The effect of APOL1 risk variants on emergent outcomes in kidney disorders: A meta-analysis of individual participant data

Keywords: Apolipoprotein L1, graft failure, hemodialysis, kidney disease, renal risk variants.

Abstract

Abstract. Kidney diseases associated with APOL1 polymorphisms are human immunodeficiency virus-associated nephropathy, idiopathic focal segmental glomerulosclerosis, hypertension-attributed chronic kidney disease, lupus nephritis and sickle cell nephropathy. This research aimed to investigate the risk of genetic variants on disease contribution.

Methods. In this individual participant data meta-analysis, eighteen patients with kidney dysfunction and at risk of APOL1 genotype were investigated. Clinical features, laboratory data at initial presentation, management and outcomes were collected. The paper has written based on searching PubMed Central and Google Scholar to identify potentially relevant articles. Median, percentage, mean ± standard deviation (SD), two-tailed t and chi-square tests were used for statistical analyses. Moreover, relative risk, odds ratio for statistical analyses were used.

Results: The average age of patients at the time of diagnosis in APOL1-associated kidney disorders was 41.09 ± 20.63 years (ranging from 8 years to 70 years). Relative risk for kidney failure and persistent hemodialysis therapy in APOL1-associated nephropathy patients with renal risk variants (RRVs) were assessed 1.13 and odds ratio of 1.5 with 95% CI of 0.08-26.86 and the value of 0.0764 by chi-square test but there was no significant statistical result in this research (p-value of 0.782). The relative risk for patients of allograft failure with RRVs was assessed 1,0 odds ratio of 1,0 95% CI of 0.06-15.99 and p-value of 0.81.

Conclusion: The present study revealed the risk and odds of APOL1 gene effect on the onset of kidney failure with replacement therapy in patients at risk of APOL1 genotype but results were not significant statistically. Future clinical research is required for investigating APOL1 gene effect on non-African ancestry.

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References

Palmer ND, Freedman BL. APOL1 and progression of nondiabetic nephropathy. J Am Soc Nephrol. 2013;24(9):1344-1346. doi: 10.1681/ASN.2013060589.

Anigilaje EA. A Putative Role of Apolipoprotein L1 Polymorphism in Renal Parenchymal Scarring Following Febrile Urinary Tract Infection in Nigerian Under-Five Children: Proposal for a Case-Control Association Study. JMIR Res Protoc. 2018;7(6):e156. doi:10.2196/resprot.9514

Kronenberg F. HDL in CKD—The Devil Is in the Detail. J Am Soc Nephrol. 2018; 29(5): 1356–1371. doi: 10.1681/ASN.2017070798.

Ross MJ. New Insights into APOL1 and Kidney Disease in African Children and Brazilians Living With End-Stage Kidney Disease. Kidney Int Rep. 2019;4(7):908-910. Published 2019 Apr 29. doi:10.1016/j.ekir.2019.04.015

Katsuma A, Yamakawa T, Nakada Y, Yamamota I, Yokoo T. Histopathologic findings in transplanted kidney. Renal Replacement Ther. 2017;3(6):1-18. doi: 10.1186/s41100-016-0089-0.

Steenkamp DW, Alexanian SM, Sternthal E. Approach to the patient with atypical diabetes. CMAJ. 2014;186(9):678-684. doi:10.1503/cmaj.130185

Rysz J, Gluba-Brzózka A, Rysz-Górzyńska M, Franczyk B. The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease. Int J Mol Sci. 2020;21(2):601. doi:10.3390/ijms21020601

Husain SA, Chang JH. Searching for Second Hits for the Development of APOL1-Associated Kidney Disease. Kidney Int Rep. 2019;4(7):911-913. Published 2019 May 17. doi:10.1016/j.ekir.2019.05.007

Mazaheri M, Assadi F. Simplified algorithm for evaluation of proteinuria in clinical practice: How should a clinician approach? Int J Prev Med 2019;10 (35):1-5.doi: 10.4103/ijpvm.IJPVM_557_18.

Cheung MK, Wong FY, Liang J. Assessment and management of diabetic albuminuria. Hong Kong Pract 2011; 33:14-19.

Eknoyan G, Lameire N, Eckcardt KU. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl 2012; 2 (5):343-46. doi: 10.1038/kisup.2012.1.

