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Background: Renal cyst bleeding is a frequent problem in patients with autosomal dominant polycystic kidney disease (ADPKD). However, information is still limited on its frequency, causative factors, and effects on enlargement of polycystic kidneys in ADPKD., Methods: We investigated the total volume of acute renal intracystic hemorrhage and its association with total kidney volume (TKV) in a large series of patients with ADPKD on dialysis, referred for renal transcatheter arterial embolization. All patients had undergone CT scan and MRI scan before the procedure. We evaluated factors potentially associated with acute renal intracystic hemorrhage. The association between the  volume of acute renal intracystic hemorrhage and the potential predisposing and associated factors was analysed by univariable and multivariable regressions.  RESULTS: We enrolled 199 patients who underwent renal transcatheter arterial embolization from 2014 to 2018 (107 men, 92 women; mean age 59.1 ± 8.6 years). The median volume of acute renal intracystic hemorrhage was 97.3 ml (interquartile range 36.6-261.7 ml). Multivariable analysis revealed that body weight, kidney stones, systolic blood pressure, and total volume of acute renal intracystic hemorrhage were significantly associated with TKV; age, body mass index, smoking, renal cyst infection, serum alkaline phosphatase, and TKV were significantly associated with the volume of acute renal intracystic hemorrhage ; and sex, age, dialysis vintage, TKV, and total volume of acute renal intracystic hemorrhage were significantly associated with the number of microcoils required to achieve renal  transcatheter arterial embolization. Total volume of acute renal intracystic hemorrhage was significantly associated with TKV (r = 0.15, p = 0.0325) and was greater in younger patients (r= - 0.32, p < 0.0001). Total volume of acute renal intracystic hemorrhage was also correlated with the number of microcoils required for renal transcatheter arterial embolization (r = 0.23, p = 0.0012)., Conclusion: Acute renal intracystic hemorrhage is frequent among ADPKD patients on dialysis, and total volume of acute renal intracystic hemorrhage significantly associated with  TKV. Total volume of acute renal intracystic hemorrhage  was greater in younger patients with higher renal artery luminal size. These results suggest that renal cyst bleeding and renal artery blood flow may synergistically accelerate the enlargement of polycystic kidneys in ADPKD patients on dialysis., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background and Purpose: We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA)., Methods: We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990-1999 (n = 48); period 2, 2000-2009(n = 57); period 3, 2010-2019 (n = 51)., Results: Membranous nephropathy, nephrosclerosis, AA-amyloidosis, and IgA nephropathy were the four major renal manifestations of RA. AA-amyloidosis was diagnosed by kidney biopsy in 21 patients: period 1, 7 patients (15%); period 2, 10 patients (18%); and period 3, 4 patients (8%). The 4 patients in period 3 were in the years 2010-2014, and no new case of AA-amyloidosis was recorded from 2015 to 2019. In all 21 of the patients with AA-amyloidosis, neither a biologic agent nor methotrexate was administered. Fifteen of the 21 patients required dialysis, and 13 died in periods 1-3 because of amyloid-related cardiac dysfunction less than 2 years after the initiation of dialysis. Two of them are doing well using biologic agent despite dialysis. The remaining three patients who received a biologic agent or methotrexate does not progress to end-stage renal failure. In addition, the other renal complications showing progression to dialysis also decreased over time., Conclusion: Advances in treatment strategies have improved renal outcome and reduced mortality in patients with RA., (© 2021. The Author(s).)

Purpose and Method: Patients on hemodialysis develop carpal tunnel syndrome (CTS) due to an accumulation of dialysis-related β2 microglobulin (β2m) amyloid (DRA). In Japan, dialysis technology has progressed remarkably in the past 40 years and has increased the time until patients require surgery for CTS. However, unclear is whether the time from the start of hemodialysis to the first surgery for CTS is associated with β2m clearance by the different hemodialysis techniques. Therefore, we retrospectively evaluated β2m clearance, serum β2m levels, and the change in the length of this period in patients across 4 periods according to the year that first surgery for CTS was performed: period 1, 1982-1989; period 2, 1990-1999; period 3, 2000-2009; and period 4, 2010-2019., Result: A total of 222 patients who met the selection criteria were included. Mean β2m clearance was -1.8 ± 16.7% in period 1, and improved to 65.4 ± 8.6% in period 3. Accordingly, the serum β2m value after hemodialysis decreased significantly. The time from the start of hemodialysis to the first surgery for CTS was 12.4 ± 2.9 years in period 1 but increased to 21.8 ± 6.3 years in period 3. In multivariable linear regression analysis, the significant factors contributing to β2m clearance were periods 2, 3, and 4. In particular, the relation between removal of β2m and the extension of the dialysis vintage in period 1 and 2 was remarkable compared with periods 3 and 4., Conclusion: Our findings indicate that improvement of β2m clearance via advances in dialysis technology might result in a significant extension in the time between starting HD and the first surgery for CTS., (© 2021. The Author(s).)

