Search

Abstract Background Kidney transplantation has long been associated with the incidence of lymphoma. These lymphomas are typically Epstein–Barr virus-associated B cell lymphomas. However, T cell lymphomas occur rarely. Case presentation We present the case of a 57-year-old Japanese man. He underwent a living kidney transplantation twice at age 43 and 46 years. However, the kidney function abolished after 9 years, and he restarted hemodialysis at age 55. After 2 years, an ulcer appeared on his right lower leg. It was not ameliorated but enlarged and became too painful to walk. Skin biopsy diagnosed with primary cutaneous gamma–delta (γδ) T cell lymphoma (PCGD-TCL) on his right leg. PCGD-TCL is one of the highly aggressive lymphomas that express gamma–delta T cell receptor gene arrangement and is difficult to diagnose and treat. He underwent cyclophosphamide 350 mg/m2(50% dose), hydroxydaunorubisin 50 mg/m2, vincristine 1.4 mg/m2, and prednisolone 100 mg/body (CHOP) therapy four times, but these were not effective and caused many complications such as septic febrile neutropenia. Although he decided to undergo amputation of his right leg finally, he died following postoperative cytomegalovirus meningitis. Conclusions This is the first case of PCGD-TCL after kidney transplantation. It shows that the transplanted kidney can lead to lymphoma development, even after the functional loss of the transplanted kidney, and that it is crucial to consider performing the biopsy aggressively for untreatable leg ulcers in hemodialysis patients.

We experienced a 46-year-old man with rapidly declining renal function over the past 5 years. By strict diet and exercise regimen, he reduced his body mass index (BMI) from 35.1 to 24.8 over 15 months, which prevented the progression of renal dysfunction for the next 10 years. Kidney biopsy showed focal segmental glomerulosclerosis (FSGS) corresponding to obesity-related glomerulopathy. Besides suppressing the progression of renal function decline, resolution of the significant obesity reduced proteinuria and improved blood pressure control. We concluded that obesity itself caused FSGS, probably via hyperfiltration, which caused refractory hypertension and triggered proteinuria, resulting in renal function decline.

A kidney biopsy was performed in a 64-year-old woman with type 2 diabetes mellitus and less than 1 g of proteinuria who rapidly progressed to end-stage renal failure after approximately 2 years of treatment with two dipeptidyl peptidase 4 (DPP-4) inhibitors for type 2 diabetes mellitus. The biopsy revealed not only a coincidental diagnosis of renal cell carcinoma, which was not evident on pre-biopsy computed tomography, but also severe thrombotic microangiopathy (TMA)-like glomerular endothelial cell damage in the noncancerous areas. These results suggest that DPP4 inhibitors may have been involved in two kidney diseases.

Abstract Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation.

We present a 51-year-old male patient with a history of Child-Pugh Grade B alcoholic liver cirrhosis (ALC) who developed renal impairment (serum creatinine of 2.00 mg/dL) and nephrotic syndrome (a urinary protein level of 4.35 g/gCr). The patient was diagnosed with immunoglobulin A nephropathy (IgAN) associated with ALC based on findings from comprehensive evaluations, including markedly elevated serum IgA levels (883.7 mg/dL), a kidney biopsy revealing significant IgA deposition in the para-mesangial area, and a liver diagnosis showing long-standing advanced ALC. Our treatment approach involved initiating dapagliflozin therapy, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, alongside strict alcohol abstinence. Remarkably, the patient demonstrated a dramatic reduction in proteinuria within one week of dapagliflozin administration. No hypoglycemic events were observed. This case adds valuable clinical insights into the potential therapeutic role of SGLT2 inhibitors in IgAN associated with ALC. Specifically, in cases where conventional steroid therapies may be contraindicated due to coexisting comorbidities such as diabetes or obesity, dapagliflozin emerges as a potentially efficacious alternative. Further investigations are warranted to validate these preliminary observations.

Objective: To examine the changes in total kidney volume (TKV) and total liver volume (TLV) before and after dialysis initiation in patients with autosomal dominant polycystic kidney disease. Patients and Methods: This was a retrospective, single-center cohort study to investigate the changes in TKV and TLV before and after dialysis initiation, along with influencing factors, using linear mixed models. We enrolled 95 patients with autosomal dominant polycystic kidney disease (85 receiving hemodialysis [HD] and 10 receiving peritoneal dialysis [PD]) who began receiving dialysis at Toranomon Hospital from January 1, 2008, to December 31, 2020. Results: The least squares mean TKV ratio (TKV at each time point/TKV at dialysis initiation) was 63.8% (95% confidence interval [CI], 54.7%-72.9%) at 6 years before dialysis initiation and 95.5% (95% CI, 82.9%-108.2%) at 6 years after dialysis initiation (P

A 63-year-old Japanese woman was admitted to our institute for the evaluation of proteinuria. The patient was diagnosed with medullary sponge kidney, distal type renal tubular acidosis, and renal infection at the age of 37. Thereafter, the patient had repeated renal infections. Urinary proteinuria appeared at around the age of 61 and gradually increased up to 1.0 g daily. In the same period, glycated hemoglobin (HbA1c) increased to 7.0%. On kidney biopsy, light microscopy showed a nodular glomerular lesion and capsular drop. Linear staining for immunoglobulin G along the glomerular basement membrane was observed by immunofluorescence. Electron microscopy showed thickening of the glomerular basement membrane to a width of 800–900 nm. A class III glomerular lesion was diagnosed according to the Tervaert classification. This case indicates that mild but prolonged hyperglycemia for more than 10 years may also contribute to the formation of nodular lesions, although long-standing repeated chronic renal infection and chronic acidosis may have been a precipitating factor in the formation of diabetic nephropathy, including nodular glomerular lesions. This hypothesis is of interest because nodular lesions specific to diabetes are currently considered to be associated with long-term severe hyperglycemia.

