Presepsin as a predictor of critical colonization in CLI hemodialysis patients.

Infection during critical limb ischemia (CLI) is a challenging issue. Plasma presepsin is a novel biomarker for infection, which is related to bacterial phagocytosis by macrophages. The purpose of this study was to investigate the validity of presepsin as an indicator and predictor for early detection of infectious CLI. A retrospective observational study was conducted among 20 CLI patients (Rutherford 5 and 6) on hemodialysis (HD). Twenty CLI patients on HD (mean age 70.7 ± 5.6 years, male 85%) and 15 healthy patients on HD without CLI and infection (control group) were analyzed. All CLI patients received appropriate revascularization and plastic surgical treatment. CLI patients were classified into two groups: the healing group with complete epithelialization without discharge and the nonhealing group with infection signs. Plasma presepsin was measured and compared among the two groups and the control group using an automated immunoanalyzer, PATHFAST, based on a noncompetitive chemiluminescent enzyme immunoassay. The median plasma presepsin and its interquartile range were 1,320 (1,055-1,465) pg/mL in the control group, 1,320 (1,050-1,613) pg/mL in the healing group and 3,193 (2,519-3,832) pg/mL in the nonhealing group. The plasma presepsin concentrations were significantly higher in the nonhealing group compared with the control group (p < 0.001) and the healing group (p < 0.01). A receiver operating characteristic curve analysis revealed that presepsin had highest accuracy (0.979) among various inflammatory markers, including C-reactive protein and the white blood cell count. The diagnostic cutoff value of 2,083 pg/mL was able to distinguish the nonhealing group and healing group with a sensitivity of 100% and a specificity of 88.9%. Our results suggest that plasma presepsin may be useful for predicting "critical colonization" and "infection" in nonhealing CLI in HD patients, therefore, the definitive cutoff value may be used for determinating the indication for reintervention and/or major limb amputation.

Effect of zinc supplementation on bone formation in hemodialysis patients with normal or low turnover bone.

Zinc (Zn) is an essential trace element, which has been shown to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption in vitro. In thalassemia, major patients Zn supplementation was reported to increase whole-body bone mineral content and areal bone mineral density. Therefore, we investigated the effect of Zn supplementation on bone formation in hemodialysis (HD) patients. Nine male patients with age of 66 (35-78) years indicated by median (range), HD vintage of 57 (4-97) months and serum intact parathyroid hormone (PTH) of 113 (6-310) pg/mL were supplemented with polaprezinc containing 34 mg Zn/day for 18 months. Doses of vitamin D were not changed during supplementation. Blood was collected at baseline, 3, 6, 12 and 18 months. Serum Zn increased significantly from 58 (52-65) µg/dL to 71 (57-93) µg/dL at three months and remained unchanged until 18 months. No changes were observed in serum intact PTH during supplementation. Although we found no changes in serum bone alkaline phosphatase (BAP) during Zn supplementation analyzed by Friedman test and Scheffe post hoc test, a significant trend of increase in serum BAP was verified by Jonckheere-Terpstra test (p = 0.0409). On the contrary, there was no trend in serum TRACP5b by Jonckheere-Terpstra test. Therefore, we suggested the effect of Zn supplementation on promoting bone formation, not affected by the status of PTH and vitamin D, in HD patients with normal or low turnover bone.

[Association between smoking and tuberculosis infection].

PURPOSE: Several reports show smoking as a risk factor of tuberculosis (TB) infection, especially in prisoners, emigrants, the homeless, or people in areas where TB is endemic. These reports mostly used the tuberculin test to detect TB. However, there is no report evaluating smoking as a risk factor of TB infection among people coming into contact with TB with the use of the Interferon-Gamma Release Assays (IGRA) test. MATERIAL & METHOD: We compared TB infection in smokers and non-smokers who came into contact with TB infection by using the IGRA test. We retrospectively collected information about people coming into contact with TB who visited the Daiichi Dispensary from July 1, 2011 to June 30, 2012. They were divided into 2 groups (IGRA positive or negative) and smoking (present/past or never). RESULT: Out of 390 subjects who came into contact with TB examined, 229 were male and 161 were female. The mean age was 39.0 years, 98 were present smokers, 69 were past smokers, and 223 were never-smokers. There were 19 IGRA-positive and 371 IGRA-negative subjects. The IGRA positive rate was 4.9%. Out of 19 IGRA-positive subjects, 13 were smokers or ever-smoker (68.4%). Out of 371 IGRA-negative subjects, 154 cases were smoker or ever-smoker (41.5%). Smoking experience (present and past) was statistically significant in the IGRA-positive group. There were no significant differences in sex, age, drinking habits, and level of contact. Multivariate analysis showed smoking was only one independent risk factor for being IGRA-positive (odds ratio 3.06, 95% confidence interval: 1.14-8.21, p = 0.027). DISCUSSION: Our results suggest that smoking experience in subjects coming into contact with TB is a risk factor for TB infection. TB cases in smokers are reported to be more severe and have delayed detection of disease. They are also more likely to infect those who come in contact with them. If TB source cases and their contacts are both smokers and co-exist in a narrow and limited area, the contacts might be at higher risk of exposure to TB-contaminated air than non-smokers.

