Introduction. Graves' disease causes kidney injury through multiple mechanisms, including the treatment for this condition. Nephrotic syndrome due to minimal change disease (MCD) is an unusual form of such kidney injury; the association between methimazole use and MCD is also rare.
Case presentation. 36-year-old woman with a history of Graves' disease in use of methimazole for several months, who presented with edematous syndrome due to nephrotic syndrome associated with a KDIGO stage 3 acute kidney injury. Thionamide-induced hypothyroidism and the need of thyroid hormone replacement therapy was evidenced at the time of consultation. Based on a renal biopsy, the patient was diagnosed with MCD. Her condition worsened as she experienced oliguria and hypervolemia, and renal replacement therapy with hemodialysis was temporarily required. Methimazole administration was suspended, and treatment consisting of prednisolone administration and levothyroxine supplementation was started, achieving hemodialysis suspension, gradual improvement of proteinuria until remission and full and maintained recovery of renal clearance. Radioiodine therapy was implemented as definitive treatment for Graves' disease, obtaining a successful outcome.
Conclusions. Graves' disease and methimazole use are possible causes of minimal change disease. Systemic corticosteroid therapy is a possible management. However, further basic, clinical and epidemiological research on this subject is required.
Iglesias P, Bajo MA, Selgas R, Díez JJ. Thyroid dysfunction and kidney disease: An update. Rev Endocr Metab Disord. 2017; 18(1): 131-144. https://doi.org/10.1007/s11154-016-9395-7
Dagdeviren Cakir A, Canpolat N, Saygili S, Kilicaslan I, Turan H, Ercan O, et al. Proteinuria in a patient with Graves' disease: Answers. Pediatr Nephrol. 2019; 34(8): 1383-1385 https://doi.org/10.1007/s00467-019-04221-x
Dousdampanis P, Trigka K, Vagenakis GA, Fourtounas C. The thyroid and the kidney: a complex interplay in health and disease. Int J Artif Organs. 2014 Jan;37(1): 1-12. https://doi.org/10.5301/ijao.5000300
Mariani LH, Berns JS. The renal manifestations of thyroid disease. J Am Soc Nephrol. 2012; 23(1): 22-6. https://doi.org/10.1681/asn.2010070766
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2(1): 1–138.
Hasnain W, Stillman IE, Bayliss GP. Minimal-change renal disease and Graves' disease: a case report and literature review. NDT Plus. 2011 Apr;4(2): 96-8. https://doi.org/10.1093/ndtplus/sfq213
Becker BA, Fenves AZ, Breslau NA. Membranous glomerulonephritis associated with Graves' disease. Am J Kidney Dis. 1999; 33(2): 369-73. https://doi.org/10.1016/S0272-6386(99)70314-8
Kim HJ, Baek JE, Ha HJ, Yang JI, Hahm JR, Chang SH, et al. A case of membranous nephropathy in a patient with Graves' disease. Korean J Med. 2003; 64(1): 130-136.
Esteve V, Fontseré N, Saurina A, Ramírez de Arellano M. Graves disease, hypothyroidism, and minimal-change glomerulonephritis. Nefrologia 2008; 28(2): 230–231
Holt S, Kingdon E, Morganstein D, Sweny P. Simultaneous relapse of Graves' disease and minimal change glomerular disease. Nephrol Dial Transplant. 2002; 17(4): 666-8. https://doi.org/10.1093/ndt/17.4.666
Mündlein E, Greten T, Ritz E. Graves' disease and sarcoidosis in a patient with minimal-change glomerulonephritis. Nephrol Dial Transplant. 1996;11(5):860-2. https://doi.org/10.1093/oxfordjournals.ndt.a027415
Tanwani LK, Lohano V, Broadstone VL, Mokshagundam SP. Minimal change nephropathy and graves' disease: report of a case and review of the literature. Endocr Pract. 2002; 8(1): 40-3. https://doi.org/10.4158/ep.8.1.40
Saha A, Bagri N, Mehera N, Dubey NK, Batra V. Membranoproliferative glomerulonephritis associated with autoimmune thyroiditis. J Pediatr Endocrinol Metab. 2011; 24 (9-10): 789-92. https://doi.org/10.1515/JPEM.2011.372
Kajita Y, Miyoshi Y, Hachiya T, Miyazaki T, Yoshimura M, Ijiichi H, et al. Urinary excretion of LATS in a patient with Graves' disease complicated by nephrotic syndrome. Endocrinol Jpn. 1980; 27(6): 727-32. https://doi.org/10.1507/endocrj1954.27.727
Keenswijk W, Degraeuwe E, Hoorens A, Dorpe JV, Vande Walle J. A case of Graves' disease associated with membranoproliferative glomerulonephritis and leukocytoclastic vasculitis. J Pediatr Endocrinol Metab. 2018; 31(10): 1165-1168. https://doi.org/10.1515/jpem-2018-0186
Methimazole tablets. Spring Valley, NY: PAR Pharmaceutical Companies, Inc; 2012 jan. Package insert.
