S100A12 gene expression is increased in peripheral leukocytes in chronic kidney disease stage 4-5 patients with cardiovascular disease.

BACKGROUND/AIMS: S100A12 induces vascular inflammation contributing to the development of atherosclerosis. Serum S100A12 concentration is shown to be elevated in patients with chronic kidney disease (CKD), however the reason remains unclear. METHODS: Transcriptional levels of S100A12 and RAGE (receptor for advanced glycation end products) were measured in peripheral leukocytes by quantitative real-time RT-PCR. Subjects were 40 patients with CKD stage 4-5, 20 of whom were affected with cardiovascular disease (CVD), and 20 healthy subjects. Serum concentrations of S100A12 and soluble RAGE were measured using enzyme-linked immunosorbent assay. RESULTS: The serum concentration of S100A12 was significantly higher in CKD patients than in healthy subjects (78.5 ± 70.5 vs. 23.7 ± 19.2 ng/ml, p = 0.0035), but that of soluble RAGE was not. The relative quantity of S100A12 mRNA was significantly greater in leukocytes from CKD patients than in those from healthy subjects [mean (95% confidence interval of the mean): 3.1 (2.2-3.9) vs. 1.2 (0.8-1.7), p = 0.0001], however that of RAGE mRNA was not. The serum concentration of S100A12 was significantly correlated with the relative quantity of S100A12 mRNA among uremic CKD patients (r(2) = 0.656, p < 0.0001). Both the serum concentration and gene expression of S100A12 were significantly higher in patients who had CVD than in those who did not. CONCLUSION: Excessive expression of the S100A12 gene in uremic leukocytes is relevant to its increased serum concentration, particularly in those affected with CVD.

Association between high-molecular-weight adiponectin and bone mineral density in hemodialysis patients.

BACKGROUND: Chronic kidney disease-mineral and bone disorder is a regular complication seen in hemodialysis patients and leads to substantial increases in the fracture rate, morbidity, and mortality. Discovered a few years ago, several clinical studies have shown a negative correlation between adiponectin and bone mineral density (BMD) independently of confounding factors. The relationship between adiponectin and bone metabolism in hemodialysis patients has not been fully described yet. We conducted this study to investigate the relationship between serum adiponectin concentration and the BMD in hemodialysis patients. METHODS: We enrolled 92 hemodialysis patients who were receiving maintenance hemodialysis therapy at Towa Hospital. A peripheral blood sample was obtained, and standard biological data and the serum high-molecular-weight (HMW) adiponectin level were measured. BMD was assessed using dual-energy X-ray absorptiometry scans. RESULTS: In male hemodialysis patients, BMD was negatively related to age (r = -0.299, P = 0.012), duration of hemodialysis therapy (r = -0.31, P = 0.009), and log [HMW-adiponectin] (r = -0.31, P = 0.009) and positively related to body weight (r = 0.332, P = 0.004) and BMI (r = 0.297, P = 0.013). In female hemodialysis patients, BMD was negatively related to age (r = -0.499, P = 0.018) and log [HMW-adiponectin] (r = -0.46, P = 0.030) and positively related to triglyceride (r = 0.491, P = 0.020). CONCLUSIONS: HMW adiponectin may affect bone metabolism in both male and female hemodialysis patients.

Successful steroid treatment of a patient with autosomal dominant polycystic kidney disease complicated by sarcoidosis.

The patient was a 54-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) who developed complicating systemic sarcoidosis. Hypercalcemia and an abrupt increase in serum creatinine levels were observed during the clinical course. Steroid therapy was initiated and produced a distinct improvement in renal function. A kidney biopsy was not feasible because ADPKD is a contraindication for renal needle biopsy. The clinical findings strongly suggested renal disorder secondary to tubulointerstitial nephritis caused by renal sarcoidosis with complicating hypercalcemia. In addition to controlling hypertension and improving the hypercalcemia and dehydration, steroid therapy also improved the renal function in this patient.

Influence of serum high-molecular-weight and total adiponectin on arteriosclerosis in IgA nephropathy patients.

