Background: Stem cell transplantation (SCT) places a heavy burden on the kidneys, often resulting in renal dysfunction or nephrotic syndrome. This study attempted to show that early-onset proteinuria predicts the development of overt nephropathy. Methods: A total of 831 patients who received allogeneic SCT were surveyed. Excluding those with prior kidney disease and those lacking in an observation period ≥1 year after SCT, 251 patients were eligible for the study. Dipstick proteinuria ≥1+ within 1 year after SCT was defined as ‘incident proteinuria', and subsequent persistence of an estimated glomerular filtration rate of <60 ml/min/1.73 m2 at 1 year or longer after SCT was defined as ‘incident chronic kidney disease (CKD)'. Between-group differences were analyzed using the chi-square or Mann-Whitney U test. Factors associated with the incidence of CKD were investigated by multivariate Cox proportional regression analysis. Kidney-biopsied tissue was examined in all nephrotic syndrome patients. Results: The mean duration of follow-up was 4 years. Thirty-four (13.5%) and 66 (26.3%) patients developed incident proteinuria and incident CKD, respectively. Nine (3.6%) patients developed nephrotic syndrome mainly due to membranous nephropathy. The incidence of CKD was significantly greater in patients with incident proteinuria than those without (61.8 vs. 20.7%, p < 0.0001), and incident dipstick proteinuria was a significant risk for incident CKD (hazard ratio 4.39, 95% CI 2.44-7.73, p < 0.0001). Conclusion: SCT patients who manifest dipstick proteinuria are predisposed to overt nephropathy. Routine monitoring of the urine dipstick test is strongly recommended, as it facilitates early nephrology care for post-SCT patients.

1.
Parikh CR, Coca SG: Acute renal failure in hematopoietic cell transplantation. Kidney Int 2006;69:430-435.
2.
Humphreys BD, Soiffer RJ, Magee CC: Renal failure associated with cancer and its treatment: an update. J Am Soc Nephrol 2005;16:151-161.
3.
Imai H, Oyama Y, Miura AB, Endoh M, Sakai H: Hematopoietic cell transplantation-related nephropathy in Japan. Am J Kidney Dis 2000;36:474-480.
4.
Cohen EP: Radiation nephropathy after bone marrow transplantation. Kidney Int 2000;58:903-918.
5.
Hingorani S: Chronic kidney disease in long-term survivors of hematopoietic cell transplantation: epidemiology, pathogenesis, and treatment. J Am Soc Nephrol 2006;17:1995-2005.
6.
Levey AS, de Jong PE, Coresh J, El Nahas M, Astor BC, Matsushita K, Gansevoort RT, Kasiske BL, Eckardt KU: The definition, classification, and prognosis of chronic kidney disease: a KDIGO controversies conference report. Kidney Int 2011;80:17-28.
7.
Morito T, Ando M, Kobayashi T, Kakihana K, Ohashi K, Akiyama H, Tsuchiya K, Nitta K, Sakamaki H: New-onset microalbuminuria following allogeneic myeloablative SCT is a sign of near-term decrease in renal function. Bone Marrow Transplant 2013;48:972-976.
8.
Hingorani SR, Seidel K, Lindner A, Aneja T, Schoch G, McDonald G: Albuminuria in hematopoietic cell transplantation patients: prevalence, clinical associations, and impact on survival. Biol Blood Marrow Transplant 2008;14:1365-1372.
9.
Yamamoto K, Yamamoto H, Yoshida K, Niwa K, Nishi Y, Mizuno A, Kuwabara M, Asano T, Sakoda K, Niinuma H, Nakahara F, Takeda K, Shindoh C, Komatsu Y: The total urine protein-to-creatinine ratio can predict the presence of microalbuminuria. PLoS One 2014;9:e91067.
10.
Lambers Heerspink HJ, Gansevoort RT, Brenner BM, Cooper ME, Parving HH, Shahinfar S, de Zeeuw D: Comparison of different measures of urinary protein excretion for prediction of renal events. J Am Soc Nephrol 2010;21:1355-1360.
11.
Cirillo M: Evaluation of glomerular filtration rate and of albuminuria/proteinuria. J Nephrol 2010;23:125-132.
12.
Lim D, Lee DY, Cho SH, Kim OZ, Cho SW, An SK, Kim HW, Moon KH, Lee MH, Kim B: Diagnostic accuracy of urine dipstick for proteinuria in older outpatients. Kidney Res Clin Pract 2014;33:199-203.
