Michio Umezu

Effect of Intravenous Saccharated Ferric Oxide on Serum FGF23 and Mineral Metabolism in Hemodialysis Patients

Background/Aims: Fibroblast growth factor-23 (FGF23) plays a central role in the development of hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D induced by iron therapy for iron-deficiency anemia. The aim of this study was to examine the effect of intravenous saccharated ferric oxide on serum FGF23 levels and mineral metabolism in hemodialysis patients. Methods: This prospective study enrolled 27 hemodialysis patients who had iron-deficiency anemia defined by a hemoglobin concentration <10.5 g/dl and serum ferritin <100 ng/ml. Intravenous saccharated ferric oxide at a dose of 40 mg was administered three times weekly over 3 weeks. The dose of active vitamin D and phosphate binders was kept unchanged. Serum FGF23, intact parathyroid hormone (PTH) and other parameters were prospectively monitored for 5 weeks. Results: Serum FGF23 levels were markedly elevated [3,453 (338–6,383) pg/ml] at baseline. After 3 weeks of intravenous saccharated ferric oxide treatment, serum FGF23 further increased to 4,701 (1,251–14,396) pg/ml, and returned to the baseline values after 2 weeks of observation. There was also a significant decrease in intact PTH but no changes in serum calcium and phosphorus. Conclusions: Intravenous saccharated ferric oxide induces further increase in elevated FGF23 levels in hemodialysis patients. This increase does not induce hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D in the absence of functioning kidney, but may result in transient PTH suppression – possibly by directly acting on the parathyroid.

Leukocytapheresis therapy for steroid-naïve patients with active ulcerative colitis: its clinical efficacy and adverse effects compared with those of conventional steroid therapy.

Background: Steroid administration currently plays a central role in the medical management of ulcerative colitis (UC); however, long‐term steroid usage causes adverse effects, which necessitates stoppage of drug intake, leading to worsening of the disease. A steroid‐sparing, well‐tolerated treatment is therefore required. As several investigators have reported the efficacy of leukocytapheresis (LCAP) combined with steroid therapy, we investigated the clinical usefulness and safety of LCAP for steroid‐naïve patients with active UC for comparison with those of conventional steroid therapy.

Heme-Oxygenase Upregulation Ameliorates Angiotensin II-Induced Tubulointerstitial Injury and Salt-Sensitive Hypertension

Background: Heme oxygenase-1 (HO-1) has been implicated in the modulation of several diseases including hypertension (HTN) and renal injury. The tubulointerstitial (TI) injuries are supposed to be the main determinants for the development of salt-sensitive HTN. Therefore, this study examined the role of HO-1 in angiotensin II (AngII)-induced TI injury and salt-sensitive HTN. Methods: Sprague-Dawley rats on a high salt diet were treated by AngII infusion plus either hemin, an inducer of HO-1, or hemin + zinc protoporphyrin, a HO-1 inhibitor, for 2 weeks, and then followed for 6 weeks. Results: The AngII infusion resulted in acute HTN and proteinuria. Light microscopy revealed focal areas of tubular atrophy with mononuclear cell infiltration and interstitial expansion. The overexpression of osteopontin and TGF-β1 accompanied by diminished expression of rat endothelial cell antigen-1, the hallmarks of TI injury, were observed. At 2 weeks, all interventions were withdrawn and systolic blood pressure returned towards normal. After a brief normal salt diet, rats were again placed on high salt diet, resulting in progressive increase in systolic blood pressure in the HO-1-inhibited group. Conclusion: The induction of HO-1 attenuated the development of HTN, suggesting that HO-1 plays a crucial role in significant attenuation of AngII-mediated TI injury and resultant salt-sensitive HTN.

Controversy about COOPERATE ABPM Trial Data

mm Hg, 63% between 120 and 150 mm Hg, and the remaining 19% more than 150 mm Hg. A similar incidence was observed among treatment groups. Interestingly, the high variability of the systolic BP values was more characteristic among patients who were able to effectively restrict their salt intake. As compared with the systolic values, the nighttime values were constant throughout the measurements, partly because the drugs were taken at night or bedtime. Naoyuki Nakao, MD, PhD Division of Nephrology Rokko Island Hospital Koh-Yoh Cho Naka 2-11 Higashinada, Kobe, Japan

Prediction of Glomerular Filtration Rate in Cancer Patients by an Equation for Japanese Estimated Glomerular Filtration Rate