[Liver dysfunction during treatment of latent tuberculosis infection].

PURPOSE: The indications for treatment for latent tuberculosis infection were revised in 2007 to reflect that any subject with a higher risk of tuberculosis regardless of age should be treated. We worried about the incidence of liver dysfunction due to isoniazid (INH) in patients older than 30 yrs. of age. We evaluated the frequency of liver dysfunction due to INH according to age and discussed the possibility of its prevention. METHODS: We reviewed the clinical records of 99 patients younger than 29 yrs. and 229 patients older than 30 yrs. who were treated for latent tuberculosis infection from August 2007 to December 2008 at our clinic. The liver function tests (AST and ALT) were performed before the treatment, one and a half months after the start of the treatment, and almost every month during the treatment. We defined liver dysfunction as an AST and/or ALT greater than 100 IU/L. RESULTS: Seven out of the 99 younger patients (7.1%) and 42 out of the 229 (18.3%) older patients developed liver dysfunction. The difference between the two age groups was statistically significant according to the chi-square test (p < 0.01). After the occurrence of liver dysfunction, 35 out of 49 patients (71%) completed the treatment by maintaining the same or a decreased dose of INH, while the medication was discontinued in 9 patients who were then followed up by chest X-ray examination. Two of these 49 patients discontinued the medication by themselves. CONCLUSIONS: The frequency of liver damage due to INH was higher in persons older than 30 yrs. In this group, 3 persons developed severe liver damage with ALT and/or AST higher than 1000 IU/L. Early detection is required to avoid serious damage. Thus, we decided to perform liver function tests more often, i.e., at 2 weeks after the onset of treatment and every month thereafter.

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis with rheumatoid arthritis: a comparison of patients without rheumatoid arthritis.

BACKGROUND: Several cases of rheumatoid arthritis (RA) with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated crescentic glomerulonephritis (CrGN) have been reported. However, its clinical characteristics are not clear. METHODS: We summarized 3 patients of concurrent RA and MPO-ANCA-associated CrGN, diagnosed in our hospital from 1992 to 2006, and compared their clinicopathological data with those of 10 MPO-ANCA-associated CrGN patients without RA in the same period. RESULTS: All three RA patients were middle-aged or young adult women with 7-14 years of RA history. The initial clinical symptom was microhematuria, and mean duration from hematuria onset to histological confirmation of CrGN was 17 months. At renal biopsy, serum creatinine concentration (sCr) was modestly elevated, with the mean value of 3.4 mg/dl. Crescents were detected in 30% of glomeruli, whereas advanced glomerular sclerosis, tubular atrophy, and interstitial fibrosis were also observed. In comparison with patients without RA, patients with RA were significantly younger and showed a longer duration from the onset to histological confirmation of CrGN. Serum creatinine concentration at referral was significantly lower; however, estimated glomerular filtration rate (eGFR) was comparable. The Birmingham Vasculitis Activity Score and the Disease Extent Index were significantly lower, and pathological examination showed less crescent formation and a tendency to advanced glomerular sclerosis in patients with RA. CONCLUSIONS: In patients with RA, MPO-ANCA-associated CrGN appeared to develop at younger ages and often showed a slowly progressive deterioration of the renal function with slight extrarenal manifestations. These smoldering clinical features may result in late referral from rheumatologists to nephrologists and therefore poor prognosis.

[Relationship between coronary and abdominal calcification score, serum osteoprotegerin (OPG), and serum tartrate-resistant acid phosphatase (TRACP) -5b in pre-dialysis CKD patients].

