Urinary Thrombin as a Marker of Glomerular Inflammation Associated with Renal Injury in Type 2 Diabetes.

Glomerular inflammation is a putative aggravation factor for type 2 diabetic nephropathy and urinary thrombin is a novel marker of glomerular inflammation. To clarify the relationship between glomerular inflammation and progression of the nephropathy, we measured urinary thrombin in 118 patients with type 2 diabetic nephropathy at different stages. To investigate the implications of urinary thrombin in the nephropathy, we compared urinary thrombin with expression of tissue factor, the trigger of blood coagulation activation, in glomeruli and with markers of renal injury (estimated glomerular filtration rate (eGFR) and proteinuria). Urinary thrombin was found in 4.9% (3/61), 0.0% (0/12), 29.6% (8/27) and 50.0% (9/18) of patient groups at stages 1, 2, 3 and 4, respectively. Thus, urinary thrombin was negligible in the patients at early stages (stages 1 and 2), but was present predominantly in the patients at advanced stages (stages 3 and 4). Tissue factor was expressed in accumulated macrophages in glomeruli, which indicates that thrombin may be generated in inflamed glomeruli presumably via inflammation-induced activation of the exudated coagulation factors into glomerular tissues and then be excreted in urine. Urinary thrombin was significantly associated with both decreased eGFR and increased proteinuria in type 2 diabetic nephropathy. Therefore, increased urinary thrombin in patients with advanced stages of type 2 diabetic nephropathy suggests that glomerular inflammation may injure the tissues, thereby impairing renal function. Monitoring an effect of anti-diabetic treatments on glomerular inflammation in the patients with type 2 diabetic nephropathy may be a possible application of urinary thrombin.

Suboptimal initiation predicts short-term prognosis and vulnerability among very elderly patients who start haemodialysis.

AIM: A recent, growing concern regarding haemodialysis in Japan is a sustained increase in the elderly population. Among very elderly people who start haemodialysis, the prognosis is considered to be poor; however, this has not been fully elucidated. This study aimed to discover the short-term prognosis and related factors in very elderly patients who commence haemodialysis. METHODS: Between January 2008 and December 2013, 122 patients aged ≥85 years at haemodialysis initiation were documented in our hospital. Predictors of 90-day and 1-year mortality after haemodialysis initiation were assessed with Cox proportional hazards regression analysis. Selection of covariates for the multivariate model was based on forward stepwise selection using the probability of a likelihood ratio statistics. RESULTS: The subjects' mean age was 87.4 ± 2.5 years, and 48% were female. The most common cause of death was infection (38% of patients) and the leading cause of infectious death was pneumonia. The 90-day and 1-year survival rates were 81% and 62%, respectively. Suboptimal initiation was a significant prognostic factor for 90-day [hazard ratio (HR) 3.98, 95% confidence interval (CI) 1.18-13.43] and 1-year [HR 3.19, 95% CI 1.51-6.76] mortality after adjusting for confounders in multivariate analysis. CONCLUSION: Very elderly patients who started haemodialysis had a poor prognosis, and suboptimal initiation significantly predicted outcome. Shared decision-making with patients and their families is needed for initiating haemodialysis on the conditions that appropriate information on the expected prognosis is provided.

Efficacy of low-density lipoprotein apheresis combined with corticosteroids for cholesterol crystal embolism.

