Hyperferritinemia and Other Factors Related to Glomerular Injury in Beta-Thalassemia Major
DOI:
https://doi.org/10.18502/kls.v4i12.4174Abstract
Beta-thalassemia major (BTM) is a hereditary hemoglobinopathy, characterized by anemia, increased free radicals and iron overload which can lead to hyperferritinemia, glomerular injury, and kidney dysfunction. This research aimed to analyze the association between hyperferritinemia and urinary podocalyxin (uPCX) as the indicator of glomerular injury in BTM. This retrospective cohort study was conducted on 60 BTM patients aged ≤18 years who came to the pediatrics unit of Dr. Moewardi Hospital Surakarta from April to May 2017. The data were analyzed to determine relative risk and 95%CI for each variable, followed by multivariate analysis with logistic regression. The prevalence of elevated uPCX in BTM patients in this research was 50%. The results
showed an association of hyperferritinemia (RR2.51, 95%CI 1.28-4.93, p=0.002), the degree of anemia(RR2.00, 95%CI 1.14-3.52, p=0.01), the number of transfusion (RR 1.75, 95%CI 1.09-2.82, p=0.028), the duration of transfusion (RR 1.83, 95%CI 0.98-3.42, p=0.035), the duration of illness (RR 1.60, 95%CI 0.95-2.72, p=0.071) and the duration of iron chelation therapy (RR 1.58,95%CI 0.79-3.17, p=0.152) with glomerular injury. The
multivariate analysis showed that hyperferritinemia and degree of anemia remained significantly associated with glomerular injury (RR 5.46; 95%CI 1.30-23.01; p=0.021 and RR 4.13; 95%CI 1.15-14.85; p=0.030). This study demonstrates a statistically significant association between hyperferritinemia, the degree of anemia, the number of transfusion and the duration of transfusion with kidney injury in BTM patients. Routine monitoring
of renal function in BTM is recommended.
Keywords: Beta-thalassemia major, hyperferritinemia, urinary podocalyxin, glomerular injury
References
Galanello R, Origa R. 2010 Beta Thalassemia: Review. OJRD. 5(11): 1–15.
De Sanctis V, Kattamis C, Canatan D, Soliman AT, Elsedfy H et al, 2017 Beta thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis 9 (1): e2017018.
Thavorncharoensap M, 2010 Factors affecting health-related quality of life in thalassemia Thai children with thalassemia Journal BMC Dis 10 (1) 1-10.
Kementerian Kesehatan RI. 2016 Petunjuk Teknis Deteksi Thalassemia di Sekolah( Jakarta: Kemkes) pp 1-54.
Bulan S. 2009 Faktor-faktor yang berhubungan dengan kualitas hidup anak thalassemia beta mayor Tesis Program pascasarjana magister ilmu biomedik dan program dokter spesialis I. Ilmu Kesehatan Anak (Semarang: FK-UNDIP).
Chintana S, Tangvarasittichai O, Chantanaskulwong P, Pimanprom A, Wantaneeyawong S, Choowet A, Tangvarasittichai S. 2014. Association of iron overload with oxidative stress, hepatic damage and dyslipidemia in transfusion-dependent βthalassemia/HbE patients. Ind J Clin Biochem. 29(3):298-305.
Chiou SS, Chang TT, Tsai S, Jang RC, Lin SK, Lee SC and Tsai SM 2006 Lipid peroxidation and antioxidative status in β-Thalassemia Major patients with or without hepatitis C virus infection Clin Chem 10 1226-1233.
Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL and Loscalzo J 2012 Harrison’s Principles of Internal Medicine 18
Wirawan R, Kusnandar S, Suherli A and Gatot D 2003 Renal impairment in β thalassemia major patients receiving repeated blood transfusion Med J Indones 12 (4) 215-223.
Quinn CT, Kim HY, Vogiatzi MG, Johnson VL, Trachtenberg F, Kwiatkowski JL, Neufeld EJ et al. 2011 Renal dysfunction in patients with thalassemia. Br J Haematol 153 111-117.
Nangaku M 2006 Mechanism of tubulointerstitial injury in the kidney: final common pathway to end-stage renal failure J Am Soc Nephrol 17 17-25.
Gerstein HC, Johanes FE, Man YQ and Zinman B 2001 Albuminuria and risk of cardiovascular events, death and heart failure in diabetic and nondiabetic individuals JAMA 286 (4) 421-426.
Sheikh AS, Baig JA, Iqbal T, Kamzi T, Baiq M and Husain SS 2009 Prevalence of microalbuminuria with relation to glycemic control in type 2 diabetic patients in Karachi J Ayub Med Coll Abottabad 21 (3) 83-86.
