Publications (67)124.95 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Background/aims: The Oxford classification of IgA nephropathy (IgAN) was proposed by international working group in 2009. Interobserver reproducibility of each pathological definition was already evaluated, but that of four pathological prognostic parameters score has not yet been assessed. We first assess the reproducibility of each pathological definition in Japanese patients. Our study is aimed to assess that of four pathological prognostic parameters score among the five Japanese pathologists. Methods: The renal specimens from 411 Japanese patients, aged 3-85 years, with biopsied proven primary IgAN were collected from 50 facilities between 2006 and 2012. The reproducibility of pathological definitions was assessed by the intraclass correlation coefficient (ICC) and that of four pathological prognostic parameters score (mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T)) was assessed by kappa statistics. Results: The ICC of M, E, S, T, global sclerosis and cellular crescents and/or fibrocellular crescents were good or moderate agreement among the five pathologists and were well agreed with results of the Oxford study. Kappa statistics was moderate agreement for M and T score assessed with the semi-quantitative method by the Oxford group, but that was poor agreement for S and E score based on a simple "present" or "absent" assessment. Conclusion: This is the first report to assess the reproducibility of pathological prognostic parameters score in the Oxford classification. Our study supports the utilization of the pathological lesions in routine diagnosis. The methodological assessment of pathological prognostic parameters score should be reconsidered.
- [Show abstract] [Hide abstract] ABSTRACT: Background: The significance of immunosuppressants as an adjunct treatment with corticosteroids for IgA nephropathy (IgAN) has not been well demonstrated. This study was performed to compare two treatment regimens, steroid-pulse therapy or combined with mizoribine (MZR) in progressive IgAN. Methods: Study design was a prospective randomized controlled trial of 40 patients with moderate to severe glomerular injuries who were randomly administered either pulse methylprednisolone followed by a 25-month course of oral prednisolone (P group, n = 20) or in combination with MZR (150 mg/day for 24 months, M + P group, n = 20). The primary endpoint was a reduction of proteinuria by ≥50 % of the baseline value. Secondary endpoints were increased serum creatinine (Cr) by ≥50 %, or a decrease in estimated glomerular filtration rate by ≤50 %. Results: Twenty-five months after the initiation of treatment, urinary protein excretion significantly declined from the median of 0.98 to 0.17 g/gCr in the P group (P < 0.05) and from 1.01 to 0.38 g/gCr in the M + P group (P < 0.05). There was no statistical difference in the serial changes of proteinuria between two groups (P = 0.81). All patients reached the primary endpoint, and the cumulative incidence of the reduction of proteinuria was not significantly different (P = 0.76). No patient reached the secondary endpoint during the 25 months of treatment. Conclusions: Both therapeutic regimens significantly reduced the levels of proteinuria. We could not find the additional effect of MZR in combination with steroid-pulses in this small-scale controlled trial. Steroid-pulse therapy with a 25-month course of oral steroids seems to be effective for progressive IgAN.
Dataset: Supplementary material 1
- [Show abstract] [Hide abstract] ABSTRACT: Background: The impact of renin-angiotensin system blockade (RASB) on the incidence of end-stage renal disease (ESRD) remains unclear in IgA nephropathy (IgAN). Methods: This study assessed associations between RASB treatment and the incidence of ESRD in IgAN using propensity score approaches. We retrospectively analyzed 1273 patients with IgAN biopsied between 1979 and 2010. Propensity scores were calculated using logistic regression. Associations between RASB and ESRD were examined using a Cox regression model adjusted by inverse probability of treatment weighted, regression, stratification and matching. Results: During follow-up (median 5.1 years), 130 patients developed ESRD. With Cox regression adjusted by inverse probability of treatment weighted, RASB use was significantly associated with a lower risk of ESRD (hazard ratio 0.58; 95 % confidence interval 0.42-0.80). Significant associations were observed for other propensity score-based approaches. In stratified analysis, a beneficial association between RASB and ESRD was observed in patients ≥35 years, with hypertension, reduced estimated glomerular filtration rate (<60 mL/min/1.73 m(2)), mesangial proliferation and segmental glomerulosclerosis (P for interaction <0.05), and tended to be greater in patients with proteinuria (≥1.0 g/24 h), extracapillary proliferation and receiving methylprednisolone pulse therapy (P for interaction <0.10). Conclusion: Treatment with RASB was associated with a lower incidence of ESRD in the real-world practice of IgAN.
