Tatsuya Suwabe

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-d-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

BACKGROUND AND OBJECTIVES Some biomarkers of renal tubular injury are reported to be useful for predicting renal prognosis in the early stage of diabetic nephropathy (DN). Our study compared predictions of the renal prognosis by such biomarkers and by histologic tubulointerstitial damage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Among 210 patients with type 2 diabetes and biopsy-proven DN managed from 1985 to 2011, 149 patients with urinary N-acetyl-β-d-glucosaminidase (NAG) and urinary β2-microglobulin (β2-MG) data at the time of renal biopsy were enrolled. The primary outcome was a decline in eGFR of ≥50% from baseline or commencement of dialysis for ESRD. RESULTS The median follow-up period was 2.3 years (interquartile range, 1.1-5.3), and the primary outcome was noted in 94 patients. Mean eGFR was 46.3±23.2 ml/min per 1.73 m(2), and 132 patients (89%) had overt proteinuria at baseline. Cox proportional hazards analysis revealed that the association of urinary NAG and β2-MG with the outcome was attenuated after adjustment for known promoters of progression (+1 SD for log NAG: hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.84 to 1.55; +1 SD for log β2-MG: HR, 1.23; 95% CI, 0.94 to 1.62). In contrast, the interstitial fibrosis and tubular atrophy (IFTA) score was still significantly correlated with the outcome after adjustment for the same covariates (+1 for IFTA score: HR, 2.31; 95% CI, 1.56 to 3.43). Moreover, adding the IFTA score to a model containing known progression indicators improved prediction of the outcome (increase of concordance index by 0.02; 95% CI, 0.00 to 0.05; category-free net reclassification improvement by 0.54; 95% CI, 0.03 to 1.05; and relative integrated discrimination improvement by 0.07; 95% CI, -0.08 to 0.22). CONCLUSIONS Adding urinary NAG and β2-MG excretion to known promoters of progression did not improve prognostication, whereas adding the IFTA score did. The IFTA score may be superior to these tubulointerstitial markers for predicting the renal prognosis in advanced DN.

Induction of Anti-Carbonic-Anhydrase-II Antibody Causes Renal Tubular Acidosis in a Mouse Model of Sjögren’s Syndrome

Background/Aim: We recently reported that renal tubular acidosis (RTA) in Sjögren’s syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS. Methods: PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect. Results: CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis. Conclusion: CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.

Renal prognosis a long time after renal biopsy on patients with diabetic nephropathy

Background A new classification of diabetic nephropathy was reported by Tervaert et al., but the association between pathological findings and the clinical outcomes remains unclear. Methods Among 310 patients with diabetes mellitus who underwent renal biopsy from March 1985 to January 2010 and were confirmed to have diabetic nephropathy according to the Tervaerts classification, 205 patients were enrolled in this study. Cox proportional hazard regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for death-censored renal death. Each regression analysis employed two levels of multivariate adjustment. Results After adjustment for age, gender, estimated glomerular filtration rate, type of diabetes, urinary protein excretion, systolic blood pressure, body mass index, HbA1c, diabetic retinopathy and red blood cells in urinary sediment at the time of renal biopsy, compared with glomerular class IIA, the HRs for death-censored renal death of glomerular classes I, IIB, III and IV were 0.21 (95% CI: 0.04–1.25), 2.12 (0.89–5.04), 4.23 (1.80–9.90), and 3.27 (1.32–8.10), respectively. Also, compared with an interstitial fibrosis and tubular atrophy score 1 group, HRs for score 0 group, score 2 group and score 3 group were 0.08 (0.01–0.57), 2.17 (0.96–4.91), 4.78 (1.96–11.68), respectively. Conclusions The progression of glomerular, tubulointerstitial and vascular lesions was associated with higher HRs for renal death. These results suggest the clinical utility of Tervaerts pathological classification.

Tocilizumab improves cardiac disease in a hemodialysis patient with AA amyloidosis secondary to rheumatoid arthritis

A 58-year-old Japanese woman on hemodialysis (HD) was admitted for intractable rheumatoid arthritis. Even after HD was started due to end-stage renal failure in 2004, her arthropathy worsened. A soluble tumor necrosis factor receptor inhibitor (etanercept at 25 mg twice weekly), tacrolimus (2 mg daily), and prednisolone (10 mg daily) had been administered since 2005, but high disease activity had persisted. She was admitted to our hospital in July 2007. C-reactive protein (CRP) was 6.8 mg/dL, and the DAS-CRP score was calculated to be 8.3. The cardiothoracic ratio (CTR) was 62% on a chest radiograph, but dialysis hypotension was remarkable. Left ventricular mass (LVM) was calculated as 320 g using echocardiography. Endoscopic biopsy of the stomach and duodenum revealed heavy deposition of AA amyloid. Etanercept was discontinued and tocilizumab was started at a dose of 320 mg (8 mg/kg) monthly. Even after predonisolone and tacrolimus were tapered gradually and discontinued because of her good response, CRP and DAS-CRP became 0.0 mg/dL and 1.5, respectively. In September 2011, re-evaluation was performed. CTR was reduced to 51% and LVM was decreased to 180 g. Endoscopic biopsy of the stomach and duodenum revealed disappearance of AA amyloid. Although AA amyloidosis of the gastrointestinal tract has already been reported to be improved by tocilizumab, this is the first report on improvement of myocardial hypertrophy as well as dialysis hypotension.

