The Effect of Hyperfiltration on Kidney Function in Living Donor Kidney Transplantation: A Prospective Cohort Study

Maruhum Bonar H. Marbun, Endang Susalit, Diana Aulia, Jacub Pandelaki, Saptawati Bardosono, Bambang Purwanto

Abstract


Background: living kidney donation is a safe medical procedure. Kidney function after donation is crucial for donors’ health and quality of life. Kidney hyperfiltration is a compensatory mechanism, which will preserve kidney function after unilateral nephrectomy. The number of studies regarding hyperfiltration in living kidney donors is limited. Our study aimed to explain kidney hyperfiltration mechanism and evaluate its effect on the kidney function within 30 days after surgery. Methods: our study was a prospective cohort study with 46 living-kidney donors participating in the study between April and December 2019. We evaluated main outcomes, the 30-day post-surgery kidney function, which was evaluated by calculating estimated glomerular filtration rate (eGFR) and Urinary Albumin to Creatinine Ratio (ACR). The subjects were categorized into two groups based on their 30-day outcomes, which were the adaptive (eGFR > 60 mL/min/1.73 m2 and/or ACR > 30 mg/g) and maladaptive (eGFR < 60 mL/min/1.73 m2 and/or ACR > 30 mg/g) groups. A series of evaluation including calculating the renal arterial resistive index (RI) and measuring urinary vascular endothelial growth factor (VEGF), neutrophil gelatinase-associated lipocalin (NGAL), and heparan sulfate (HS) levels were performed before surgery and serially until 30 days after surgery. Multivariate analysis with adjustments for confounding factors was done. Results: forty donors were included and mostly were female (67.5%). The average age and body mass index (BMI) were 45.85 (SD 9.74) years old and 24.36 (SD 3.73) kg/m2, respectively. Nineteen donors (47.5%) had maladaptive hyperfiltration outcomes. The hyperfiltration process was demonstrated by significant changes in renal arterial RI, urinary VEGF, NGAL, and HS levels (p<0.005). There was no significant difference regarding RI, urinary VEGF, NGAL, and HS levels between both groups. Several confounding factors (BMI over 25 kg/m2, familial relationship, age over 40 years old, and arterial stiffness) were significantly influenced by kidney hyperfiltration and outcomes (p<0.05). Conclusion: the hyperfiltration process does not affect the 30-day post-nephrectomy kidney function of the donors. Several other factors may influence the hyperfiltration process and kidney function. Further study is necessary to evaluate kidney function and its other related variables with a longer period of time study duration.


Keywords


Heparan Sulfate; Hyperfiltration; Living-Donor; Neutrophil Gelatinase-Associated Lipocalin; Resistive Index; Kidney Transplantation; Vascular Endothelial Growth Factor

References


Tonelli M, Wiebe N, Knoll G, et al. Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J transplant. 2011;11(10):2093-109.

Taminato M, Fram D, Grothe C, Pereira RRF, Belasco A, Barbosa D. Prevalence of infection in kidney transplantation from living versus deceased donor: systematic review and meta-analysis. Revista da Escola de Enfermagem da USP. 2015;49:502-7.

Gill JS, Tonelli M. Understanding rare adverse outcomes following living kidney donation. JAMA. 2014;311(6):577-9.

de Groot IB, Veen JIE, van der Boog PJ, et al. Difference in quality of life, fatigue and societal participation between living and deceased donor kidney transplant recipients. Clinical Transplant. 2013;27(4):E415-E23.

Mueller TF, Luyckx VA. The natural history of residual renal function in transplant donors. J Am Soc Nephrol. 2012;23(9):1462-6.

Choi KH, Yang SC, Joo DJ, et al. Clinical assessment of renal function stabilization after living donor nephrectomy. Transplantation Proceedings. 2012;44(10):2906-9.

Fehrman-Ekholm I, Nordén G, Lennerling A, et al. Incidence of end-stage renal disease among live kidney donors. Transplantation. 2006;82(12):1646-8.

Kwon HJ, Kim DH, Jang HR, et al. Predictive factors of renal adaptation after nephrectomy in kidney donors. Transplantation Proceedings. 2017;49(9):1999-2006.

Chen Z, Fang J, Li G, et al. Compensatory changes in the retained kidney after nephrectomy in a living related donor. Transplantation Proceedings. 2012;44(10):2901-5.

Lenihan CR, Busque S, Derby G, Blouch K, Myers BD, Tan JC. Longitudinal study of living kidney donor glomerular dynamics after nephrectomy. J Clin Invest. 2015;125(3):1311-8.

Nekouei S, Ahmadnia H, Abedi M, Alamolhodaee MH, Abedi MS. Resistive index of the remaining kidney in allograft kidney donors. Exp Clin Transplant. 2012;10(5):454-7.

Kuppe C, Rohlfs W, Grepl M, et al. Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures. Nephrology Dialysis Transplantation. 2018.

Schrijvers BF, Flyvbjerg A, Tilton RG, Rasch R, Lameire NH, De Vriese AS. Pathophysiological role of vascular endothelial growth factor in the remnant kidney. Nephron Experimental nephrology. 2005;101(1):e9-e15.

