Tubulointerstitial Nephritis and Uveitis Syndrome Associated with Renal Tryptaseand Chymase-positive Mast Cell Infiltration

We report the clinical course and immunohistochemical analysis of a patient who presented with tubulointerstitial nephritis and uveitis syndrome (TINU syndrome). The patient, a 40-year-old woman, was referred to our hospital with general fatigue and a slight fever from another hospital. Mast cells are closely related to the development of renal interstitial fibrosis in patients with glomerulonephritis. To determine the role of mast cells in renal interstitial injury in TINU patients, we performed immunohistochemical studies on renal biopsy specimens using anti-human tryptase and anti-human chymase antibodies specific for mast cells. Double immunostaining of tryptase and chymase was also performed in renal tissues. In double immunofluorescence, cells with both chymase and tryptase (MCtc) were marked in the regions of interstitial fibrosis in this patient. It appears that mast cells are one of the constitutive cells of interstitial fibrosis in patients with TINU syndrome

High serum magnesium levels are associated with favorable prognoses in diabetic hemodialysis patients, retrospective observational study.

BackgroundRecent studies have found hypomagnesemia is linked to a heightened risk of cardiovascular events and mortality in hemodialysis (HD) patients; however, the level of serum magnesium (s-Mg) necessary for promoting overall health in these patients and the effects of s-Mg in diabetes HD patients remains to be clarified.MethodsHD outpatients (n = 148 under, age ≤ 70 y) were followed over a 6-y period. They were divided into four groups according to their average s-Mg during the first year (L; low level, H; high level) and if they had DM or not (non-DM). The endpoint was mortality and hospitalization for decline of Activities of Daily Living (death/hospitalization). A receiver operating characteristics curve was used in diagnostic tests to identify s-Mg associated with this endpoint. Kaplan-Meier, log-rank test, and a Cox proportional hazards model were used to evaluate prognoses. Fisher's exact test and multiple regressions examined the causes of the endpoints between the four groups and the factors predictive of s-Mg.Resultss-Mg at 2.7 mg/dL was associated with death/hospitalization. The 5-y survival rate was 38.1%, 86.7%, 73.2% and 87.5%, in the DM/Mg(L), DM/Mg(H), non-DM/Mg(L) and non-DM/Mg(H) groups, respectively (P Conclusionss-Mg greater than 2.7 mg/dL associated with a favorable prognosis in HD patients with DM, suggesting that s-Mg is a factor independent of diabetes

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors and Iron Metabolism

The production of erythropoietin (EPO), the main regulator of erythroid differentiation, is regulated by hypoxia-inducible factor (HIF). HIF2α seems to be the principal regulator of EPO transcription, but HIF1α and 3α also may have additional influences on erythroid maturation. HIF is also involved in the regulation of iron, an essential component in erythropoiesis. Iron is essential for the organism but is also highly toxic, so its absorption and retention are strictly controlled. HIF also induces the synthesis of proteins involved in iron regulation, thereby ensuring the availability of iron necessary for hematopoiesis. Iron is a major component of hemoglobin and is also involved in erythrocyte differentiation and proliferation and in the regulation of HIF. Renal anemia is a condition in which there is a lack of stimulation of EPO synthesis due to decreased HIF expression. HIF prolyl hydroxylase inhibitors (HIF-PHIs) stabilize HIF and thereby allow it to be potent under normoxic conditions. Therefore, unlike erythropoiesis-stimulating agents, HIF-PHI may enhance iron absorption from the intestinal tract and iron supply from reticuloendothelial macrophages and hepatocytes into the plasma, thus facilitating the availability of iron for hematopoiesis. The only HIF-PHI currently on the market worldwide is roxadustat, but in Japan, five products are available. Clinical studies to date in Japan have also shown that HIF-PHIs not only promote hematopoiesis, but also decrease hepcidin, the main regulator of iron metabolism, and increase the total iron-binding capacity (TIBC), which indicates the iron transport capacity. However, concerns about the systemic effects of HIF-PHIs have not been completely dispelled, warranting further careful monitoring

Low-Dose Oral Iron Replacement Therapy Is Effective for Many Japanese Hemodialysis Patients: A Retrospective Observational Study

Western guidelines recommend the use of intravenous iron supplementation for hemodialysis patients. However, in Japanese patients with well-controlled inflammation, iron replacement may be achieved with oral iron supplementation. This study involved 108 courses in 77 outpatient hemodialysis patients who received low-dose oral iron replacement therapy. Data from baseline to week 28 of treatment were analyzed to identify factors associated with effectiveness. Changes over time in erythrocyte- and iron-related parameters and erythropoiesis-stimulating agent (ESA) dose were investigated in the effective group. A total of 84 courses (77.8%) satisfied the effectiveness criteria. Compared with the effective and ineffective groups, only C-reactive protein (CRP) was significantly different (p p < 0.001). In the ESA maintenance group, the serum ferritin gradually increased and then remained constant at about 60 ng/mL. Our data suggest that patients with CRP ≤ 0.1 mg/dL may benefit from low doses of oral iron supplementation. Approximately 60 ng/mL serum ferritin may be sufficient during stable hematopoiesis

