosclerosis with calcification and decreasing renal function,2 they have contributed to histopathologic evidence underlying the increased cardiovascular risk in chronic kidney disease (CKD). Accordingly, screening for coronary artery calcification (CAC) is important in patients with CKD, especially those with end-stage disease. However, as it is not feasible to assess the coronary artery calcification score, a good predictor of mortality, in every dialysis patient using multidetector computed tomography, we conducted a study to assess whether calcification in any of the four areas, namely, aortic valve, carotid artery, and thoracic and abdominal aortas, had any associations with CAC. A total of 163 autopsy cases of dialysis patients (age 63.5±16.0 years, 102 male:61 female, 46 diabetic:117 nondiabetic, dialysis duration 4.4±5.3 years) were examined. Our results demonstrated that thoracic aorta calcification (odds ratio (OR): 5.04, P-value: 0.023, 95% confidence interval (CI): 1.252–20.26) had the strongest association with CAC (aortic valve OR: 1.50, P-value: 0.434, 95% CI: 0.544–4.136, carotid artery OR: 1.40, P-value: 0.532, 95% CI: 0.486–4.039, and abdominal aorta OR: 2.01, P-value: 0.362, 95% CI: 0.447–9.062). This suggests that screening for thoracic aorta calcification on CXR in dialysis patients may serve as a useful and practical tool for selecting groups of patients who should undergo further coronary artery evaluation.

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.

Middle molecular uremic substances retention itself might influence the bioincompatibility of PD solution

To the Editor: It was demonstrated that a higher peritoneal membrane solute transport rate is associated with a higher mortality risk and a trend to higher technique failure. It has been suggested that the bioincompatible nature of conventional peritoneal dialysis (PD) solutions contributes to the structural peritoneal membrane changes that lead to deterioration in solute transport characteristics and loss of ultrafiltration. However, Fan et al. reported that the clinical outcomes (residual kidney function, peritoneal membrane function, technique survival, and peritonitis rates) were the same, irrespective of standard or biocompatible PD solutions. In the HEMO dialysis study, it became apparent that serum b2 microglobulin (b2M) levels, not KT/V, were the strong predictors of mortality. It was reported that the clearance of b2M by hemodialysis (when high-flux membranes were used) was higher than that by PD. We stained peritoneal tissue from continuous ambulatory peritoneal dialysis (CAPD) patients (n1⁄4 19) for b2M (rabbit anti-human b2M; DAKO, Glostrup, Denmark). In almost all the patients, deposits of b2M were found in the compact zone (Figure 1). We previously investigated the associations of b2M clearance with PD and residual renal function, and serum b2M levels with duration of dialysis in 20 subjects on continuous ambulatory peritoneal dialysis and found that serum b2M levels increased with duration of dialysis. As for b2M clearance by residual renal function per se, it was significantly lower in subjects with long duration of dialysis even though no difference was observed in the total daily b2M clearance. 6 We also reported that b2M is useful as a screening test for the onset of encapsulating peritoneal sclerosis and that the accumulation of both b2M and middle molecular uremic substances may be related to the pathophysiology of encapsulating peritoneal sclerosis. b2 Microglobulin may have a pathogenic role, which is unproven; however still, if middle molecular uremic substance retention itself influences the bioincompatibility of PD solution, it might be worthwhile to attempt combined continuous ambulatory peritoneal dialysis and hemodialysis treatment in patients with high b2M levels for whom sufficient clearance cannot be maintained with continuous ambulatory peritoneal dialysis alone, but this also requires further study. We should not pay attention only to PD solution but also to middle molecular uremic substance retention.

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 patients 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.