Background: Autologous platelet-rich plasma (PRP) therapy is ambiguously thought to be more effective in elite athletes than in sedentary patients, although the possible importance of recipient responsiveness remains poorly understood. To address this issue, along with the well-known PRP quality, in this initial study, we evaluated two candidate biomarkers: body composition indices (BCIs), which reflect systemic physical conditions, and resting platelet ATP levels, which reflect platelet energy expenditure and the mass of energy generation units.Methods: In this cross-sectional cohort study, blood samples were collected from male professional soccer players (PSPs) on a local professional team during the off-season and platelet ATP levels were quantified using an ATP luminescence assay kit. BCIs were measured using the body mass impedance method. Age-matched male sedentary participants were used as the controls.Results: Among the BCIs, the body mass index, basal metabolic rate (BMR), and skeletal muscle weight levels were higher in the PSPs than in the controls. The platelet ATP levels in the PSPs group were significantly lower than those in the control group. The correlation between BMR and platelet ATP levels was moderately negative in the control group, but weakly positive in the PSPs group.Conclusion: Owing to regular physical exercise, PSPs had higher BMR levels and lower platelet ATP levels without a significant mutual correlation compared to sedentary controls. This study did not indicate the influence of these biomarkers on the success of PRP therapy but provided evidence for a better understanding of PRP therapy, particularly for elite athletes.

A man in his 20s initiated intermittent peritoneal dialysis in the late 1960s. He subsequently transitioned to hemodialysis and survived for more than 50 years, spanning low-flux and high-flux hemodialysis eras. He underwent surgery for cervical and lumbar spinal canal stenosis after 30 and 35 years, respectively, and both surgeries revealed similar degrees of severe amyloid deposition. At autopsy, significant improvement was seen in lumbar amyloid deposition. During the previous 25 years, serum β2 microglobulin levels had decreased from 40 mg/L and been maintained at 20 mg/L. This case indicates that advances in dialysis therapy aimed at lowering β2 microglobulin concentrations have reduced highly deposited amyloid.

Anti-melanoma differentiation–associated gene 5 antibody-positive dermatomyositis is the poorest prognosis of all dermatomyositis due to its associated rapidly progressive interstitial lung disease. Intensive treatment is required from the onset and triple therapy with prednisolone, calcineurin inhibitors, and intravenous cyclophosphamide is recommended. However, some patients are refractory or dependent on this treatment and additional immunosuppressive therapy is required. Recently, the efficacy of tofacitinib, a JAK inhibitor, has been reported. Here, we describe a case of a 50-year-old woman with anti-melanoma differentiation–associated gene 5 antibody-positive dermatomyositis who became refractory to triple therapy and prednisolone reduction, and achieved remission with the addition of peficitinib, a JAK inhibitor. This is the first report showing that peficitinib is effective for anti-melanoma differentiation–associated gene 5 antibody-positive dermatomyositis and it may be a potential treatment option.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney disease and is well known to have extrarenal complications. Cardiovascular complications are of particular clinical relevance because of their morbidity and mortality; however, unclear is why they occur so frequently in patients with ADPKD and whether they are related to the genotypes. Methods: We extracted and retrospectively analyzed clinical data on patients with ADPKD who underwent echocardiography and whose genotype was confirmed by genetic testing between April 2016 and December 2020. We used next-generation sequencing to compare cardiac function, structural data, and the presence of cardiac valvular disease in patients with 1 of 3 genotypes: PKD1, PKD2, and non-PKD1, 2. Results: This retrospective study included 65 patients with ADPKD. Patients were divided into 3 groups: PKD1, n = 32; PKD2, n = 12; and non-PKD1, 2, n = 21. The prevalence of mitral regurgitation (MR) was significantly higher in the PKD1 group than in the PKD2 and non-PKD1, 2 group (46.9% vs. 8.3% vs. 19.0%, respectively; p = 0.02). In contrast, no significant difference was found for other cardiac valve complications. Conclusion: This study found a significantly higher prevalence of MR in patients with the PKD1 genotype than in those with the PKD2 or non-PKD1, 2 genotypes. Physicians may need to perform echocardiography earlier and more frequently in patients with ADPKD and the PKD1 genotype and to control fluid volume and blood pressure more strictly in these patients to prevent future cardiac events.