Yang CY, Chen FA, Chen CF, et al. Diagnostic Accuracy of Urine Protein/Creatinine Ratio Is Influenced by Urine Concentration. PLoS One. 2015;10(9):e0137460. doi:10.1371/journal.pone.0137460

Kofman T, Audard V, Narjoz C, Gribouval O, Matignon M, Leibler C, Desvaux D, Lang P, Grimbert P. APOL1 polymorphisms and development of CKD in an identical twin donor and recipient pair. Am J Kidney Dis. 2014 May;63(5):816-9. doi: 10.1053/j.ajkd.2013.12.014.

Kofman T, Narjoz C, Raimbourg Q, Loriot MA, Karras A, Roland M, Hill G, Jacquot C, Nochy D, Thervet E. Collapsing glomerulopathy associated lupus in a black female with homozygous APOL1 mutation. Lupus. 2012 Nov;21(13):1459-62. doi: 10.1177/0961203312460114.

Khalighi MA, Gallan AJ, Chang A, Meehan SM. Collapsing Glomerulopathy in Lambda Light Chain Amyloidosis: A Report of 2 Cases. Am J Kidney Dis. 2018;72(4):612-616. doi:10.1053/j.ajkd.2018.04.009

Shah PB, Cooper JE, Lucia MS, Boils C, Larsen CP, Wiseman AC. APOL1 Polymorphisms in a Deceased Donor and Early Presentation of Collapsing Glomerulopathy and Focal Segmental Glomerulosclerosis in Two Recipients. Am J Transplant. 2016;16(6):1923-1927. doi:10.1111/ajt.13748.

Zwang NA, Shetty A, Sustento-Reodica N, Gordon EJ, Leventhal J, Gallon L, Friedewald JJ. APOL1-Associated End-Stage Renal Disease in a Living Kidney Transplant Donor. Am J Transplant. 2016;16(12):3568-3572. doi: 10.1111/ajt.14035.  

Chang JH, Husain SA, Santoriello D, Stokes MB, Miles CD, Foster KW, Li Y, Dale LA, Crew RJ, Cohen DJ, Kiryluk K, Gharavi AG, Mohan S. Donor's APOL1 Risk Genotype and "Second Hits" Associated With De Novo Collapsing Glomerulopathy in Deceased Donor Kidney Transplant Recipients: A Report of 5 Cases. Am J Kidney Dis. 2019 Jan;73(1):134-139. doi: 10.1053/j.ajkd.2018.05.008.

Watanabe A, Feltran LS, Sampson MG. Genetics of Nephrotic Syndrome Presenting in Childhood: Core Curriculum 2019. Am J Kidney Dis. 2019;74(4):549-557. doi:10.1053/j.ajkd.2019.01.033

Besse W, Mansour S, Jatwani K, Nast CC, Brewster UC. Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation. BMC Nephrol. 2016;17(1):125. doi:10.1186/s12882-016-0330-7.

Attias P, Moktefi A, Matignon M, et al. Monotypic plasma cell interstitial nephritis as the only clinical manifestation in a patient with previously undiagnosed indolent multiple myeloma: A case report. Medicine (Baltimore). 2016;95(31):e4391. doi:10.1097/MD.0000000000004391

Tillman EM, Skaar TC, Eadon MT. Nephrotoxicity in a Patient With Inadequate Pain Control: Potential Role of Pharmacogenetic Testing for Cytochrome P450 2D6 and Apolipoprotein L1. Front Pharmacol. 2020;10:1511. doi:10.3389/fphar.2019.01511

Abid Q, Best Rocha A, Larsen CP, Schulert G, Marsh R, Yasin S, Patty-Resk C, Valentini RP, Adams M, Baracco R. APOL1-Associated Collapsing Focal Segmental Glomerulosclerosis in a Patient With Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset in Infancy (SAVI). Am J Kidney Dis. 2020;75(2):287-290. doi: 10.1053/j.ajkd.2019.07.010.

Larsen CP, Bourne TD, Wilson JD, Saqqa O, Sharshir MA. Collapsing Glomerulopathy in a Patient With Coronavirus Disease 2019 (COVID-19). Kidney Int Rep. 2020 Apr 9;5(6):935–9. doi: 10.1016/j.ekir.2020.04.002.

Sepahi MA, Bhaskar L, Tolouian A, Tolouian R. Apolipoprotein L1 associated nephropathy; an overview. J Renal Inj Prev. 2019;8(4):311-5. doi: 10.15171/jrip.2019.57.

