[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
Full-text · Article · Jan 2016 · Clinical Journal of the American Society of Nephrology
[Show abstract][Hide abstract] ABSTRACT: A 63-year-old Japanese woman with Sjögren's syndrome and peripheral neuropathy was admitted for evaluation of purpura on her lower extremities. Skin biopsy revealed leukocytoclastic vasculitis with the deposition of IgM, and serum cryoglobulin was positive. Accordingly, cryoglobulinemic vasculitis was diagnosed. There was no response to high-dose steroid therapy and plasmapheresis, but intravenous cyclophosphamide pulse therapy was effective for 4 years. Thereafter, proteinuria and hematuria developed, with cryoglobulinemic glomerulopathy being diagnosed by renal biopsy. Because the total dose of cyclophosphamide had reached 8000 mg, treatment with rituximab was selected. While rituximab was initially effective for her skin lesions and nephropathy, relapse occurred within 2 years and additional administration of this agent was required. The long-term efficacy of treatment for cryoglobulinemic vasculitis remains uncertain in patients with Sjögren's syndrome.
No preview · Article · Jan 2016 · Modern Rheumatology
[Show abstract][Hide abstract] ABSTRACT: 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 (BMT). MGN was diagnosed in 5 patients after UCBT (vs. none after BMT), and occurred concomitantly with chronic graft-versus-host-disease after cessation of immunosuppression. LM 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. IF demonstrated granular deposits of IgG (IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), while case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. EM revealed electron-dense deposits (EDD) in the subepithelial space of the GBM in cases 1-4. In case 5, EDD 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 two patients during follow up. Serum anti-PLA2R autoantibody was negative in three patients. HSCT-related MGN only occurred after umbilical cord blood transplantation (UCBT). We believe that there were two morphologic patterns; early MGN and membranoproliferative pattern glomerulonephritis.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Nov 2015 · Journal of the American Society of Nephrology
[Show abstract][Hide abstract] ABSTRACT: Background:
In addition to renin-angiotensin system inhibition (RAS), corticosteroids are recommended for patients who have immunoglobulin A nephropathy (IgAN) with ≧1 g/day proteinuria. Tonsillectomy plus corticosteroid pulse therapy (TSP) had been reported as more effective in producing clinical remission of IgAN than just oral-corticosteroid (OS) or steroid-pulse (SP) therapy-but that remained unconfirmed. Accordingly, this study compared the effects of TSP, corticosteroid therapies, and RAS on a multicenter, large-scale, long-term cohort.
1127 biopsy-proven IgAN patients with chronic kidney disease (CKD), G1-3, treated in our hospitals March 1981-December 2013 with TSP (n = 209), SP (n = 103), OS (n = 300), or RAS, alone (n = 515), were followed until end-stage renal disease (ESRD) or death, renal survival compared by treatment and proteinuria level. Hazard ratios (HRs) of ESRD were analyzed after adjusting for sex, age, BMI, eGFR, albumin, proteinuria, hematuria, blood pressure, medications, and renal-biopsy year, with propensity-score-matched analyses performed.
With TSP as referent, the overall HRs of SP, OS, and RAS were, respectively, 1.33 (0.44-4.04), 3.56 (1.45-8.71), and 3.64 (1.48-8.96); with proteinuria ≧1.0 g/gCre, respective HRs were 2.99 (0.71-12.54), 5.04 (1.44-17.67), and 7.23 (1.98-26.40); with proteinuria <1.0 g/gCre, 0.42 (0.04-4.89), 3.24 (0.79-13.30), and 2.05 (0.52-8.05); and for patients with CKD G3, 0.37 (0.10-1.41), 2.14 (0.77-5.94), and 2.03 (0.72-5.72). Similar results were observed in models including pathological grading and/or propensity-score matching.
TSP may decrease the risk of ESRD in IgAN patients better than other therapies in CKD G1-2, with proteinuria ≧1.0 g/gCre, while outcome was similar to SP in CKD G3, or with proteinuria <1.0 g/gCre.
No preview · Article · Nov 2015 · Clinical and Experimental Nephrology
[Show abstract][Hide abstract] ABSTRACT: Once-weekly 56.5-μg teriparatide treatment was significantly associated with the increase in lumbar spine bone mineral density at 48 weeks among hemodialysis patients with hypoparathyroidism and low bone mass; however, discontinuation of treatment because of adverse events was frequently observed. Careful monitoring for adverse events should be required.
Once-weekly 56.5-μg teriparatide is reportedly effective for treating osteoporotic patients without renal insufficiency. However, little is known about the efficacy and safety of once-weekly teriparatide in hemodialysis patients.
We conducted a 48-week prospective, observational cohort study including 22 hemodialysis patients aged 20 years or older with hypoparathyroidism and low bone mass who received once-weekly teriparatide at 56.5 μg at a tertiary care hospital between January 2013 and January 2015. Primary outcomes were within-subject percent changes of bone mineral density (BMD) at the lumbar spine, femoral neck, and distal one-third radius at 24 and 48 weeks. Secondary outcomes included percent changes of serum bone turnover markers (osteocalcin, bone-specific alkaline phosphatase (BAP), N-terminal propeptide of procollagen type 1 (P1NP), and tartrate-resistant acid phosphatase 5b (TRAP-5b)). Adverse events were evaluated.
The BMD increased at the lumbar spine by 3.3 ± 1.9 % (mean ± SEM) and 3.0 ± 1.8 % at 24 and 48 weeks but not in the femoral neck and distal one-third radius. Serum osteocalcin, BAP, and P1NP increased significantly at 4 weeks, maintaining higher concentrations up to 48 weeks, although TRAP-5b decreased gradually during treatment. The baseline BAP was significantly associated with the 48-week percent change in lumbar spine BMD. Transient hypotension was the most common adverse event. Ten patients discontinued treatment because of adverse events.
