Side Effects of Immunosuppressive Treatments in Primary Glomerulonephritis

Öz

Abstract Background: It is imperative to closely monitor patients for adverse effects of immunosuppressive (IS) agents, widely used in treating glomerulonephritis (GN). Our study aimed to investigate the occurrence of any drug-related adverse events in patients with primary GN, explicitly focusing on IS. Methods: The present study analyzed 162 adult GN patients treated with IS drugs. The study scrutinized the demographic and clinical profiles of the patients, laboratory findings, and any side effects associated with IS drugs. We further investigated the patients for frequency and nature of infections, musculoskeletal and gastrointestinal symptoms, thromboembolism, new-onset diabetes, avascular necrosis, neuropsychiatric side effects, and premalignant conditions. Results: The study comprised a diverse group of patients with a male majority of 51.9% and a mean age of 37.2±12.9 years. The patients were under clinical observation for an average of 69.6±40.1 months, and during the treatment, 71% experienced at least one adverse effect. After evaluating the data, we did not find a significant correlation between the GN type and the presence of side effects. Research demonstrates that patients receiving corticosteroids (CS) exhibit a higher incidence of myopathy than those receiving other IS therapies (p=0.001). Hypoalbuminemia (OR: 2.05; 95% CI: 1.82–2.28; p =0.001) and steroid treatment (OR: 1.04; 95% CI: 1.01–1.06; p = 0.009) are significantly associated with increased risk of adverse outcomes. Conclusion: In cases of GN, it is not unusual for patients to encounter adversities associated with IS treatment, primarily when there is a comorbidity of hypoalbuminemia and CS exposure. The probability of these side effects occurring may increase under such circumstances. Main Points: • Patients diagnosed with GN should undergo meticulous monitoring to detect any potential adverse effects that may arise from the administration of IS agents • The probability of experiencing side effects is higher when hypoalbuminemia and CS exposure are present. • The present study suggests no discernible correlation between the type of GN and side effects.

Anahtar Kelimeler

• glomerulonephritis
• side effects
• immunosuppressive treatment
• infections

Primer Glomerülonefritlerde İmmünosüpresif Tedavilerin Yan Etkileri

Öz

Amaç: Glomerülonefrit (GN) tedavisinde yaygın olarak kullanılan immünosupresif (IS) ajanların yan etkileri açısından hastaların yakından izlenmesi gerekmektedir. Çalışmamız, özellikle IS'ye odaklanarak, primer GN'li hastalarda ilaca sekonder görülen yan etkileri araştırmayı amaçladı. Yöntemler: Bu çalışmaya IS ajanlarla tedavi edilen 162 yetişkin GN hastası dahil edildi. Çalışmada hastaların demografik ve klinik özellikleri, laboratuvar bulguları ve IS ilaçlarla ilişkili yan etkiler incelendi. Hastalar; enfeksiyonların sıklığı ve natürü, muskuloskeletal ve gastrointestinal semptomlar, tromboembolizm, yeni başlayan diyabet, avasküler nekroz, nöropsikiyatrik yan etkiler ve premalign durumlar açısından da araştırıldı. Bulgular: Hastaların %51,9'u erkekti ve yaş ortalaması 37,2±12,9 yıldı. Hastalar ortalama 69,6±40,1 ay süreyle klinik gözlem altında tutuldu ve tedavi sırasında %71'inde en az bir yan etki görüldü. Veriler incelendiğinde GN tipi ile yan etki varlığı arasında anlamlı bir korelasyon saptanmadı. Kortikosteroid (KS) alan hastaların, diğer IS tedavilere göre daha yüksek miyopati insidansı sergilediği gösterildi (p=0,001). Hipoalbüminemi (OR: 2,05; %95 GA: 1,82–2,28; p =0,001) ve steroid tedavisi (OR: 1,04; %95 GA: 1,01–1,06; p = 0,009), yan etki riskinin artmasıyla anlamlı şekilde ilişkili bulundu. Sonuç: GN vakalarında, özellikle hipoalbüminemi ve KS maruziyetinin eşlik ettiği durumlarda, hastaların IS tedavisiyle ilişkili yan etkilerle karşılaşma olasılığı artabilir. Ana noktalar: • GN tanılı hastalar, IS ajanlardan kaynaklanabilecek olası yan etkileri tespit etmek için dikkatli bir şekilde izlenmelidir. • Hipoalbuminemi ve kortikosteroide maruziyet, yan etki görülme olasılığını artırır. • Bu çalışmada, GN tipi ile yan etkiler arasında anlamlı bir ilişki olmadığı görülmüştür.