13.
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A; Collaborators Developing the Japanese Equation for Estimated GFR: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009;53:982-992.
14.
Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010;375:2073-2081.
15.
Hara M, Ando M, Maeda Y, Tsuchiya K, Nitta K: Proteinuria is a simple sign of systemic inflammation that leads to a poor prognosis in individuals affected with non-Hodgkin lymphoma. Clin Nephrol 2014;82:51-57.
16.
Abraham P, Indirani K, Sugumar E: Effect of cyclophosphamide treatment on selected lysosomal enzymes in the kidney of rats. Exp Toxicol Pathol 2007;59:143-149.
17.
Kolli VK, Abraham P, Isaac B, Selvakumar D: Neutrophil infiltration and oxidative stress may play a critical role in methotrexate-induced renal damage. Chemotherapy 2009;55:83-90.
18.
Naesens M, Kuypers DR, Sarwal M: Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 2009;4:481-508.
19.
Russo LM, Sandoval RM, McKee M, Osicka TM, Collins AB, Brown D, Molitoris BA, Comper WD: The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: retrieval is disrupted in nephrotic states. Kidney Int 2007;71:504-513.
20.
Takatsuka H, Takemoto Y, Yamada S, Wada H, Tamura S, Fujimori Y, Okamoto T, Suehiro A, Kanamaru A, Kakishita E: Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome. Bone Marrow Transplant 2000;26:419-426.
21.
Konta T, Hao Z, Takasaki S, Abiko H, Ishikawa M, Takahashi T, Ikeda A, Ichikawa K, Kato T, Kawata S, Kubota I: Clinical utility of trace proteinuria for microalbuminuria screening in the general population. Clin Exp Nephrol 2007;11:51-55.
22.
Hong DS, Oh IH, Park JS, Lee CH, Kang CM, Kim GH: Evaluation of urinary indices for albuminuria and proteinuria in patients with chronic kidney disease. Kidney Blood Press Res 2016;41:258-266.
23.
Clark WF, Macnab JJ, Sontrop JM, Jain AK, Moist L, Salvadori M, Suri R, Garg AX: Dipstick proteinuria as a screening strategy to identify rapid renal decline. J Am Soc Nephrol 2011;22:1729-1736.
24.
Gomez-Garcia P, Herrera-Arroyo C, Torres-Gomez A, Gomez-Carrasco J, Aljama-Garcia P, Lopez-Rubio F, Martinez-Guibelalde F, Fornes-Torres G, Rojas-Contreras R: Renal involvement in chronic graft-versus-host disease: a report of two cases. Bone Marrow Transplant 1988;3:357-362.
25.
Byrne-Dugan CJ, Collins AB, Lam AQ, Batal I: Membranous nephropathy as a manifestation of graft-versus-host disease: association with HLA antigen typing, phospholipase A2 receptor, and C4d. Am J Kidney Dis 2014;64:987-993.
26.
Beyar-Katz O, Davila EK, Zuckerman T, Fineman R, Haddad N, Okasha D, Henig I, Leiba R, Rowe JM, Ofran Y: Adult nephrotic syndrome after hematopoietic stem cell transplantation: renal pathology is the best predictor of response to therapy. Biol Blood Marrow Transplant 2016;22:975-981.
27.
Cho YH, Kang SH, Kim Y, Lee MH, An GH, Chung BH, Choi BS, Yang CW, Kim YS, Choi YJ, Park CW: De novo glomerulitis associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a single-center experience. Kidney Res Clin Pract 2013;32:121-126.
28.
Sato N, Kishi K, Yagisawa K, Kasama J, Karasawa R, Shimada H, Nishi S, Ueno M, Ito K, Koike T, et al: Nephrotic syndrome in a bone marrow transplant recipient with chronic graft-versus-host disease. Bone Marrow Transplant 1995;16:303-305.
29.
Bruijn JA, Hogendoorn PC, Corver WE, van den Broek LJ, Hoedemaeker PJ, Fleuren GJ: Pathogenesis of experimental lupus nephritis: a role for anti-basement membrane and anti-tubular brush border antibodies in murine chronic graft-versus-host disease. Clin Exp Immunol 1990;79:115-122.
30.
Seconi J, Watt V, Ritchie DS: Nephrotic syndrome following allogeneic stem cell transplantation associated with increased production of TNF-alpha and interferon-gamma by donor T cells. Bone Marrow Transplant 2003;32:447-450.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.