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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2019  |  Volume : 30  |  Issue : 3  |  Page : 732-737
Acute kidney injury due to sucrose-containing intravenous immunoglobulins


1 Department of Renal Medicine, The Royal Hospital, Muscat, Oman
2 Saudi Center for Organ Transplantation, Riyadh, Saudi Arabia
3 Department of Medicine, MOHAP, Dubai, United Arab Emirates
4 Department of Histopathology, Sultan Qaboos University Hospital, Muscat, Oman

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Date of Submission27-May-2018
Date of Acceptance11-Jul-2018
Date of Web Publication26-Jun-2019
 

   Abstract 


Intravenous immunoglobulins (IVIGs) are pooled polyvalent immunoglobulin G antibodies extracted from the human plasma. Stabilizers in IVIG may include sugars, such as sucrose, glucose, or maltose. Sucrose in IVIG preparations may cause acute kidney injury (AKI). We report the case of a renal transplant patient who developed AKI due to sucrose nephropathy following the administration of sucrose-containing IVIG.

How to cite this article:
Siddiqui W, Al Lawati S, Shaheen Faissal A M, Hannawi S, Al Riyami M, Al Salmi I. Acute kidney injury due to sucrose-containing intravenous immunoglobulins. Saudi J Kidney Dis Transpl 2019;30:732-7

How to cite this URL:
Siddiqui W, Al Lawati S, Shaheen Faissal A M, Hannawi S, Al Riyami M, Al Salmi I. Acute kidney injury due to sucrose-containing intravenous immunoglobulins. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Sep 18];30:732-7. Available from: http://www.sjkdt.org/text.asp?2019/30/3/732/261361



   Introduction Top


Intravenous immunoglobulins (IVIGs) are pooled polyvalent immunoglobulin G (IgG) antibodies extracted from the human plasma.[1] While the initial indications were mainly immunodeficiency states and some autoimmune diseases, usage of IVIGs has been widened to include several immune-mediated diseases, viral infections, and organ transplant rejection.[2] Stabilizers in IVIG may include sugars, such as sucrose, glucose, or maltose. Sucrose in IVIG prepa-rations may cause acute kidney injury (AKI).[3],[4] We report the case of a renal transplant patient who developed AKI due to sucrose nephropathy following the administration of sucrose-containing IVIG.


   Case Report Top


Informed consent was obtained from the patient before reporting the case.

Mr. SN is a 57-year-old Omani male who developed end-stage kidney disease due to an unknown etiology. He underwent dialysis for about a year before having a living unrelated renal transplant. Immunosuppression induction was performed with basiliximab and intravenous methylprednisolone. Maintenance immunosuppression consisted of cyclosporine, mycophenolate mofetil (MMF), and steroids. His serum creatinine (SCr) on the 7th day after transplantation was 104 μmol/L, corresponding to an estimated glomerular filtration rate (eGFR) [by the Modification of Diet in Renal Disease (MDRD) formula] of 68 mL/min/1.73 m2.

Four months after the transplantation, he was referred to our hospital for deterioration of kidney function with eGFR (by the MDRD formula) of 27 mL/min. Cytomegalovirus (CMV) polymerase chain reaction (PCR) was positive (3300 copies/mL). Cyclosporine levels were high (C2: 2937 ng/mL) and hence, cyclos-porine dose was adjusted. Induction therapy with injection ganciclovir for two weeks, followed by a therapeutic dose of oral valganciclovir, was administered for the treatment of CMV infection. Skin examination revealed annular purple patches, suspicious of Kaposi sarcoma, on the upper limbs. Skin biopsy confirmed the diagnosis.

The management of Kaposi sarcoma consisted of conversion from calcineurin inhibitors to mTor inhibitors. MMF was reduced from 750 to 500 mg twice a day. Prednisolone was reduced to 15 mg/day.

Kidney functions showed significant improvement with SCr decreasing to 100 μmol/L and eGFR to 71 mL/min. However, on subsequent follow-up visits few weeks later, blood polyomavirus (BKV) PCR turned out to be positive with 844 mEq/mL.

