ALTERED PURINE METABOLITES AMONG A NICARAGUAN POPULATION WITH ACUTE KIDNEY INJURY AND HIGH RISK OF MESOAMERICAN NEPHROPATHY

E-Poster

https://storage.unitedwebnetwork.com/files/1099/042e10c5ab9a9706ac48088b090fd58a.pdf

Abstract Title

First Name *

Diane

Last Name *

Santos

Co-author 1

Nathan Raines nraines@bidmc.harvard.edu Beth Israel Deaconess Medical Center Division of Nephrology, Department of Medicine Boston

Co-author 2

Dominic Leone nleone@bu.edu Boston University School of Public Health Department of Epidemiology Boston

Co-author 3

Juan Amador juanjoseamador3011@gmail.com Boston University School of Public Health Department of Epidemiology Boston

Co-author 4

Damaris Lopez-Pilarte dalp1342@gmail.com Boston University School of Public Health Department of Epidemiology Boston

Co-author 5

Oriana Ramirez oriana.ramirez@isglobal.org Barcelona Institute for Global Health Global Health Barcelona

Co-author 6

Iris Delgado idelgado@bu.edu Boston University School of Public Health Department of Epidemiology Boston

Co-author 7

Calum Tattersfield ctatters@bidmc.harvard.edu Beth Israel Deaconess Medical Center Division of Nephrology, Department of Medicine Boston

Co-author 8

Jessica Leibler jleibler@bu.edu Boston University School of Public Health Department of Environmental Health Boston

Co-author 9

John Asara jasara@bidmc.harvard.edu Beth Israel Deaconess Medical Center Division of Signal Transduction Boston

Co-author 10

Madeleine K Scammell mls@bu.edu Boston University School of Public Health Department of Epidemiology Boston

Co-author 11

Daniel Brooks danbrook@bu.edu Boston University School of Public Health Department of Epidemiology Boston

Co-author 12

David Friedman dfriedma@bidmc.harvard.edu Beth Israel Deaconess Medical Center Division of Nephrology, Department of Medicine Boston

Co-author 13

Co-author 14

Co-author 15

Introduction

Mesoamerican Nephropathy (MeN) is an epidemic of chronic kidney disease (CKD) in Mesoamerica that primarily affects young men working in sugar cane agriculture. The etiology of MeN remains unclear and may be linked to recurrent acute kidney injury (AKI) leading to CKD driven by heat stress. Individuals with MeN commonly present with hyperuricemia. Decreased urine levels of the purine breakdown metabolites inosine, guanosine, and adenosine are associated with other forms of AKI and are of particular interest in the context of MeN given their subsequent breakdown product uric acid is characteristically high in MeN.

Methods

In this paired cross-sectional study, we compared serum uric acid and urine inosine, guanosine, and adenosine between 45 sugar cane workers with AKI (AKI) and 45 sugarcane workers without AKI (NoKI) matched 1:1 for age and job features. Urine metabolites were identified using liquid chromatography-tandem mass spectrometry. We also analyzed in vitro transcriptomic changes associated with purine catabolism among isolated renal proximal tubule epithelial cells exposed to temperatures of 39°C for 2 hours.

Results

Serum uric acid levels were significantly higher in the AKI than NoKI groups (median 7.54 [IQR 6.71-9] vs 5.39[IQR 4.97-6.3], p= 4.39E-8), while urine uric acid did not differ between groups (P>0.8, Figure 1). Urine inosine and adenosine were significantly lower in the AKI than NoKI group (p< 0.03), but guanosine did not differ between groups (p> 0.1). No differential transcriptome expression was observed among enzymes related to purine catabolism in renal proximal tubular cells exposed in vitro to heat.

Figure 1: Increased serum uric acid (UA), decreased renoprotective purines, and unchanged urine UA in the AKI group vs NoAKI group indicates increased production of UA.

Conclusions

Patterns of metabolites related to purine breakdown differentiate individuals with AKI in a population at risk for MeN and are consistent with patterns seen in other forms of AKI. In vitro analysis of related catabolic enzymes in renal proximal tubular cells did not reveal any changes associated with heat exposure but may not accurately model whole organism physiology under heat stress. Further research should explore in vivo transcriptomic features of AKI arising in populations at risk for MeN.

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