Abstract: SA-PO518
Tubular Secretory Clearance Is Associated with Whole-Body Insulin Clearance
Session Information
- Diabetic Kidney Disease: Basic - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Huber, Matthew P., University of Washington, Seattle, Washington, United States
- Zelnick, Leila R., Kidney Research Institute, Seattle, Washington, United States
- de Boer, Ian H., Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, United States
- Kestenbaum, Bryan R., Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, United States
Background
The kidneys eliminate insulin via glomerular filtration plus tubular reabsorption and by extraction from the basolateral surface of proximal tubule cells. The relative contributions of each mechanism are incompletely understood. We tested associations of proximal tubular secretory clearances and estimated glomerular filtration rate (eGFR) with whole-body insulin clearance.
Methods
The Study of Glucose and Insulin in Renal Disease performed the hyperinsulinemic-euglycemic clamp in 57 non-diabetic persons with CKD (eGFR <60 mL/min/1.73m2) and 38 persons without kidney disease or diabetes (eGFR ≧60 mL/min/1.73m2). We defined insulin clearance as the intravenous insulin infusion rate divided by the steady-state plasma insulin concentration. We measured plasma and 24-hour urine concentrations of 7 tubular secretory solutes using targeted liquid chromatography-tandem mass spectrometry. We estimated GFR using the CKD Epidemiology Collaboration equation.
Results
Mean age was 63 ± 13 years and mean insulin clearance was 924 ± 228 mL/min. After adjustment for demographics and body composition, lower eGFR and lower kidney clearances of 3 solutes were associated with lower insulin clearance accounting for multiple comparisons (Table). Lower kidney clearances of isovalerylglycine and xanthosine remained associated with lower insulin clearance after further adjustment for eGFR.
Conclusion
Lower kidney clearances of tubular secretory solutes are associated with lower insulin clearance, suggesting an important role of tubular secretory pathways in renal insulin metabolism.
Associations of kidney functions with insulin clearance
| Insulin Clearance (mL/min) | ||||
| Model 1 | Model 2 | |||
| Difference (95% CI)* | p-value | Difference (95% CI)* | p-value | |
| eGFR | -28 (-50, -6) | 0.01** | -- | -- |
| Cinnamoylglycine | -6 (-15, 4) | 0.27 | 1 (-10, 12) | 0.87 |
| Indoxyl sulfate | -17 (-32, -2) | 0.02 | -12 (-27, 3) | 0.10 |
| Isovalerylglycine | -17 (-28, -6) | 0.002** | -14 (-27, -1) | 0.04 |
| Kynurenic acid | -14 (-30, 2) | 0.09 | 1 (-22, 23) | 0.94 |
| Pyridoxic acid | -13 (-26, 0) | 0.05 | -6 (-22, 9) | 0.43 |
| Tiglylglycine | -19 (-30, -7) | 0.001** | -15 (-30, 1) | 0.06 |
| Xanthosine | -24 (-34, -13) | < 0.0001** | -21 (-32, -9) | 0.0004** |
Model 1: Adjusted for age, sex, Black race, fat mass, fat free mass, and log (albumin excretion rate). Model 2: Model 1 + log(eGFR). *Difference in insulin clearance (mL/min) per 20% lower kidney function. **Statistical significance after accounting for multiple comparisons (Bonferroni adjustment).
Funding
- NIDDK Support