He was administered sucrose-containing IVIG. It was planned to give total IVIG of 2 g/kg in four daily divided doses. After completion of the second dose, the SCr increased to 370 μmol/L. He was clinically asymptomatic and euvolemic; his vital signs were stable, urine output remained normal, and urinalysis was inactive.

Ultrasound of the transplant kidney was normal with normal resistivity index. IVIG was stopped. He was well hydrated and underwent ultrasound-guided biopsy. Graft biopsy showed acute tubular injury with flattening and vacuolation of tubular epithelial cells. Mitosis indicating tubular regeneration was seen. There was mild focal interstitial inflammation (20%) with mild lymphocytic tubulitis not amounting to graft rejection. Immuno-histochemistry for both C4d and polyoma-virus (BKV) was negative. The features were consistent with sucrose-induced nephropathy [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d.
Figure 1: (a) Tubules appear dilated with flattening and sloughing of their epithelial lining and contain some proteinaceous material (H and E, ×20). (b) Tubules also show coarse cytoplasmic vacuolation (H and E, ×40). (c) Mitotic figures were seen indicating regenerative activity (black arrow) (H and E, ×40). (d) Glomeruli were unremarkable (PAS, ×20).

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Subsequent visits showed a decrease in serum BKV-PCR level and eventually unde tected serum level of BKV-PCR at follow-up about a month later.


   Discussion Top


IVIG therapy was introduced in 1952 to treat patients with immunoglobulin deficiencies and provide passive immunity to patients with chronic lymphocytic leukemia. Since then, because of its immunomodulatory effect, the indication for IVIG has been extended to a wide variety of immune-related disorders, such as idiopathic thrombocytopenic purpura, myasthenia gravis, inflammatory demyelinating neuropathy, systemic lupus erythematous, and glomerulonephritis.[6],[7],[8],[9] The mechanism of action is not completely known and may include several components. In congenital and acquired immunodeficiency states,[8],[10] IVIG confers a direct anti-infectious effect. In autoimmune diseases, IVIG reduces or modulates immunity by interacting with Fc receptors on phagocytic cells. IVIGs have also an anti-idiotypic activity directed against circulating autoantibodies. These anti-idiotypic antibodies provide a negative feedback signal capable of down regulating the pathogenic immune response.[8],[9],[11]

The therapeutic benefit of IVIG has been ascribed to Ρογ receptor blockade, antibody-mediated autoantibody neutralization, inhibittion of complement-mediated damage, modulation of cytokine production, down-regulation of B- or T-cell responses, effects on antigen-presenting cells, and modulation of dendritic cells.[9],[10],[12],[13],[14]

BKV viremia occurs in 13% and BKV nephropathy (BKVN) occurs in 8% of kidney transplant recipients.[15],[16],[17] Viral replication begins early after transplantation and progresses through detectable stages: viruria followed by viremia and then nephropathy.[18],[19] Viruria can be detected by PCR for BKV DNA, reverse transcription-PCR for BKV RNA, urine cytology for BKV inclusion-bearing epithelial cells termed “decoy cells,” or electron microscopy for viral particles.[15],[18],[20]

Untreated BKVN can lead to graft loss. The cornerstone of treatment of BKVN is a decrease in maintenance immunosuppression. Various interventions have been pursued, most commonly withdrawal of MMF or tacro-limus,[16],[17],[19],[21],[22],[23],[24] replacement of tacrolimus by cyclosporine, and overall reduction of the immunosuppressive load.[19],[21],[25] Simultaneous occurrence of acute rejection and BKVN is a frequent clinical problem. The treatment of acute rejection with pulse steroids has been associated with an increased risk of BKVN.[15],[25] In addition, reduction of immunosuppression to treat BKVN evidently carries a high risk (25%–45%) of acute rejection.[16],[17],[19],[21],[23]

