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

PURPOSE: Creatinine 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. METHODS: GFR 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). RESULTS: Before 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. CONCLUSION: The 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.

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.

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.

[Case of goodpasture syndrome associated with minimal change nephrotic syndrome (MCNS) in a patient with rheumatoid arthritis (RA)].

In early June 2004, a 50-year-old female was admitted to the hospital for slight fever, general fatigue, hemoptysis, dyspnea, and renal dysfunction (serum creatinine[Cr] : 6.05 mg/dL). She had been treated with prednisolone (PSL : 10-20 mg/day) for RA. She was diagnosed with Goodpasture syndrome based on a high titer of anti-glomerular basement membrane antibody (87 EU), and pulmonary hemorrhage. The renal and pulmonary impairments were markedly improved by the pulse therapy, plasma exchange and temporary hemodialysis. However, the Cr level remained at 2.0 mg/dL, indicating nephrotic syndrome. Light microscopy with Periodic acid-Shiff(PAS) staining demonstrated global sclerosis in three of ten glomeruli. Five glomeruli showed the formation of cellular, and fibrocellular crescents, and the formation of fibrous crescents. Tubular damage and interstitial fibrosis were severe. Immunofluorescence microscopy disclosed major depositions of IgG in a linear pattern along the glomerular basement membrane(GBM). Electron microscopy revealed foot process effacement (>50%)and no electron-dense deposits. Therefore, we diagnosed Goodpasture syndrome associated with minimal change nephrotic syndrome (MCNS). Some reports have dealt with the association of RA and Goodpasture syndrome with D-penicillamine, and of RA and antineutrophil cytoplasmic antibodies (ANCA)-related vasculitis with pulmonary hemorrhage, but none has dealt with cases complicated with RA and Goodpasture syndrome associated with MCNS. Accordingly, whether or not there is a causal relationship between RA and Goodpasture syndrome remains obscure, but since the number of reported cases is small, experience with more cases is necessary to clarify this matter.

[Usefulness of the formula for predicting creatinine clearance from serum cystatin C].

Estimation of Glomerular filtration rate (GFR) is crucial for the detection of renal insufficiency. In clinical practice, GFR is generally estimated from Ccr by some prediction formulas including the serum creatinine concentration and some variables: age, sex, body size. It has been suggested that serum cystatin C is less influenced by sex, body size, muscular mass or inflammation. In several studies, serum cystatin C performed better than serum creatinine did as a marker to detect GFR reduction. We developed the formula for predicting creatinine clearance (Ccr) from serum cystatin C, serum creatinine and serum beta 2-microgroburin by multiple regression analysis. In this study, we analysed 24-hour Ccr and variables (sex, age and BMI) in 82 subjects with renal diseases to develop suitable formulas. Our serum cystatin C formula is as follows: Ccr (ml/min/1.73m2) = (12.14-0.03 x age-1.72 x serum cystatin C) 2. Correlation between measured 24-hour Ccr and predicted Ccr by our serum cystatin C formula was higher (r=0.852) than our serum creatinine formula (r=0.755), serum beta 2-microgroburin formula (r=0.793), Cockcroft-Gault formula (r=0.836) and Horio formula (r=0.825). Accuracy within 15% was higher (39.0%) than other formulas (25.6-30.5%). Our formula using serum cystatin C for predicting Ccr is a useful and precise marker for Ccr than other commonly used formulas using serum creatinine.

Tako-tsubo cardiomyopathy associated with brain metastasis of seminoma in a patient with chronic kidney disease.

We report a case of tako-tsubo cardiomyopathy associated with brain metastasis of seminoma. This disease is characterized by transient cardiac wall motion abnormalities, electrocardiographic changes and minimal myocardial enzymatic release. During the hospital days, acute congestive heart failure suddenly appeared. The electrocardiogram showed a ST segment elevation in V1-3 and a giant negative T wave in I, aVL, aVF and V3-6. The echocardiogram revealed left ventricular dysfunction with severe hypokinesis to akinesis of anterior and apical wall regions, and hyperkinesis of the basal wall despite the lack of cardiac enzymatic abnormalities. With proper treatment, the patient's overall condition, wall motion and electrocardiographic abnormalities greatly improved.

Relationship between parathyroid hormone and cardiac abnormalities in chronic dialysis patients.

BACKGROUND: It has been shown that parathyroid hormone (PTH) influences cardiac abnormalities in dialysis patients. The purpose of this study was to evaluate the relationship between the plasma PTH level and cardiac abnormalities in these patients without overt cardiac disease. METHODS: A total of 81 of the 208 patients who received chronic dialysis treatment at our institution were included in this study. Plasma PTH level measurement, other blood examinations and echocardiography were performed in all patients. The subjects were divided into two groups based on plasma PTH level (<300 pg/ml: group A; > or =300 pg/ml: group B). RESULTS: There were no significant differences in echocardiographic parameters between group A and group B. The plasma PTH level was not significantly correlated with any echocardiographic parameter in any patient. In addition, we chose 10 patients with a plasma PTH level of more than 500 pg/ml from group B and 20 patients matched for various characteristics (excluding PTH level) from group A and compared the echocardiographic parameters between them. LVMI and intraventricular septum thickness (IVST) were significantly greater in patients with a plasma PTH level of greater than 500 pg/ml. CONCLUSION: PTH was not strongly associated with cardiac abnormalities such as LVH or decreased left ventricular function in the overall group of patients. PTH may not play a major role in the pathogenesis of cardiac abnormalities in these patients. However, PTH could influence LVH in patients with remarkably elevated plasma PTH levels.

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-beta(1) 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.

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. METHODS: Twenty-nine Japanese patients with active UC without a history of steroid usage were selected to be treated with LCAP (n = 9) or prednisolone (PSL) (n = 20). LCAP administration continued for 10 weekly cycles. In the PSL group, patients with moderately severe disease received 0.5 mg/kg per day of PSL and those with severe disease 1.0 mg/kg per day. The PSL dosage was gradually tapered in accordance with improvement. RESULTS: Eight (88.9%) of the LCAP group and 16 (80.0%) of the PSL group showed clinical improvement and three (33.3%) of the LCAP group and seven (35.0%) of the PSL group achieved remission. As for the treatment complications, three major adverse effects were observed in the PSL group, but none were observed in the LCAP group. CONCLUSION: The results of this study suggest that the efficacy and safety of LCAP are equivalent, and in terms of severe adverse effects, superior to those of steroid therapy. LCAP therapy may thus be a promising candidate therapy for steroid-naïve patients with active UC.