Urinary Phenotyping in Mesoamerican Nephropathy

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Background: Mesoamerican nephropathy (MN) is a leading cause of CKD in Central America. Studies suggest an underlying tubulointerstitial nephritis with coexisting electrolyte wasting in affected individuals. The Colt-MRC cohort is a community-based study in Nicaragua, which recruited individuals at risk of MN, measuring serum creatinine (Cr) and collecting questionnaire data and biosamples at annual study visits for 7 years. In this sub-study, we aimed to compare the urinary phenotype of individuals from the cohort who develop early kidney injury (EKI) - defined by a significant decline in eGFR from a healthy baseline, with healthy controls (HC) and those with established MN (eMN). Methods: We compared concurrent serum and urine samples from EKI cases pre and post decline in eGFR to two samples from HC matched for age, sex, community and study visit, and samples from two consecutive study visits from un-matched eMN participants (Table 1). All serum and urine samples were tested for: Cr, Na, K, PO4 & Mg, and fractional excretions (FE) of electrolytes were calculated. Urine was also tested for MCP-1 (ELISA) and corrected for urine Cr. Data were analysed using mixed-effects modelling. Results: FE of all electrolytes were raised in the eMN group, but serum Na and Mg were lower. MCP1 was significantly raised in cases in the visit post EKI compared to pre-EKI, HC and eMN. See Table 1. Conclusions: Urinary MCP1 levels are higher in cases after incident EKI versus HC and eMN, suggesting acute inflammation at the onset of MN that subsequently subsides. Participants with eMN had raised FE of all measured electrolytes, a common feature of CKD due to decreased nephron mass. However, they also had lower serum Na and Mg, with 50% exhibiting clinical hypomagnesemia, which is not a feature of CKD and suggests ongoing impairment of tubular function in established MN. Funding: Private Foundation Support, Government Support - Non-U.S. - Mean values HC (n=43) EKI (n=43) eMN (n=21) Visit 1 Visit 2 Visit 1 (pre-decline) Visit 2 (post-decline) Visit 1 Visit 2 No. Males 36 (84%) 36 (84%) 21 (100%) Age (years) 25 26 25 26 26.5 27.5 eGFR ml/min/1.72m2 118 114 111 84.5 46.5 46 Serum PO4 (mmol/L) 1.14 1.2 1.21 1.2 1.2 1.15 FE PO4 (%) 7.2 7.2 8.4 8.5 14.5* 12.9* Serum Mg (mmol/L) 0.82 0.82 0.8 0.8 0.7* 0.7* FE Mg (%) 3.4 3.8 3.9 4.9 11.7* 12.4* No. Mg <0.7mmol/L 1 (2.3%) 2 (4.6%) 4 (9.2%) 2 (4.6%) 10 (48%) 11 (52%) Serum Na (mmol/L) 140.6 140.1 140.2 140.2 139.4** 138.4** FE Na (%) 0.9 0.9 1.1 1.1 2.1* 2.1* Serum K (mmol/L) 4.5 4.5 4.3 4.3 4.4 4.3 FE K (%) 7.8 8.7 8.5 10.3 17.8* 18.6* MCP-1/Crt (ng/mmol) 4.8 3.6 5 11.7˜ 6.1 9.2 *p<0.001**p<0.05 eMN vs HC & EKI˜p<0.05 post-decline EKI vs pre-decline, HC and eMN.

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