The use of immunoglobulins may be a valuable treatment option in patients with BKVN and co-existing rejection.[15],[16],[17] The choice of IVIG is also of vital importance. Adverse effects associated with IVIG are relatively uncommon, occurring in 1%–13% of infusions.[2],[26],[27],[28],[29],[30] Fever, chills, flushing, headache, myalgia, elevated blood pressure, chest pain, and dyspnea are likely related to complement activation by immunoglobulin aggregates.[26],[27],[28],[29],[31],[32] To minimize the formation of immunoglobulin aggregates, sugars such as maltose, dextrose, and sucrose are added to IVIG as stabilizing agents.[4],[33]

Intravenous immunoglobulin preparations nowadays are highly purified and contain around 90% of polyvalent IgG.[1],[10],[30],[34] Stabilizers are used to minimize the formation of immunoglobulin aggregates which can generate adverse events. These include sugars such as sucrose, glucose, and maltose or amino acids such as glycine or proline. After paren-teral infusion, sucrose is exclusively eliminated by the kidney. Because the kidneys do not produce the enzyme disaccharidase, sucrose administered intravenously cannot be metabolized, accumulating in the proximal tubules and causing hyperosmolality, which leads to renal injury.[35],[36],[37],[38] Predisposing risk factors for sucrose nephropathy include pre-existing kidney insufficiency, diabetes mellitus, dehydration, age above 65 years, sepsis, paraprotei-nemia, and concomitant use of nephrotoxic agents.[2],[4],[6],[33],[39],[40],[41],[42],[43],[44]

Sucrose nephropathy is characterized by marked proximal cell swelling, vacuolization, and lumen narrowing and/or occlusion.[30],[45],[46] A major element in the pathogenesis of sucrose nephropathy is the absence, in kidney tubular cells, of the enzyme disaccharidase which metabolizes sucrose.[1],[47] Proximal tubules take up filtered sucrose via pinocytosis. The latter accumulates in the cytoplasm, creating an osmotic gradient.[35],[38],[46],[48],[49],[50]

Water enters the proximal tubular cells through aquaporines AQP1, leading to cell swelling and subsequent narrowing and occlusion of tubule lumen.[38],[46],[48] Some authors have reported that sucrose could produce injury in normal human kidneys at a dose of 6 g/kg body weight given in 1 week.[35],[41],[51],[52],[53]

The threshold for kidney injury is much lower in patients with kidney dysfunction, with as little sucrose as 1 g/kg being sufficient to cause AKI.[54],[55] When used for immune disorders, the daily dose of IVIG ranges from 0.35 to 2.0 g/kg, corresponding to sucrose load of 0.58 to 3.4 g/kg. Most cases of IVIG- induced AKI have been reported with this treatment regimen.[1],[2],[29],[31],[56],[57]


   Conclusion Top


In this article, we present a case of a living unrelated kidney transplant recipient who developed BKVN and developed impaired kidney function. The patient also had new-onset diabetes mellitus after kidney transplantation but was otherwise in good general health. Treatment included sucrose-containing IVIG. The patient subsequently developed AKI. The outcome was favorable with recovery of filtration rate to the baseline within 21 days without the need for dialysis. We conclude that the administration of sucrose-containing IVIG may lead to AKI. We recommend the use of sucrose-free IVIG whenever possible. In all cases, caution is required when administrating IVIG.

Conflict of interest: None declared.



 
   References Top

1.
Jin F, Tayab ZR, Balthasar JP. Pharmaco-kinetic and pharmacodynamic effects of highdose monoclonal antibody therapy in a rat model of immune thrombocytopenia. AAPS J 2006;7:E895-902.  Back to cited text no. 1
    
2.
Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: Adverse effects and safe administration. Clin Rev Allergy Immunol 2005;29:173-84.  Back to cited text no. 2
    
3.
Ahsan N, Wiegand LA, Abendroth CS, Manning EC. Acute renal failure following immunoglobulin therapy. Am J Nephrol 1996; 16:532-6.  Back to cited text no. 3
    
4.
Dantal J. Intravenous immunoglobulins: In-depth review of excipients and acute kidney injury risk. Am J Nephrol 2013;38:275-84.  Back to cited text no. 4
    