Osteoprotegerin (OPG) inhibits interaction of the receptor-activator of nuclear factor-kappaB (RANK) ligand (RANKL) with its receptor RANK, which is expressed on osteoclasts. OPG appeared to accelerate vascular calcification in vitro by the inhibition of vascular osteoclast-like cells. On the contrary, early-onset arterial calcification was observed in OPG-deficient mice. We measured the coronary artery calcification score (CACS) and abdominal aortic calcification score (AAoCS) by multi-detector computed tomography in 30 pre-dialysis CKD patients (eGFR 20 mL/min on average). Biomarkers were measured, including serum OPG, soluble RANKL (sRANKL) and tartrate-resistant acid phosphatase (TRACP) -5b (the biomarker of osteoclasts independent of renal function). The median values of CACS and AAoCS were 54.4 and 1,088 Agatston units (AU), respectively. Serum OPG was increased and serum sRANKL was decreased. In a multivariate logistic regression analysis using CACS > or = 100 AU as the outcome variable, CACS was found to be positively correlated with serum corrected Ca x iP product and serum OPG, though it was not correlated with serum TRACP-5b. ROC curve analysis showed that the serum OPG cutoff value predicting CACS > or = 100 AU was 5.2 pmol/L (624 pg/mL). In a stepwise regression analysis, log (AAoCS + 1) was positively correlated with serum OPG alone, but it was not correlated with age, eGFR, serum albumin and bone alkaline phosphatase (BAP). No correlation was found between serum OPG and serum TRACP-5b. In conclusion, vascular calcification in pre-dialysis CKD patients was correlated with an increase in OPG, but was independent of serum TRACP-5b. The decrease in serum sRANKL may have been caused by the increase in OPG production.

[Clinical outcome assessment of membranous nephropathy].

Appropriate treatment of idiopathic membranous nephropathy (IMN) remains a controversial issue. Whereas some authors recommend a conservative approach, based on the considerable rate of spontaneous remissions, others utilize early immunosuppressive treatment for most nephrotic patients with IMN. Our retrospective study consisted of 34 patients who presented with IMN between the period from 1987 to 2002. The patients were divided into two groups based on the type of treatment they received the immunosuppressive group comprised 18 patients who received corticosteroids with/without other immunosuppressive drugs and the supportive group comprised 16 patients who were treated with anti platelet drugs as supportive therapy. The amount of proteinuria at the base line was significantly higher in the immunosuppressive group than in the supportive group(4.7 +/- 2.9 vs. 2.7 +/- 2.7 g/24 h). At the end of the follow-up, complete remission was achieved more frequently in the immunosuppressive group than in the supportive group(9/18 vs. 3/16). This suggests that immunosuppressive treatment has the effect of decreasing proteinuria. At the end of the follow-up, 3 patients in the immunosuppressive group and 2 patients in the supportive group showed renal insufficiency (serum creatinine concentration > or = 1.5 mg/dl). Side effects besides diabetes were not seen as a result of immunosuppressive treatment. Our findings suggest that immunosuppressive treatment in IMN cases appears to be beneficial for decreasing proteinuria, but the effect on prevention of renal failure was not evident.

Glucose dialysate induces mitochondrial DNA damage in peritoneal mesothelial cells.