Singer E, Markó L, Paragas N, et al. Neutrophil gelatinase-associated lipocalin: pathophysiology and clinical applications. Acta physiologica (Oxford, England). 2013;207(4):663-72.

Stefanidis I, Heintz B, Stöcker G, Mrowka C, Sieberth H-G, Haubeck H-D. Association between heparan sulfate proteoglycan excretion and proteinuria after renal transplantation. J Am Soc Nephrol. 1996;7(12):2670-6.

Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13(1):9-22.

Chen J, Bhattacharya S, Sirota M, et al. Assessment of postdonation outcomes in US living kidney donors using publicly available data sets. JAMA. 2019;2(4):e191851-e.

Hart A, Smith J, Skeans M, et al. OPTN/SRTR 2018 Annual Data Report: Kidney. Am J Transplant. 2020;20:20-130.

Bloembergen WE, Port FK, Mauger EA, Briggs JP, Leichtman AB. Gender discrepancies in living related renal transplant donors and recipients. J Am Soc Nephrol. 1996;7(8):1139-44.

Lim JU, Lee JH, Kim JS, et al. Comparison of World Health Organization and Asia-Pacific body mass index classifications in COPD patients. Int J Chronic Obstruct Pulmonary Dis. 2017;12:2465.

Niemi M, Mandelbrot DA. The outcomes of living kidney donation from medically complex donors: Implications for the donor and the recipient. Curr Transplant Rep. 2014;1(1):1-9.

Fesler P, Mourad G, Cailar Gd, Ribstein J, Mimran A. Arterial stiffness: an independent determinant of adaptive glomerular hyperfiltration after kidney donation. Am J Physiol - Renal Physiol. 2015;308(6):F567-F71.

Yoon Y, Lee H, Na J, Han W. Prospective assessment of urinary NGAL in living kidney donors: toward understanding differences between chronic kidney diseases of surgical and medical origin. BJU Int. 2018.

Bohlouli A, Tarzamni MK, Zomorrodi A, Abdollahifard S, Hashemi B, Nezami N. Postnephrectomy changes in Doppler indexes of remnant kidney in unrelated kidney donors. Urol J. 2009;6(3):194-8.

Shokeir AA, Abubieh EA, Dawaba M, El-Azab M. Resistive index of the solitary kidney: a clinical study of normal values. J Urol. 2003;170(2):377-9.

Sigmon DH, Gonzalez-Feldman E, Cavasin MA, Potter DAL, Beierwaltes WH. Role of Nitric Oxide in the renal hemodynamic response to unilateral nephrectomy. J Am Soc Nephrol. 2004;15(6):1413-20.

Valdivielso JM, Pérez-Barriocanal F, García-Estañ J, López-Novoa JM. Role of nitric oxide in the early renal hemodynamic response after unilateral nephrectomy. Am J Physiol-Regulatory, Integr Compar Physiol. 1999;276(6):R1718-R23.

Molema G, Aird WC, editors. Vascular heterogeneity in the kidney. Seminars in nephrology. New York: Elsevier; 2012.

Ow CP, Ngo JP, Ullah MM, Hilliard LM, Evans RG. Renal hypoxia in kidney disease: cause or consequence? Acta Physiologica. 2018;222(4):e12999.

Kanellis J, Mudge SJ, Fraser S, Katerelos M, Power DA. Redistribution of cytoplasmic VEGF to the basolateral aspect of renal tubular cells in ischemia-reperfusion injury. Kidney Int. 2000;57(6):2445-56.

El Awad B, Kreft B, Wolber E-M, et al. Hypoxia and interleukin-1β stimulate vascular endothelial growth factor production in human proximal tubular cells. Kidney Int. 2000;58(1):43-50.

Flyvbjerg A, Schrijvers BF, De Vriese AS, Tilton RG, Rasch R. Compensatory glomerular growth after unilateral nephrectomy is VEGF dependent. Am J Physiol-Endocrinol Metabolism. 2002;283(2):E362-E6.

Yoon YE, Cho YI, Kim SY, et al. Plasma Neutrophil Gelatinase-associated Lipoprotein in living kidney and donors. Transplantation Proceedings. 2016;48(3):738-41.

Jeon HG, Lee SR, Joo DJ, et al. Predictors of kidney volume change and delayed kidney function recovery after donor nephrectomy. J Urol. 2010;184(3):1057-63.

Konno O, Nakamura Y, Yokoyama T, Kihara Y, Iwamoto H, Kawachi S, editors. Postoperative compensatory changes and blood flow parameter of the preserved kidney in elderly living related donors evaluated by Doppler ultrasonography. Transplantation proceedings; 2016: Elsevier.

Skrunes R, Svarstad E, Reisæter AV, Vikse BE. Familial clustering of ESRD in the Norwegian population. Clin J Am Soc Nephrol. 2014;9(10):1692-700.

Fallahzadeh MK, Jafari L, Roozbeh J, et al. Comparison of health status and quality of life of related versus paid unrelated living kidney donors. Am J Transplant. 2013;13(12):3210-4.

Chang AR, Zafar W, Grams ME. Kidney function in obesity—challenges in indexing and estimation. Advance Chronic Kidney Dis. 2018;25(1):31-40.


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