Kidney Week

Abstract: SA-PO135

Urinary Serum Amyloid A and Clinical Outcomes in Advanced Diabetic Kidney Disease

Session Information

• Diabetic Kidney Disease: Basic - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Dieter, Brad, Providence Health Care, Spokane, Washington, United States

Brad Dieter,

• McPherson, Sterling, Washington State University College of Medicine, Spokane, Washington, United States

Sterling McPherson,

• Afkarian, Maryam, University of California, Davis, Sacramento, California, United States

Maryam Afkarian,

• Meek, Rick L., Providence Sacred Heart Medical Center, Spokane, Washington, United States

Rick L. Meek,

• de Boer, Ian H., Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, United States

Ian H. de Boer,

• Mehrotra, Rajnish, University of Washington, Seattle, Washington, United States

Rajnish Mehrotra,

• Tuttle, Katherine R., University of Washington School of Medicine, Spokane, Washington, United States

Katherine R. Tuttle,

Background

Serum amyloid A (SAA) is elevated in the kidneys from humans and mice with diabetic kidney disease (DKD). SAA promotes a broad inflammatory response and overexpression of SAA exacerbates albuminuria and glomerulosclerosis in diabetic mice. The study aim was to determine the relationship of urinary SAA to clinical outcomes in patients with advanced DKD.

Methods

Urinary SAA was measured (enzyme-linked immunosorbent assay) in a cohort with type 2 diabetes and advanced DKD defined by urine protein-to-creatinine ratio >500 mg/g. Associations of urinary SAA with ESRD and death were tested using Cox-proportional hazard models. The models were adjusted for DKD risk factors: age, sex, race, hemoglobin A1c, and systolic blood pressure.

Results

Baseline characteristics included: age 57±8 (mean±SD) years, women (65/115; 57%), Mexican-American (82/115; 71%), hemoglobin A1c 8.6±2.3%, systolic blood pressure 153±28 mm Hg, urine albumin-to-creatinine ratio 1874, 756-3950 mg/g (median, interquartile range), estimated glomerular filtration rate (eGFR; CKD-EPI-creatinine) 56±22 mL/min/1.73m², diabetes duration 15±6 years, body mass index 32±9 kg/m², renin angiotensin system inhibitor use (92/115; 80%). Participants with SAA-positive urine (58/115; 50%) had lower eGFR (SAA-positive 51±19 mL/min/1.73m² versus SAA-negative 60±24 mL/min/1.73m², p=0.025), and higher albuminuria (SAA-positive 3094 [1180–4677] versus SAA-negative 1089 [55 –1955], p=0.030). SAA positivity in urine was associated with ESRD (hazards ratio [HR] 2.50, 95% confidence interval [CI] 1.23–5.08, p=0.011), but not death (HR 0.92, 95% CI 0.44–1.94, p=0.83) over a median of 3.5 years. After DKD risk factor adjustment, risk of ESRD imparted by SAA positivity in urine remained similar (HR 2.42, 95% CI 1.15 – 5.12, p=0.020).

Conclusion

In patients with advanced DKD, those with SAA-positive urine had lower eGFR and higher albuminuria compared to those with SAA-negative urine. Urinary SAA forecasted ESRD after adjustment for DKD risk factors. These relationships point to SAA as a candidate mechanism for DKD progression in diabetic patients with advanced DKD.