Introduction: Currently, there are no reports of diaphyseal femoral fracture equivalent to atypical femoral fractures (AFFs) in patients receiving long-term hemodialysis (HD)., Case Report: A 56-year-old Japanese man receiving long-term HD for 34 years was admitted to our hospital due to a delay in postoperative healing. The patient began maintenance hemodialysis at 22 years of age. The patient then underwent surgical parathyroidectomy (PTX) for secondary hyperparathyroidism at 43 years of age, which resulted in decreased levels of parathyroid hormone (PTH). Thereafter, this patient's serum 1,25(OH) 2 D 3 level was very low because active vitamin D 3 derivative was not administered. At 54 years of age, a transverse fracture of the femoral shaft equivalent to AFF occurred. Surgery with open reduction and internal fixation using intramedullary nailing was performed; however, the delay of postoperative healing continued for 16 months. A left iliac crest bone biopsy was performed and showed osteoid-like lesion and an increase of woven bone. The patient received active vitamin D 3 derivative and recombinant human PTH (1-34) derivative. Twenty-nine months after the first surgery, a reoperation was performed. Simultaneously, a right iliac crest bone biopsy was performed. Bone morphometrical improvement was confirmed. Six months after resurgery, the bone union was achieved. Severe vitamin D 3 deficiency and decreased levels of PTH may induce a higher osteoid state and an increase of woven bone, which may then attribute to the development of diaphyseal femoral fracture and impairment of postoperative bone healing. It is hypothesized that treatment with active vitamin D 3 and teriparatide acetate may be a therapeutic option via the accelerated formation of lamellar bone for refractory diaphyseal femoral fracture of long-term dialysis.

Both thin basement membrane nephropathy (TBMN) and autosomal dominant Alport syndrome (ADAS) are types of hereditary nephritis resulting from heterozygous mutations in COL4A3 or COL4A4 genes. Although TBMN is characterized by hematuria and thinning of the glomerular basement membrane (GBM) with excellent renal prognosis, some patients develop end-stage renal disease (ESRD) later in life. In contrast, although AS is characterized by progressive nephropathy with lamellation of the GBM, there are some patients diagnosed with ADAS from a family history of ESRD but who only suffer from hematuria with GBM thinning. These findings indicate a limitation in distinction between TBMN and ADAS. Diagnosis of AS is significant because it facilitates careful follow-up and early treatment, whereas diagnosis of TBMN can underestimate the risk of ESRD. However, some experts are against using the term ADAS as the phenotypes of heterozygous variants vary from no urinary abnormality to ESRD, even between family members with the same mutations, indicating that unknown secondary factors may play a large role in the disease severity. These diagnostic difficulties result in significant confusion in clinical settings. Moreover, recent studies revealed that the number of patients with chronic kidney disease caused by these gene mutations is far higher than previously thought. The aim of this article is to review differing opinions regarding the diagnosis of heterozygous COL4A3 or COL4A4 variants, and to highlight the importance for nephrologists to recognize this disease, and the importance of the need to reclassify this disease to minimize the current confusion.

Associations between treatment outcomes of immune checkpoint inhibitors and metastatic sites in advanced non-small cell lung cancer (NSCLC) are not well known. Therefore, this multicenter retrospective study aimed to investigate the predictive factors of metastatic sites after first-line pembrolizumab treatment for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%. We retrospectively analyzed advanced NSCLC patients with a PD-L1 TPS ≥50% who underwent first-line pembrolizumab therapy at 11 institutions between February 2017 and April 2018. Clinical data collected from medical records included metastatic sites at the time of pembrolizumab treatment. Treatment outcomes of pembrolizumab were assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. In total, 213 patients were included in the study. The median age was 71 years (range 39-91 years). Of the 213 patients, 176 (83%) were men and 172 (81%) had an Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 0-1. The most common metastases were thoracic lymph node metastasis (77%), intrapulmonary metastasis (31%), bone metastasis (28%), and malignant pleural effusion (26%). On multivariate analysis, a poor ECOG-PS score (hazard ratio: 1.95, 95.0% confidence interval: 1.25-3.04; P = 0.003) and malignant pleural effusion (hazard ratio: 1.52, 95.0% confidence interval: 1.01-2.29; P = 0.043) were independent predictors of shorter progression-free survival in patients treated with pembrolizumab. For NSCLC patients with malignant pleural effusion, pembrolizumab monotherapy is not a suitable first-line treatment because of its insufficient effectiveness, even though their PD-L1 TPS was high.