Once-weekly teriparatide was associated with increased lumbar spine BMD in hemodialysis patients with hypoparathyroidism and low bone mass. Careful monitoring should be required for treatment of such patients.
No preview · Article · Nov 2015 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Nov 2015 · Therapeutic Apheresis and Dialysis
[Show abstract][Hide abstract] ABSTRACT: A 37-year-old man was admitted to our hospital for an evaluation of renal dysfunction and hypertension. The C-reactive protein level was 6.0 mg/dL, and the serum renin activity was extremely high. A renal biopsy showed malignant nephrosclerosis-like lesions with an onion skin pattern. He had a history of recurrent abdominal pain associated with periodic fevers above 38 degrees that resolved within three days. A MEditerranean FeVer (MEFV) gene analysis revealed that he was homozygous for the E148Q polymorphism (exon 2) and heterozygous for the L110P polymorphism (exon 2). The present case demonstrates that persistent subclinical inflammation can lead to malignant nephrosclerosis in familial Mediterranean fever patients with this genotype.
[Show abstract][Hide abstract] ABSTRACT: Renovascular lesions of lupus nephritis (LN) were classified into five categories by D'Agati in Heptinstall's Pathology of the Kidney, with thrombotic microangiopathy (TMA) and clinical thrombotic thrombocytopenic purpura (TTP) being combined. We encountered 2 cases with histological LN (class III and lass V), and they presented with clinical features of TTP, such as acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever, and central neurologic symptoms. Immunosuppressive therapy with plasmapheresis was performed in both patients. Case 1 progressed to end-stage renal failure requiring dialysis and died, while case 2 responded to treatment. In case 1, small renal arteries showed positive mural staining for IgG and C3, while intraluminal material was negative for IgG and C3 [although it was positive for phosphotungstic acid-hematoxylin (PTAH), indicating fibrin deposition]. In case 2, small renal arteries showed mural staining for IgG, C1q, and C3, with the intraluminal material also being positive for these immunoglobulins, but negative for PTAH. These cases suggest that immunosuppressive therapy with plasmapheresis can control LN when intravascular thrombosis is related to immune complexes associated with activation of the early complement components C1q and C3. In contrast, immunosuppressive therapy with plasmapheresis may not be effective when intravascular thrombosis is unrelated to these factors and involves fibrin deposition. Accordingly, in LN patients with clinical features of TTP, we report two types of renovascular lesions, in addition to typical vascular change of TMA with no immune deposits seen in nonlupus patients.
[Show abstract][Hide abstract] ABSTRACT: A 65-year-old woman was admitted to our hospital for the evaluation of rapidly progressive renal dysfunction with serum creatinine of 2.7 mg/dl and urinary protein of 1.5 g daily. C-reactive protein (CRP) was 0.1 mg/dl. Kidney-limited intravascular large B-cell lymphoma (IVL) localized to the glomerular capillaries was diagnosed because the intraglomerular cells were positive for CD20 and CD79a, while there was no positivity in the extraglomerular kidney and extrarenal organs. Treatment with rituximab, cyclophosphamide, hydroxydaunomycin, vincristine, and prednisolone was started, and the patient has since been doing well. When IVL is limited to the intraglomerular capillaries, CRP may not be elevated.
[Show abstract][Hide abstract] ABSTRACT: A 52-year-old Japanese woman was admitted to our hospital with the renal pelvic mass lesion detected on a health screening examination. The surgical specimen contained a mass exhibiting the histological features of immunoglobulin (Ig)G4-related disease, including lymphoplasmacytic infiltration and sclerosis with numerous IgG4-producing plasma cells. Postoperatively, an elevation of the serum IgG4 level was confirmed at 403 mg/dL; however, there was no evidence of tubulointerstitial nephritis or glomerulopathy, including membranous nephropathy, and the urothelium of the renal pelvis was intact without inflammation. We herein report this case in which IgG4-related disease of the renal pelvic region presented with a mass lesion in the intrarenal sinus near the renal pelvis, not 'pyelitis' (as described by Stone).
No preview · Article · Aug 2015 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: A 49-year-old Japanese woman with polycystic liver disease (PLD) was admitted for right hypochondrial pain. CT showed a huge enhancing mass in the liver. She tested negative for other liver diseases, such as hepatitis B and C and alcoholic liver disease. After the patient expired due to hepatic failure, an autopsy revealed poorly differentiated hepatocellular carcinoma (HCC) surrounded by multiple hepatic cysts. The small amount of residual hepatic parenchyma showed nonalcoholic fatty liver disease (NAFLD) with severe steatosis. Severe emaciation was also apparent. This case suggests that malnutrition in patients with symptomatic PLD may contribute to the development of HCC via NAFLD.
[Show abstract][Hide abstract] ABSTRACT: A 65-year-old woman with a limited form of systematic sclerosis (SSc) and Sjögren's syndrome (SS) was admitted to our hospital for the evaluation of renal dysfunction. Her serum creatinine was 1.6 mg/dl, proteinuria was 1.6 g/day, and the urine sediment contained 20-29 erythrocytes/high-power field. Myeloperoxidase anti-neutrophil cytoplasmic antibodies, anti-SS-A/SS-B antibodies and anti-centromere antibodies were positive. A renal biopsy showed focal necrotizing glomerulonephritis with focal interstitial lymphoplasmacytic infiltration. A diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) was made. A steroid therapy was initiated and AAV subsided. This is a rare case of AAV in a patient with anti-centromere-positive limited SSc and SS.
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Apr 2015 · European Journal of Clinical Microbiology
No preview · Article · Apr 2015 · Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy