Abstract
Abstract Para-aminohippuric acid (PAH)-derived effective renal plasma flow (ERPF) is increasingly being used in parallel with the revived interest in kidney hemodynamic function due to the development of sodium glucose co-transporter 2 (SGLT2) inhibitors. In our trial (Kidney Int 2020;97: 202-12) we measured ERPF by urinary PAH clearance and calculated fractional PAH extraction ratios, which initially were very low during both the hyperglycemic clamps at baseline, as well as the euglycemic conditions following treatment with SGLT2 inhibitor dapagliflozin. Previous literature showed that hyperglycemic i.e. glucosuric conditions reduce urinary PAH concentrations, due to a Schiff base that is formed between the para-amino group of PAH and the aldehyde group of glucose. By using hydrochloric acid (HCl) any PAH that has been glycosylated can be reconverted, independent of storage time. After treatment with HCL we indeed found higher PAH extraction ratios in the expected range. In addition, a negative correlation between storage time and PAH extraction ratio in people treated with SGLT2 inhibitor dapagliflozin during a euglycemic clamp before treatment with HCl. Besides these human data, comparable results were observed in male obese ZSF1 rats with hyperglycemia. Therefore, researchers should be aware that even under euglycemic conditions, SGLT2 inhibitors induce glucosuria that interferes with accurate ERPF measurement due to glycosylation of PAH in stored urine samples. Pre-treatment of urine with NaOH or adding HCl prior to measurement will overcome this problem.
Highlights
Effective renal plasma flow (ERPF) is defined as the total plasma volume delivered to all nephrons per time unit
The gold standard nonradioactive method to measure ERPF is by urinary clearance of para-aminohippuric acid (PAH),[1] since, in low doses, PAH is almost completely cleared from the circulation during a single pass through the kidneys, with an extraction ratio of about 0.92.2 PAH can be used to measure ERPF in mechanistic renal physiology studies
In people with type 2 diabetes, we observed a reduction of inulin-measured glomerular filtration rate; as ERPF was preserved, our data indicated that sodium glucose cotransporter 2 (SGLT2) inhibition induced efferent arteriolar vasodilation.[5]
Summary
Effective renal plasma flow (ERPF) is defined as the total plasma volume delivered to all nephrons per time unit. In people with type 2 diabetes, we observed a reduction of inulin-measured glomerular filtration rate; as ERPF was preserved, our data indicated that SGLT2 inhibition induced efferent arteriolar vasodilation.[5] In our trial,[5] we measured ERPF by urinary PAH clearance.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