BACKGROUND: Corticosteroids have been widely used in patients with cholesterol crystal embolism (CCE) and low-density lipoprotein apheresis (LDL-A) was reported to reduce the risk of end-stage renal disease in patients with CCE. This study was designed to evaluate the renoprotective effects of LDL-A in combination with corticosteroids in patients with CCE. METHODS: Thirty-five patients with CCE who, between 2008 and 2013, had shown renal deterioration after vascular interventions were retrospectively evaluated. All patients received corticosteroids; of these, 24 also received LDL-A and 11 did not, designated LDL-A and control groups, respectively. Differences in eGFR (ΔeGFR), 3 months and 1 year after CCE diagnosis, were compared in the two groups. RESULTS: The median estimated glomerular filtration rate (eGFR) in all patients was 38.9 [interquartile range (IQR) 31.9-49.4] ml/min/1.73 m2 at baseline (before vascular intervention). At diagnosis, it was 14.4 (IQR 11.3-21.8) ml/min/1.73 m2. The initial corticosteroid dose was 0.34 ± 0.10 mg/kg/day. The mean number of LDL-A treatment sessions in the LDL-A group was 4.3 ± 1.8. eGFR was increased significantly after LDL-A treatments, from 15.0 (IQR 12.3-20.1) to 19.6 (IQR 14.3-23.6) ml/min/1.73 m2 (P < 0.05). ΔeGFR tended to be higher in the LDL-A than in the control group at 3 months [median 6.5 (IQR 5.1-9.3) vs. 2.6 (IQR -0.6 to 6.3) ml/min/1.73 m2, P = 0.095] and was significantly higher at 1 year [median 7.5 (IQR 5.4-8.7) vs. 2.2 (IQR -3.8 to 5.1) ml/min/1.73 m2, P = 0.019]. CONCLUSIONS: LDL-A plus corticosteroids may restore deteriorated renal function better than corticosteroids alone in patients with CCE.

Impact of hemoglobin levels on renal and non-renal clinical outcomes differs by chronic kidney disease stages: the Gonryo study.

BACKGROUND: Anemia greatly affects the development of renal and cardiovascular outcomes in chronic kidney disease (CKD) patients. However, the impact based on CKD stage remains unclear. METHODS: We prospectively followed 2,602 Japanese CKD patients under the care of nephrologists. CKD was defined according to cause, estimated glomerular filtration rate <60 mL/min, and/or proteinuria. Patient outcomes [primary end-points: cardiovascular events (CVEs), all-cause mortality, and end-stage kidney disease (ESKD) requiring renal replacement therapy] were assessed in association with basal hemoglobin (Hb) levels (<10, 10-12 and ≥12 g/dL), stratified by CKD stages. RESULTS: During follow-up, 123 patients developed CVEs, 41 died, and 220 progressed to ESKD. For stages G3, G4 and G5, ESKD frequencies were 2.8, 64.4, and 544.8 person-years, while CVEs and death were 25.6, 45.6, and 76.3 person-years, respectively. The combined endpoint rate was significantly higher in patients with Hb <10 versus Hb 10-12 g/dL, but a higher risk for CVEs and death with Hb <10 g/dL was found only in G3 [hazard ratio (HR) 4.49, (95 % confidence interval (95 % CI) 2.06-9.80)]. In contrast, risk for ESKD with Hb <10 g/dL was found only in G4 [HR 3.08 (95 % CI 1.40-6.79)] and G5 [HR 1.43 (95 % CI 1.01-2.05)]. No increased risks with higher Hb levels were found. CONCLUSION: The impact of renal anemia of Hb <10 g/dL on clinical outcomes differed by CKD stage, with a significantly high risk for CVEs and all-cause mortality in G3 and progression to ESKD in G4 and G5.

Effects of cyclophosphamide on the prognosis of Japanese patients with renal vasculitis associated with anti-neutrophil cytoplasmic antibody-positive microscopic polyangiitis.

BACKGROUND: The aim of this study was to determine the efficacy of cyclophosphamide (CY) on anti-neutrophil cytoplasmic antibody (ANCA)-positive microscopic polyangiitis (MPA) with renal involvement in Japanese patients. METHODS: Eighty-two patients with newly diagnosed ANCA-positive MPA were enrolled in this retrospective study. Patients were divided into two groups based on whether they received combination therapy with a corticosteroid (CS) plus CY (CY group) or CS alone or with other therapies (non-CY group). The primary outcome was defined as the combination of death and end-stage renal disease (ESRD). RESULTS: The CY and non-CY groups included 29 and 53 patients, respectively. In the non-CY group, 31 patients were treated with CS alone, and 22 with a combination of CS and other therapeutics. The percentage of males and mean Birmingham vasculitis activity scores were higher in the CY group than those in the non-CY group, but other factors such as age, serum creatinine, serum albumin, or CRP at baseline were equivalent in the two groups. No differences were observed in remission rates using induction therapy for the two groups. However, the survival rate 5 years after induction therapy was lower in the CY group than in the non-CY group (0.50 vs. 0.73; P = 0.041), although the hazard ratio of CY for the primary outcome adjusted for all confounding factors was 1.321 [95 % confidence interval (CI), 0.662-2.637; P = 0.171]. CONCLUSIONS: CY may not have an additive effect on induction therapy with CS for Japanese patients with renal vasculitis associated with ANCA-positive MPA.