Objectives As first line therapy, pembrolizumab provides longer progression free survival (PFS) and overall survival (OS) than platinum doublets in programmed death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) with tumor propensity scores (TPS) ≥50%. However, clinical trials do not represent real-world patients. Materials and Methods This multicenter retrospective study conducted across 11 medical centers in Japan analyzed clinical data from patients receiving first-line pembrolizumab for NSCLC between February 1, 2017 and April 30, 2018. The efficacy, safety, and suitability of pembrolizumab monotherapy were evaluated. Results The median age of the 213 enrolled patients was 71 (range: 39-91) years. Among them, 176 (82.6%) were male, 20 (9.4%) were never smokers (median Brinkman index: 900), 172 (80.8%) had an ECOG PS of 0-1, 55 (25.8%) had squamous-cell carcinoma (SQ). PD-L1 TPS were 50-74%, 75-89%, and 90-100% in 97 (45.5%), 47 (22.1%), and 69 (32.4%) patients, respectively. Adverse events (AEs) of grades ≥3 were observed in 39 (18.3%) patients. Pneumonitis was the most common severe AE, occurring in 10 patients (4.7%) including 1 with grade 4 toxicity; no severe AE-related deaths occurred. The overall response rate, median PFS, and median OS was 51.2%, 8.3 months, and 17.8 months, respectively. On multivariate analysis, ECOG PS (0-1 vs. ≥2: HR: 1.69, 95.0% CI: 1.05-2.72; p = 0.03138), CRP/Alb (<0.3 vs. ≥0.3: HR: 1.92, 95.0% CI: 1.28-2.87; p = 0.00153), steroid usage (not usage vs. usage: HR: 2.94, 95.0% CI: 1.45-5.95; p = 0.00267), and PD-L1 TPS (50-89% vs. 90-100%: HR: 0.65, 95.0% CI: 0.43-1.00; p = 0.04984) were significantly and independently correlated with PFS of pembrolizumab. Conclusion The results confirm the efficacy and safety of pembrolizumab in real-world patients. Poor PS and steroid usage at the time of commencing pembrolizumab treatment indicate poor outcomes. First-line pembrolizumab particularly benefits patients with PD-L1 TPS ≥90% or low inflammatory states (CRP/ALB<0.3).

Background: Cholesterol crystal embolism (CCE) causes renal damage, and there is an extremely high risk of end-stage renal disease. However, the time course of CCE-related renal deterioration varies and little is known about the subsequent risk of dialysis among patients with biopsy-proven CCE., Methods: We performed a retrospective cohort study of 38 Japanese patients in whom a histological diagnosis of CCE was made from September 1992 to July 2005. Competing risk regression analysis was used to investigate the association between declining renal function ( ≥ 1.5 elevation of serum creatinine within 26 weeks after CCE) or its subtypes (acute [ < 1 week after CCE], subacute [1 to < 6 weeks], and chronic [6 to < 26 weeks]) and the risk of dialysis, with adjustment for age, baseline serum creatinine, and the precipitating event (iatrogenic or spontaneous)., Results: During a median follow-up period of 25.9 weeks, 14 patients (35.9%) started dialysis. Multivariable analysis showed that patients with declining renal function had a higher risk of commencing dialysis than those without declining function (subdistribution hazard ratio [SHR] 9.47; 95% confidence interval [CI] 1.34-66.8). Patients with different renal presentations had a similarly increased risk of commencing dialysis, with the risk being significantly higher for the subacute and chronic patterns of declining renal function (adjusted SHR [95% CI] for acute, subacute, and chronic declining renal function[vs. no decline]: 7.36 [0.85-63.6], 11.9 [1.36-101], and 10.7 [1.49-77.0], respectively)., Conclusion: Declining renal function after CCE, even later than 6 weeks, was significantly associated with the subsequent risk of dialysis.

Introduction: In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction., Materials and Methods: We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90)., Results: Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients., Conclusion: While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.

