Masahiro Kawada

Quality of life of patients with ADPKD—Toranomon PKD QOL study: cross-sectional study

BackgroundThe quality of life (QOL) of patients with autosomal dominant polycystic kidney disease (ADPKD) has not been investigated well. This study was performed to clarify the QOL of patients with ADPKD and to identify factors that affected their QOL.MethodsThe present cross-sectional study is part of a prospective observational study on the QOL of ADPKD patients. Patients with ADPKD who were referred to Toranomon Hospital between March 2010 and November 2012 were enrolled. The short form-36 (SF-36) questionnaire and our original 12-item questionnaire were used to evaluate QOL. We analyzed the results of the questionnaire survey and then investigated correlations between QOL and clinical features.ResultsA total of 219 patients (93 men and 126 women) were enrolled and their mean age was 55.1±10.8 years. There were 108 patients on dialysis. The SF-36 scores (PCS, MCS, and RCS) of all patients were significantly lower than the mean scores for the Japanese population. Stepwise multiple regression analysis demonstrated that Hb, serum Alb, ascites, and cerebrovascular disease all had a significant influence on the PCS, while mental disease had a significant influence on the MCS and serum Alb significantly influenced the RCS. The total liver and kidney volume (TLKV) and the dialysis status were not significantly associated with any of the SF-36 scores by multiple regression analysis, but TLKV was closely correlated with abdominal distention and distention had an important influence on QOL. Pain, sleep disturbance, heartburn, fever, gross hematuria, and anorexia also affected QOL, but these variables were not correlated with TLKV.ConclusionsSeveral factors influence QOL, so improving symptoms unrelated to TLKV as well as reducing abdominal distention can improve the QOL of ADPKD patients.

Denosumab for Low Bone Mass in Hemodialysis Patients: A Noncontrolled Trial

bALP (mg/L) 20.0 [17.5 to 27.5] 11.2 [10.9 to 16.4] 0.01 Osteocalcin (ng/mL) 100 [26.0 to 120] 23.0 [21.0 to 31] 0.008 Intact PINP (mg/L) 114.5 [88.4 to 222.3] 44.1 [29.7 to 80.8] 0.005 TRACP-5b (mU/dL) 660 [540 to 1,100] 299 [114 to 418] 0.003 BMD (T score) LS 22.7 [23.7 to 21.5] 21.7 [23.0 to 0.7] 0.006 FN 22.4 [22.7 to 21.9] 22.3 [22.5 to 21.7] 0.007 RS 23.8 [24.5 to 22.2] 24.1 [24.5 to23.0] 0.1 Correspondence

Suitability of Patients with Autosomal Dominant Polycystic Kidney Disease for Renal Transcatheter Arterial Embolization

In patients with autosomal dominant polycystic kidney disease (ADPKD), massive renal enlargement is a serious problem. Renal transcatheter arterial embolization (TAE) can reduce renal volume (RV), but effectiveness varies widely, and the reasons remain unclear. We investigated factors affecting renal volume reduction rate (RVRR) after renal TAE in all 449 patients with ADPKD who received renal TAE at Toranomon Hospital from January of 2006 to July of 2013, including 228 men and 221 women (mean age =57.0±9.1 years old). One year after renal TAE, the RVRR ranged from 3.9% to 84.8%, and the least squares mean RVRR calculated using a linear mixed model was 45.5% (95% confidence interval [95% CI], 44.2% to 46.8%). Multivariate analysis using the linear mixed model revealed that RVRR was affected by the presence of large cysts with wall thickening (regression coefficient [RC], -6.10; 95% CI, -9.04 to -3.16; P<0.001), age (RC, -0.82; 95% CI, -1.03 to -0.60; P<0.001), dialysis duration (RC, -0.10; 95% CI, -0.18 to -0.03; P<0.01), systolic BP (RC, 0.39; 95% CI, 0.19 to 0.59; P<0.001), and the number of microcoils used for renal TAE (RC, 1.35; 95% CI, 0.83 to 1.86; P<0.001). Significantly more microcoils were needed to achieve renal TAE in patients with younger age and shorter dialysis duration. In conclusion, cyst wall thickening had an important effect on cyst volume reduction. Renal TAE was more effective in patients who were younger, had shorter dialysis duration, or had hypertension, parameters that might associate with cyst wall stiffness and renal artery blood flow.

Peritoneal Dialysis is Limited by Kidney and Liver Volume in Autosomal Dominant Polycystic Kidney Disease.

We evaluated the influence of kidney volume (KV) and liver volume (LV) on continuation of peritoneal dialysis (PD) in patients with autosomal dominant polycystic kidney disease (PKD). Twenty‐two PKD patients on PD were retrospectively investigated after being divided into two groups. Group 1 comprised 15 patients who started PD at our hospital and group 2 was composed of seven patients referred from other hospitals for treatment of renomegaly by transcatheter arterial embolization (TAE) at 47.1 ± 21.8 months after commencing PD. In group 1, KV for both kidneys (mean ± SD) was 2787 ± 1945 mL (range: 1043 to 6816 mL), LV was 2198 ± 1139 mL (1005 to 4116 mL), and the total organ volume (TV = KV + LV) was 4985 ± 1815 mL (2320 to 8912 mL). In the patient with the largest TV from group 1 (KV of 6816 mL, TV of 8912 mL, and TV/BMI ratio of 426, PD was stopped due to dialysate leakage. However, dialysate leakage did not occur in the other 14 patients (TV ≦ 7963 mL and TV/BMI ratio of 353 at the start of PD). In group 2, KV was 5822 ± 1597 mL (3832 to 8862 mL), LV was 1776 ± 519 mL (1271 to 2671 mL), and TV was 7597 ± 1431 mL (5505 to 10358) before TAE. Leakage of dialysate did not occur with a mean infusion volume of 1530 ± 370 mL (1000 mL to 2000 mL), even after renomegaly and hepatomegaly progressed to the maximum TV/BMI ratio of 359. Six patients from the two groups developed new abdominal hernias at 36 ± 5 months (6–55 months) after starting PD. These findings suggest that performance of PD may be limited by renomegaly and hepatomegaly in patients with PKD.

