Abstract
Chronic Kidney Disease (CKD) continues to increase globally. In a New Zealand, a community based prevalence study, Pacific peoples had a 2.56 fold higher risk of CKD, controlling for diabetes. Likewise Pacific people (predominantly Samoan) in NZ with a family history of ESKD have an increased risk of nephropathy independent of diabetes, suggesting a genetic component. Recent studies have identified the CREBRF p.Arg457Gln gene variant prevalent among Samoans, which predisposes against obesity, yet protects against diabetes, yet fails to show any association with CKD. This cross sectional pilot study aimed to identify whether an association between the CREBRF p.Arg457Gln gene and early signs of kidney damage, as defined by proteinuria, as a way of identifying those individuals at potential risk for progressive CKD.
175 Samoans from a local church community in Upolu Samoa, were recruited for the study. They underwent screening for blood pressure, urine dipstick and point of care testing for urinary albumin creatinine ratio (UACR) serum creatinine and eGFR (CKD-EPI), and HbA1c. 20 were excluded due to newly identified diabetes (HbA1c >50mmol/mol) and/or serum creatinine >150 mmol/L. 141 blood samples were collected in the end for genetic analysis.
155 participants (83males) were included, whose ages ranged from 20 -50 years. 64% of females and 33% males were either severely obese or morbidly obese according to BMI. 26% had normal renal function with no urinary abnormalities. 35% had dipstick positive proteinuria and an elevated urinary ACR. 62% of males had evidence of an impaired eGFR, 48% had stage 2 CKD and 15% eGFR<60ml/min/1.73m2. When corrected for BSA, 31% had an eGFR between 60 & 89 ml/min/1.73m2. 68% of females had an impaired eGFR, and following correction for BSA 52% still had impaired eGFR. 33% of females and 16% of males were hypertensive. Proteinuria was not associated with hypertension, but was associated with increasing obesity. 44% of those morbidly obese had proteinuria.
Of the 141 with blood samples for testing for the CREBRF p.Arg457Gln gene variant, , no statistical significant findings were detected. After adjusting for sex, those in the AA/ AG genotype group had an increased risk of proteinuria (RRR 1.59 (95% CI 0.78-3.21, p value 0.20)), obesity (1.84 (95% CI 0.85-3.99, p value 0.12)), compared to those in the GG genotype.
This Samoan community survey identified that 34% of the sample had positive proteinuria, and 47% were either severely or morbidly obese. When comparing with the CREBRF p.Arg457Gln gene variant, there was a 59% increased risk of proteinuria, and 84% increased obesity risk among those with the A allele, compared with those homozygous for G allele. The findings were not significant due to two main possibilities, either such an association does not exist or our pilot study was insufficiently powered to detect a true difference. This study needs to be undertaken in a larger and more representative sample size to explore this potential association.