This study assessed the association of pathological kidney lesions with cardiovascular events in biopsy-proven diabetic kidney disease (DKD) with type 2 diabetes. This multicenter, retrospective study involved 244 patients with no previous cardiovascular events before biopsy, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 at biopsy (baseline), and ≥ 1 year of observation after biopsy. The outcomes were the first occurrence of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, coronary intervention, or non-fatal stroke), and non-cardiovascular deaths before cardiovascular events were considered competing events. The association between the severity of each pathological lesion and cardiovascular events was investigated. During follow-up (median: 6.4 years), 43 patients experienced cardiovascular events. The baseline clinical characteristics did not differ according to cardiovascular events. The cumulative incidence of cardiovascular events was higher in patients with mesangiolysis, global glomerulosclerosis ≥ 50

Background Progression of renal anemia has been shown to be associated with advanced renal tubulointerstitial lesions. This retrospective study investigated the impact of lower hemoglobin (Hb) levels and renal interstitial fibrosis and tubular atrophy (IFTA) on long-term outcomes in type 2 diabetes with biopsy-proven diabetic nephropathy. Methods A total of 233 patients were enrolled. The severity of IFTA was scored according to the classification by the Renal Pathology Society. Patients were stratified according to baseline Hb tertiles by IFTA status. The outcomes were the first occurrence of renal events (requirement for dialysis or 50 % decline in estimated glomerular filtration rate from baseline) and all-cause mortality. Results At baseline, 151 patients had severe IFTA. There were no patients who have been received erythropoiesis-stimulating agents at the time of renal biopsy. The severity of IFTA was the independent pathological factor of lower Hb levels. During the mean follow-up period of 8.6 years (maximum, 32.4 years), 119 renal events and 42 deaths were observed. Compared with the combined influence of the highest tertile of Hb and mild IFTA, the risks of renal events were higher for the middle tertile and for the lowest tertile of Hb in severe IFTA, whereas the risk of renal events was higher for the lowest tertile of Hb in mild IFTA. The risk of mortality was higher for the lowest tertile of Hb only in severe IFTA. There were significant interactions of tertile of Hb and IFTA in renal events and mortality. Conclusions Impacts of lower Hb levels on long-term outcomes of diabetic nephropathy were greater in severe IFTA than in mild IFTA.

Abstract Aims/Introduction The present retrospective study investigated the impact of renal arteriosclerosis (AS) and hypertension (HT) on long‐term renal and cardiovascular outcomes in Japanese type 2 diabetes patients with biopsy‐proven diabetic nephropathy. Materials and Methods A total of 185 patients were enrolled. Patients were divided into four groups stratified by renal AS status and the presence of HT. The outcomes for this study were the first occurrence of renal events (a need for dialysis or a 30% decline in estimated glomerular filtration rate from baseline) and cardiovascular events (cardiovascular death, non‐fatal myocardial infarction, coronary intervention or non‐fatal stroke). Results The proportion of renal AS scores ≥1 was 88.3% among patients with normal‐range blood pressure (BP) and 95.4% among patients with HT. During a mean follow‐up period of 7.6 years, 129 episodes of renal composite events and 55 episodes of cardiovascular events were observed. Compared with patients with no renal AS and normal‐range BP, a renal AS score ≥1 increased the risk of renal composite events with a multivariable‐adjusted hazard ratio of 3.21 (95% confidence interval [95% CI] 1.27–8.14) in patients with normal‐range BP and 4.99 (95% CI 1.98–12.54) in patients with HT, whereas renal AS score ≥1 increased the risk of cardiovascular events with a multivariable‐adjusted hazard ratio of 6.06 (95% CI 1.24–29.61) in patients with normal‐range BP and 10.02 (95% CI 1.92–52.39) in patients with HT. Conclusions Renal AS was associated with increasing risks for renal composite events and cardiovascular events in both normal‐range BP and HT. The risks of renal composite events and cardiovascular events were the highest in both renal AS and HT.

Background The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). Methods Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. Results During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01–8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission. Conclusions The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

Background The current (2012) histological classification of immunoglobulin A nephropathy was established using a case‐control study of 287 patients. However, the risk of progression to end-stage renal disease (ESRD) has not been validated for the previous (2002) classification. This study aimed to determine whether the previous classification could identify the risk of long-term renal outcome through re-analysis of the 2012 cohort. Methods On the basis of the 2002 classification, namely ‘good prognosis’, ‘relatively good prognosis’, ‘relatively poor prognosis’, and ‘poor prognosis’, we examined the clinical data at the time of biopsy, the correlation between the 2002 classification and long-term renal outcomes, and a patient-by-patient correlation between the 2002 and 2012 classification systems. This was performed by analyzing samples from the 287 patients used to establish the 2012 classification. Results The rate of decline of estimated glomerular filtration rate was greater and the odds ratio of progression to ESRD was higher in the ‘poor prognosis’ group. In contrast, the odds ratio for renal death was comparable between the groups described as ‘relatively poor prognosis’ and ‘relatively good prognosis’ in the 2002 classification. Many patients in the 2002 classification were classified with a lower histological grade in the current classification, but none were classified with a higher grade.

The current (2012) histological classification of immunoglobulin A nephropathy was established using a case–control study of 287 patients. However, the risk of progression to end-stage renal disease (ESRD) has not been validated for the previous (2002) classification. This study aimed to determine whether the previous classification could identify the risk of long-term renal outcome through re-analysis of the 2012 cohort.

Low birth weight ( LBW ) is thought to be one of the risk factors for the progression of kidney diseases. This study hypothesized that the onset age of kidney disease, the rate of progression of kidney disease, or the age at the time of hemodialysis ( HD ) induction among HD patients that were born with LBW is different from those without a history of LBW . A questionnaire survey in nine dialysis units in J apan was performed and 427 answer sheets were collected. There were statistically significant differences in the present age, the age of kidney disease onset, and the age of HD induction between LBW group and normal birth weight group ( NBW ). An analysis limited to participants whose underlying disease was diabetic nephropathy revealed that the duration from the onset of nephropathy to HD induction was much shorter in HD patients with a history of LBW than those with a NBW history. In addition, the Pearson's correlation coefficient between the birth weight and the period from onset of diabetic nephropathy to HD induction was 0.283. Although these results might partly support the primary hypothesis, the necessity to perform other clinical studies is also emphasized.

OBJECTIVE We evaluated the structural-functional relationships and the prognostic factors for renal events, cardiovascular events, and all-cause mortality in type 2 diabetic patients with biopsy-proven diabetic nephropathy. RESEARCH DESIGN AND METHODS Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy (n = 260) were enrolled. Patients were stratified by albuminuria (proteinuria) and estimated glomerular filtration rate (eGFR) at the time of renal biopsy. The outcomes were the first occurrence of renal events (requirement of dialysis or a 50% decline in eGFR from baseline), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, coronary interventions, or nonfatal stroke), and all-cause mortality. RESULTS The factors associated with albuminuria (proteinuria) regardless of eGFR were hematuria, diabetic retinopathy, low hemoglobin, and glomerular lesions. The factors associated with low eGFR regardless of albuminuria (proteinuria) were age and diffuse, nodular, tubulointerstitial, and vascular lesions. The glomerular, tubulointerstitial, and vascular lesions in patients with normoalbuminuria (normal proteinuria) and low eGFR were more advanced compared to those in patients with normoalbuminuria (normal proteinuria) and maintained eGFR. In addition, compared to patients with micro-/macroalbuminuria (mild/severe proteinuria) and low eGFR, their tubulointerstitial and vascular lesions were similar or more advanced in contrast to glomerular lesions. The mean follow-up period was 8.1 years. There were 118 renal events, 62 cardiovascular events, and 45 deaths. The pathological determinants were glomerular lesions, interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis for renal events, arteriosclerosis for cardiovascular events, and IFTA for all-cause mortality. The major clinical determinant for renal events and all-cause mortality was macroalbuminuria (severe proteinuria). CONCLUSIONS Our study suggests that the characteristic pathological lesions as well as macroalbuminuria (severe proteinuria) were closely related to the long-term outcomes of biopsy-proven diabetic nephropathy in type 2 diabetes.

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.

BACKGROUND: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.METHODS/DESIGN: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.DISCUSSION: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.TRIAL REGISTRATION:UMIN-Clinical Trial Registration, UMIN000004784.