A 59-year-old Japanese woman with a 22-year history of long-term hemodialysis was admitted to our hospital for further examination of hyperglycemia and anemia. Five months before hospitalization, her fasting plasma glucose value was 99 mg/dL and her glycated hemoglobin was 5.7%. On admission, her fasting plasma glucose value was 873 mg/dL, glycated hemoglobin was 16.2%, C-peptide reactivity was 22.3 ng/mL (reference range, 0.5-3.0), and homeostasis model assessment of insulin resistance (HOMA-IR) was 10.6 (reference range,

A 71-year-old Japanese woman with a history of rheumatoid arthritis of 50 years’ duration was admitted to our hospital with refractory diarrhea. Endoscopic biopsy revealed AA amyloid deposition in the large intestine. Although the patient had been prescribed 5 tumor necrosis factor inhibitors over the past 10 years, rheumatoid arthritis was poorly controlled, with a Disease Activity Score 28 using C-reactive protein score of 6.52 on admission. Treatment with tocilizumab (8 mg/kg every 2 weeks) was initiated, but this was ineffective. After 3 months, abatacept (cytotoxic T-lymphocyte–associated antigen 4 immunoglobulin) was initiated (750 mg/mo) and the patient’s diarrhea began to improve. After 3 months of abatacept treatment, serum albumin, C-reactive protein, and serum amyloid A levels had all decreased to within normal ranges. After 3 years of abatacept treatment, a repeat biopsy of the large intestine revealed a marked improvement in amyloid deposition. Interleukin 6 is a key factor in AA amyloid formation, but this case suggests that T-cell activation increases the production of cytokines (including interleukin 6) via a mechanism involving cytotoxic T-lymphocyte–associated antigen 4, resulting in a second key factor of AA amyloid formation.

Polycystic liver disease (PLD) is a common extrarenal complication of autosomal dominant polycystic kidney disease (ADPKD), which causes compression-related syndrome and ultimately leads to liver dysfunction. Tolvaptan, a V2 receptor antagonist, is widely used to protect kidney function in ADPKD but its effect on PLD remains unknown. An observational cohort study was conducted to evaluate tolvaptan’s effect on patients with PLD due to ADPKD. After screening 902 patients, we found the 107 ADPKD patients with PLD who met the criteria of tolvaptan use in Japan. Among them, tolvaptan was prescribed for 62 patients (tolvaptan group), while the other was defined as the non-tolvaptan group. Compared with the non-tolvaptan group, the tolvaptan group had larger height-adjusted total kidney volume (median 994(range 450–4152) mL/m, 513 (405–1928) mL/m, p = 0.01), lower albumin level (mean 3.9±SD 0.4 g/dL, 4.3±0.4g/dL, p

Summary: The suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling required to prevent excessive cellular responses. In particular, SOCS3 is involved in the regulation of metabolic syndromes, such as obesity and diabetes, by suppressing leptin and insulin signals. SOCS3 also suppresses the inflammatory response associated with metabolic stress, but this specific role remains undefined. Wild-type mice on a high-fat diet (HFD) exhibited only fatty liver, whereas systemic deletion of SOCS3 resulted in excessive myeloid hematopoiesis and hepatic inflammation. In addition, depletion of the gut microbiota resulted in considerable improvement in excess granulopoiesis and splenomegaly, halting the progression of systemic inflammation in SOCS3KO mice on the HFD. This result suggests that intestinal dysbiosis is involved in inflammation associated with SOCS3KO. Although contributing to diet-induced obesity and fatty liver, SOCS3 is nevertheless critical to suppress excess myeloid hematopoiesis and severe systemic inflammation associated with intestinal dysbiosis on HFD.

Introduction Data on the association between longitudinal trajectory patterns of albuminuria and subsequent end-stage kidney disease (ESKD) and all-cause mortality in diabetic kidney disease (DKD) are sparse.Research design and methods Drawing on nationally representative data of 329 patients with biopsy-proven DKD and an estimated glomerular filtration rate above 30 mL/min/1.73 m2 at the time of biopsy, we used joint latent class mixed models to identify different 2-year trajectory patterns of urine albumin to creatinine ratio (UACR) and assessed subsequent rates of competing events: ESKD and all-cause death.Results A total of three trajectory groups of UACR were identified: ‘high-increasing’ group (n=254; 77.2%), ‘high-decreasing’ group (n=24; 7.3%), and ‘low-stable’ group (n=51; 15.5%). The ‘low-stable’ group had the most favorable risk profile, including the baseline UACR (median (IQR) UACR (mg/g creatinine): ‘low-stable’, 109 (50–138); ‘high-decreasing’, 906 (468–1740); ‘high-increasing’, 1380 (654–2502)), and had the least subsequent risk of ESKD and all-cause death among the groups. Although there were no differences in baseline characteristics between the ‘high-decreasing’ group and the ‘high-increasing’ group, the ‘high-decreasing’ group had better control over blood pressure, blood glucose, and total cholesterol levels during the first 2 years of follow-up, and the incidence rates of subsequent ESKD and all-cause death were lower in the ‘high-decreasing’ group compared with the ‘high-increasing’ group (incidence rate of ESKD (per 1000 person-years): 32.7 vs 77.4, p=0.014; incidence rate of all-cause death (per 1000 person-years): 0.0 vs 25.4, p=0.007).Conclusions Dynamic changes in albuminuria are associated with subsequent ESKD and all-cause mortality in DKD. Reduction in albuminuria by improving risk profile may decrease the risk of ESKD and all-cause death.