Relationship between low blood pressure and renal/cardiovascular outcomes in Japanese patients with chronic kidney disease under nephrologist care: the Gonryo study.

BACKGROUND: Previous studies established a J-shaped association between blood pressure (BP) and cardiovascular disease (CVD) in chronic kidney disease (CKD), and the different clinical profiles of CVD by ethnicity. However, the adequately lower BP target remains unclear in Asian patients with CKD. METHODS: This prospective observational study included 2,655 Japanese outpatients with CKD under nephrologist care who met the inclusion criteria, namely estimated glomerular filtration rate <60 mL/min and/or presenting proteinuria. The patients were divided by 10-mmHg BP increments by clinical data. The end points were death, cardiovascular events (CVEs), and end-stage kidney disease (ESKD) that requires renal replacement therapy. RESULTS: During a 3.02-year median follow-up, 64 patients died, 120 developed CVEs, and 225 progressed to ESKD. In the adjusted Cox models, the risks of CVEs and all-cause mortality were higher in the patients with systolic BPs (SBPs) < 110 mmHg than in those with SBPs of 130-139 mmHg. Moreover, the risk was higher in those with diastolic BPs (DBPs) < 70 mmHg than in those with DBPs of 80-89 mmHg. Although SBPs ≥ 140 mmHg were associated with higher incidence rates of ESKD, no significant increased risk was associated with BPs < 130/80 mmHg. CONCLUSIONS: SBPs < 110 mmHg and DBPs < 70 mmHg were independent risk factors of CVEs and all-cause mortality. No lower BPs were observed as significant risk factors of progression to ESKD. This study suggests that the lower BP target in Asian patients with CKD should be ≥110/70 mmHg.

Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy.

BACKGROUND: The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity. METHODS: We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3-5 years. RESULTS: Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B. CONCLUSION: Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.

[Awareness about and educational intervention for chronic kidney disease in the general population: from a survey of participants at the CKD educational lecture in Miyagi prefecture].

BACKGROUND: The prevalence of chronic kidney disease (CKD) and its complications, such as cardiovascular disease (CVD), cerebral vascular disease and end-stage kidney disease (ESKD), has been increasingly recognized as a global health problem in Japan. OBJECTIVE: We surveyed the awareness about CKD among medical professionals and the general public in Miyagi Prefecture. Additionally, we considered ways to lower the prevalence of CKD, CVD and ESKD. METHOD: We offered an annual educational lecture on CKD for the general population in Miyagi prefecture from 2010 to 2012. At each lecture, we distributed an anonymous survey to the participants about CKD and its complications. RESULTS: The number of survey respondents was 355, and their mean age was 63.9 years. Awareness about CKD among the participants, excluding medical professionals, was 58.0 %. Terms such as "serum creatinine" and "estimated GFR" were recognized in only about 60% and 40% of the respondents, respectively. Knowledge of risk factors for CKD, such as "elderly person" and "smoker," was at a low level. Furthermore, anemia and osteoporosis were not well-recognized as comorbidities of CKD. CONCLUSION: We found that the participants at the CKD educational lectures had limited knowledge about CKD and its complications; therefore, educational intervention regarding CKD, CVD and ESKD should be continued. Public awareness about CKD must be addressed to reduce CVD not only to prevent ESKD. The educational intervention will require a wide range of specialists in CKD care, general physicians, health nurses, and nutritionists, who contribute to community-based health care.

Effect of allopurinol on cardiovascular incidence among hypertensive nephropathy patients: the Gonryo study.