Objectives: Hypertrophic pachymeningitis (HP) is a rare complication in patients with anti-neutrophil antibody-associated vasculitis (AAV); its clinical features, incidence, and risk factors remain unknown. We aimed to clarify the prevalence, clinical features, and factors associated with new-onset HP in patients with AAV., Method: A retrospective cohort study involving 93 patients with AAV was conducted. HP incidence between patients with granulomatosis with polyangiitis (GPA) and those with microscopic polyangiitis (MPA) was compared to investigate risk factors associated with HP. We performed only univariate analysis using logistic regression and classification tree (CART) analysis due to the small number of HP cases., Results: Among the 93 patients (76 with MPA and 17 with GPA), only 6 patients developed HP (1 with MPA, 5 with GPA) over an average observation period of 4 years; all patients who developed HP were positive for myeloperoxidase anti-neutrophil antibody. HP incidence was significantly higher in patients with GPA than in those with MPA (60.2 versus 3.3 persons per 1000 person-years, respectively, P = 0.002). The univariate analysis revealed that otitis media (P < 0.001) and sinusitis (P = 0.014) were associated with new-onset HP. Univariate CART analysis grouped the patients into patients with HP who have otitis media (33%) and patients with HP who have sinusitis (21%). The odds ratio of otitis media adjusted by age and first diagnosis of AAV was 38.1 (95% confidence interval, 3.08-331.4; P = 0.004)., Conclusions: Although only in the univariate analysis, otitis media was the most discriminating factor to predict new-onset HP in patients with AAV.

Background: A recent study demonstrated that tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in later-stage autosomal dominant polycystic kidney disease (ADPKD) patients. However, Japanese patients were not included in that trial, therefore tolvaptan's efficacy in Japanese patients with advanced chronic kidney disease (CKD) has remained unknown., Methods: In this prospective cohort study, 54 patients with ADPKD who had eGFR ≥ 15 ml/min/1.73 m 2 and total kidney volume (TKV) ≥ 750 ml were treated with tolvaptan. The primary endpoint was the change in height-adjusted total kidney volume (htTKV) and eGFR after 1-year treatment with tolvaptan. Then, we compared the primary endpoint between later CKD stage (baseline eGFR < 45 ml/min/1.73 m 2 ) and earlier CKD stage (baseline eGFR ≥ 45 ml/min/1.73 m 2 )., Results: The rate of kidney growth during the 1-year treatment did not differ significantly between earlier and later CKD stages. The median and interquartile range of relative change in htTKV in later CKD stage was 8.2%/year [4.4, 26.6], as compared with 5.7%/year [1.6, 16.4] in earlier CKD stage (p = 0.17). Nor did the rate of eGFR decline between earlier and later CKD stages. The relative annual change in eGFR in later CKD stage was - 9.7%/year [- 15.9, - 2.1], as compared with - 6.8%/year [- 11.1, 0.1] in earlier CKD stage (p = 0.18)., Conclusion: This analysis indicates that the efficacy of tolvaptan for Japanese patients with later stage ADPKD was not significantly different from that of Japanese patients with earlier stage ADPKD.

Background: Ceftriaxone (CTRX) is a known cause of biliary pseudolithiasis (BPL) mainly in children. Biliary elimination of CTRX increases in patients with renal dysfunction. However, the influence of renal dysfunction on the incidence of CTRX-associated BPL has not been well investigated. The aim of this study was to investigate the cumulative incidence of CTRX-associated BPL in adults and to assess if renal dysfunction is a risk factor., Methods: We retrospectively analyzed the medical records of 478 patients treated with CTRX to assess the incidence and risk factors of CTRX-associated BPL. We examined age, sex, body weight, dosage, and duration of CTRX therapy, and the concentrations of serum creatinine, estimated glomerular filtration rate (eGFR), albumin, and serum calcium in all the patients. The cumulative incidence of BPL was calculated using a competing risk model. The multivariate analysis of each variable for the development of BPL was assessed by a Cox proportional hazards model., Results: A total of 362 patients (75.7%) had renal dysfunction (eGFR: < 60 mL/min). The cumulative incidence of BPL in patients with renal dysfunction was significantly higher than that in patients with normal kidney function (4.1 vs. 0.6%, p = 0.017). Renal dysfunction (Hazard ratio (HR) 8.14, 95% CI 1.05-63.0, p = 0.045) and female sex (HR 5.35, 95% CI 1.17-24.5, p = 0.031) were independent risk factors of CTRX-associated BPL, which was confirmed using multivariate analysis (renal dysfunction: HR 7.93, 95% CI 1.04-60.5, p = 0.046) (female sex HR 4.65, 95% CI 1.03-21.1, p = 0.046)., Conclusions: Renal dysfunction is an independent risk factor of CTRX-associated BPL in adults.