- [Show abstract] [Hide abstract] ABSTRACT: Background: The IgA nephropathy (IgAN) Study Group in Japan conducted a multicenter, randomized, controlled trial of tonsillectomy with steroid pulse therapy (TSP) versus steroid pulse monotherapy in patients with IgAN (UMIN Clinical Trial Registry Number; C000000384). The effects of therapies in relation to pathological severity were analyzed in this study. Methods: The patients with IgAN, urinary protein 1.0-3.5 g/day, serum creatinine of 1.5 mg/dl or less were randomly assigned to receiving TSP (Group A) or steroid pulses alone (Group B). The primary endpoint was the disappearance of proteinuria and/or hematuria. Twenty-six biopsies in Group A and 33 in Group B were available. The histological grades (HG) according to the percentage of glomeruli with crescent or sclerosis and the Oxford classification were analyzed. Results: The patients in Group A had a 4.32- to 12.1-fold greater benefit of disappearance of proteinuria and 3.61- to 8.17-fold greater benefit of clinical remission (disappearance of proteinuria and hematuria) than those in Group B in patients with HG2-3, acute lesions (cellular or fibrocellular crescent) affecting more than 5 % of glomeruli, chronic lesions (fibrous crescents or sclerosis) affecting more than 20 % and S1. In contrast, odds ratios for disappearance of proteinuria or clinical remission in Group A to Group B were not significant in patients with HG 1, acute lesion in 5 % or less of glomeruli, chronic lesion in 20 % or less and S0. The disappearance of hematuria showed no relation to pathological severity. Conclusion: TSP might be better employed according to the pathological severity.
- [Show abstract] [Hide abstract] ABSTRACT: We report a case of probable light- and heavy-chain deposition disease (LHCDD) in a diabetic patient, a rare and educational case. The patient was a 71-year-old man having a long history of uncontrolled diabetes mellitus with retinopathy. He showed heavy proteinuria and renal insufficiency, and did not have paraproteins. Renal biopsy revealed nodular glomerulosclerosis with severe mesangial widening and microaneurysm. Immunofluorescence (IF) showed weak staining of kappa light chain, IgG and C1q along glomerular basement membrane (GBM). At first, we interpreted these IF findings to be nonspecific, thus we diagnosed as diabetic nodular glomerulosclerosis. Later, we recognized one of a few case reports of monoclonal immunoglobulin deposition disease (MIDD) in diabetic patients, and reconsidered the first diagnosis. The added electron microscopy (EM) showed obvious electron-dense materials in GBM, while tubular basement membrane deposits were not identified. A concurrence of LHCDD and diabetic nodular glomerulosclerosis may be suggested in this case. Like this case, IF staining in MIDD is often weak, so it is difficult to diagnose MIDD accurately without EM. Reports of MIDD in diabetic patients are extremely rare, possibly due to being often overlooked. This case emphasizes that overall pathological examination including IF and EM is important for the accurate differentiation of nodular glomerulosclerosis, even in diabetic patients.