We report the renal histology of a 66-year-old man with hypertension, cardiovascular disease, and a 30-year history of type 2 diabetes mellitus with proliferative diabetic retinopathy, diabetic neuropathy, and diabetic foot status post toe amputation. Urinary protein excretion was 1.4 g/gCr, serum creatinine level 0.86 mg/dL, estimated glomerular filtration rate 69 mL/min/1.73 m2, and HbA1c 13–15%, despite using insulin. Light microscopy showed global glomerulosclerosis in 37% of the glomeruli, but the remaining glomeruli were intact. Significant polar vasculosis was present, while arteriolar sclerosis was mild. Electron microscopy revealed a thickened glomerular basement membrane, which is compatible with the early stage of diabetic glomerulopathy. The presented case was unique because glomerular changes seen typically in diabetes were not seen in the patient, despite the long-standing history of diabetes and diabetic comorbidities, while prominent polar vasculosis was found. Polar vascular formation helps preserve the glomeruli by allowing hyperosmotic blood bypass the glomeruli; this decreases intraglomerular pressure and minimizes glomerular endothelial damage.

Abstract Although allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a curative therapy for high‐risk acute leukemia (AL), some patients still relapse. Since patients simultaneously have many prognostic factors, difficulties are associated with the construction of a patient‐based prediction algorithm of relapse. The alternating decision tree (ADTree) is a successful classification method that combines decision trees with the predictive accuracy of boosting. It is a component of machine learning (ML) and has the capacity to simultaneously analyze multiple factors. Using ADTree, we attempted to construct a prediction model of leukemia relapse within 1 year of transplantation. With the model of training data (n = 148), prediction accuracy, the AUC of ROC, and the κ‐statistic value were 78.4%, 0.746, and 0.508, respectively. The false positive rate (FPR) of the relapse prediction was as low as 0.134. In an evaluation of the model with validation data (n = 69), prediction accuracy, AUC, and FPR of the relapse prediction were similar at 71.0%, 0.667, and 0.216, respectively. These results suggest that the model is generalized and highly accurate. Furthermore, the output of ADTree may visualize the branch point of treatment. For example, the selection of donor types resulted in different relapse predictions. Therefore, clinicians may change treatment options by referring to the model, thereby improving outcomes. The present results indicate that ML, such as ADTree, will contribute to the decision‐making process in the diversified allo‐HSCT field and be useful for preventing the relapse of leukemia.

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) may manifest non-nephrotic range proteinuria, but is rarely complicated with nephrotic syndrome. Limited number of reports describe the histology of ADPKD with nephrotic syndrome in detail. Case presentation We encountered a 23-year-old man with polycystic kidney disease (PKD) with small kidney volume and nephrotic syndrome, which eventually progressed to end-stage renal disease. Renal histology showed typical focal segmental glomerulosclerosis and remarkable glomerular cyst formation, but did not reveal tubular cysts. PKD1 mutation was detected in him and his father, who also had PKD with small kidney volume. Conclusions In contrast to tubular cysts which develop along ADPKD progression, glomerular cysts may likely be associated with ADPKD with slower volume progression manifesting small kidney volume. Although previous investigations report that ADPKD with smaller kidney volume is attributed to slower decline in renal function, coexistence of nephrotic-range proteinuria implies complication of other glomerular diseases and needs histological evaluation since it may lead to poor renal outcome.

An 88-year-old Japanese man received bevacizumab for colorectal cancer with liver and peritoneal metastasis, during which nephrotic range proteinuria occurred (7.66 g/day). Renal biopsy showed endothelial damage with subendothelial swelling and a double contour of the glomerular basement membrane, which indicated a diagnosis of thrombotic microangiopathy (TMA). After bevacizumab was stopped, proteinuria decreased to 1 g/day. During the clinical course, this patient had no extrarenal manifestations. This case suggests that renal injury induced by bevacizumab is characterized by nephrotic range proteinuria and histological TMA, and is a renal-limited condition that differs from systemic TMA related to thrombotic thrombocytopenic purpura.

Currently, the pathogenesis of nontraumatic heterotopic ossification (HO), e.g., bone-like tissue in calcific tendinopathy remains unclear. Here, we report a 75-year-old, right-handed Japanese woman who had been on hemodialysis for 3 years and was admitted to our hospital to evaluate pain and swelling of the right forearm. She worked as a cook, and her main job over the 3 most recent years had been the frequent and continuous shredding of cabbage. A radiograph showed the highly radiopaque material on the dorsal aspect of the right wrist and in the right shoulder. The biopsy of this radiopaque material revealed HO with marrow, as well as calcified material. Histomorphometric analysis of the HO identified a severe type of osteitis fibrosa with a fibrous tissue volume to total volume of 19.8% (>0.5% required for diagnosis) and an osteoid volume to bone volume of 20.0% (>15% required for diagnosis). We found more woven bone-like tissue than lamellar bone-like tissue. However, the intact parathyroid hormone level was 3-times the normal upper limit with 203 pg/mL, but histomorphometric analysis of the right iliac crest revealed normal bone structure. These findings indicate that the frequent and continuous shredding action with the right hand contributed to the nontraumatic HO localized on the dorsal aspect of the right wrist.

BackgroundUncertainty underlies the effectiveness of somatostatin analogues for slowing the progression of polycystic kidney or liver disease.MethodsEligible studies included randomized controlled trials (RCTs) evaluating somatostatin analog as therapy for patients with polycystic kidney disease (PKD) or polycystic liver disease (PLD) compared to placebo or standard therapy. Two reviewers independently screened studies identified from databases (MEDLINE, EMBASE, Cochrane Database), clinical trial registries, and references from pertinent articles and clinical practice guidelines. Outcome measurements were changes in total liver volume (TLV), total kidney volume (TKV), and estimated glomerular filtration rate (eGFR).ResultsOf 264 nonduplicate studies screened, 10 RCTs met the inclusion criteria. The body of evidence provided estimates warranting moderate confidence. Meta-analysis of 7 RCTs including a total of 652 patients showed that somatostatin analogs are associated with a lower %TLV growth rate compared to control (mean difference, -6.37%; 95% CI -7.90 to -4.84, pConclusionsCurrent body of evidence suggests that somatostatin analogs therapy slows the increase rate of TLV and TKV in patients with PKD or PLD compared to control within a 3-year follow-up period. It does not seem to have an effect on the change in eGFR. Somatostatin analogs therapy can be a promising treatment for ADPKD or ADPLD, and we need to continue to research its effectiveness for ADPKD or ADPLD.