Background: The ongoing effort to prevent dialysis-related amyloidosis (DRA) has been hampered by lack of any way to measure DRA's severity. Yet, such measurement is essential for assessing the effect of DRA treatment. Accordingly, we developed a scoring system focused on the physical manifestations of DRA., Methods: Forty-four patients on maintenance hemodialysis with DRA, and 96 without it, were enrolled. The SF-36v2 Health Survey ascertained whether patients experienced general bodily pain and/or physical dysfunction with any attendant specific pain (dysfunction). If so, the association of those conditions with a finding of DRA was analyzed-including laboratory and radiographic data-and a scoring system reflecting the extent of that dysfunction was devised using the significant variables in the multivariate analysis., Results: Both dysfunction and general bodily pain were severe in patients with DRA. Presence of polyarthralgia, trigger finger, carpal tunnel syndrome (CTS), and dialysis-related spondyloarthropathy (DRS) were associated with that dysfunction after appropriate adjustments. The new scoring system used those four variables in the model, with a 3 given for polyarthralgia and DRS, and 2 for trigger finger and CTS (possible range 0-10). Based on the physical functioning score of SF-36v2, we categorized A-score into three stages: mild (A-score 3-4), moderate (5-7), and severe (8-10). The corresponding area under the receiver-operating characteristics curve for diagnosis of DRA was 0.9345 when we set the cutoff value as 4., Conclusion: This validated scoring system for quantitatively estimating the severity of DRA can serve as A useful measure in clinical practice.

A 41-year-old man was referred to our hospital for the evaluation of hypergammaglobulinemia (IgG 2898 mg/dL and IgA 587 mg/dL), inflammation (CRP 6.7 mg/dL and serum interleukin-6 (IL-6) 15.1 ng/L), and anemia (Hb 10.9 mg/dL). Castleman's disease (CD) was diagnosed by axillary lymph node biopsy. Five months later, painful purpura (multiple palpable 5 mm lesions) developed on his legs, gradually spreading to the upper limbs, thighs, and trunk, accompanied by arthralgia of the wrists, ankles, and knees. Skin biopsy revealed leukocytoclastic vasculitis with IgA deposits in dermal vessels. Accordingly, IgA vasculitis (Henoch-Schönlein purpura) was diagnosed. Tocilizumab (an anti-IL-6 receptor antibody) was administered intravenously at 8 mg/kg and treatment was repeated at monthly intervals. His purpura and clinical findings specific to CD improved rapidly. CD is well known to cause various skin lesions. The findings in this case indicate that overproduction of IL-6 contributes to IgA vasculitis (Henoch-Schönlein purpura) as well as to the pathogenesis of CD.

Cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD). Lipid-soluble antibiotics like fluoroquinolones show good penetration into cysts and are recommended for cyst infection, but causative microorganisms are often resistant to these agents. This study investigated the profile of the microorganisms causing cyst infection in ADPKD, their susceptibility to lipid-soluble antibiotics, and clinical outcomes. This retrospective study reviewed all ADPKD patients admitted to Toranomon Hospital with a diagnosis of cyst infection from January 2004 to March 2014. All patients who underwent cyst drainage and had positive cyst fluid cultures were enrolled. Patients with positive blood cultures who satisfied our criteria for cyst infection or probable infection were also enrolled. There were 99 episodes with positive cyst fluid cultures and 93 episodes with positive blood cultures. The majority of patients were on dialysis. The death rate was high when infection was caused by multiple microorganisms or when there were multiple infected cysts. Gram-negative bacteria accounted for 74-79 % of the isolates in all groups, except for patients with positive hepatic cyst fluid cultures. The susceptibility of Escherichia coli to fluoroquinolones was very low in patients with hepatic cyst infection, especially those with frequent episodes and those with hepatomegaly. Fungi were detected in two episodes. Fluoroquinolone-resistant microorganisms showed a high prevalence in cyst infection. It is important to identify causative microorganisms to avoid the overuse of fluoroquinolones and to improve the outcome of cyst infection in ADPKD.

Background: Transcatheter arterial embolization (TAE) has become a therapeutic option for symptomatic polycystic kidney disease (PKD) and polycystic liver disease (PLD). However, factors affecting survival with renal TAE remain unknown., Methods: All symptomatic patients with severe PKD and/or PLD who received renal and/or hepatic TAE at our center from October 1996 through March 2013 (n = 1,028) were followed until death. Their survival was compared with that of the general PKD population on dialysis in Japan. Factors affecting survival were analyzed using the Cox hazard model., Results: After renal TAE, 5- and 10-year survival was, respectively, 0.78 (95% confidence interval, 0.74-0.82) and 0.56 (0.49-0.63); with hepatic TAE, 0.69 (0.58-0.77) and 0.41 (0.22-0.60); and with dual TAE (renal and hepatic), 0.82 (0.72-0.88) and 0.45 (0.31-0.59). Survival after dialysis initiation was better among patients with renal TAE than among general PKD patients. Factors affecting survival after renal TAE were age [hazard ratio (HR) 3.02 (1.44-6.33) for every 10 years] and albumin [HR 0.70 (0.55-0.89) per 0.1 g/dl]. Kidney volume was not associated with patient death after TAE. The main causes of death among patients after renal TAE were similar to those of the general PKD population on dialysis whereas, after hepatic TAE, the main cause was cyst infection with liver failure (12.5% with PLD and 5.9% with PKD, p < 0.01)., Conclusion: Survival after renal TAE with severe PKD was better than for the general PKD population on dialysis, suggesting that renal TAE could overcome the disadvantage due to huge organ size.