Chadban S, Howell M, Twigg S, Thomas M, Jerums G, Alan C, Campbell D, et al 2009 National Evidence Based Guideline for Diagnosis, prevention and Management of Chronic Kidney Disease in Type 2 Diabetes (Canberra: Diabetes Australia & NHMRC) 4-94.
ADA 2016 Standard of medical care in diabetes-2016 Diabetes Care 36 (Suppl 1) S72-S80.
Garovic VD, Wagner SJ, Turner TS, Rosenthal DW, Watson WJ, Brost BC, Rose CH, Gavrilova L, Craigo P, Bailey KR, Achenbach J, Schiffer M, Grande JP, et al 2007 Urinary podocyte exretion as marker for preeclampsia American Journal of Obstetrics Gynecology 196 320-322.
Bakr A, Al-Tonbary Y, Osman G, El-Ashry R. 2014. Renal complications of β– thalassemia major in children Am J Blood Res 41:1-6.
Mallat NS, Mallat SG, Musallam KM and Taher AT 2013 Potential mechanisms for renal damage in beta thalassemia J Nephrol 26 (5) 821-828.
Ali BA, Mahmoud AM 2014 Frequency of glomerular dysfuction in children with betathalassemia major SQU Med J 14 (1) 88-94.
Tanaka T, Miyata T, Inagi R, Fujita T and Nangaku M 2004 Hypoxia in renal disease with proteinuria and/or glomerular hypertension Am J of Pathol 165 (6) 1979-1990.
O’Callaghan CA 2009 At a Glance Sistem Ginjal 2nd ed. ( Jakarta: Erlangga) pp 12-13.
Vogelmann SU, Nelsson WJ, Myers BD and Lemley KV 2003 Urinary excretion of viable podocyte in health and renal disease Am J Physiol Renal Physiol 285 40-48.
Anonim 2007 Podocyturia is marker of preeclampsia. Research Highlights Natural Clinical Practice Nefrology 3 407.
Kajiyama H, Hiromura K, Ikuma D, Ikeuchi H, Kurosawa H, Hirayama Y, Gondaira F, Hara M, Nojima Y and Minura T 2013 Role of urinary podocyte number and urinary podocalyxin level as biomarker of glomerulonephritis in systemic lupus erythematosus an ANCA-associated vasculitis (Abstract) ACR Meeting Abstract, ACR/ARHP Annual Meeting. Abstract number: 880.
Hara M, Yamagata K, Tomino Y, Saito A, Hirayama Y, Ogasawara S, Kurosawa H, Sekine S, et al, 2012 Urinary podocalyxin is an early marker for podocyte injury in patients with diabetes: establishment of a highly sensitive ELISA to detect urinary podocalyxin Diabetologia 55 2913-2919.
Mohamed AH, Heibah HA, Ibrahim HE, Abdeen HM and Badawy A 2016 Urinary podocalyxin; a potential new marker for early diabetic nephropathy in type 2 diabetes mellitus Indian Journal of Applied Research 6 (1) 246-250.
Quinn CT, Johnson VL, Kim HY, Trachtenberg F, Vogiatzi MG, Kwiatkowski JL, Neufeld EJ, Fung E, Oliveri N, Kirby M and Giardina PJ 2011 Renal dysfunction in patients with thalassaemia British Journal of Haematology 153 111–117.
Lai ME, Spiga A, Vasquer S, Carta MP, Corrias C and Ponticelli C 2012 Renal function in patients with β-thalassemia major: a long-term follow-up study Nephrol Dial Transplant 27 3547-3551.
Poggiali E, Cassinerio E, Zanaboni L, Capellini MD, 2012 An update on iron chelation therapy. Blood Transfus 10:411-422.
Rund D, Rachmileweitz E. 2005 β-Thalassemia N Engl J Med 353 1135-1146.
Gokce M, Kup H, Tugcu D, Salcioglu Z, Aydogan G, Akcay A and Akici F 2014 Insidious renal damage in patients with thalassemia major: Is it more serious than appreciated? J Hematol Thrombo Dis. 2 (6) 1-4.
Permono B, Ugrasena I 2005 Buku Ajar Hematologi-Onkologi Anak ( Jakarta: Ikatan Dokter Anak Indonesia (IDAI) p 64-84
Dimiati H, Lubis SY 2014 14(3) 159-66
Thavorncharoensap M et al 2010 BMC Blood Disord. 10(1) 1-10
Kementerian Kesehatan RI 2016 Petunjuk Teknis Deteksi Thalassemia di Sekolah ( Jakarta: Kemkes) p 1-54.