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.

Infected hepatic and renal cysts: differential impact on outcome in autosomal dominant polycystic kidney disease.

Background: Infected cysts are a frequent and serious complication of autosomal dominant polycystic kidney disease. Such infections are classified into those affecting hepatic cysts and those affecting renal cysts. The purpose of this study was to compare the clinical course of infected hepatic cysts with that of infected renal cysts in patients with autosomal dominant polycystic kidney disease. Methods: We analyzed 43 patients referred to us for additional treatment of severely infected cysts between January 2004 and December 2006. All patients who required further treatment in addition to antibiotic therapy were included. Results: Aspiration was performed in all 28 patients with infected hepatic cysts. As a result, 17 patients were cured, 4 remain under treatment, and 6 died. One patient was cured by partial hepatectomy. Among the 15 patients with renal cysts, aspiration was performed in 4 with identifiable infected cysts, while renal transcatheter arterial embolization after appropriate antibiotic therapy was performed in 11 without identifiable infected cysts. No patient developed recurrence. Conclusion: In patients with infected renal cysts, aspiration or renal transcatheter arterial embolization after appropriate antibiotic therapy was effective. Although aspiration was often effective in patients with infected hepatic cysts, a good outcome was less likely than in those with renal cysts.

Tocilizumab improves systemic rheumatoid vasculitis with necrotizing crescentic glomerulonephritis

Abstract We report a Japanese woman with systemic rheumatoid vasculitis (SRV) complicated by necrotizing crescentic glomerulonephritis (NCGN). Rheumatoid arthritis first occurred at the age of 19 years, followed by interstitial pneumonia, hepatitis, rheumatoid nodules, mononeuritis multiplex, and hypocomplementemia in chronological order. At the age of 51 years, rapidly progressive renal failure occurred with nephrotic proteinuria, and NCGN with subepithelial deposits was revealed by renal biopsy. Severe destructive changes of multiple joints and scleritis were detected, but anti-neutrophil cytoplasmic antibody was negative on enzyme-linked immunosorbent assays and indirect immunofluorescence. SRV was diagnosed due to involvement of multiple extra-articular organs. An anti-interleukin (IL)-6 receptor antibody (tocilizumab) was started at dosage of 280 mg (8 mg/kg) monthly. After 18 months, her serum creatinine decreased from 1.7 to 1.3 mg/dL, and urinary protein excretion declined from 5.2 to 1.2 g daily. Tocilizumab may be a therapeutic option for SRV associated with NCGN.

Clinical and pathological predictors of estimated GFR decline in patients with type 2 diabetes and overt proteinuric diabetic nephropathy

The effect of clinical and pathological parameters on the estimated glomerular filtration rate (eGFR) decline has not been investigated in patients with type 2 diabetes and overt proteinuric biopsy‐proven diabetic nephropathy.

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

Plasma Adiponectin: A Predictor of Coronary Heart Disease in Hemodialysis Patients – A Japanese Prospective Eight-Year Study

Background/Aim: Plasma adiponectin may play a protective role in the pathogenesis of cardiovascular disease in hemodialysis (HD) patients. We examined the effect of plasma adiponectin levels on the prognosis of the HD patients. Methods: 68 HD patients (male:female = 38:30) were subjected to plasma adiponectin measurement in 1998 and followed up over 8 years. Results: Plasma adiponectin concentrations differed between male and female patients (9.3 vs. 15.7 μg/ml). The plasma adiponectin concentration as a whole was positively correlated with serum high-density lipoprotein cholesterol and negatively with serum creatinine and waist circumference. During an 8-year follow-up, the cardiac events occurred in 7 of 38 men and in 10 of 30 women. Cox’s proportional hazard model analysis in a stepwise manner revealed that coronary heart disease (CHD) was associated with intact parathyroid hormone concentration, age, and the presence of diabetes in men whereas plasma adiponectin concentration was the most powerful single predictor in women. The impact of the plasma adiponectin concentration was strengthened by Kaplan-Meier survival analysis. In the group with a lower plasma adiponectin concentration, CHD events were significantly increased in men (p = 0.043) and in women (p = 0.007). Conclusion: Plasma adiponectin concentration may predict CHD outcomes in HD patients.