Background: Previous studies on membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemic glomerulopathy (CG) were based upon case series that were performed before hepatitis C virus (HCV) infection was routinely investigated. Therefore, it remains unknown how far HCV contributes to MPGN or CG, and there have only been a few reports about HCV-negative idiopathic MPGN., Patients and Methods: Thirty-five patients with MPGN diagnosed by renal biopsy who underwent examination for HCV infection at our institute between 1990 and 2008 were recruited for this study. Patients with HCV infection at presentation were included, but patients with complications such as underlying lymphoproliferative disorders, autoimmune diseases like lupus nephritis, infection, and liver disease due to hepatitis B virus or alcohol abuse were excluded. A total of 35 patients were enrolled and they were divided into two groups according to the presence/absence of circulating cryoglobulins (cryo). The 23 patients who had cryo-negative and HCV-negative idiopathic MPGN were divided into subgroups with type 1 and type 3 disease., Results: In the cryo-positive group (n = 9), 7 patients were positive for HCV infection, while 2 patients were negative. In the cryo-negative group (n = 26), 3 patients were positive for HCV infection, while 23 patients were negative (idiopathic MPGN). Compared with the cryo-negative group, the cryo-positive group had several characteristics such as more severe thrombocytopenia, higher serum immunoglobulin (Ig)G and IgM levels, lower levels of hemolytic complement (CH50) and complement component (C)4, predominant IgM staining, and type 1 histology. Patients with cryo-negative and HCV-negative 'idiopathic' MPGN showed predominant staining for IgG in both type 1 and type 3 cases, unlike the predominant staining for IgM in the cryo-positive group. Compared with type 3 cases, type 1 cases had a younger age, lower levels of CH50, C3 and C4, and less proteinuria. In the cryo-positive group, 4 patients (44.4 %) died, with death from B cell lymphoma and liver failure in 2 patients each, while 1 patient (8 %) developed end-stage renal failure requiring dialysis. In contrast, all patients in the cryo-negative group remained alive during follow-up, although 4 patients (2 type 1 cases and 2 type 3 cases) required dialysis., Conclusion: Cryo-positive MPGN shows a close relationship with HCV infection and IgM, resulting in a poor prognosis. Cryo-negative and HCV-negative idiopathic MPGN has a close relationship with IgG staining, and type 1 cases feature characteristics such as a younger age, more severe hypocomplementemia, and less proteinuria than in type 3 cases.

Background and Objectives: Cyst infection and cyst hemorrhage are frequent and serious complications of autosomal dominant polycystic kidney disease (ADPKD), often being difficult to diagnose and treat. The first objective of this study is to clarify the clinical features of ADPKD patients with cyst hemorrhage or infection. The second objective is to establish diagnostic criteria for ADPKD patients with cyst infection or cyst hemorrhage., Patients and Methods: Patients with definite cyst infection or hemorrhage were enrolled from among the ADPKD patients referred to us between January 2004 and October 2011. We investigated their symptoms, laboratory data, and the computed tomography (CT)/magnetic resonance imaging (MRI) features of infected cysts (before and after onset), normal cysts, and cysts with hemorrhage., Results: There were 24 patients with cyst infection (36 infected cysts) and 12 patients with acute cyst hemorrhage (13 bleeding cysts). White blood cell (WBC) count >10,000/μl, serum C-reactive protein (CRP) >15.0 mg/dl, and body temperature >38 °C strongly suggested cyst infection. All of the cysts with hemorrhage contained a high-density mass-like area or showed overall high density on CT, and all patients with cyst hemorrhage had abdominal pain or gross hematuria. On the other hand, infected cysts showed an increase of intensity on MRI [diffusion-weighted imaging (DWI)], while a fluid-fluid level, wall thickening, and gas were also evidence of infection. Abdominal pain and/or sequential changes on MRI after onset of symptoms were useful for localizing infected cysts., Conclusion: Acute cyst hemorrhage and infection can be identified from symptoms, laboratory data, and CT/MRI findings.

