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      Water intoxication induced by low-dose oral cyclophosphamide in a patient with anti-neutrophil cytoplasmic antibody-related glomerulonephritis

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          Abstract

          We reported the case of a 70-year-old woman with moderate renal failure due to anti-neutrophil cytoplasmic antibody-related glomerulonephritis who developed symptomatic water intoxication (serum Na: 108 mEq/L) following treatment with oral low-dose cyclophosphamide (CY) (50mg/day). Estimated glomerular filtration rate was 29.5 mL/min/1.73 m 2. She had drunk >2 L of fluid in 12 h prior to the development of cerebral oedema. This rare case suggests that oral low-dose CY could be an occult cause of water intoxication in patients with chronic kidney disease taking large fluid volumes.

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          Modification of the Modification of Diet in Renal Disease (MDRD) Study equation for Japan.

          Akira Hishida, Kunitoshi Iseki, Seiichi Matsuo … (2007)
          Glomerular filtration rate (GFR)-estimating equations based on serum creatinine level may not be accurate across racial groups because of differences among races in creatinine generation. The Modification of Diet in Renal Disease (MDRD) Study equation was developed in whites and African Americans, but performance was not evaluated in Japanese. Diagnostic test accuracy. Cross-sectional retrospective study of 3 patient groups. Equation development in 2 groups (n = 247 in 2002 to 2004; n = 214 in 2003 to 2004 with measured GFR <90 mL/min/1.73 m(2)); external validation in a separate group (n = 153 from 1988 to 1994). Hospitalized Japanese patients with chronic kidney disease in 3 medical centers. Measured GFR (mGFR) computed from renal clearance of inulin. Estimated GFR (eGFR) using the isotope dilution mass spectrometry (IDMS)-traceable 4-variable MDRD Study equation, a modified IDMS MDRD Study equation with a Japanese Society of Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) coefficient derived in the development data set, and a new equation derived by refitting coefficients in the MDRD Study equation in the development data set. Current creatinine assays were calibrated to standardized creatinine. Performance of equations was assessed as bias, accuracy, root-mean-squared error, and correlation coefficient of eGFR versus mGFR. In the development data set, eGFR using the IDMS MDRD Study equation overestimated mGFR throughout the entire range. In the validation data set, the IDMS MDRD Study equation with the JSN-CKDI coefficient 0.741 and the new equation (JSN-CKDI) performed with significantly less bias and greater accuracy than the IDMS MDRD Study equation, but were similar to each other in accuracy and bias in patients with eGFR less than 60 mL/min/1.73 m(2). In the combined development and validation data sets, the JSN-CKDI coefficient was 0.763 (95% confidence interval, 0.743 to 0.783). Possible drift in creatinine assays over time, possible lower creatinine generation in hospitalized patients, exclusion of patients with higher GFR from the development data set. GFR estimates using the IDMS MDRD Study equation with the JSN-CKDI coefficient or the new JSN-CKDI equation are more accurate than the IDMS MDRD Study equation in hospitalized Japanese patients with eGFR less than 60 mL/min/1.73 m(2). More studies are necessary to verify the accuracy of the JSN-CKDI coefficient and JSN-CKDI equation in other settings in Japan and elsewhere in Asia.
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            Cyclophosphamide pharmacokinetics and dose requirements in patients with renal insufficiency.

            F I Bohnenstengel, Ute Hofmann, Matthias Schwab … (2002)
            Intravenous pulse administration of cyclophosphamide (CYC) has been successfully used for the treatment of various autoimmune diseases. These patients often present with impaired renal function or even end-stage renal failure. Nevertheless, data concerning pharmacokinetics of CYC in renal insufficiency (RI) and on hemodialysis (HD) are rare and contradictory. The pharmacokinetics of CYC (0.5 to 1 g/m2 as a one-hour infusion) were determined in patients with renal involvement of autoimmune diseases. Group A (N = 6) patients had a creatinine clearance (CCr) of 25 to 50 mL/min, group B patients' (N = 5) CCr was 10 to 24 mL/min, and group C (N = 6) patients had CCr values <10 mL/min and HD. Concentrations of CYC in serum, dialysate and urine were measured by HPLC. Twelve previously investigated patients with normal renal function served as controls. Mean clearance (CL) of CYC was significantly reduced with decreased renal function (79 vs. 57 and 47 mL/min, controls vs. A and B, respectively, P < 0.05), but only moderately lower in the patients who received a three-hour HD during the study period (group C, 64 mL/min, NS). This resulted in reciprocal increases in systemic drug exposure (dose corrected AUC was 216, 298, 382 and 266 microg x h/mL x g, controls, A, B and C, respectively). Urinary excretion of CYC was markedly reduced in all patients with RI (renal CL was 14.9 vs. 3.4, 2.4 and 2.1 mL/min, controls vs. A, B and C, respectively, P < 0.001). However, in patient group C, a mean of 22% of administered CYC dose was eliminated by a three hour HD starting seven hours after CYC administration. Individual CCr values were significantly (P < 0.001) correlated with renal and systemic CL of CYC, respectively, and negatively correlated with dose corrected AUC. Clearance of CYC is decreased in patients with reduced renal function, thereby resulting in an increased systemic drug exposure. However, in hemodialysis-dependent patients, removal of CYC into the dialysate has to be taken into account. For optimal dosing of CYC in patients with renal insufficiency, the severity of renal impairment and the use and timing of hemodialysis have to be considered.
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              Water intoxication in man after cyclophosphamide therapy. Time course and relation to drug activation.

              R. DeFronzo, O Michael Colvin, H G Braine … (1973)
              Article 0 comments Cited 9 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): NDT Plus
                Journal ID (publisher-id): NDTPLUS
                Journal ID (hwp): ndtplus
                Title: NDT Plus
                Publisher: Oxford University Press
                ISSN (Print): 1753-0784
                ISSN (Electronic): 1753-0792
                Publication date (Print): October 2008
                Publication date (Electronic): 24 June 2008
                Publication date PMC-release: 24 June 2008
                Volume: 1
                Issue: 5
                Pages: 286-288
                Affiliations
                [1 ]Division of Blood Purification, Hamamatsu University School of Medicine
                [2 ]Department of Nephrology, Seirei Mikatahara General Hospital
                [3 ]Department of Health and Nutritional Science, Hamamatsu University
                [4 ]First Department of Medicine, Hamamatsu University School of Medicine , Shizuoka, Japan
                Author notes
                Correspondence and offprint requests to: Akihiko Kato, Division of Blood Purification, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. Tel. and Fax: +81-53-435-2756; E-mail: a.kato@ 123456hama-med.ac.jp
                Article
                Publisher ID: sfn076
                DOI: 10.1093/ndtplus/sfn076
                PMC ID: 2535761
                PubMed ID: 18795141
                SO-VID: ed5a4a7d-3445-4b4c-945b-52f32b495db9
                Copyright © © The Author [2008].
                License:

                The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

                History
                Date received : 15 April 2008
                Date accepted : 30 May 2008
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Nephrology
                Keywords: chronic kidney disease,cyclophosphamide,fluid intake,symptomatic hyponatraemia
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: chronic kidney disease, cyclophosphamide, fluid intake, symptomatic hyponatraemia

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