BACKGROUND/AIM: Adiponectin has attracted a great deal of attention because of its antiatherogenic properties. Previous studies have reported that high-molecular-weight (HMW) adiponectin may be the active form of this protein, but there have been no reports on the relationship between serum adiponectin and arteriosclerosis. The aim of our study was to determine whether HMW or total adiponectin levels are associated with arteriosclerosis in patients with IgA nephropathy. METHODS: We enrolled 72 patients aged 34.3 +/- 12.7 years, from whom interlobular arteries were obtained by renal biopsy in our hospital between 2003 and 2006 and who were confirmed to have IgA nephropathy. We assessed them in relation to age, gender, body mass index, presence of hypertension, serum total cholesterol, triglyceride, uric acid, high-sensitive C-reactive protein and HMW adiponectin and total adiponectin levels, creatinine clearance, and urinary protein excretion. The severity of arteriosclerosis was semiquantitatively evaluated and classified into the following four grades: 0 = none; 1 = mild; 2 = moderate, and 3 = severe. RESULTS: Multiple stepwise regression analysis showed associations between arteriosclerosis grade and age [standard regression coefficient (st beta) = 0.560, p < 0.001], total adiponectin (st beta = -0.218, p = 0.026), triglyceride (st beta = 0.222, p = 0.033), and presence of hypertension (yes = 1, no = 0; st beta = 0.182, p = 0.036) in the IgA nephropathy patients as a whole and associations between arteriosclerosis grade and age (st beta = 0.708, p < 0.001), HMW adiponectin (st beta = -0.321, p = 0.035), and triglyceride (st beta = 0.292, p = 0.038) in the male IgA nephropathy patients. CONCLUSIONS: Serum total adiponectin levels are an independent determinant of arteriosclerosis in IgA nephropathy patients. It was noteworthy that in males the serum HMW adiponectin levels correlated more strongly with arteriosclerosis grade than the total adiponectin levels did. Adiponectin may prevent renal arteriosclerosis.

[Effects of steroid therapy on membranous nephropathy].

BACKGROUND: Although membranous nephropathy is a common cause of nephrotic syndrome in adults, its treatment remains under debate. METHODS: To clarify the effects of steroid therapy, the data of 51 Japanese adult patients with idiopathic membranous nephropathy who received treatment at our department were analyzed retrospectively. We divided the patients with nephrotic syndrome and a serum creatinine level <1.7 mg/dL, into two groups: the steroid therapy group (n=20) and the non-steroid therapy group (n=7), and compared the clinical characteristics between the two groups. RESULTS: Significantly decreased proteinuria levels (p<0.05) after 2 and 5 years were observed in the steroid therapy group as compared to the non-steroid therapy group. There was no significant difference in the serum creatinine levels after 2 and 5 years between the steroid therapy group and the non-steroid therapy group. CONCLUSION: Steroid therapy in idiopathic membranous nephropathy showed good efficacy in patients with nephrotic syndrome.

Characteristics of patients on hemodialysis therapy for more than 30 years.

Since its experimental introduction in 1960, hemodialysis has become a widely performed and relatively safe procedure. Therapeutic strategies have been developed, and the numbers of long-term survivors of hemodialysis therapy have been increasing. Hemodialysis therapy was introduced at Sangenjaya Hospital in October 1970, and the 16 patients who have survived for more than 30 years on hemodialysis therapy since its introduction at the hospital were enrolled in this study to investigate the characteristics of long-term hemodialysis patients. For comparison, 50 patients on hemodialysis for less than 30 years were also studied (21 patients with <10 years hemodialysis, 13 with 10-20 years hemodialysis and 16 with 20-30 years hemodialysis). Background information (age, gender, and cause of renal disease), dialysis dose (single pool [sp.] Kt/V), mineral metabolism (serum phosphate), anemia management (serum hemoglobin), and nutrition (serum albumin and reduced interdialytic weight gain) were assessed. Hemodialysis was instituted at 28.7 +/- 6.4 years of age. The primary cause of end-stage renal disease was chronic glomerulonephritis in all of the patients except one, and in that patient it was polycystic kidney disease. As an index of the dialysis dose, sp. Kt/V was 1.2 +/- 0.11. As an index of mineral metabolism, serum phosphate was 5.4 +/- 0.9 mg/dL. As an index of anemia management, serum hemoglobin was 10.2 +/- 1.2 g/dL. As indexes of nutrition, serum albumin was 4.0 +/- 0.2 g/dL and interdialytic weight gain was 4.43 +/- 1.36%. The sp. Kt/V-value, serum phosphate, serum hemoglobin and interdialytic weight gain did not differ between the four different hemodialysis duration groups. Serum albumin was lower in the >30 group (4.0 +/- 0.2 g/dL) than in the <10 group (4.2 +/- 0.3 g/dL) (P = 0.046). As the duration of hemodialysis has increased, the age at hemodialysis induction has become younger. The cause of the renal failure was chronic glomerulonephritis in most of the cases. None had diabetic nephropathy. Improvement of the prognosis of patients with diabetic nephropathy is required. Most of the indexes of these patients nearly satisfied the recommended values.