Data regarding renal disease in the elderly (age ≥65 years old) and very elderly (age ≥80 years old) Japanese are extremely limited. The aim of this study was to examine the causes of renal disease and their clinical presentations in elderly patients who underwent renal biopsy.

The presence of chronic kidney disease in humans is associated with a risk of kidney function loss as well as the development of cardiovascular disease. Fibrocytes have been shown to contribute to organ fibrosis. In this study, the presence of fibrocytes was investigated immunohistochemically in kidney biopsy specimens from 100 patients with chronic kidney disease. In addition, 6 patients with thin basement membrane disease were studied as a disease control. In patients with chronic kidney disease, the infiltration of fibrocytes was observed mainly in the interstitium. The number of interstitial fibrocytes in patients with chronic kidney disease was higher than that in patients with thin basement membrane disease. The number of infiltrated fibrocytes in the interstitium correlated well with the severity of tubulointerstitial lesions, such as interstitial fibrosis, in patients with chronic kidney disease. In addition, there were significant correlations between the number of interstitial fibrocytes and the number of CD68-positive macrophages in the interstitium as well as urinary monocyte chemoattractant protein-1/CCL2 levels. In particular, there was an inverse correlation between the number of interstitial fibrocytes and kidney function at the time of biopsy. Finally, the numbers of interstitial fibrocytes and macrophages as well as urinary CCL2 levels were significantly decreased during convalescence induced by glucocorticoid therapy. These results suggest that fibrocytes may be involved in the pathogenesis of chronic kidney disease through the interaction with macrophages as well as CCL2.

BACKGROUND:Crescent formation in glomeruli means an acute active lesion that develops a rapidly progressive course. Therapies using pulse methylprednisolone, oral corticosteroids, and cyclophosphamide are recommended, but no agreement has been reached on the optimal therapy. There have been no controlled trials, because of the severity of this condition and because withholding treatment would become an ethical issue.METHODS:We evaluated the safety and efficacy of deoxyspergualin (DSG), an immunosuppressant, in a multicenter, prospective trial of 44 patients with crescent formation in over 10% of glomeruli, who were randomly placed into groups that received daily doses of 0.1 mg/kg (n = 21) and 0.2 mg/kg (n = 23) of DSG, given by a 1-h infusion for 4 weeks, and who were then monitored for 3 months. All patients received DSG in this open-label prospective study. We evaluated the levels of urinary protein and hematuria, and examined renal function after the DSG treatment.RESULTS:Urinary protein significantly decreased with each dose after starting the DSG administration and this efficacy was sustained for 2 months after the discontinuation of DSG. In the groups receiving 0.1 mg/kg and 0.2 mg/kg, mean urinary protein levels were 2.1 g/day and 2.3 g/day at the initiation of the DSG administration, 1.4 g/day and 1.6 g/day at week 4, and 1.5 g/day and 1.3 g/day at week 12, respectively. Hematuria was markedly improved by a dose of 0.2 mg/kg and was not exacerbated following the termination of DSG. Exacerbation of renal dysfunction, as measured by creatinine clearance, serum creatinine, and blood urea nitrogen was prevented by both doses of DSG. The most common adverse reaction was reversible neutropenia.CONCLUSIONS:Short-term treatment with DSG may be effective and tolerated in patients suffering from nephropathies with crescent formation.