A 56-year-old Japanese woman with a history of palmoplantar pustulosis was admitted for examination due to left femur pain. Radiography and computed tomography showed thickening of the bone on the outer portion of the left femur. Bone scintigraphy of the left femur showed intense radioactive uptake. Consequently, the patient was diagnosed with SAPHO syndrome. Bone histomorphometric analysis of the left femur showed cancellous bone with thickened cortical bone. Whilst normal bone shows cancellous bone with double labeling (normal turn over), and cortical bone with no labeling (low turn over, adynamic state), this case presented with both cancellous and cortical bone with marked double labeling (indicating high turn over), abundant osteoid and woven bone. Immunohistological analysis showed that cells lining the bone surface consisted of osteoblasts and were positive for alkaline phosphatase (ALP). Few to little of these cells were positive for tartrate-resistant acid phosphatase (TRAP)-5B, cathepsin K and matrix metallopeptidase 9 (MMP-9). These results indicate that, in this case study, excessive production of osteoblasts contributed to hyperostosis of the left femur, with abundant osteoid and woven bone. This type of bone formation in SAPHO syndrome is not lamellar bone seen in normal bone, but rather fragile and mechanically weak bone, resulting in bone pain. Doxycycline may be a therapeutic option for bone pain in this patient.

Background & Aims: Isolated autosomal-dominant polycystic liver disease (ADPLD) is generally considered a rare disease. However, the frequency of truncating mutations to ADPLD genes in large, population sequencing databases is 1:496. With the increasing use of abdominal imaging, incidental detection of hepatic cysts and ADPLD has become more frequent. The present study was performed to ascertain the incidence and point prevalence of ADPLD in Olmsted County, MN, USA, and how these are impacted by the increasing utilisation of abdominal imaging. Methods: The Rochester Epidemiology Project and radiology databases of Mayo Clinic and Olmsted Medical Center were searched to identify all subjects meeting diagnostic criteria for definite, likely, or possible ADPLD. Annual incidence rates were calculated using incident cases during 1980–2016 as numerator, and age- and sex-specific estimates of the population of Olmsted County as denominator. Point prevalence was calculated using prevalence cases as numerator, and age- and sex-specific estimates of the population of Olmsted County on 1 January 2010 as denominator. Results: The incidence rate and point prevalence of combined definite and likely ADPLD were 1.01 per 100,000 person-years and 9.5 per 100,000 population, respectively. Only 15 of 35 definite and likely incident ADPLD cases had received a diagnostic code, and only 8 had clinically significant hepatomegaly. The incidence rates were much higher when adding possible cases, mainly identified through radiology databases, particularly in recent years and in older patients because of the increased utilisation of imaging studies. Conclusions: Clinically significant isolated ADPLD is a rare disease with a prevalence

Abstract Background Cyst infection is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often refractory. Carbapenems are frequently needed to treat to patients with refractory cyst infection, but little is known about the penetration of newer water-soluble carbapenems into cysts. This study investigated the penetration of meropenem (MEPM) into infected cysts in patients with ADPKD. Methods Between August 2013 and January 2014, 10 ADPKD patients (14 infected cysts) receiving MEPM at Toranomon Hospital underwent drainage of infected cysts and definite cyst infection was confirmed through detection of neutrophils by cyst fluid analysis. The serum concentration of MEPM was measured just after intravenous administration and was compared with that in fluid aspirated from infected cysts. Results In the patients undergoing cyst drainage, the mean serum MEPM concentration was 35.2 ± 12.2 μg/mL (range: 19.7 to 59.2 μg/mL, while the mean cyst fluid concentration of MEPM in the drained liver cysts (n = 12) or kidney cysts (n = 2) was 3.03 ± 2.6 μg/mL (range: 0 to 7.3 μg/mL). In addition, the mean cyst fluid/serum MEPM concentration ratio was 9.46 ± 7.19% (range: 0 to 18.8%). There was no relationship between the cyst fluid concentration of MEPM and the time until drainage after MEPM administration or between the cyst fluid/serum MEPM concentration ratio and the time until drainage. Conclusion These findings suggest that MEPM shows poor penetration into infected cysts in ADPKD patients. Trial registration This study was registered with the University Hospital Medical Information Network (UMIN) as “Penetration of meropenem into cysts in patients with autosomal dominant polycystic kidney disease (ADPKD)”, UMIN ID 000011292 on July 26th, 2013.