BACKGROUND: The present study aimed to clarify the beneficial effect of allopurinol on cardiovascular morbidity and mortality in a cohort of hypertensive nephropathy patients with impaired kidney function. METHODS: One hundred and seventy-eight patients diagnosed with hypertensive nephropathy and presenting with impaired kidney function (estimated glomerular filtration rate <45 mL/min/1.73 m(2)) were recruited from nephrology clinics. Oral allopurinol was prescribed in 67 of these patients. The effects of allopurinol use on the development of cardiovascular disease (i.e. ischemic heart disease, congestive heart failure, and stroke) and all-cause death was analyzed using the Cox proportional hazard model. RESULTS: During the follow-up of 18.4 months (mean), 28 primary events occurred. Basal use of allopurinol was a significant beneficial factor (hazard ratio = 0.342, p = 0.0434, standard error = 0.53058) after adjusting for confounding factors. CONCLUSION: The use of allopurinol in hypertensive subjects with impaired kidney function appears to be beneficial in preventing cardiovascular morbidity and all-cause mortality, indicating that this xanthine oxidase inhibitor protects the vascular system, at least in this specific group.

Significance of the duration of nephropathy for achieving clinical remission in patients with IgA nephropathy treated by tonsillectomy and steroid pulse therapy.

BACKGROUND: Because of the well-established annual urinalysis screening system in Japan, the duration of nephropathy (DN) can be estimated in more than half of all patients with IgA nephropathy (IgAN). Treatment using a combination of tonsillectomy and steroid pulse (TSP) therapy has been reported as an effective method for obtaining clinical remission (CR), defined as negative hematuria and proteinuria, in IgAN patients. The present study aims to identify the correlation between DN and CR rate in IgAN patients treated by TSP therapy. METHODS: We retrospectively investigated 830 IgAN patients who were followed up for 81.6 months after TSP therapy. DN could be estimated in 495 of the 830 patients. RESULTS: The CR rate among patients with DN ≤36 months was 87.3% (295/338 patients). The CR rate among patients with DN of 37-84 months was 73.3% (63/86 patients), while that among patients with DN ≥85 months was 42.3% (30/71 patients). The CR rate among the remaining 335 patients in whom DN could not be estimated because of missing annual urinalysis results was 43.6% (146/335 patients). A multivariate Cox regression model using data from the former group of 495 patients showed that DN ≤36 months was a significant predictor of CR (hazard ratio 1.839; 95% confidence interval 1.410-2.398; P < 0.001). CONCLUSION: Shorter DN is associated with higher likelihood of clinical remission in IgAN patients treated by TSP therapy.

Different clinical outcomes for cardiovascular events and mortality in chronic kidney disease according to underlying renal disease: the Gonryo study.

PURPOSE: Chronic kidney disease (CKD) can result from a wide variety of diseases, but whether clinical outcomes differ in the same CKD stages according to the underlying renal disease remains unclear. Clarification of this issue is important for stratifying risk of cardiovascular disease (CVD) and death in patients before dialysis. PATIENTS AND METHODS: The study comprised 2,692 patients recruited from 11 outpatient nephrology clinics, classified by underlying disease of primary renal disease (PRD) (n = 1,306), hypertensive nephropathy (HN) (n = 458), diabetic nephropathy (DN) (n = 283), or other nephropathies (ON) (n = 645). Risks of events such as ischemic heart disease, congestive heart failure, stroke, and all-cause mortality within 12 months were examined by logistic regression analysis in each group. RESULT: During the 12-months' observation from recruitment, 200 cases were lost to follow-up, and 113 cases were introduced to chronic dialysis therapy. A total of 69 CVD events occurred (stroke in 27 cases), and 24 patients died. In total, increased odds ratios (OR) for the events by CKD stage (cf. CKD1 + 2: unadjusted) were CKD3, 1.29 [95% confidence interval (CI), 0.70-2.17]; CKD4, 2.73 (1.55-4.83); and CKD5, 4.66 (2.63-8.23). Regarding events in respective groups, no significant differences were seen by CKD stage except for the group with HN, but significant differences were seen by underlying diseases (cf. PRD: adjusted for confounding factors, including estimated glomerular filtration rate): HN, 2.57 (1.09-6.04); DN, 12.21 (3.90-38.20); and ON, 4.14 (1.93-8.89). CONCLUSION: Risk of CVD and mortality due to CKD needs to be stratified according to the underlying renal diseases.