Prevalence of intracranial artery calcification in hemodialysis patients--a case-control study.

BACKGROUND: Intracranial artery calcification has been reported to be an independent risk factor for ischemic stroke. Also, existence of a positive correlation has been reported between the presence of arterial calcification and that of ischemic changes in the area supplied by such arteries. While intracranial artery calcification has frequently been observed on computed tomographic (CT) images of the brain in hemodialysis patients, its prevalence has not been reported previously. We investigated our hemodialysis outpatients to determine the prevalence of intracranial artery calcification in these patients in comparison with that in healthy controls. METHODS: Brain CT examinations were performed in 107 patients under maintenance hemodialysis therapy. For comparison, 43 representatives of the general population who underwent a brain CT examination as part of a health checkup were also studied as control subjects. RESULTS: Intracranial calcifications were more frequently found among hemodialysis patients (87.9%) than among control subjects (53.5%, P = 0.0003), and the prevalences of calcification in each of the intracranial arteries in the two groups were as follows: vertebral artery (65.5% vs. 25.6%, P = 0.0002), internal carotid artery (62.1% vs. 18.6%, P < 0.0001), basilar artery (34.5% vs. 34.9%, ns), anterior cerebral artery (0 vs. 2.3%, ns), middle cerebral artery (24.1% vs. 20.9%, ns), and posterior cerebral artery (5.2% vs. 4.7%, ns). CONCLUSIONS: A much higher rate of intracranial artery calcification was observed in hemodialysis patients than in the general population, and the most frequently involved sites of calcification in these patients were the relatively large intracranial arteries.

Intracranial artery calcification in hemodialysis patients.

Intracranial artery calcification is an independent risk factor for ischemic stroke, and while it is frequently observed on computed tomographic images of the brain in hemodialysis patients, its distribution has not been well studied. Fifty patients on maintenance hemodialysis were enrolled in this study. We divided the patients with intracranial artery calcification into two groups according to the duration of maintenance hemodialysis and compared the frequency of intracranial calcification of each of the intracranial arteries between the two groups. Intracranial artery calcification was found in 36 of the 50 hemodialysis patients. Among the 36 patients with intracranial artery calcification, the prevalence of calcification of each of the arteries was as follows: vertebral artery, 58.3%; internal carotid artery, 61.1%; basilar artery, 41.7%; anterior cerebral artery, 16.7%; middle cerebral artery, 30.6%; posterior cerebral artery, 8.3%. The prevalence of calcification of each of the intracranial arteries did not differ significantly between the patients with a hemodialysis duration of more than 20 years and those less than 20 years. The most frequently involved site of calcification was the internal carotid artery. The prevalence of calcification of the other intracranial arteries, particularly of the basilar artery, were relatively high. The prevalence of calcification of each of the intracranial arteries did not differ significantly between the patients with a hemodialysis duration of more than 20 years and less than 20 years.

Psoas abscess in hemodialysis patients.

BACKGROUND: The insidious onset and occult characteristic of psoas abscess can cause diagnostic delays, resulting in high mortality and morbidity rates. Here, we investigated the characteristics of psoas abscess in hemodialysis patients. METHODS: This study was carried out in eight patients with psoas abscess who were admitted in our hospital. The clinical data were retrospectively collected. RESULTS: The frequency of polycystic kidney disease as the primary cause of end-stage kidney disease was significantly higher in the hemodialysis patients with psoas abscess (25.0%) than in prevalent Japanese hemodialysis patients (3.4%, P = 0.028). All patients had a preceding infection (discitis in two, blood access-related infections in two, colitis in two, infection of a hematoma in the kidney in one, and endocarditis in one). Seven patients survived, while the remaining one patient died. CONCLUSION: Psoas abscess could be a complication of discitis, blood access infection and colitis in hemodialysis patients. The frequency of polycystic kidney disease as the primary cause of ESKD was significantly higher in the hemodialysis patients with psoas abscess than in prevalent Japanese hemodialysis patients. We should consider psoas abscess as a possibility in hemodialysis patients with infection of unknown cause, especially in patients with polycystic kidney disease.