5.
Berger M. A history of immune globulin therapy, from the Harvard crash program to monoclonal antibodies. Curr Allergy Asthma Rep 2002;2:368-78.  Back to cited text no. 5
    
6.
Lozeron P, Not A, Theaudin M, et al. Safety of intravenous immunoglobulin in the elderly treated for a dysimmune neuromuscular disease. Muscle Nerve 2016;53:683-9.  Back to cited text no. 6
    
7.
Ilahe A, Budhiraja P, Kaplan B. Polyclonal and monoclonal antibodies in renal transplant: An update. Curr Opin Nephrol Hypertens 2015;24:563-9.  Back to cited text no. 7
    
8.
Bussel JB, Hilgartner MW. The use and mechanism of action of intravenous immuno-globulin in the treatment of immune haema-tologic disease. Br J Haematol 1984;56:1-7.  Back to cited text no. 8
    
9.
Knezevic-Maramica I, Kruskall MS. Intravenous immune globulins: An update for clinicians. Transfusion 2003;43:1460-80.  Back to cited text no. 9
    
10.
Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 2011;475:110-3.  Back to cited text no. 10
    
11.
Laidlaw S, Bainton R, Wilkie M, Makris M. Acute renal failure in acquired haemophilia following the use of high dose intravenous immunoglobulin. Haemophilia 1999;5:270-2.  Back to cited text no. 11
    
12.
Aubin É, Proulx DP, Trepanier P, Lemieux R, Bazin R. Prevention of T cell activation by interference of internalized intravenous immuno-globulin (IVIg) with MHC II-dependent native antigen presentation. Clin Immunol 2011;141: 273-83.  Back to cited text no. 12
    
13.
Knowles WA, Gibson PE, Hand JF, Brown DW. An M-antibody capture radioimmuno-assay (MACRIA) for detection of JC virus-specific IgM. J Virol Methods 1992;40:95-105.  Back to cited text no. 13
    
14.
Maderazo DG, Ward PA, Woronick CL, Quintiliani R. Partial characterization of a cell-directed inhibitor of leukotaxis in human serum. J Lab Clin Med 1977;89:190-9.  Back to cited text no. 14
    
15.
Hirsch HH, Knowles W, Dickenmann M, et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med 2002;347:488-96.  Back to cited text no. 15
    
16.
Randhawa PS, Finkelstein S, Scantlebury V, et al. Human polyoma virus-associated interstitial nephritis in the allograft kidney. Transplantation 1999;67:103-9.  Back to cited text no. 16
    
17.
Trofe J, Roy-Chaudhury P, Gordon J, et al. Outcomes of patients with rejection postpolyomavirus nephropathy. Transplant Proc 2005;37:942-4.  Back to cited text no. 17
    
18.
Ding R, Medeiros M, Dadhania D, et al. Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. Transplantation 2002 ;74: 987-94.  Back to cited text no. 18
    
19.
Brennan DC, Agha I, Bohl DL, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005;5:582-94.  Back to cited text no. 19
    
20.
Nickeleit V, Klimkait T, Binet IF, et al. Testing for polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy. N Engl J Med 2000; 342:1309-15.  Back to cited text no. 20
    
21.
Barri YM, Ahmad I, Ketel BL, et al. Polyoma viral infection in renal transplantation: The role of immunosuppressive therapy. Clin Transplant 2001;15:240-6.  Back to cited text no. 21
    
22.
Howell DN, Smith SR, Butterly DW, et al. Diagnosis and management of BK polyo-mavirus interstitial nephritis in renal transplant recipients. Transplantation 1999;68:1279-88.  Back to cited text no. 22
    
23.
Ramos E, Drachenberg CB, Papadimitriou JC, et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol 2002;13:2145-51.  Back to cited text no. 23
    
24.
Trofe J, Cavallo T, First MR, et al. Polyo-mavirus in kidney and kidney-pancreas transplantation: A defined protocol for immunosuppression reduction and histologic monitoring. Transplant Proc 2002;34:1788-9.  Back to cited text no. 24
    