Clinical effectiveness of steroid pulse therapy combined with tonsillectomy in patients with immunoglobulin A nephropathy presenting glomerular haematuria and minimal proteinuria.

AIM: The effectiveness of steroid pulse therapy combined with tonsillectomy (ST) has been shown in immunoglobulin A nephropathy (IgAN) patients with moderate or severe urinary abnormalities. The present study aimed to clarify whether the effectiveness may be extrapolated to IgAN with minor urinary abnormalities, and whether the effectiveness may depend on the histological severity with minor urinary abnormalities. METHODS: Data on 388 IgAN patients diagnosed by renal biopsies between 1987 and 2000 in Sendai Shakaihoken Hospital, who presented glomerular haematuria and minimal proteinuria (

A nationwide survey of rapidly progressive glomerulonephritis in Japan: etiology, prognosis and treatment diversity.

BACKGROUND: The etiology, prevalence, and prognosis of rapidly progressive glomerulonephritis (RPGN) including renal vasculitis vary among races and periods. METHOD: To improve the prognosis of Japanese RPGN patients, we conducted a nationwide survey of RPGN in the nephrology departments of 351 tertiary hospitals, and found 1772 patients with RPGN (Group A: diagnosed between 1989 and 1998, 884 cases; Group B: diagnosed between 1999 and 2001, 321 cases; and Group C: diagnosed between 2002 and 2007, 567 cases). ANCA subclasses, renal biopsy findings, treatment, outcome and cause of death were recorded. RESULT: The most frequent primary disease was renal-limited vasculitis (RLV) (42.1%); the second was microscopic polyangiitis (MPA) (19.4%); the third was anti-GBM-associated RPGN (6.1%). MPO-ANCA was positive in 88.1% of RLV patients and 91.8% of MPA patients. The proportion of primary renal diseases of RPGN was constant during those periods. The most frequent cause of death was infectious complications. The serum creatinine at presentation and the initial dose of oral prednisolone decreased significantly in Groups B and C compared to Group A. However, both patient and renal survival rates improved significantly in Groups B and C (survival rate after six months in Group A: 79.2%, Group B: 80.1%, and Group C: 86.1%. Six-month renal survival in Group A: 73.3%, Group B: 81.3%, and Group C: 81.8%). CONCLUSION: Early diagnosis was the most important factor for improving the prognosis of RPGN patients. To avoid early death due to opportunistic infection in older patients, a milder immunosuppressive treatment such as an initial oral prednisolone dose reduction with or without immunosuppressant is recommended.

[Clinical significance of urinary cholesterol/total protein ratio as a marker of selectivity of proteinuria: comparison with selectivity index].

Selectivity index (SI) has been reported to reflect the selectivity of proteinuria, and it has a relationship with tubulointerstitial damage. Moreover it has a predictive value on functional outcome. However, it is necessary to measure serum IgG, serum transferrin, urinary IgG, and urinary transferrin to calculate SI. We measured urinary micro-cholesterol (mCHO) levels in sixty-three patients with proteinuria (urinary total protein > or = g/gCr) and compared urinary mCHO/total protein(uTP) ratio and SI. The patients' diseases were minimal change nephrotic syndrome (MCNS, n = 12), focal and segmental glomerular sclerosis (FSGS, n = 12), membranous nephropathy (MN, n = 17), and diabetic nephropathy (DMN, n = 22). Urinary mCHO levels were measured by the ECC method using cholesterol ester hydrolase (CEH) and cholesterol dehydrogenase, and this method was performed conveniently by automatic analyzer. No correlation was observed between urinary mCHO/gCr and serum lipid levels. There was no difference of urinary protein levels among each disease group. We found urinary mCHO/uTP ratio has a good positive correlation with SI(R = 0.722, p < 0.001). Although the difference between ROC curves of SI and urinary mCHO/uTP ratio in distinguishing MCNS from other diseases (FSGS+MN+DMN) did not reach the statistical significance, the area under the curve was larger for mCHO/uTP ratio. These results suggest that measurement of urinary mCHO by ECC method can be a simple and useful tool for predicting selectivity of proteinuria and lipoprotein-loading tubulopathy.