Ursodeoxycholic Acid for Treatment of Enlarged Polycystic Liver

Patients with autosomal dominant polycystic kidney disease and polycystic liver disease (PLD) often have elevated serum levels of alkaline phosphatase (ALP) and gamma‐glutamyl transpeptidase (GGT). Ursodeoxycholic acid (UDCA) is used to treat biliary tract diseases, but its effect on PLD remains unclear. UDCA was administered for 1 year at a dose of 300 mg daily to seven PLD patients with elevated ALP or GGT levels who were selected for this treatment by experienced clinicians. Laboratory data and liver volumes were compared among three time points: 1 year before UDCA treatment, at the start of UDCA therapy, and 1 year after the start of therapy. Median GGT did not show a significant change between 1 year before UDCA (180 IU/L) and the start of UDCA therapy (209 IU/L), but it decreased significantly to 98 IU/L after 1 year of UDCA therapy (P = 0.015 vs. the start of therapy). ALP showed a significant increase from 1 year before UDCA (456 IU/L) to the start of UDCA therapy (561 IU/L), and then decreased significantly after 1 year of UDCA therapy (364 IU/L). Median liver volume did not show any significant changes among these three time points of assessment. UDCA may be effective for reducing biliary enzyme levels and inhibiting the growth of liver cysts in patients with PLD.

Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation–related membranous glomerulonephritis☆☆☆

Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis.

Effect of Proteinuria and Glomerular Filtration Rate on Renal Outcome in Patients with Biopsy-Proven Benign Nephrosclerosis

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 <30 mL/min/1.73 m2 and proteinuria ≥0.5 g/day had a 26.7-fold higher risk (95% CI, 3.97–179.4) of renal events than patients with both eGFR ≥60 mL/min/1.73 m2 and proteinuria <0.5 g/day. Conclusions Reduced eGFR and increased proteinuria as well as lower serum albumin at the time of renal biopsy are independent risk factors for renal events among patients with biopsy-proven benign nephrosclerosis.

AA-negative and Kappa-positive Amyloidosis in a Patient with Rheumatoid Arthritis

A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain. Combination therapy with high-dose melphalan and autologous stem cell transplantation was performed according to the regimen for AL amyloidosis. Her proteinuria and RA subsided, but relapsed after 3 years. This is the first report regarding kappa light chain amyloidosis in an RA patient.

Renal histology in a patient with TAFRO Syndrome: A case report

An 84-year-old Japanese man was admitted due to anasarca, thrombocytopenia, systemic inflammation, and progressive renal insufficiency, resistance to diuretics, glucocorticoid therapy, and plasma exchange. Renal biopsy showed diffuse endocapillary proliferation and mesangiolysis without any immune deposits. Tocilizumab suppressed systemic inflammation, resulting in improvement of anasarca and renal dysfunction, but thrombocytopenia persisted and platelet-associated IgG antibody was elevated. Although romiplostim was effective for thrombocytopenia, the patient died of aspiration pneumonia after cerebral hemorrhage. Autopsy showed hyaline vascular-type Castleman disease-like lymphadenopathy and reticulin myelofibrosis with an increase of megakaryocytes. Renal finding showed that endocapillary injury improved, and collapsed glomeruli were noted. This patient fitted the criteria for TAFRO (thrombocytopenia [T], anasarca [A], fever [F], reticulin myelofibrosis [R], and organomegaly [O]) syndrome. The clinical course suggests that 2 factors, including overproduction of interleukin 6 and autoimmune-mediated thrombocytopenia via thrombopoietin receptor, may have contributed to the pathogenesis of TAFRO syndrome in this patient.

Tocilizumab for AA Amyloidosis after Treatment of Multicentric Castleman Disease with Steroids, Chemotherapy and Rituximab for Over 20 Years.

We herein report the long-term outcome (30 years) of a human immunodeticiency virus- and human herpesvirus 8-negative Japanese man who was diagnosed to have multicentric Castleman disease (MCD) of the plasmacytic type after investigation of generalized lymphadenopathy at 34 of age in 1983. He received chemotherapy based on lymphoma regimens (combinations of prednisolone, vincristine, vindesine, cyclophosphamide, etoposide, melphalan, and ranimustine, etc.) for over 20 years. Although the systemic lymphadenopathy resolved, AA amyloidosis-related nephropathy occurred, with a serum creatinine (Cre) level of 0.9 mg/dL and urinary protein excretion (UP) of 7.5 g daily. Rituximab was started, but Cre increased to 2.6 mg/dL in 2010 and UP was unchanged. Therefore, treatment with tocilizmab was started. As a result, his hypergammaglobulinemia was well controlled, C-reactive protein became normal, UP decreased to 3.5 g daily, and Cre remained at 2.5 mg/dL in 2013. When AA amyloid nephropathy occurred after long-term chemotherapy, lituximab could not control it, but tocilizmab stopped the progression of nephropathy. This case suggests that MCD and AA amyloidosis may both have a close relationship to the overproduction of interleukin-6.