- [Show abstract] [Hide abstract] ABSTRACT: It is unknown whether the use of diuretics is optimal over other antihypertensive agents in patients with chronic kidney disease (CKD) whose blood pressure remains uncontrolled despite treatment with renin-angiotensin system (RAS) inhibitors. In this study, we assessed the additive effects of hydrochlorothiazide (HCTZ) on reducing proteinuria in CKD patients under treatment with losartan (LS). We conducted a multicenter, open-labeled, randomized trial. One hundred and two CKD patients with hypertension and overt proteinuria were recruited from nine centers and randomly assigned to receive either LS (50 mg, n=51) or a combination of LS (50 mg per day) and HCTZ (12.5 mg per day) (LS/HCTZ, n=51). The primary outcome was a decrease in the urinary protein-to-creatinine ratio (UPCR). The target blood pressure was <130/80 mm Hg, and antihypertensive agents (other than RAS inhibitors and diuretics) were added if the target was not attained. Baseline characteristics of the two groups were similar. After 12 months of treatment, decreases in the UPCR were significantly greater in the LS/HCTZ group than in the LS group. There were no significant differences in blood pressure or the estimated glomerular filtration rate between the two groups. LS/HCTZ led to a greater reduction in proteinuria than treatment with LS, even though blood pressure in the LS group was similar to that in the LS/HCTZ group following the administration of additive antihypertensive agents throughout the observation period. This finding suggests that LS/HCTZ exerts renoprotective effects through a mechanism independent of blood pressure reduction.Hypertension Research advance online publication, 26 June 2014; doi:10.1038/hr.2014.110.
- [Show abstract] [Hide abstract] ABSTRACT: The risk assessment for developing ESRD remains limited in patients with IgA nephropathy (IgAN). The aim of this study was to develop and validate a prediction rule for estimating the individual risk of ESRD in patients with IgAN. A total of 698 patients with IgAN diagnosed by renal biopsy at Kyushu University Hospital (derivation cohort) between 1982 and 2010 were retrospectively followed. The Oxford classification was used to evaluate the pathologic lesions. The risk factors for developing ESRD were evaluated using a Cox proportional hazard model with a stepwise backward elimination method. The prediction rule was verified using data from 702 patients diagnosed at Japanese Red Cross Fukuoka Hospital (validation cohort) between 1979 and 2002. In the derivation cohort, 73 patients developed ESRD during the median 4.7-year follow-up. The final prediction model included proteinuria (hazard ratio [HR], 1.30; 95% confidence interval [95% CI], 1.16 to 1.45, every 1 g/24 hours), estimated GFR (HR, 0.84; 95% CI, 0.74 to 0.96, every 10 ml/min per 1.73 m(2)), mesangial proliferation (HR, 1.85; 95% CI, 1.10 to 3.11), segmental sclerosis (HR, 3.21; 95% CI, 1.37 to 7.51), and interstitial fibrosis/tubular atrophy (T1: HR, 5.30; 95% CI, 2.63 to 10.7; T2: HR, 20.5; 95% CI, 9.05 to 46.5) as independent risk factors for developing ESRD. To create a prediction rule, the score for each variable was weighted by the regression coefficients calculated using the relevant Cox model. The incidence of ESRD increased linearly with increases in the total risk scores (P for trend <0.001). Furthermore, the prediction rule demonstrated good discrimination (c-statistic=0.89) and calibration (Hosmer-Lemeshow test, P=0.78) in the validation cohort. This study developed and validated a new prediction rule using clinical measures and the Oxford classification for developing ESRD in patients with IgAN.
- [Show abstract] [Hide abstract] ABSTRACT: A woman in her fifties was admitted to our hospital with generalized weakness in July, 2008. Her blood urea nitrogen was 102.1 mg/dL and creatinine was 9.9 mg/dL. We performed hemodialysis with catheterization into her right femoral vein on the admission day. The catheter was an Argyle® double lumen hemofiltration catheter, slide type. Four days later, the catheter was exchanged using a guide wire because of blood flow failure. In 2010, the migration of the catheter into her heart was discovered in another institute. Retrospectively chest X-ray imaging in our hospital after the replacement procedure showed that the inner catheter had migrated into the right ventricle via the superior vena cava and the right atrium. It was retrospectively clarified that the catheter had separated into the inner and outer parts because of cutting at the bifurcation, and so the inner catheter had migrated into the patient's heart. In the catheter manual, there is a caution which states that; “cutting is prohibited because of the risk of migration into the patient's body”. This accident was due to a very careless mistake in the catheter replacement procedure. We very deeply regretted that one of our staff had replaced catheter without reading the manual. Reading a manual for a catheter, or indeed any piece of equipment, is a fundamental attitude that all physicians should continuously bear in mind, especially when they have had no prior experience with the same type of catheter. This patient has been carefully followed up with warfarin, and a pulmonary embolism was found with a regular pulmonary blood flow scintigram in August, 2012. We increased the dosage of warfarin immediately. There has been no symptom so far. We report herein on a case with migration of a hemodialysis catheter into a patient's heart because of a very careless mistake on the part of our staff.
