Abstract: FR-PO827

Methylguanidine in Normal Subjects and ESRD Patients

Session Information

Category: Dialysis

  • 601 Standard Hemodialysis for ESRD

Authors

  • Alkhathlan, Ahmed Zaid, University Hospitals Case Medical Center, Beachwood, Ohio, United States
  • Hai, Xin, Case Western Reserve University, Cleveland, Ohio, United States
  • Dobre, Mirela A., Case Western Reserve University, Cleveland, Ohio, United States
  • Meyer, Timothy W., Stanford University, Palo Alto, California, United States
  • Hostetter, Thomas H., Case Western Reserve University, Cleveland, Ohio, United States
Background

Methylguanidine (MG), a guanidino compound, is a small water-soluble solute that accumulates in uremic patients and has been implicated in some uremic toxicities. We studied the behavior of MG in end-stage renal disease patients on chronic dialysis compared to normal controls.

Methods

We studied six normal controls and seven chronic hemodialysis patients. Blood and 24-hour urine samples collected from the control group; while blood and dialysate samples were collected from the dialysis group (start, mid, and end of dialysis sessions). Urea, creatinine (Cr), and MG were measured by a LC-MS/MS method. Mean levels, clearance, and production/excretion rates were calculated assuming first order kinetics, and statistical methods (Student’s t test, Pearson correlation coefficient) were used for data analysis. Results are expressed as mean ± standard deviation (SD).

Results

The mean predialysis plasma MG level in chronic dialysis subjects was significantly higher (more than 100-fold) than in the control group (5.17 ± 2.61 vs. 0.047 ± 0.01 µM, respectively; P = 0.0005). In comparison, the mean predialysis urea level was only three-fold the normal level (44.05 ± 23.06 vs. 14.89 ± 3.23 mg/dL, respectively; P = 0.02), and Cr was 13-fold the normal level (10.8 ± 3.1 vs. 0.83 ± 0.18 mg/dL, respectively; P = 0.0001). The mean production rates of MG were 47.12 (± 13.6) and 4.21 (± 3.4) µmol/day in chronic dialysis patients and healthy individuals, respectively (P < 0.05). The effective clearance rates for urea and Cr in dialysis patients were 239 (± 69) and 173 (± 51) ml/min, respectively; which were significantly higher than the effective clearance rate for MG 122 (± 26) ml/min (P < 0.05).

Conclusion

MG accumulates to more than 100 fold the normal level in ESRD patients. This accumulation likely reflects 1) its clearance rate (and therefore its reduction ratio) is significantly less than that of urea and Cr, which is likely due to its previously described large distribution volume, and 2) increased production from Cr oxidation.

Table 1. Solute Plasma Levels, Clearance and Excretion Rates in Controls and ESRD Patients
 Plasma Levels aClearance bExcretion/Removal c
SoluteUN d
(mg/dl)
Cr (mg/dl)MG (µM)Urea (ml/min)CrMGUrea (g/day)MG (µmoles/day)
Normal (n=6)14.89 ± 3.230.83 ± 0.180.047 ± 0.01355.19 ± 13.75119.07 ± 22.0368.09 ± 62.0724.89 ± 6.244.6 ± 4.2
ESRD (n=7)44.05 ± 23.0610.8 ± 3.15.17 ± 2.61238.83 ± 69.4173.04 ± 51.1122.53 ± 26.512.65 ± 6.6247.12 ± 18.35