Bulan S 2009 Faktor-faktor yang berhubungan dengan kualitas hidup anak thalassemia beta mayor Tesis Program pascasarjana magister ilmu biomedik dan program dokter spesialis I. Ilmu Kesehatan Anak (Semarang: FK-UNDIP).
Amelia M, Garnida D A and Reniarti L 2014 Sari Pediatri 16(1) 1-4
Chiou S S, Chang T T, Tsai S, Jang R C, Lin S K, Lee S C sand Tsai S M 2006 Clin. Chem. 10 1226-33.
Longo D L, Fauci A S, Kasper D L, Hauser S L, Jameson J L, and Loscalzo J 2012 Harrison’s Principles of Internal Medicine18
Wirawan R, Kusnandar S, Suherli A and Gatot D 2003 Med J Indones 12(4) 215-23
Quinn C T, Kim H Y, Vogiatzi M G, Johnson V L, Trachtenberg F, Kwiatkowski J L, Neufeld E J et al. 2011 Br J Haematol 153 111-7
Nangaku M 2006 JAm Soc Nephrol 17 17-25
Gerstein H C, Johanes F E, Man Y Q and Zinman B 2001 JAMA 286(4) 421-6
Sheikh A S, Baig J A, Iqbal T, Kamzi T, Baiq M and Husain S S 2009 J Ayub Med Coll Abottabad 21(3) 83-6
Chadban S, Howell M, Twigg S, Thomas M, Jerums G, Alan C, Campbell D, et al 2009 National Evidence Based Guideline for Diagnosis, prevention and Management of Chronic Kidney Disease in Type 2 Diabetes (Canberra: Diabetes Australia & NHMRC)4-94
ADA 2016 Diabetes Care 36 (Suppl 1) S72-S80
Garovic V D, Wagner S J, Turner T S, Rosenthal D W, Watson W J, Brost B C, Rose C H, Gavrilova L, Craigo P, Bailey K R, Achenbach J, Schiffer M, Grande J P, et al 2007 Am. J. Obstet Gynecol 196 320-2
Doloksaribu R, Husna R and Oehadian A 2017 MKB 49(1) 22-27
Mallat NS, Mallat S G, Musallam K M and Taher A T 2013 J Nephrol 26(5) 821-8
Ali BA, Mahmoud AM 2014 SQU Med J 14(1) 88-94
Tanaka T, Miyata T, Inagi R, Fujita T, and Nangaku M 2004 Am J of Pathol 165 (6) 1979-90
O’Callaghan CA 2009 At a Glance Sistem Ginjal 2nd ed. ( Jakarta: Erlangga) pp 12-13
Vogelmann S U, Nelsson W J, Myers B D and Lemley KV 2003 Am J Physiol Renal Physiol 285 40-8
Anonim 2007 Podocyturia is marker of preeclampsia. Research Highlights Natural Clinical Practice Nefrology 3 407
Kajiyama H, Hiromura K, Ikuma D, Ikeuchi H, Kurosawa H, Hirayama Y, Gondaira F, Hara M, Nojima Y and Minura T 2013 Role of urinary podocyte number and urinary podocalyxin level as biomarker of glomerulonephritis in systemic lupus erythematosus an ANCA-associated vasculitis (Abstract) ACR Meeting Abstract, ACR/ARHP Annual Meeting. Abstract number: 880
Hara M, Yamagata K, Tomino Y, Saito A, Hirayama Y, Ogasawara S, Kurosawa H, Sekine S, et al, 2012 Diabetologia 55 2913-19
Mohamed A H, Heibah H A, Ibrahim H E, Abdeen H M, and Badawy A 2016 Indian J Appl Res 6(1) 246-50
Quinn C T, Johnson V L, Kim H Y,Trachtenberg F,Vogiatzi M G, Kwiatkowski J L, Neufeld E J, Fung E, Oliveri N, Kirby M, and Giardina P J 2011 Br J Haematol 153 111-7
Lai ME, Spiga A, Vasquer S, Carta MP, Corrias C and Ponticelli C 2012 Nephrol Dial Transplant 27 3547-51
Poggiali E, Cassinerio E, Zanaboni L, Capellini MD, 2012 An update on iron chelation therapy. Blood Transfus 10:411-22
Rund D, Rachmileweitz E. 2005 N Engl J Med 353 1135-46
Gokce M, Kup H, Tugcu D, Salcioglu Z, Aydogan G, Akcay A and Akici F 2014 J Hematol Thrombo Dis. 2(6) 1-4