Low levels of serum ferritin and moderate transferrin saturation lead to adequate hemoglobin levels in hemodialysis patients, retrospective observational study

<div><p>Background</p><p>Optimal iron levels in patients on hemodialysis are currently unknown, and a higher level than that for the healthy population is usually set for such patients considering the use of erythropoiesis-stimulating agents or the occurrence of chronic inflammation. However, excessive iron causes oxidative stress and impairment of its utilization by cells. Therefore we investigated the relationship between hemoglobin (Hb) level and iron status in hemodialysis patients to identify the optimal iron levels for patients undergoing hemodialysis.</p><p>Methods</p><p>A total of 208 outpatients on maintenance hemodialysis were followed up between July 2006 and June 2007. Men accounted for 64.9% cases [mean age, 59.3 ± 13.1 years and median dialysis history, 7.7 (3.6–13.2) years], and diabetic nephropathy accounted for 25.0% cases. Hemoglobin level was measured twice a month and serum ferritin, serum iron, and total iron-binding capacity were measured once a month. The doses of recombinant human erythropoietin and low-dose iron supplement were adjusted to maintain a hemoglobin level of 10–11 g/dL, according to the guidelines of the Japanese Society for Dialysis Therapy. Hepcidin was measured at baseline. Using the mean values for 1-year period, the relationships among hemoglobin, serum ferritin levels, and transferrin saturation levels were investigated based on a receiver operating characteristic curve and a logistic regression model. In addition, the correlations among serum ferritin, transferrin saturation, and hepcidin levels were analyzed by Pearson product—moment correlation coefficient and linear regression model.</p><p>Results</p><p>By receiver operating characteristic curve, the cutoff point of serum ferritin and transferrin saturation levels with a hemoglobin ≥10 g/dL showed <90 ng/mL (sensitivity: 69.1%, specificity: 72.1%, p < 0.001) and ≥20% (sensitivity: 77.6%, specificity: 48.8%, p = 0.302).</p><p>Upon logistic regression model analysis with a hemoglobin ≥10 g/dL as the endpoint, the analysis of odds ratios relative to a group with serum ferritin ≥90 ng/mL and transferrin saturation <20% revealed that the group with serum ferritin <90 ng/mL and transferrin saturation ≥20% had the highest ratio: 46.75 (95% confidence interval: 10.89–200.70, p < 0.001). In Pearson product—moment correlation coefficient, hepcidin showed a strong positive correlation with serum ferritin [r = 0.78 (95% confidence interval: 0.72–0.83, p < 0.001)] and a weak positive correlation with transferrin saturation [r = 0.18 (95% confidence interval: 0.04–0.31, p = 0.010)]. In the multivariable analyses of the linear regression model, a positive relationship was shown between hepcidin and serum ferritin [β-coefficient of 0.30 (95% confidence interval: 0.27–0.34, p < 0.001)]; however, no relationship was shown with transferrin saturation [β-coefficient of 0.09 (95% confidence interval: −0.31–0.49, p = 0.660)].</p><p>Conclusions</p><p>In this study, the iron status of serum ferritin <90 ng/mL and transferrin saturation ≥20% was optimal in hemodialysis patients receiving recombinant human erythropoietin for anemia therapy. This result indicates that the threshold values for the optimal iron status may be lower than those currently recommended in iron-level management guideline.</p></div

Usefulness of a Body Composition Analyzer, InBody 2.0, in Chronic Hemodialysis Patients

The objective of the present study was to investigate whether InBody 2.0 might be useful in measuring the dry weight of chronic hemodialysis (HD) patients. Thirty-five HD patients (22 males and 13 females; mean age 62.6 ± 14.0 years; mean HD duration 101.0 ± 118.06 months) were examined. Multifrequency bioelectric impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water (TBW). The body resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index was determined at a low frequency (5 kHz) and correlated closely with ECW, using sodium bromide dilution as standard comparison. The levels of serum albumin, prealbumin, total cholesterol (TC), triglycerides (TG), transferrin, and human atrial natriuretic peptide (hANP) were measured by routine methods in our hospital. The ECW/TBW ratio was significantly associated with the levels of hANP (p < 0.05). However, no associations between the levels of serum albumin, TC, TG, or transferrin and the ECW/TBW were observed. It appears that the body composition analyzer, InBody 2.0, may be useful for estimating the dry weight in chronic HD patients

The relationship for ferritin and TSAT with hepcidin by multiple linear regression model.

<p>The relationship for ferritin and TSAT with hepcidin by multiple linear regression model.</p

Diagnostic accuracy of serum ferritin.

<p>(A) The ROC curve of serum ferritin with Hemoglobin ≥10g/dL. (B) Dot plot of serum ferritin in Hemoglobin <10g/dL and ≥10g/dL. The cutoff point for s-ft was found to be below 90 ng/mL (sensitivity: 69.1%, specificity: 72.1%, p < 0.001).</p

The relationship for serum ferritin and transferrin saturation with hepcidin.

<p>(A) Serum ferritin showed a strong positive correlation with hepcidin [r = 0.78 (95% CI: 0.72–0.83, p < 0.001)]. (B) Transferrin saturation indicated a weak positive correlation with hepcidin [r = 0.18 (95% CI: 0.04–0.31, p = 0.010)].</p