A 72-year-old Japanese woman with a history of autoimmune hepatitis-associated liver cirrhosis and portosystemic shunt was admitted to our hospital for evaluation of renal dysfunction, nephrotic range proteinuria, a high titer of anti-double-stranded DNA antibody, and hypocomplementemia. Renal biopsy showed massive subendothelial deposits (wire loop lesions), and class IV-G (A/C) lupus nephritis was diagnosed. Immunosuppressants, such as steroids (including intravenous methylprednisolone pulse therapy) and mycophenolate mofetil, could not prevent renal dysfunction. It was assumed that circulating immune deposits produced in the gastrointestinal tract entered the systemic circulation from the portal vein via the portosystemic shunt without hepatic clearance, resulting in massive subendothelial and mesangial accumulation compared to lupus nephritis patients without a shunt and causing renal injury. Keywords: Lupus nephritis, Systemic lupus erythematosus, Autoimmune hepatitis-associated liver cirrhosis, Portosystemic shunt, Wire loop lesion

We evaluated the efficacy of everolimus in 3 patients who had huge renal angiomyolipomas associated with tuberous sclerosis complex. Two patients with large lipid-rich angiomyolipomas had a history of renal transarterial embolization for renal bleeding, but the effect had only been temporary and the embolized kidneys had continued to enlarge. In case 1, case 2, and case 3, total renal volume was respectively 3,891, 4,035, and 1,179 cm3 before administration of everolimus, decreasing to 3,016 (77%), 3,043 (75%), and 1,051 (89%) cm3 after 1 year of everolimus therapy and to 2,832 (73%), 3,209 (80%), and 1,102 (93%) cm3 after 3 years. New renal bleeding did not occur, but elevation of serum creatinine and urinary protein were noted in 2 patients. While previous reports have largely assessed the effect of everolimus for angiomyolipomas of < 10 cm in the longest diameter, our findings suggest that this drug might also be effective for huge lesions of > 20 cm in diameter. However, total renal volume still exceeds 2,000 cm3 in 2 of our patients, suggesting limited size reduction of lipid-rich angiomyolipomas. In addition, occurrence of everolimus-related nephropathy needs to be monitored carefully.

We report a 33-year-old Japanese man diagnosed with mixed connective tissue disease (MCTD) who developed nephrotic proteinuria. Both speckled antinuclear antibody (ANA) and anti-U1 ribonucleoprotein (RNP) antibody were positive, but anti-double-stranded DNA (dsDNA) antibody and anti-Smith (Sm) antibody were negative, while complement levels were normal. Renal biopsy revealed membranous glomerulonephritis (MGN) with diffuse thickening of the glomerular basement membrane (GBM) plus spike and bubble formation. Immunofluorescence demonstrated granular deposits of IgG and C3 along the GBM. Analysis of IgG subclasses showed predominant deposition of IgG1 and IgG4, unlike typical lupus nephritis in which there is predominant deposition of IgG1, IgG2, IgG3, and C1q. Electron microscopy identified numerous large electron-dense deposits (EDD) of various types in the subepithelial region of the GBM, but there were no EDD localized in the mesangium or subendothelium. Based on these findings, MGN was considered to be closely related to MCTD in this patient. Keywords: Membranous glomerulonephritis, Mixed connective tissue disease

A 59-year-old Japanese woman was admitted for evaluation of muscle weakness. Autosomal dominant polycystic kidney disease had been diagnosed at the age of 47 years, followed by primary aldosteronism at 53 years. At the age of 58, tolvaptan was started (60 mg/day) to treat her renal disease. After 8 months of tolvaptan therapy, hypokalemia-related muscle weakness became prominent, and hypertension became refractory. Finally, treatment with low-dose tolvaptan (30 mg/day) and high-dose spironolactone (100 mg/day) normalized serum potassium and the blood pressure. Tolvaptan can induce urinary excretion of potassium in patients with primary aldosteronism, and possible mechanisms are discussed.

We report the case of a 67-year-old Japanese woman with type 1 diabetes mellitus. At 47 years of age, her hemoglobin A1c (HbA1c) was 10.0%, and she had overt nephropathy. The first renal biopsy yielded a diagnosis of diabetic nephropathy. Intensive glycemic control was initiated and her HbA1c improved to 6.0%. Renal dysfunction showed no progression for 15 years. At 62 years of age, a second renal biopsy was performed. Glomerular lesions did not show progression but tubulointerstitial fibrosis and vascular lesions showed progression compared with the first biopsy. Intensive glycemic control can prevent the progression of glomerular lesions, but might not be effective for interstitial and vascular lesions.

Abstract Background Various renal manifestations are known to develop in patients with liver disease, including chronic hepatitis and cirrhosis. Case presentation We evaluated renal disease in two 47-year-old Japanese men with liver cirrhosis and chronic alcoholism for 34 years and 27 years, respectively. Renal biopsy demonstrated massive wire loop-like deposits in the subendothelial space of the glomerular basement membrane and in the mesangium. However, immunofluorescence was only positive for IgA and C3, and electron microscopy did not reveal any organized structures in the electron-dense deposits. IgA nephropathy was diagnosed, although the features were different from primary IgA nephropathy. Both patients had portosystemic shunts associated with liver cirrhosis. Their renal deposits and proteinuria resolved completely after 1 year of steroid therapy. Conclusion Alcohol abuse may have contributed to development of secondary IgA nephropathy in these two patients, probably via their portosystemic shunts.