- [Show abstract] [Hide abstract] ABSTRACT: A 43-year-old woman was admitted to our hospital because of generalized bone pain. Arterial blood gas showed pH 7.266, HCO3− 13.5 mEq/l, and anion gap (AG) 12. Since her urine pH was 7.0 despite metabolic acidosis with normal AG, we diagnosed distal renal tubular acidosis (RTA). Serum phosphate was 2.5 mg/dl, the level of β2 microglobulin was 41100 μg/l, and aminoaciduria was present. These results indicated proximal tubular dysfunction. The radiograph showed pseudofracture in the pubic bone, indicating osteomalacia. Bone scintigram showed abnormal accumulations of 99mTc-HMDP in multiple joints. Then, her generalized bone pain was considered to be a symptom of osteomalacia. Despite the absence of overt Sicca syndrome, the evaluation of Sjögren’s syndrome (SjS) as a cause of distal RTA was performed. Antibodies to the SS-A level was 127U/ml. Tear break-up time was 3 s bilaterally and salivary gland scintigraphy showed low uptake of 99mTc in the submandibular glands and the parotids. Thus, we diagnosed SjS finally. Gallium scintigraphy showed mild abnormal uptake in bilateral kidneys, suggesting acute tubulointerstitial nephritis. After treatment with prednisolone, alfacalcidol, and sodium bicarbonate, bone pain was remarkably relieved. Additionally, aminoaciduria disappeared and the level of β2 microglobulin decreased. We speculated that the coincidence of proximal tubular dysfunction and distal RTA cause a severe manifestation of osteomalacia.
- [Show abstract] [Hide abstract] ABSTRACT: Background: The peritoneum begins to undergo morphologic changes before the start of peritoneal dialysis (PD), particularly in diabetic patients. The present study was conducted to investigate the effects of diabetes on the peritoneum. Methods: This study involved 17 patients who began receiving PD and had diabetes as an underlying disease (DM group), and 30 patients without diabetes who served as a control group (nonDM group). At the start of PD, the parietal peritoneum was sampled to assess submesothelial connective tissue thickness, number of capillaries and postcapillary venules, and indications of vasculopathy (grades 0 - 3). Results: Submesothelial connective tissue thickness was significantly greater in the DM group than in the nonDM group (p < 0.01). The number of capillaries was significantly greater in the DM group (p < 0.01). Based on multivariate linear regression analysis, diabetes was identified as a significant independent variable of both submesothelial connective tissue thickness and number of capillaries (p < 0.01). Conclusions: In diabetic patients, morphologic changes of the peritoneum are marked at the start of PD.
