Mesoamerican Nephropathy and C3 Glomerulonephritis Leading to Kidney Failure in a Young Male from Guatemala

Introduction: Mesoamerican nephropathy (MeN) refers to nonproteinuric CKD that presents in young, agricultural workers predominantly in Central America, in the absence of common etiologies for CKD. C3 glomerulopathy that includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are glomerular disorders triggered by dysregulation of the alternative complement pathway. We present a rare case of a young Central-American male with kidney biopsy features suggestive of C3GN and MeN. Case Description: A 28-year-old Hispanic male without significant medical history presented with reduced urine output and uremic symptoms. He worked on a sugarcane ranch in Guatemala prior to moving to the US. He did not take any medications. Physical exam was unremarkable. Workup revealed BUN 116 mg/dL, Cr 11 mg/dL, Sr albumin 4 g/dL, and UPCR 5700 mg/g. Urinalysis revealed acanthocytes and RBC casts. C3 level was low at 80 mg/dL; C4 level was normal. Comprehensive GN workup was negative; infection was ruled out. Kidney USG revealed bilateral shrunken kidneys. Kidney biopsy revealed 13/21 globally sclerosed glomeruli. The interstitium contained moderate inflammatory infiltrates, mainly monocytes, and IFTA was 60%. IF revealed granular and smudgy C3 (3+) along the capillaries and mesangium; rest of immunoreactants were negative. Functional C3G panel revealed elevated C5 and C5b-9 levels. Genetic C3G panel was negative. Given evidence of advanced chronicity features, immunosuppression was not offered and dialysis was started. Discussion: C3GN affecting younger patients usually are mediated by genetic abnormalities of the alternative complement pathway. Our patient had a negative genetic C3G panel highlighting the fact that his C3GN is truly not mediated by a genetic abnormality or that he has a genetic abnormality that our current assays are not detecting (unlikely given the significant advancements made in this area). The co-existing severe tubulointerstitial disease likely points to a concomitant MeN given his place of origin and occupation. It is more likely that the patient had 2 different pathologies affecting the glomeruli (C3GN) and tubulointerstitium (MeN).