Patterns in the prevalence of hepatitis C virus infection at the start of hemodialysis in Japan.

BACKGROUND: Although hepatitis C virus (HCV) infection is a persistent public health concern in hemodialysis patients, there seem to have been only a few reports on the prevalence of HCV at the start of hemodialysis. In this study we investigated whether patients starting on hemodialysis therapy are positive for anti-HCV antibody or not. METHODS: The 400 patients who began regular hemodialysis between February 2003 and June 2007 were enrolled in this study. Clinical data such as age, anti-HCV antibody and primary cause of end-stage kidney disease (ESKD) were examined. As healthy controls we used 70,717 healthy blood donors in 2005 whose data were obtained from Tokyo Metropolitan Red Cross Blood Center. Anti-HCV antibody was used as an indicator of HCV infection. Since the prevalence of HCV infection is affected by age in Japan, we classified the patients by age group. RESULTS: The anti-HCV antibody prevalence rate among the patients who were new to hemodialysis was 7.3%, as opposed to 0.15% in the healthy volunteers. The prevalence of HCV in the 31-45-, 46-60-, and 61-year-old groups was significantly higher among the hemodialysis patients than among the healthy volunteers (P = 0.0209, <0.0001, and <0.0001, respectively). The prevalence rate of anti-HCV antibody was higher among men (10.0%) than among women (1.5%, P < 0.0001) in the hemodialysis patients. The anti-HCV-antibody-positive patients were significantly older than the anti-HCV-antibody-negative patients (66.4 +/- 14.3 years versus 58.6+/-16.6 years; P = 0.0152). Diabetic nephropathy was a more frequent cause of ESKD among the anti-HCV-antibody-positive patients (30.4%) than among the anti-HCV-antibody-negative patients (19.9%, P = 0.0122). Among the anti-HCV-antibody-positive patients, 55.2% had received a blood transfusion. The rate was significantly higher than that among the anti-HCV-antibody-negative patients (19.4%, P < 0.0001). CONCLUSION: The results showed a much higher rate of anti-HCV antibody positivity in patients new to hemodialysis than in healthy volunteers. Older age, blood transfusion, male gender, and diabetic nephropathy seemed to be risk factors for anti-HCV antibody positivity in Japan.

Wegener's granulomatosis complicated by intestinal ulcer due to cytomegalovirus infection and by thrombotic thrombocytopenic purpura.

A 61-year-old woman was admitted to our hospital because of acute kidney injury. She complained of general fatigue, appetite loss, and a high fever. Nodular lesions were observed on chest X-rays and there were >100 erythrocytes per high power field in her urinary sediment. A renal biopsy revealed necrotizing granulomatous glomerulonephritis, and her serum proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) titer was elevated (55 EU). Based on these findings we made a diagnosis of Wegener's granulomatosis (WG). Hemodialysis was started immediately after admission. Steroid therapy was administered and her symptoms were relieved, but her renal function did not improve. On the 50th hospital day her condition suddenly became complicated by hemoperitoneum and massive intestinal bleeding, and the descending, transverse, ascending colon and part of the ileum were surgically resected. The cytomegalovirus (CMV) antigen titer was elevated, and histologic examination of the bowel specimen showed positive staining for CMV in the ulcer lesion, suggesting that CMV infection had caused the bowel hemorrhage. After treatment with ganciclovir, the bleeding was resolved and the CMV antigens became negative. We considered that this patient was further complicated by thrombotic thrombocytopenic purpura (TTP) because of thrombocytopenia, hemolytic anemia and neurologic symptoms. She was treated by plasma exchange. We report here a case of WG complicated by acute intestinal ulcer due to CMV infection and by TTP.