BACKGROUND Assessment of renal function is important for safe cancer chemotherapy, and eligibility criteria for clinical trials often include creatinine clearance. However, creatinine clearance overestimates glomerular filtration rate, and various new formulae have been proposed to estimate glomerular filtration rate. Because these were developed mostly in patients with chronic kidney disease, we evaluated their validity in cancer patients without kidney disease. METHODS Glomerular filtration rate was measured by inulin clearance in 45 Japanese cancer patients, and compared with creatinine clearance measured by 24-h urine collection as well as that estimated by the Cockcroft-Gault formula, Japanese estimated glomerular filtration rate developed in chronic kidney disease patients, the Modification of Diet in Renal Disease study equation and the Chronic Kidney Disease Epidemiology Collaboration equation. The Modification of Diet in Renal Disease study and Chronic Kidney Disease Epidemiology Collaboration equations were adjusted for the Japanese population by multiplying by 0.808 and 0.813, respectively. RESULTS The mean inulin clearance was 79.2 ± 18.7 ml/min/1.73 m(2). Bias values to estimate glomerular filtration rate for Japanese estimated glomerular filtration rate, the Cockcroft-Gault formula, creatinine clearance measured by 24-h urine collection, the 0.808 × Modification of Diet in Renal Disease study equation and the 0.813 × Chronic Kidney Disease Epidemiology Collaboration equation were 0.94, 9.75, 29.67, 5.26 and -0.92 ml/min/1.73 m(2), respectively. Precision (root-mean square error) was 14.7, 22.4, 39.8, 16.0 and 14.1 ml/min, respectively. Of the scatter plots of inulin clearance versus each estimation formula, the Japanese estimated glomerular filtration rate correlated most accurately with actual measured inulin clearance. CONCLUSION The Japanese estimated glomerular filtration rate and the 0.813 × Chronic Kidney Disease Epidemiology Collaboration equation estimated glomerular filtration rate with lower bias and higher precision than the other formulae. We therefore propose Japanese estimated glomerular filtration rate for the estimation of glomerular filtration rate in Japanese cancer patients.

Validity of new methods to evaluate renal function in cancer patients treated with cisplatin

PurposeCreatinine clearance (Ccr) is used as a marker of renal function in cancer chemotherapy, but it is not correlated with glomerular filtration rate (GFR) after high-dose cisplatin treatment. In addition to Ccr, measured using 24-h urine collection (24-h Ccr) or Cockcroft–Gault formula (CGF), the Chronic Kidney Disease Epidemiology Collaboration (CKD–EPI) equation and the Japanese GFR estimation equation (the Japanese equation) have been recently developed to estimate GFR for predicting renal function. However, these equations remain to be evaluated, particularly in cancer patients treated with cisplatin. Therefore, we investigated the validity of these equations for predicting the GFR in cancer patients treated with cisplatin.MethodsGFR was measured by inulin clearance (Cin) in 50 cancer patients and compared with GFR estimated by the CKD–EPI equation, the Japanese equation, and Ccr estimated by CGF or measured by 24-h Ccr before the first and third cisplatin-containing chemotherapy cycles (considered pretreatment and posttreatment, respectively).ResultsBefore treatment, the CKD–EPI and the Japanese equations estimated GFR with higher accuracy than Ccr. Posttreatment bias values for GFR estimation using the CKD–EPI and the Japanese equations were lower than those for Ccr. The CKD–EPI and the Japanese equations were also more precise than Ccr. However, for patients with low renal function, these equations still overestimated Cin.ConclusionThe CKD–EPI and the Japanese equations estimated GFR with lower bias and higher precision than Ccr pre- and postcisplatin treatment. This study is registered at UMIN: 000002167.

Consultants for the American Journal of Nephrology 2006

Kevin Abbott Christina Abrass Rajiv Agarwal Farah Ali Efthyvoulos Anastassiades Gema Ariceta Akhtar Ashfaq John Asplin Phyllis August Susan Bagby Asad Bakir George Bakris Vinod Bansal Amelia Bartholomew Amy Barton Pai David Basile Enrico Benedetti Angelito Bernardo Rajendra Bhimma Peter Blake Amy Bobrowski Michael Braun Carolyn Brecklin Ursula Brewster Ellen Brooks Nigel Brunskill Vito Campese Huseyin Celiker Michael Choi Giorgio Coen Richard Cohn Jay Cohn Terezila Coimbra James Cook Scott Cotler Mario Cozzolino Stanislaw Czekalski Mohamed Daha Farhard Danesh Robert Danziger Jie Ding