Introduction: An increased renal resistive index (RRI) and proteinuria can predict an estimated glomerular filtration rate (eGFR) decline in patients with chronic kidney disease (CKD) of various causes. This study hypothesized that the RRI and proteinuria interact to determine disease progression in patients with CKDs of unknown origin. Patients and Methods: One hundred and fifty six patients (age 76.0 ± 8.1 years, 63.5% males) were analyzed for anthropometric, kidney morphology, blood pressure, 24 h urinary protein excretion, and RRI. The CKD-EPI equation was used to calculate the eGFR at baseline and after a two-year follow-up. Patients with an elevated (≥0.80) or normal (<0.80) RRI and significant (≥150 mg/day) or physiological (<150 mg/day) proteinuria were evaluated for the likelihood of at least a 30% drop in the eGFR or the onset of end-stage kidney disease (endpoint). Results: Hypertension and diabetes were the predominant cardiovascular risk factors (90.4%). Fifty patients (32%) met the endpoint. Elevated RRIs (odds ratio, OR, 4.28; 95% confidence interval, CI, 1.82-10.6; p = 0.001) and significant proteinuria (OR 3.59, 95% CI 1.59-8.48, p = 0.003) were independent predictors of the endpoint in a multivariate logistic model. Patients with an elevated RRI and significant proteinuria were more likely to meet the endpoint (R1P1: 65.2%) compared to those with only proteinuria (R0P1: 39.5%, p = 0.043) or both normal factors (R0P0: 10.9%, p < 0.001) but not to those with only an elevated RRI (R1P0: 42.3%, p = 0.094). Continuous RRIs (partial correlation r = -0.245, p < 0.001) and 24 h urinary protein excretion (partial r = -0.226, p = 0.003) were inversely and independently correlated with eGFR% change. R1P1 showed a higher eGFR% reduction (-38.0% ± 20.4%) compared to R0P1 (-25.3% ± 19.0%, p = 0.043) and R0P0 (-8.8% ± 25.1%, p < 0.001) but not to R1P0 (-29.6% ± 21.0%, p = 0.192). Conclusions: An increased RRI and proteinuria were independent predictors of disease progression. When interaction was considered, the negative effect of an elevated RRI on CKD progression was evident in both proteinuric and non-proteinuric patients, whereas the negative effect of proteinuria on disease progression was only significant in patients with no elevated RRIs.
Keywords: atherosclerosis; cardiovascular risk; glomerular filtration rate; interaction analysis; kidney function; urinary protein excretion.