25.
Casadei DH, del C Rial M, Opelz G, et al. A randomized and prospective study comparing treatment with high-dose intravenous immuno-globulin with monoclonal antibodies for rescue of kidney grafts with steroid-resistant rejection. Transplantation 2001;71:53-8.  Back to cited text no. 25
    
26.
Daphnis E, Stylianou K, Alexandrakis M, et al. Acute renal failure, translocational hypo-natremia and hyperkalemia following intravenous immunoglobulin therapy. Nephron Clin Pract 2007;106:c143-8.  Back to cited text no. 26
    
27.
Haskin JA, Warner DJ, Blank DU. Acute renal failure after large doses of intravenous immune globulin. Ann Pharmacother 1999;33:800-3.  Back to cited text no. 27
    
28.
Itkin YM, Trujillo TC. Intravenous immuno-globulin-associated acute renal failure: Case series and literature review. Pharmacotherapy 2005;25:886-92.  Back to cited text no. 28
    
29.
Katz U, Achiron A, Sherer Y, Shoenfeld Y. Safety of intravenous immunoglobulin (IVIG) therapy. Autoimmun Rev 2007;6:257-9.  Back to cited text no. 29
    
30.
Lakshmanadoss U, Balakrishnan E, DiSalle MR. Sucrose nephropathy following IV immuno-globulin. J Basic Clin Pharm 2010;1:125-7.  Back to cited text no. 30
    
31.
Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Transfus Med Rev 2003;17:241-51.  Back to cited text no. 31
    
32.
Ziedan A, Bhandari S. Protocol and baseline data for a prospective open-label explorative randomized single-center comparative study to determine the effects of various intravenous iron preparations on markers of oxidative stress and kidney injury in chronic kidney disease (IRON-CKD). Trials 2019;20:194.  Back to cited text no. 32
    
33.
Chacko B, John GT, Balakrishnan N, Kirubakaran MG, Jacob CK. Osmotic nephro-pathy resulting from maltose-based intravenous immunoglobulin therapy. Ren Fail 2006;28:193-5.  Back to cited text no. 33
    
34.
Fukuda M. Evaluation and clinical significance of circulating immune complexes after renal transplantation. Transplantation 1983;36:155-60.  Back to cited text no. 34
    
35.
Bayati A, Hellberg O, Odlind B, Wolgast M. Prevention of ischaemic acute renal failure with superoxide dismutase and sucrose. Acta Physiol Scand 1987;130:367-72.  Back to cited text no. 35
    
36.
Dorman HR, Sondheimer JH, Cadnapaphornchai P. Mannitol-induced acute renal failure. Medicine (Baltimore) 1990;69:153-9.  Back to cited text no. 36
    
37.
Loyher ML, Mutin M, Woo SK, Kwon HM, Tappaz ML. Transcription factor tonicity-responsive enhancer-binding protein (TonEBP) which transactivates osmoprotective genes is expressed and upregulated following acute systemic hypertonicity in neurons in brain. Neuroscience 2004;124:89-104.  Back to cited text no. 37
    
38.
Yordy MR, Bowen JW. Na, K-ATPase expression and cell volume during hypertonic stress in human renal cells. Kidney Int 1993;43:940-8.  Back to cited text no. 38
    
39.
Agarwal R, Vasavada N, Sachs NG, Chase S. Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Kidney Int 2004;65:2279-89.  Back to cited text no. 39
    
40.
Angeli P, Scaglione F. Nephrotoxicity of intravenous immunoglobulin in the setting of liver transplantation or HBV-related cirrhosis: An undervalued topic. Minerva Gastroenterol Dietol 2008;54:259-75.  Back to cited text no. 40
    
41.
Bishu K, Agarwal R. Acute injury with intravenous iron and concerns regarding long-term safety. Clin J Am Soc Nephrol 2006;1 Suppl 1:S19-23.  Back to cited text no. 41
    
42.
Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst Pharm 2005;62:S5-11.  Back to cited text no. 42
    