[Soluble fibrin is not excreted in urine and its plasma level is elevated in nephrotic syndrome].

Soluble fibrin (SF) is produced by activated blood coagulation reaction and is useful to diagnose thrombotic diseases. We measured plasma and urine SF levels in nephritic patients to assess the hypercoagulability state associated with the disease. Before they received anti-coagulation or anti-platelet therapies, 60 patients underwent measurement of plasma SF and D-dimer levels by Latex agglutination turbidimetric immnoassay (LA). Urinary SF levels were also measured by LA. Plasma and urinary thrombin antithrombin III complex (TAT) levels were measured by enzyme immunoassay (EIA). Plasma SF levels showed a good correlation with plasma TAT levels but only weak positive correlations were observed between plasma D-dimer and SF or TAT levels. Plasma SF and D-dimer levels were significantly higher in the Iatients with nephrotic-range hypoalbuminemia (< or =3 g/dL) than those without it. Contrarily there was no significant difference in plasma TAT levels between these two groups of patients. In almost all patients, urinary SF levels were under the detection limit. However, TAT was excreted into urine more frequently in patients showing the nephrotic range of hypoalbuminemia at 38.2% than in non-nephrotic patients at 8.0%. Thus, plasma SF levels more precisely indicate activated blood coagulation reaction than plasma TAT levels in nephrotic patients, probably because the plasma SF is not excreted into urine, while plasma TAT is.

Chemokine Receptor 8 Can Distinguish Antineutrophil Cytoplasmic Antibody-Associated Vasculitis From Infectious Complications.

INTRODUCTION: Diagnosing vasculitis is frequently difficult because its clinical symptoms are similar to those of common infectious diseases and other inflammatory disorders. This study focused on chemokine receptor 8 (CCR8) in peripheral blood mononuclear cells to find a new biomarker that distinguishes vasculitis from infectious complications. METHODS: A cross-sectional study was conducted among 113 patients with systemic vasculitis who were referred to Japan Health Care Organization Sendai Hospital from 2014 to 2016, including those with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, anti-glomerular basement membrane disease, lupus nephritis, and Henoch-Schonlein purpura. Peripheral blood mononuclear cells were extracted from blood, and CCR8 expression was examined by real time polymerase chain reaction and flow cytometry. RESULTS: CCR8 gene expression was significantly higher in patients with ANCA-associated vasculitis, which was confirmed by upregulated CCR8 protein expression in flow cytometry (P < 0.001 and P = 0.01, respectively). Neither lupus nephritis nor Henoch-Schonlein purpura showed upregulated CCR8. Elevated CCR8 in the active phase decreased significantly in remission (P = 0.002), which was correlated with decreased serum inflammatory markers. Despite elevated serological inflammatory markers, the CCR8 levels at the time of infection, including bacterial, viral, and fungal, did not increase, indicating that infectious complications did not affect CCR8 expression (P = 0.02). CONCLUSION: CCR8 in peripheral blood mononuclear cells may be a useful diagnostic marker for ANCA-associated vasculitis to differentiate between active vasculitis and infectious inflammation.

A case of primary aldosteronism associated with renal artery stenosis and preclinical Cushing's syndrome.

We identified a left adrenal tumor, left renal atrophy, and left renal artery stenosis (RAS) in a 52-year-old man by MRI/magnetic resonance angiography (MRA) during evaluation of hypertension. Laboratory tests revealed hypokalemia, a high plasma aldosterone concentration (PAC), low plasma renin activity (PRA), and normal plasma cortisol. An excessive response of aldosterone and cortisol to adorenocorticotrophic hormone (ACTH) was found upon selective sampling of the left adrenal vein. Selective renal venous sampling showed a left/right renal venous PRA ratio of 1.7. A dexamethasone (8 mg) suppression test showed insufficient suppression of cortisol. We diagnosed this patient as having aldosterone-producing adrenal adenoma (APA) associated with renovascular hypertension (RVH) and preclinical Cushing's syndrome. As an initial treatment, percutaneous transluminal renal angioplasty was performed. Postoperatively, the patient's blood pressure decreased. One month later, the tumor was removed by complete laparoscopic left adrenalectomy. Postoperatively, blood pressure decreased further and both PAC and PRA were normalized. However, antihypertensive therapy could not be completely stopped. The renal dysfuntion that occurred prior to treatment seemed to prevent complete normalization of blood pressure.