Background: Since 1996, transcatheter renal artery embolization (renal TAE) has been performed to reduce the volume of the kidneys in patients with autosomal dominant polycystic kidney disease (ADPKD) and complications of nephromegaly at our hospital. Respiratory dysfunction is often a serious problem in these patients before TAE., Patients and Methods: Between January 2006 and October 2008, renal TAE was performed and lung function testing [percent vital capacity (%VC) and percent forced expiratory volume in 1 s (%FEV(1.0))] was done by spirometry in 28 patients on maintenance hemodialysis who had respiratory symptoms., Results: Renal volume was 6,330.5 ± 3,126.5 cm(3) (range 1,771-12,761 cm(3)) before TAE, and decreased significantly to 2,892.2 ± 1,841.7 cm(3) (range 622-6,961 cm(3)) by 12 months after TAE (p = 0.0001). The percent decrease of renal volume at 12 months after TAE versus baseline was 45.6 ± 14.6% (range 6.6-67.3%). %VC showed a significant increase from 95.9 ± 14.8% (range 63-127%) before renal TAE to 100.1 ± 11.7% (range 78-120%) at 12 months after TAE (p < 0.01). %FEV(1.0) was also significantly increased from 87.9 ± 15.0% (range 55-110%) before renal TAE to 92.5 ± 14.4% (range 58.0-115.0%) at 12 months after TAE (p < 0.01). The changes of VC (ΔVC%) and FEV(1.0) (ΔFEV(1.0)%) both showed a significant positive correlation with the reduction of renal volume (Δ renal volume) (p = 0.001 and p = 0.004, respectively)., Conclusion: Since TAE not only led to a significant decrease of renal volume in ADPKD patients with nephromegaly, but also improved lung function (both %VC and %FEV(1.0)), pulmonary dysfunction should be recognized as one of the extrarenal complications of ADPKD.

Background: High-dose melphalan and autologous stem cell transplantation (HDM) is an effective treatment for systemic amyloid light chain (AL) amyloidosis but the eligibility criteria exclude many patients with this disorder. The aim of this study was to determine appropriate treatment strategies for systemic AL amyloidosis according to each patient's clinical condition in Japan., Methods: Historical cohort study. Fifty-three patients with systemic AL amyloidosis (those with malignancies were excluded) were treated in our hospital with HDM (15 patients), melphalan + prednisolone (MP) (17 patients), vincristine + adriamycin + dexamethasone (VAD) (11 patients), or supportive treatment (no chemotherapy, 10 patients). We compared the survival rates among these treatment groups., Results: Mean survival was significantly longer in the HDM group than in the other three groups (P < 0.01, log-rank test). This trend remained the same when patients were divided into those with and without cardiac amyloid involvement. Furthermore, in patients with heart involvement, survival in the VAD therapy group was significantly inferior to that in the MP therapy group (P < 0.01 by log-rank test). Significant factors related to the survival rate included the presence or absence of heart involvement and treatment modality., Conclusions: HDM should be considered the treatment of choice in eligible patients with systemic AL amyloidosis even in the presence of cardiac amyloidosis. If HDM is not eligible, indications for VAD therapy should be carefully evaluated in patients with cardiac amyloidosis.

Acute promyelocytic leukemia (APL) has the best prognosis among acute leukemias, but there is little data about APL in patients on hemodialysis. A 64-year-old hemodialysis patient was successfully treated for APL by induction therapy with all-trans retinoic acid (ATRA), three courses of consolidation therapy with Ara-C, mitomycin C (MIT), daunorubicin (DNR), and idarubicin (IDR), and maintenance therapy with ATRA. Complete remission has been maintained for 42 months in this patient. With dose modification, ATRA and chemotherapy may be safely given to patients on hemodialysis.

A 40-year-old Japanese man was admitted to our hospital for investigation of fever and right flank pain starting after watery diarrhea. Salmonella enteritidis was cultured from samples of stool and blood. Although his diarrhea subsided soon, high fever persisted and flank pain got worse. Magnetic resonance imaging (MRI) revealed four areas of abnormal intensity in renal cysts and computed tomography showed the same findings. Renal cysts infection was diagnosed. After ultrasound-guided aspiration of these cysts, his fever subsided. Culture of each aspirate grew Salmonella enteritidis. Although the route of cyst infection in ADPKD generally remains unclear, the clinical course of our patient may indicate that gastrointestinal tract infection progressed to renal cyst infection when bacteremia occurred due to bacterial translocation.