43.
Shah S, Vervan M. Use of i.v. Immune globulin and occurrence of associated acute renal failure and thrombosis. Am J Health Syst Pharm 2005;62:720-5.  Back to cited text no. 43
    
44.
Winward DB, Brophy MT. Acute renal failure after administration of intravenous immuno-globulin: Review of the literature and case report. Pharmacotherapy 1995;15:765-72.  Back to cited text no. 44
    
45.
Renjen PN, Ahamed K, Kumar A. Sucrose nephropathy “acute renal failure caused by intravenous immunoglobulin therapy”. J Assoc Physicians India 2004;52:840-1.  Back to cited text no. 45
    
46.
Zhang R, Szerlip HM. Reemergence of sucrose nephropathy: Acute renal failure caused by high-dose intravenous immune globulin therapy. South Med J 2000;93:901-4.  Back to cited text no. 46
    
47.
Moulis G, Sailler L, Sommet A, Lapeyre-Mestre M, Montastruc JL; French Association of Regional Pharmacovigilance Centers. Exposure to inhibitors of the renin-angiotensin system is a major independent risk factor for acute renal failure induced by sucrose-containing intravenous immunoglobulins: A case-control study. Pharmacoepidemiol Drug Saf 2012;21:314-9.  Back to cited text no. 47
    
48.
Ahmad N, Hostert L, Pratt JR, Billar KJ, Potts DJ, Lodge JP. A pathophysiologic study of the kidney tubule to optimize organ preservation solutions. Kidney Int 2004;66:77-90.  Back to cited text no. 48
    
49.
Ahsan N, Palmer BF, Wheeler D, Greenlee RG Jr., Toto RD. Intravenous immunoglobulin-induced osmotic nephrosis. Arch Intern Med 1994;154:1985-7.  Back to cited text no. 49
    
50.
Dickenmann M, Oettl T, Mihatsch MJ. Osmotic nephrosis: Acute kidney injury with accumulation of proximal tubular lysosomes due to administration of exogenous solutes. Am J Kidney Dis 2008;51:491-503.  Back to cited text no. 50
    
51.
Abed M, Balasaheb S, Towhid ST, Daniel C, Amann K, Lang F. Adhesion of annexin 7 deficient erythrocytes to endothelial cells. PLoS One 2013;8:e56650.  Back to cited text no. 51
    
52.
Andrews PM, Bates SB. Evaluation of a flushing solution designed to protect kidneys from in situ ischemia. Am J Kidney Dis 1985;6:53-8.  Back to cited text no. 52
    
53.
Chapman SA, Gilkerson KL, Davin TD, Pritzker MR. Acute renal failure and intravenous immune globulin: Occurs with sucrose-stabilized, but not with D-sorbitol-stabilized, formulation. Ann Pharmacother 2004;38:2059-67.  Back to cited text no. 53
    
54.
Perazella MA, Cayco AV. Acute renal failure and intravenous immune globulin: Sucrose nephropathy in disguise? Am J Ther 1998;5: 399-403.  Back to cited text no. 54
    
55.
Tortorici MA, Duffy D, Evans R, et al. Pharmacokinetics and safety of CSL112 (Apolipoprotein A-I [Human]) in adults with moderate renal impairment and normal renal function. Clin Pharmacol Drug Dev 2018; Sep. 21  Back to cited text no. 55
    
56.
Cheng MJ, Christmas C. Special considerations with the use of intravenous immuno-globulin in older persons. Drugs Aging 2011;28:729-36.  Back to cited text no. 56
    
57.
Luque Y, Anglicheau D, Rabant M, et al. Renal safety of high-dose, sucrose-free intravenous immunoglobulin in kidney transplant recipients: An observational study. Transpl Int 2016;29:1205-15.  Back to cited text no. 57
    

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Correspondence Address:
Issa Al Salmi
Department of Renal Medicine, The Royal Hospital, PO Box. 1331, Code 111, Muscat
Oman
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DOI: 10.4103/1319-2442.261361

PMID: 31249243

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