NephrologyVolume 8, Issue s4 p. A104-A106 The point of no return during the course of IgA nephropathy Mitsuhiro YOSHIMURA, Mitsuhiro YOSHIMURA Department of Internal Medicine,Search for more papers by this authorAkinori HARA, Akinori HARA Department of Internal Medicine,Search for more papers by this authorTakuyuki ISE, Takuyuki ISE Department of Internal Medicine,Search for more papers by this authorHiroshi KIDA, Hiroshi KIDA Department of Internal Medicine,Search for more papers by this authorHisao SASAKI, Hisao SASAKI Division of Clinical Research of Kanazawa National Hospital,Search for more papers by this authorTakashi WADA, Takashi WADA Department of Internal Medicine,Search for more papers by this authorHitoshi YOKOYAMA, Hitoshi YOKOYAMA Division of Blood Purification, Kanazawa University,Search for more papers by this authorKen-Ichi YAMADA, Ken-Ichi YAMADA Division of Clinical Research, Sakura National Hospital, JapanSearch for more papers by this author Mitsuhiro YOSHIMURA, Mitsuhiro YOSHIMURA Department of Internal Medicine,Search for more papers by this authorAkinori HARA, Akinori HARA Department of Internal Medicine,Search for more papers by this authorTakuyuki ISE, Takuyuki ISE Department of Internal Medicine,Search for more papers by this authorHiroshi KIDA, Hiroshi KIDA Department of Internal Medicine,Search for more papers by this authorHisao SASAKI, Hisao SASAKI Division of Clinical Research of Kanazawa National Hospital,Search for more papers by this authorTakashi WADA, Takashi WADA Department of Internal Medicine,Search for more papers by this authorHitoshi YOKOYAMA, Hitoshi YOKOYAMA Division of Blood Purification, Kanazawa University,Search for more papers by this authorKen-Ichi YAMADA, Ken-Ichi YAMADA Division of Clinical Research, Sakura National Hospital, JapanSearch for more papers by this author First published: 12 January 2004 https://doi.org/10.1111/j.1440-1797.2003.00192.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume8, Issues4January 2003Pages A104-A106 RelatedInformation

In contrast to malignant lymphomas or skin cancer, smooth muscle tumors including leiomyosarcoma are rarely associated with transplant recipients. We herein present a 33-year-old woman with end-stage renal disease who received a transplant at 27 years of age. Four years after the transplantation, at age 31, she underwent a mastectomy because of primary right breast cancer, which was found to be a 5-mm-sized mucinous carcinoma with no regional lymph node metastasis. Six years after the transplantation, a liver tumor was unexpectedly discovered. An explorative laparotomy revealed a well-encapsulated tumor occupying the posterior portion of the right lobe of the liver. The patient underwent a posterior segmentectomy. Histologically, the tumor possessed intermingling fascicles of spindle cells with eosinophilic cytoplasm and elongated nuclei. Based on an immunohistochemical examination, the tumor cells were positive for the muscle-associated antibody. In addition, RNA probes for Epstein-Barr virus were negative based on in situ hybridization. The histologic, immunohistochemical findings were considered to be diagnostic for leiomyosarcoma, which is a low-grade malignancy. Two years after surgery, the patient is doing well with no recurrence of liver tumors or breast cancer.

CAPD導入時には積極的適応の基準を満たし, 導入後は良好な経過が期待されると考えられた15例のうち, 心不全・溢水および腹膜炎を繰り返した6例をI群, 経過が良好であった9例をII群として, 生活環境およびその変化から受けるストレスに対処する能力について検討した.性・年齢・職業および生活環境についてみると, I群は独身男性, 自営業 (各2名) と幼児をもつ若年女性, 会社社長 (各1名) であった. またII群では, 30-40代の働き盛りの男性 (3名) と血液透析から移行した男性 (1名) と中年の専業主婦 (5名) であった.ストレス度は, 導入後の安定した状況下では, I群が53-159点, 平均73±17点, II群が53-212点, 平均110±12であった. しかしI群では合併症のおきる直前に118-480点, 平均295±48点に上昇した (p<0.005). ストレス増大の原因として, CAPDにおける最大の支援者である家族の入院, 転職, 職場の配置転換, 退職, 住居の新築, 育児および経済的困難などのさまざまなケースがみられた.食事管理能力は, II群の中年の専業主婦で高く, これは子供がすでに成長しており食事療法に対して専念できるためと考えられた. 一方, I群の独身男性や育児に追われている若年女性では劣っていた. これらの症例では, 麺類を多く摂ったために, 蛋白質の摂取が少なかったり, 外食の頻度も高く, 塩分制限も守られなかった.家族支援については, I群に比べてII群でより協力的であった (p<0.05).今回の研究により, 永続的な自己管理が必要なCAPD療法が, 患者に大きな精神的負担となっており, これに生活環境の変化から受ける新たなストレスが加わると, 食事管理・バッグ操作に集中できなくなり, 溢水・腹膜炎などの合併症を誘発する可能性が示された.