A 54-year-old Japanese man presented with recurrent abdominal pain, fever lasting >5 days, and renal failure. AA amyloidosis was proven by renal and gastric biopsy. Symptoms subsided with the administration of colchicine, but a subsequent recurrence of symptoms did not respond to colchicine. Mediterranean fever gene (MEFV) analysis showed that he was heterozygous for mutations in exon 2 (E148Q/R202Q) and exon 3 (P369S/R408Q), although he had none of the exon 10 mutations known to be closely related to AA amyloidosis. He did not respond to infliximab, but tocilizumab therapy was successful. The present case is a rare report of AA amyloidosis associated with familial Mediterranean fever in Japan.

A 44-year-old Japanese woman with autosomal dominant polycystic kidney disease was admitted to our hospital for evaluation of abdominal distension. Her eGFR was 53.7 mL/min/1.73 m2. Total kidney volume was 2,614 mL. Tolvaptan (60 mg/day) was started to treat renal involvement. The patient’s abdominal fullness began to improve and liver volume, indicating advanced polycystic liver disease (PLD), decreased from 9,750 mL to 8,345 mL after 17 months of tolvaptan treatment, though there was no significant change in kidney volume. This case indicates that tolvaptan may be a therapeutic option for hepatomegaly in patients with symptomatic PLD.

We report a 48-year-old Japanese man with a brown tumor of the right distal tibia. At the age of 25 years, hemodialysis was initiated due to nail-patella syndrome. Severe secondary hyperparathyroidism and osteoporosis progressed over time, so parathyroidectomy was performed at age 45. Spontaneous fracture of the right distal tibia occurred suddenly at age 48. Imaging studies revealed a bone tumor-like lesion and surgery was performed. The resected specimen was a brown mass consisting of multinucleated giant cells on a fibrous tissue background, and these findings were consistent with a diagnosis of brown tumor. Immunohistochemistry revealed that multinucleated giant cells near areas of bone matrix were positive for tartrate-resistant acid phosphatase and cathepsin K, but the majority of the giant cells in the lesion were negative for these markers. Even after parathyroidectomy, brown tumor should be considered in the differential diagnosis of bone tumor-like lesions in patients on long-term dialysis. This case suggests that osteoclast activation may not contribute to development of brown tumors, although these lesions are generally considered to arise from subperiosteal bone resorption related to osteoclast overactivity in patients with hyperparathyroidism. Keywords: Brown tumor, Parathyroidectomy, Hyperparathyroidism, Tartrate-resistant acid phosphatase, Cathepsin K, Nail-patella syndrome

Abstract Background There have been still few case reports of pseudohypoaldosteronism type II (PHA2), also known as Gordon's syndrome, genetically diagnosed, and this is the first report of familial PHA2 case in Japan with a novel D564N mutation in WNK4. Methods A 29‐year‐old woman was admitted to our hospital due to hyperkalemia (serum potassium: 6.4 mmol/L). She had mild hypertension (135/91 mm Hg), a bicarbonate level at the lower limit of the normal range (HCO3: 22 mmol/L) with a normal anion gap, low plasma renin activity (0.2 ng ml‐1 hr‐1), and high urinary calcium excretion (505.4 mg/g Cre). A hereditary condition was suspected because her mother also had the same symptoms. We performed a comprehensive genetic analysis for major inherited kidney diseases with next‐generation sequencing including the genes responsible for PHA2 (WNK1, WNK4, KLHL3, and CUL3). Results Genetic analysis revealed that the patient and her mother had a novel missense mutation (D564N) in the acidic motif in WNK4, which leads to the diagnosis of PHA2. Administration of trichlormethiazide (1 mg/day) effectively ameliorated her blood pressure (114/69 mm Hg), plasma bicarbonate (25 mmol/L), serum potassium (4.3 mmol/L), and urinary calcium excretion (27.2 mg/g Cre). Conclusion We report the first Japanese familial case of PHA2 with WNK4 mutation. D564N mutation in WNK4 is a novel genetic cause of PHA2 with a relatively mild phenotype.

The impact of the newly proposed pathological classification by the Japan Renal Pathology Society (JRPS) on renal outcome is unclear. So we evaluated that impact and created a new pathological scoring to predict outcome using this classification.A multicenter cohort of 493 biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The association between each pathological factor-Tervaert' and JRPS classifications-and renal outcome (dialysis initiation or 50% eGFR decline) was estimated by adjusted Cox regression. The overall pathological risk score (J-score) was calculated, whereupon its predictive ability for 10-year risk of renal outcome was evaluated.The J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3, presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were, respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were, respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2, and 3 were 5, 5, and 4 (J-score range, 0-19). Renal survival curves, when dividing into four J-score grades (0-5, 6-10, 11-15, and 16-19), were significantly different from each other (p