Aeddula NR, Bardhan M, Baradhi KM. Sickle Cell Nephropathy. [Updated 2020 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526017/

 Reghine ÉL, Foresto RD, Kirsztajn GM. HIV-related nephropathy: new aspects of an old paradigm. Rev Assoc Med Bras (1992). 2020;66Suppl 1(Suppl 1):s75-s81. doi:10.1590/1806-9282.66.S1.75

Kopp JB, Winkler CA. Genetic testing for APOL1 genetic variants in clinical practice: Finally starting to arrive. Clin J Am Soc Nephrol. 2020; 15:126-128. doi: 10.2215/CJN.01810219.

Franceschini N, Frick A, Kopp JB. Genetic testing in clinical settings.Am J Kidney Dis. 2018;72 (4):569-81. doi: 10.1053/j.ajkd.2018.02.351.

Kanji Z, Powe CE, Wenger JB, Huang C, Ankers E, Sullivan DA, et al. Genetic variation in APOL1 associates with younger age at hemodialysis initiation. J Am Soc Nephrol. 2011;22:2091-7. doi: 10.1681/ASN.2010121234.

Doshi MD, Ortigosa-Goggins M, Garg AX, Li L, Poggio ED, Winkler CA, et al. APOL1 genotype and renal function of black living donors. J Am Soc Nephrol. 2018; 29:1309-16. doi: 10.1681/ASN.2017060658.

Freedman BI, Moxey-Mims M. The APOL1 long-term kidney transplantation outcomes network-APOLLO. Clin J Am Soc Nephrol. 2018;13:940-942. doi: 10.2215/CJN.01510218.

Marin EP, Cohen E, Dahl N. Clinical applications of genetic discoveries in kidney transplantation: A review. Kidney 360. 2020;1(4):300-305; doi: 10.34067/KID.0000312019.

Wei J, Johansen KL, McCullouch CE, Lipkowitz M, Weir M, Lin F et al. Association between APOL1 genotype and need for kidney replacement therapy in patients without diabetes: Does age matter? Am J Kidney Dis. 2020; 75(2):294-5. doi: 10.1053/j.ajkd.2019.08.01.

Masekoameng T, Wonkam A. Sickle cell trait and targeted genomic variants in chronic kidney disease an African cohort. Dissertation; 2019. 

Rikhtegar E, Ardalan MR. Evaluation frequency of APOL1 genes variations (G1 and G2) in ESRD patients residing in northwest of Iran. Med. D. Dissertation. Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; 2019. Available from: http://dspace.tbzmed.ac.ir:8080/xmlui/handle/123456789/61268. Accessed: January 21, 2020. doi: 10.15171/jrip.2019.37.

Reeves-Daniel AM, Depalma JA, Bleyer AJ, Rocco MV, Murea M, Adams PL, et al. The APOL1 gene and allograft survival after kidney transplantation. Am J Transplant. 2011; 11(5):1025-30. doi: 10.1111/j.1600-6143.2011.03513.x.

Cohen DM, Mittalhenkle A, Scott DL, Young CJ, Norman DJ. African American living-kidney donors should be screened for APOL1 risk alleles. Transplantation. 2011;92(7):722-725. doi:10.1097/TP.0b013e31822eec39

Bikbov B. R Open Source Programming Code for Calculation of the Kidney Donor Profile Index and Kidney Donor Risk Index. Kidney Dis (Basel). 2018;4(4):269-272. doi:10.1159/000492427

Ma L, Ainsworth HC, Snipes JA, Murea M, Choi YA, Langefeld CD, Parks JS, Bharadwaj MS, Chou JW, Hemal AK, Petrovic S, Craddock AL, Cheng D, Hawkins GA, Miller LD, Hicks PJ, Saleem MA, Divers J, Molina AJA, Freedman BI. APOL1 Kidney-Risk Variants Induce Mitochondrial Fission. Kidney Int Rep. 2020;5(6):891-904. doi: 10.1016/j.ekir.2020.03.020.

Paranjpe I, Chaudhary K, Paranjpe M, O'Hagan R, Manna S, Jaladanki S, Kapoor A, Horowitz C, DeFelice N, Cooper R, Glicksberg B, Bottinger EP, Just AC, Nadkarni GN. Association of APOL1 Risk Genotype and Air Pollution for Kidney Disease. Clin J Am Soc Nephrol. 2020;15(3):401-403. doi: 10.2215/CJN.11921019.


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Published
2020-07-05
How to Cite
Amiri, F. S. (2020). The effect of APOL1 risk variants on emergent outcomes in kidney disorders: A meta-analysis of individual participant data. Ukrainian Journal of Nephrology and Dialysis, (3(67), 42-59. https://doi.org/10.31450/ukrjnd.3(67).2020.07