- [Show abstract] [Hide abstract] ABSTRACT: Background: A multicenter case-control study on IgA nephropathy (IgAN) was conducted to develop an evidence-based clinicopathologic classification of IgAN for predicting long-term renal outcome. Methods: Two hundred and eighty-seven patients including those with isolated hematuria or very mild proteinuria were enrolled. During a median follow-up of 9.3 years after biopsy, 49 patients (17%) progressed to end stage renal disease (ESRD). The associations between pathological variables and the need for chronic dialysis was examined by multivariate logistic regression analysis separately in patients who required dialysis earlier than 5 years (Early Progressors) and those who required dialysis within 5 to 10 years (Late Progressors) after biopsy. Results: Independent pathological variables predicting progression to ESRD were global sclerosis, segmental sclerosis and fibrous crescents for Early Progressors, and global sclerosis and cellular/fibrocellular crescents for Late Progressors. Four histological grades, HG 1, HG 2, HG 3 and HG 4, were established corresponding to <25%, 25-49%, 50-74% and =75% of glomeruli exhibiting cellular or fibrocellular crescents, global sclerosis, segmental sclerosis or fibrous crescents. Eleven (7%) patients in HG 1, 12 (16%) in HG 2, 13 (31%) in HG 3 and 13 (68%) in HG 4 progressed to ESRD. Multivariate logistic analysis revealed that the risk of progression to ESRD was significantly higher in HG 2, 3 and 4 than in HG 1 (odds ratio, 2.4, 5.7 and 27.6 vs. 1.0). Conclusions: Our evidence-based histologic classification can identify the magnitude of the risk of progression to ESRD and is useful for predicting long-term renal outcome in IgAN.
- [Show abstract] [Hide abstract] ABSTRACT: The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number. The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice. This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice. UMIN-Clinical Trial Registration, UMIN000004784.
- [Show abstract] [Hide abstract] ABSTRACT: BACKGROUND AND OBJECTIVES The Oxford classification of IgA nephropathy (IgAN) includes mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as prognosticators. The value of extracapillary proliferation (Ex) was not addressed. Because the Oxford classification excludes patients with urinary protein <0.5 g/d and eGFR <30 ml/min per 1.73 m(2) at biopsy, the significance of Ex should be confirmed by validation cohorts that include more rapidly progressive cases. We present such a study. The significance of pathologic features for development end-stage renal failure (ESRF) was examined by multivariate analysis in 702 patients with IgAN. The association of Ex with kidney survival was examined by univariate analysis in 416 patients who met the Oxford criteria and 286 who did not, separately. In a multivariate model, S and T were significantly associated with ESRF. With addition of Ex, not S but Ex was significant for ESRF. In univariate analysis, kidney survival was significantly lower in patients with Ex than in those without, in patients who did not meet the Oxford criteria, but such a difference was not found in patients who met it. The prognostic significance of Ex was evident in our cohort. It seems that Ex did not emerge from the Oxford classification as a prognosticator because of exclusion of severe cases (eGFR <30 ml/min per 1.73 m(2)). We suggest that extracapillary proliferation be included in the next version of the Oxford classification of IgAN to widen the scope of the classification.
- [Show abstract] [Hide abstract] ABSTRACT: The donor was 63-yr-old woman with subarachnoid hemorrhage. As she developed severe hypotension for more than four h before cardiac arrest, we biopsied the grafts and decided to transplant those kidneys. Recipient 1 was a 23-yr-old man on 13-yr dialysis program. After 19 d of delayed graft function (DGF), we discontinued hemodialysis (HD). However, the decrease in serum creatinine (sCr) was poor. The minimum sCr was 4.3 mg/dL on post-operative day (POD) 40, and increased to 6.5 mg/dL. The contralateral graft was transplanted to a 61-yr-old man (recipient 2) with 18-yr HD. After 15 d of DGF period, sCr decreased gradually and has been stable at 1.9 mg/dL. In recipient 1, graft biopsies performed on POD 15, 69, and 110, revealed progressive interstitial fibrosis and tubular atrophy (IF/TA) without evidences of acute rejection, tacrolimus associated injury, reflux nephropathy, or viral nephropathy. The second biopsy on POD 69 showed typical findings of acute tubular necrosis. We compared the clinical courses of the two recipients because certain features of recipient 1, such as age, duration of HD, total ischemic time, and body size were advantageous, whereas graft function was poorer than that in recipient 2. Recipient 1 developed severe anemia following the dissociation of graft function from recipient 2. In this case, posttransplant anemia and lower blood pressure might promote IF/TA through persistent ischemic tubular damage, and positive CMV antigenemia and its treatment could promote anemia. Especially in the kidney allograft from a marginal donor, we should consider various factors to obtain a better graft outcome.