BACKGROUND:End-stage renal disease (ESRD) is related to high morbidity, mortality, and impaired health-related quality of life. While hemodialysis (HD) is the current life-saving standard of treatment for patients with ESRD, their quality of life (QoL) remains far from desirable. Online HDF (OL-HDF), due to its convenience, could improve the QoL of patients with ESRD, however, this remains uncertain. OBJECTIVE:We aimed to assess the body of evidence of OL-HDF compared to HD regarding QoL in patients with ESRD. METHODS:We comprehensively searched in multiple data bases from their inception to February 2018. Reviewers working independently and in duplicate appraised the quality and included randomized controlled trials (RCTs) that evaluated, in patients with ESRD and HD or OL-HDF, QoL (Short Form Health Survey with 36 questions (SF-36) with physical component score (PCS) and mental component score (MCS) as well as scores about social activity, fatigue, and emotion). A meta-analysis of each outcome of interest was performed using a random-effects model. RESULTS:Six moderate quality RCTs met the inclusion criteria. Meta-analysis of 4 RCTs including a total of 1,209 patients showed that OL-HDF was associated with a lower yet non-significant score of PCS: MD (mean difference) -0.77 (95% CI -1.94 to 0.41, p = 0.20), and MCS: MD -1.25 (95% CI -3.10 to 0.59, p = 0.18); indicating a poorer QoL in patients on OL-HDF. Meta-analysis of 4 RCTs including a total of 845 patients showed OL-HDF was associated with a significant increase in the score of social activity compared to HD: SMD (standardized mean difference): 1.95 (95% CI 0.05 to 3.86, p = 0.04), indicating a better QoL in patients on OL-HDF; but regarding fatigue and emotion, there was no significant improvement when compared to HD by meta-analysis of 3 RCTs (133 patients). CONCLUSIONS:The body of evidence suggests that OL-HDF does not improve QoL in patients with ESRD when compared to HD.

A 42-year-old woman with systemic lupus erythematosus (SLE) was admitted to our hospital for evaluation of severe thrombocytopenia. She was treated with steroids, intravenous cyclophosphamide, intravenous immunoglobulin, and plasma exchange, but her thrombocytopenia did not improve. Renal biopsy showed class IV-S(C) + V lupus nephritis, according to the classification of the International Society of Nephrology/Renal Pathology Society. The PA-IgG and serum thrombopoietin (TPO) levels were elevated. Her thrombocytopenia responded to off-label administration of eltrombopag, which was discontinued after 42 months. At 18 months after stopping eltrombopag, the platelet count was 19.3 × 104/μL. Eltrombopag may be a therapeutic option for SLE patients with severe thrombocytopenia refractory to conventional therapy.

AimsGlomerular insudative lesions are a pathological hallmark of diabetic nephropathy (DN). However, paratubular basement membrane insudative lesions (PTBMIL) have not attracted much attention, and the association between such lesions and the renal prognosis remains unclear.MethodsAmong 142 patients with biopsy-proven DN and type 2 diabetes encountered from 1998 to 2011, 136 patients were enrolled in this study. Patients were classified into 3 groups (Group 1: mild, Group 2: moderate, Group 3: severe) according to the extent of cortical and medullary PTBMIL. The endpoint was a decline of the estimated glomerular filtration rate (eGFR) by ≥ 40% from baseline or commencement of dialysis for end-stage renal disease. The Cox proportional hazard model was employed to calculate hazard ratios (HRs) and 95% confidence interval (CIs) for the death-censored endpoint.ResultsDuring a median follow-up period of 1.8 years (IQR: 0.9-3.5), the endpoint occurred in 104 patients. Baseline mean eGFR was 43.9 ± 22.8 ml/min/1.73 m2, and 125 patients (92%) had overt proteinuria. After adjusting for known indicators of DN progression, the HR for the endpoint was 2.32 (95% CI: 1.20-4.51) in PTBMIL Group 2 and 3.12 (1.48-6.58) in PTBMIL Group 3 versus PTBMIL Group 1. Furthermore, adding the PTBMIL Group to a multivariate model including known promoters of DN progression improved prediction of the endpoint (c-index increased by 0.02 [95% CI: 0.00-0.04]).ConclusionsPTBMIL may be useful for predicting the renal prognosis of patients with biopsy-proven DN, but further investigation of these lesions in various stages of DN is needed.

BACKGROUND:Reduced estimated glomerular filtration rate (eGFR) and proteinuria are risk factors for end-stage renal disease (ESRD), of which benign nephrosclerosis is a common cause. However, few biopsy-based studies have assessed these associations. METHODS:We performed retrospective cohort study of 182 Japanese patients who underwent renal biopsy from June 1985 through March 2014 and who were diagnosed with benign nephrosclerosis. Competing risk regression analyses were used to investigate the effect of eGFR and proteinuria levels at the time of renal biopsy on the risk for renal events (ESRD or a 50% decline in eGFR from baseline). RESULTS:During a median 5.8-year follow-up, 63 (34.6%) patients experienced renal events. The incidence of renal events increased with lower baseline eGFR and greater baseline proteinuria levels. After adjustment for baseline covariates, lower eGFR levels (subhazard ratios [SHRs], 1.30; 95% confidence interval [CI], 1.01-1.67, per 10 mL/min/1.73 m2) and higher proteinuria levels (SHR, 1.52; 95% CI, 1.23-1.87, per 1.0 g/day) at the time of renal biopsy were associated independently with higher risk for renal events. Lower levels of serum albumin (SHR, 2.07; 95% CI, 1.20-3.55 per 1.0 g/dL) were also associated with renal events. Patients with both eGFR

We performed a postmortem bone histomorphometric analysis of iliac bone on a 38-year-old man who had been bedridden for the nine months before his death because of orthostatic hypotension and severe malnutrition related to amyloidκ-light-chain amyloidosis. Cancellous bone volume was greatly decreased, with a trabecular bone volume to total bone volume ratio of 6.77% (normal value, 19.56% ± 5.62%). Trabecular thinning was also apparent, with a trabecular thickness of 78.9 μm (normal value, 131.3 ± 28.1 μm), although the trabecula was still preserved. Cortical bone width was normal, although areas of porosity area were clear throughout the cortical bone. Our findings indicate that immobilization-related osteoporosis may be closely associated with loss of cancellous bone.