Anahtar Kelimeler

• Glomerülonefrit
• yan etkiler
• enfeksiyonlar
• immünosupresif tedaviler

Kaynakça

1. 1. Crew R, J. Radhakrishnan, and G. Appel, Complications of the nephrotic syndrome and their treatment. Clinical nephrology, 2004. 62(4): p. 245-259.
2. 2. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical Practice. 2012;120(4):c179-c84.
3. 3. McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrology Dialysis Transplantation. 2011;26(2):414-30.
4. 4. Floege J, Amann K. Primary glomerulonephritides. The Lancet. 2016;387(10032):2036-48.
5. 5. Anderson DC, York TL, Rose G, Smith CW. Assessment of serum factor B, serum opsonins, granulocyte chemotaxis, and infection in children's nephrotic syndrome. Journal of Infectious Diseases. 1979;140(1):1-11.
6. 6. Abbott KC, Koff J, Bohen EM, Oglesby RJ, Agodoa LY, Lentine KL, et al. Maintenance immunosuppression use and the associated risk of avascular necrosis after kidney transplantation in the United States. Transplantation. 2005;79(3):330-6.
7. 7. Martin PJ, Storer BE, Rowley SD, Flowers ME, Lee SJ, Carpenter PA, et al. Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease. Blood. 2009;113(21):5074-82.
8. 8. Messer J, Reitman D, Sacks HS, Smith Jr H, Chalmers TC. Association of adrenocorticosteroid therapy and peptic-ulcer disease. New England Journal of Medicine. 1983;309(1):21-4.

9. 9. Epinette WW, Parker CM, Jones EL, Greist MC. Mycophenolic acid for psoriasis: a review of pharmacology, long-term efficacy, and safety. Journal of the American Academy of Dermatology. 1987;17(6):962-71.
10. 10. FK UM. 506 Liver Study Group: A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med. 1994;331(1110):71115.
11. 11. Afifi A. Steroid myopathy. Clinical, histologic, and cytologic observation. Johns Hopkins Medical Journal. 1968;123:158-73.
12. 12. Gumprecht J, Zychma M, Grzeszczak W, Kuźniewicz R, Burak W, Żywiec J, et al. Simvastatin-induced rhabdomyolysis in a CsA-treated renal transplant recipient. Medical Science Monitor. 2003;9(9):CS89-CS91.
13. 13. Galindo M, Cabello A, Joven B, Alonso A, Carreira P, Porta J, et al. Mycophenolate mofetil induced myopathy in a patient with lupus nephritis. The Journal of rheumatology. 2005;32(1):188-90.
14. 14. Skalka HW, Prchal JT. Effect of corticosteroids on cataract formation. Archives of Ophthalmology. 1980;98(10):1773-7.
15. 15. Hirsch IB, Paauw DS. Diabetes management in special situations. Endocrinology and metabolism clinics of North America. 1997;26(3):631-45.
16. 16. Heisel O, Heisel R, Balshaw R, Keown P. New onset diabetes mellitus in patients receiving calcineurin inhibitors: a systematic review and meta‐analysis. American Journal of Transplantation. 2004;4(4):583-95.
17. 17. Maksimovic D, Stojkovic MM, STOSIC‐GRUJICIC S. Antidiabetogenic Effect of Mycophenolate Mofetil Is Associated with Down‐Regulation of Adhesive Interactions and Autoreactive Cell Activation. Annals of the New York Academy of Sciences. 2002;958(1):148-51.
18. 18. Kanis JA, Johansson H, Oden A, Johnell O, De Laet C, Melton III LJ, et al. A meta‐analysis of prior corticosteroid use and fracture risk. Journal of bone and mineral research. 2004;19(6):893-9.
19. 19. Yeo H, Beck LH, McDonald JM, Zayzafoon M. Cyclosporin A elicits dose-dependent biphasic effects on osteoblast differentiation and bone formation. Bone. 2007;40(6):1502-16.
20. 20. Glenn DA, Henderson CD, O’Shaughnessy M, Hu Y, Bomback A, Gibson K, et al. Infection-related acute care events among patients with glomerular disease. Clinical journal of the American Society of Nephrology: CJASN. 2020;15(12):1749.
21. 21. Oh GJ, Waldo A, Paez-Cruz F, Gipson PE, Pesenson A, Selewski DT, et al. Steroid-associated side effects in patients with primary proteinuric kidney disease. Kidney international reports. 2019;4(11):1608-16.
22. 22. Glenn DA, Zee J, Mansfield S, O’Shaughnessy MM, Bomback AS, Gibson K, et al. Immunosuppression Exposure and Risk of Infection-Related Acute Care Events in Patients With Glomerular Disease: An Observational Cohort Study. Kidney Medicine. 2022;4(11):100553.