- [Show abstract] [Hide abstract] ABSTRACT: National Fukuoka-Higashi Medical Center, Koga, Japan A 63-yr-old Japanese woman on 18-yr hemodialysis (HD) program underwent cadaveric kidney transplantation from non-heart beating donor. Pre-transplant lymphocytotoxicity test was negative, but flow cytometric cross-match and flow-cytometric panel reactive antibody (PRA) screening tests were positive. Flow-PRA single-antigen test revealed several anti-HLA antibodies including donor-specific antibody (DSA). She was treated with plasma exchange (PEX) and rituximab to prevent antibody-mediated rejection (AMR). Urinary output increased from post-operative day (POD) 5 and HD was discontinued from POD8. Graft biopsy performed on POD11 showed severe peritubular capillaritis (PTCitis), numerous polymorphonuclear neutrophils (PMNs), and moderate glomerulitis. Although C4d immunostaining on PTC was negative, the case was diagnosed as subclinical AMR based on the presence of pre-transplant DSA and PTCitis with predominant PMNs. The patient was treated with additional PEX and rituximab, which increased urinary output and reduced serum creatinine (sCr). Graft biopsy repeated on POD39 showed persistent severe PTCitis, moderate interstitial infiltration, and mild tubulitis. C4d on PTC was negative again. The patient was discharged from the hospital on POD40. During the seven months follow-up at the outpatient clinic, the sCr level has shown a slight increase. In this case, the patient had DSA, which can be detected only by flow-PRA. In both graft biopsies, C4d on PTC was negative despite the presence of severe PTCitis, and thus the diagnosis of AMR could not be established. However, the significance of subclinical PTCitis is reported perhaps as an early marker for chronic AMR and to emphasize the importance of close follow-up.
- [Show abstract] [Hide abstract] ABSTRACT: A 40-year-old man was transferred to our hospital because of severe anasarca. He was a heavy drinker for more than 20 years, and diagnosed with diabetes mellitus 8 years earlier and treated with retinal photocoagulation 8 months earlier. He reported loss of appetite after divorce 10 months prior to admission. On admission, he presented with systemic edema and dyspnea. Chest radiography showed massive pleural effusion and cardiomegaly. Serum total protein was 5.6 g/dl, albumin 2.6 g/dl, and urinary protein excretion was 5.3 g/day. Glucose tolerance test showed normal pattern. Ultrafiltration and continuous hemofiltration resulted in loss of 40 kg body weight in 5 days. Echocardiography revealed high-output heart failure and blood tests showed low serum thiamine level of 12 ng/ml (normal, >28 ng/ml). Accordingly, the diagnosis was established as beriberi heart disease complicated with nephrotic syndrome. Treatment with 50 mg/day thiamine intravenously and 80 mg/day furosemide resulted in increase in urine output, decrease in cardiac output, resolution of pulmonary effusion, and about 70 kg body weight loss. Percutaneous renal biopsy showed nodular glomerulosclerosis, mesangial matrix expansion, and thickening of glomerular basement membrane (GBM). Immunofluorescence study showed no glomerular deposition of immunoglobulin or complement. Electron microscopy showed GBM thickening and mesangial matrix deposition without electron-dense deposits or fibrils. These findings were compatible with diabetic glomerulosclerosis. In this patient, extreme malnutrition altered glucose tolerance but, on the other hand, nephrotic syndrome associated with diabetic nephropathy made the diagnosis of beriberi heart disease difficult.
Chiba-East National HospitalTiba, Chiba, Japan
Japan Red Cross Fukuoka HospitalHukuoka, Fukuoka, Japan
Hukuoka, Fukuoka, Japan
- Graduate School of Medical Sciences