Abstract: SA-PO756
Impaired Secretion of Uremic Solutes in Advanced CKD
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Mair, Robert, Stanford University/VAMC Nephrology, Palo Alto, California, United States
- Leong, Sheldon, Stanford University/VAMC Nephrology, Palo Alto, California, United States
- Plummer, Natalie, Stanford University/VAMC Nephrology, Palo Alto, California, United States
- Sirich, Tammy L., Stanford University/VAMC Nephrology, Palo Alto, California, United States
- Meyer, Timothy W., Stanford University/VAMC Nephrology, Palo Alto, California, United States
Background
The normal kidney clears many solutes efficiently by proximal tubular secretion. Clearance values are observed to be particularly high relative to the glomerular filtration rate (GFR) when the clearances of protein-bound solutes are calculated in terms of their free, unbound concentrations. This study examined the extent to which high secretory clearances are maintained when kidney function is markedly reduced.
Methods
Simultaneous urine and blood samples were collected from patients with stage V chronic kidney disease not on dialysis (CKD, n=16) and control subjects (control, n=17). The normally secreted and protein-bound solutes indoxyl sulfate (IS) and p-cresol sulfate (PCS) were assayed by LC/MS/MS. Clearances relative to the GFR (fractional clearances) were then estimated by dividing the urine to free plasma concentration ratios for these solutes by the urine to plasma concentration ratio for creatinine.
Results
GFR values estimated by the CKD-EPI equation were 7 ± 2 ml/min/1.73 m2 in the CKD patients and 86 ± 17 ml/min/1.73 m2 in the controls. Fractional clearances of IS and PCS were very high in controls in accord with prior results. Fractional clearances for both solutes were greatly reduced in CKD indicating impaired secretion (IS: 5 ± 2 vs. 28 ± 7, p<0.001; PCS: 3 ± 1 vs. 10 ± 3, p<0.001). Impaired kidney secretion was accompanied by prominent plasma accumulation in CKD patients with plasma concentrations of IS and PCS averaging 59 and 27 times greater than those in control subjects as compared to a 9 times greater creatinine concentration.
Conclusion
Secretory clearance of IS and PCS was impaired out of proportion to glomerular filtration in patients with advanced CKD. Prominent accumulation of these and other normally secreted solutes may contribute to uremic illness.
| Fractional Clearance | Free Plasma Concentration CKD/Control | |||
| CKD | Control | CKD/Control | ||
| Creatinine | 9 * | |||
| Indoxyl Sulfate | 5 ± 2 | 28 ± 7 | 0.2 * | 59 * |
| p-Cresol Sulfate | 3 ± 1 | 10 ± 3 | 0.3 * | 27 * |
Values are mean ± sd; * p<0.001 comparing CKD and control
Funding
- NIDDK Support