A 45-year-old Japanese woman had been diagnosed with monoclonal gammopathy of undetermined significance (MGUS) featuring urinary Bence-Jones protein of the lambda type (BJP-lambda) for 11 years. She then developed eyelid purpura, dyspnea, and flank pain. Abdominal CT scans revealed renal infarction. Biopsy of the kidney, heart, jejunum, and skin demonstrated amyloid deposits in the vessel walls, but not in the glomeruli. She was diagnosed as having AL amyloidosis with IgD-lambda monoclonal gammopathy and BJP-lambda. Autologous stem cell transplantation (SCT) was done after chemotherapy with vincristine, daunorubicin, dexamethasone (VAD), and high-dose melphalan (HDM). This reduced the IgD level from 156 to 0.1 mg/dL, along with the disappearance of BJP, despite cerebral infarction during chemotherapy. We recommend SCT for patients with IgD-associated AL amyloidosis.

We report the case of a 69-year-old Japanese woman who presented with thrombotic thrombocytopenic purpura (TTP) which had manifested soon after the onset of adult-onset Still's disease (AOSD). Her disease was multi-drug resistant. She had undergone treatment with high-dose glucocorticoids, two courses of steroid pulse therapy, and cyclosporine A. The patient initially had a favorable response to the administration of etanercept (an anti-tumor necrosis factor agent) and glucocorticoids. However, her disease became refractory to etanercept after 6 months. Therefore, we administered tocilizumab (a humanized monoclonal anti-IL-6 receptor antibody) which dramatically improved the patient's refractory AOSD with TTP. This is the first report of an effective treatment for AOSD with TTP using the biological agents. Our report strongly suggests that biological agents, especially a humanized monoclonal anti-IL-6 receptor antibody, may be a new option for a safe and effective treatment of multi-drug-resistant AOSD and TTP associated with AOSD.

Purpose: The aim of this study was to compare the safety and short-term efficacy of transcatheter arterial chemoembolization (TACE) using cisplatin-Lipiodol suspension (CP/Lp) with that using epirubicin-Lipiodol emulsion (EP/Lp) in patients with recurrent hepatocellular carcinoma (HCC)., Materials and Methods: A total of 28 HCC patients were enrolled prospectively and assigned to the CP/Lp group or EP/Lp group. Adverse effects related to TACE were graded; and the treatment effect (TE) on HCC nodules at 3 months and overall tumor response at 6 months were assessed as the endpoint., Results: No significant difference was observed between the groups regarding the frequency of adverse effects of grade 3 or less. The TE rates for 100% necrosis plus >50% necrosis in 62 HCC nodules in the CP/Lp group and 75 HCC nodules in the EP/Lp group were 72.6% and 66.7%, respectively (P = 0.894). Overall tumor response revealed that six patients (50.0%) in the CP/Lp group and six patients (37.5%) in the EP/Lp group had a partial response plus a complete response, with no significant difference (P = 0.615). TACE-free control curves for both groups revealed no significant difference (P = 0.513)., Conclusion: No significant difference was found with regard to adverse effects, the treatment effect on HCC nodules, or overall tumor response between the CP/Lp and EP/Lp groups.

A 56-year-old Japanese man was admitted to our hospital with abdominal fullness in June 2006. He had been diagnosed as having a horseshoe kidney by computed tomography in January 2002. At that time, renal dysfunction (serum creatine: 2.0 mg/dl) was detected. Even after hemodialysis was started for end-stage renal failure in March 2006, his abdominal fullness became progressively worse. CT scanning showed a markedly enlarged horseshoe kidney. Transarterial embolization (TAE) was performed via the right renal arteries with 14 platinum microcoils; the left renal arteries were not embolized in order to preserve sufficient parenchyma and a urine volume of more than 1,000 ml daily. Two years after TAE, a decrease in the size of the left kidney was noted along with the right kidney. However, urine output was still more than 1,000 ml daily. It is possible that one kidney compressed the contralateral kidney, resulting in enlargement of both components of the horseshoe kidney and renal dysfunction. TAE may be a useful option for obstructive uropathy in patients with horseshoe kidney, which has conventionally been treated surgically.

We report a 58-year-old Japanese man with primary systemic AL amyloidosis who achieved disappearance of proteinuria including Bence-Jones protein (lambda-type) after two courses of VAD therapy (vincristine, doxorubicin, and dexamethasone) and subsequent high-dose melphalan, followed by autologous peripheral blood stem cell transplantation. Because this patient did not have any apparent amyloidosis-related heart or liver damage and met all of the eligibility criteria for this therapy, this treatment was performed. Both proteinuria and M-protein disappeared completely, and he is doing well clinically at 19 months after treatment. However, amyloid deposits were still found in the kidneys, including the glomeruli and tubulointerstitium, when renal biopsy was done at 8 months after treatment. In the future, we may reach a time when clinical remission corresponds to histological remission.