BACKGROUND: It is known that peritoneal mesothelial cells (PMCs) are denuded in patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD); the mechanism of damage is not well known. A high quantity of glucose loaded onto PMCs in these patients may generate toxic radicals during the mitochondrial metabolism, leading to mitochondrial DNA damage that accumulates due to the incomplete repair system of this DNA. OBJECTIVE: To study damage to the PMCs of long-term CAPD patients, and to examine whether glucose overload accelerates this damage in vitro. DESIGN: Descriptive clinical and in vitro study. PARTICIPANTS: Stable CAPD patients and nonuremic patients undergoing elective abdominal surgery. METHODS: (1) Clinical Samples: 13 peritoneal tissue samples from CAPD patients and 5 omental tissue samples from patients with normal renal function were investigated. PMCs in dialysate effluent were collected from another 13 stable CAPD patients. (2) In Vitro Samples: Primary PMCs were incubated for up to 144 hours in medium containing one of the following: 5.6 mmol/L glucose (control), 56 mmol/L glucose (G), 222 mmol/L glucose (high G), or 222 mmol/L mannitol (high M; osmolar control for high G). The tissues and cells of clinical and in vitro samples were stained for light and immunoelectron microscopy with anti-8-hydroxy-2'-deoxyguanosine (anti-8-OH-dG) antibody, a marker of oxidative DNA damage. In vitro cells were also studied using transmission electron microscopy. Cellular ATP content, mitochondrial membrane potential, and intracellular generation of reactive oxygen species (ROS) were analyzed by luciferase-luciferin system, or by flow cytometry using rhodamine 123 and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: Biopsy specimens showed strong cytoplasmic staining with 8-OH-dG in patients on long-term CAPD, but only faint staining in patients with end-stage renal disease before the initiation of CAPD, and no staining in patients with normal renal function. Dialysate effluent showed strong granular staining with 8-OH-dG in most PMCs in all long-term CAPD patients, but only faint and focal staining in patients at the start and after 3-5 months of CAPD. In vitro experiments also showed strong granular staining by 8-OH-dG in most PMCs cultured in high G, weak staining in G and high M, and no staining in the control. Immunoelectron microscopy revealed the localization of 8-OH-dG to mitochondria. Transmission electron microscopy showed swelling of mitochondria, with decreased cristae, in PMCs cultured in high G. However, only partial expansion of mitochondria was seen in G and high M, and no changes were seen in the control. Cellular ATP content and mitochondrial membrane potential were reduced early, followed by an increase when cultured in high G. Intracellular ROS production was also increased in PMCs cultured in high G and high M. CONCLUSIONS: These data suggest that high-glucose peritoneal dialysate may promote oxidative mitochondrial DNA damage in PMCs in CAPD patients.

Improvement of MBD parameters in dialysis patients by a switch to, and combined use of lanthanum carbonate: Josai Dialysis Forum collaborative study.

The effects of lanthanum carbonate on MBD parameters were investigated in 59 hemodialysis patients who were taking calcium carbonate. Lanthanum carbonate (initial dosage: 750 mg/day), as a replacement for or in combination with calcium carbonate and/or sevelamer hydrochloride, was administered for 12 months with increase/decrease of dosages. Lanthanum carbonate replaced calcium carbonate for 21 cases and was co-administered in 38 cases. It replaced sevelamer hydrochloride in 20 cases and was co-administered in 10 cases. Both the number of cases to which calcium carbonate was administered and their dosages decreased to about 70-80% 12 months after the initiation, and cases administered sevelamer decreased to about 30%. In the cases for which lanthanum carbonate was co-administered, the dosages of calcium carbonate and sevelamer slightly decreased. A significant decrease in serum calcium level was observed. In the serum phosphorus levels (P levels), significant decrease compared with the initial level was observed only at six and nine months. Intact parathyroid hormone (iPTH) level remained stable at around 230 pg/mL without significant change. The dosage of vitamin D and cinacalcet remained without significant change. The results of this trial suggest that, if dosages of vitamin D and cinacalcet are adequately controlled, a switch to lanthanum carbonate and its concomitant use are effective to control the Ca and P levels without changing iPTH levels.

Strategies for the creation and maintenance of reconstructed arteriovenous fistulas using the forearm basilic vein.

Reconstruction of an arteriovenous fistula (AVF) after an initial failure to provide long-term patency has been desired in the era when hemodialysis patients' prognosis is improving. The forearm basilic vein AVF should be considered, before an artificial graft shunt or an AVF in the cubital region. The present study was designed to establish a strategy for the creation and maintenance of AVFs using the forearm basilic vein. This study reviewed 76 cases of reconstructed AVF including 18 cases using the basilic vein (23.7% of total cases). The following four points were considered: arm positioning of the cubital flexion position combined with the forearm supinated position; several small skin incisions with a subcutaneous tunnel; sufficient venous dilatation using Fogarty balloon catheter; and early percutaneous angioplasty introduction for immature AVF. The primary and secondary patency rates were examined. A radiobasilic AVF was created through a subcutaneous tunnel in two cases. The primary and secondary patency rates of AVF with the basilic vein were 54.7% and 76.7% respectively, whereas those of AVF with the cephalic vein were 49.3% and 71.3%. The basilic was not inferior to the cephalic vein (P-value of the log-rank test for primary and secondary patency rates were 0.927 and 0.811, respectively). Early stage percutaneous angioplasty was effective in five cases with immature AVF. The forearm basilic vein was useful in AVF reconstruction and equivalent to radiocephalic reconstruction. Careful observation and percutaneous angioplasty during the early period after the surgery were essential for long-term patency.