Bahner B, Fritzer W, Obiditsch-Mayer I. Nephrotic syndrome following methyl mercaptoimidazole therapy. Wien Z Inn Med. 1969; 50(7): 280-8.
Schaum E, Kriegel W, Eickenbusch W, Engelhardt K. Nephrotic syndrome following treatment of hyperthyroidosis with Favistan. Munch Med Wochenschr. 1973; 115(49): 2243-4.
Reynolds LR, Bhathena D. Nephrotic syndrome associated with methimazole therapy. Arch Intern Med. 1979; 139(2): 236-7.
Kakita T, Nagatoya K, Takimoto H, Matsuda H, Mori T, Kawaguchi A, et al. Antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis with membranous nephropathy treated using thiamazole. CEN Case Rep. 2013; 2(2): 165 https://doi.org/10.1007/s13730-013-0060-7
Shell A, Sullivan JW. Acute Kidney Injury Following Methimazole Initiation: A Case Report. J Pharm Pract. 2020 Feb; 33(1): 99-101. https://doi.org/10.1177/0897190018789277
Wada N, Mukai M, Kohno M, Notoya A, Ito T, Yoshioka N. Prevalence of serum anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves' disease treated with propylthiouracil and thiamazole. Endocr J. 2002; 49(3): 329-34. https://doi.org/10.1507/endocrj.49.329
Bonaci-Nikolic B, Nikolic MM, Andrejevic S, Zoric S, Bukilica M. Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides. Arthritis Res Ther. 2005;7(5): R1072-81. https://doi.org/10.1186%2Far1789
Lionaki S, Vlachopanos G, Georgalis A, Ziakas P, Gakiopoulou H, Petra C, et al. Lupus nephritis and non-Hodgkin lymphoma simultaneously diagnosed in a patient on methimazole. Lupus. 2013 Jan; 22(1): 95-8. https://doi.org/10.1177/0961203312467668
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 Aug;30(2): 239-45. https://doi.org/10.1038/clpt.1981.154
Parida S. Clinical causality assessment for adverse drug reactions. Indian J Anaesth. 2013; 57(3): 325-6. https://doi.org/10.4103%2F0019-5049.115608
Vivarelli M, Massella L, Ruggiero B, Emma F. Minimal Change Disease. Clin J Am Soc Nephrol. 2017 Feb 7; 12(2): 332-345. https://doi.org/10.2215/cjn.05000516
Meyrier A, Niaudet P. Acute kidney injury complicating nephrotic syndrome of minimal change disease. Kidney Int. 2018 Nov; 94(5): 861-869. https://doi.org/10.1016/j.kint.2018.04.024
Ford HC, Lim WC, Chisnall WN, Pearce JM. Renal function and electrolyte levels in hyperthyroidism: urinary protein excretion and the plasma concentrations of urea, creatinine, uric acid, hydrogen ion and electrolytes. Clin Endocrinol (Oxf). 1989 Mar; 30(3): 293-301. https://doi.org/10.1111/j.1365-2265.1989.tb02238.x
den Hollander JG, Wulkan RW, Mantel MJ, Berghout A. Correlation between severity of thyroid dysfunction and renal function. Clin Endocrinol (Oxf). 2005 Apr; 62(4): 423-7. https://doi.org/10.1111/j.1365-2265.2005.02236.x
Sönmez E, Bulur O, Ertugrul DT, Sahin K, Beyan E, Dal K. Hyperthyroidism influences renal function. Endocrine. 2019 Jul; 65(1): 144-148. https://doi.org/10.1007/s12020-019-01903-2
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.