High incidence of Dieulafoy's lesions in upper gastrointestinal bleeding associated with polyarteritis--clinical examination of patients of polyarteritis nodosa with rapidly progressive glomerulonephritis.

BACKGROUND/AIMS: Polyarteritis nodosa (PN) has been classified into polyarteritis (PA) and microscopic polyarteritis (MA) histologically. To clarify of the characteristics of upper gastrointestinal bleeding lesions in PN, we investigated the patients of PN with rapidly progressive glomerulonephritis (RPGN) presenting with upper gastrointestinal bleeding. METHODOLOGY: The subjects of this study were 21 patients of PN with RPGN (PA: 11, MA: 10) who presented with upper gastrointestinal bleeding. The bleeding lesions and their locations were examined endoscopically in the study subjects, and the relationship of the bleeding to the severity of renal failure, the necessity of hemodialysis (HD), presence/ absence of H. pylori infection and the gender of the patients were analyzed. RESULTS: The bleeding lesions were endoscopically identified as esophageal ulcers in 2 cases, gastric ulcers in 15 cases and duodenal ulcers in 4 cases, respectively. In 10 of the 15 cases with gastric ulcers, the ulcer assumed the form of Dieulafoy's lesions affecting the gastric body, and the underlying disease was PA in all the 10 cases. In the remaining 5 cases of gastric ulcers and 2 cases of esophageal ulcer with underlying MA or 4 cases of duodenal ulcers, in whom assumed the bleeding form of oozing from the marginal zone of ulcers. In all of the 4 cases of duodenal ulcers, and the 1 case with underlying PA and the other cases with MA, no correlation was found between the onset of the upper gastrointestinal bleeding and the severity of renal failure or the necessity for HD, presence of H. pylori infection, or the gender of the patients. CONCLUSIONS: Dieulafoy's lesions are the most frequent sources of upper gastrointestinal bleeding in cases of PA.

Steroid pulse therapy transiently destroys the discriminative histological structure of tonsils in IgA nephropathy: Tonsillectomy should be performed before or just after steroid pulse therapy.

OBJECTIVE: Tonsillectomy combined with steroid-pulse therapy is a widely accepted method for the treatment of IgA nephropathy (IgAN) in Japan. However, the indication of tonsillectomy for IgAN is still controversial, and the timing of tonsillectomy is not clearly defined for the protocol of this therapy. Based on the results of a randomized control trial in Japan, the Evidence-Based Clinical Practice Guidelines for IgA nephropathy 2014 (edited in Japan) recommended tonsillectomy combined with steroid-pulse therapy for Grade C1. However, this is not widely accepted worldwide. To clarify the validity and timing of tonsillectomy, we evaluated how the three-consecutive steroid-pulse therapy method affects the tonsil tissues of IgAN patients. METHODS: We examined tonsil specimens from 35 IgAN patients and 8 chronic tonsillitis patients. We compared the proportion of follicular area to total tonsillar area and the number of germinal centers between each group on hematoxylin and eosin stained pathological specimens to clarify the histopathological characteristics of tonsils from IgAN patients. Based on these findings, we examined the tonsils of patients after three-consecutive steroid-pulse therapy treatments (n=34) to determine the influence of this therapy on the tonsil tissues of IgAN patients. Moreover, we observed chronological changes in tonsil tissues after steroid-pulse therapy. RESULTS: The extrafollicular area was enlarged in IgAN patients before steroid-pulse therapy compared with chronic tonsillitis patients. Just after steroid-pulse therapy, the follicles became very small with blurry outlines, and the number of germinal centers was remarkably decreased. With a gradual decrease in oral prednisolone, the tonsil tissue structure was gradually restored. CONCLUSION: Tonsillectomy combined with steroid-pulse therapy is considered a reasonable treatment for IgAN. Steroid-pulse therapy-induced histological changes in tonsils were transient, indicating tonsillectomy should be performed before or just after steroid-pulse therapy.