Kidney Week

Abstract: FR-PO1218

Urinary Clearances of Indoxyl Sulfate and P-cresol Are Directly Correlated with the Functional Stress Response of the Proximal Tubule

Session Information

• CKD: Mechanisms - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Madero, Magdalena, Instituto Nacional de Cardiologia Ignacio Chavez, Ciudad de Mexico, Estado de Mexico, Mexico

Magdalena Madero, MD

• Fernandez Yepez, Ana K., Instituto Nacional de Cardiologia Ignacio Chavez, Ciudad de Mexico, Estado de Mexico, Mexico

Ana K. Fernandez Yepez, MD

• Seegmiller, Jesse C., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Jesse C. Seegmiller, PhD

• Montesinos Ojeda, Guadalupe Monserrat, Instituto Nacional de Cardiologia Ignacio Chavez, Ciudad de Mexico, Estado de Mexico, Mexico

Guadalupe Monserrat Montesinos Ojeda, MD

• Guzmán Portillo, Alan Jan, Instituto Nacional de Cardiologia Ignacio Chavez, Ciudad de Mexico, Estado de Mexico, Mexico

Alan Jan Guzmán Portillo, MD

• Estrada Escamilla, Aurora Itzel, Instituto Nacional de Cardiologia Ignacio Chavez, Ciudad de Mexico, Estado de Mexico, Mexico

Aurora Itzel Estrada Escamilla, MD

• Rodriguez-Iturbe, Bernardo, Instituto Nacional de Cardiologia Ignacio Chavez, Ciudad de Mexico, Estado de Mexico, Mexico

Bernardo Rodriguez-Iturbe, MD

Background

Urinary clearance of cardiotoxic and nephrotoxic indoxyl sulfate (IS) and p-cresol (pC) largely depends on the function of organic anionic (OAT) and cationic (OCT) transporters of the proximal tubule. Therefore, we examined the relationship between the clearance of IS and pC and the functional stress response of OAT and OCT in normal individuals and in patients with reduced glomerular filtration rate (GFR)

Methods

Studies were performed in 24 patients (GFR range 14 -129 ml/min/1.73m²). Serum and urine IS and pC were determined by mass spectrometry for clearance determinations (UV/P). GFR (iohexol), serum and urinary creatinine (autoanalyzer) and urinary furosemide (HPLC), were assayed to determine the tubular secretion of creatinine (TScr) and furosemide (TSfr), hourly for 4 hours after the oral administration of 5g of creatinine and 1-1.5 mg of furosemide intravenously. This was intended to induce maximal stimulation of OCT and OAT, respectively. Studies were performed with induced water diuresis. Complete bladder emptying was assured via ultrasound evaluation.

Results

TScr and TSfr (mg/min, mean±SD) were higher in the first hour (KDIGO 1: TScr = 4.1±2.44, TSfr =0.4±0.15; KDIGO 2: TScr= 6.8±4.37, TSfr= 0.4±0.29; KDIGO 3: TScr= 3.2±1.88, TSfr= 0.3±0.15; KDIGO 4: TScr= 2.3±2.08, TSfr= 0.2±0.13) and became stable and similar after the second hour. There was no significant correlation between GFR and TScr or TSfr (Figure 1A-1B). The TScr and TSfr of the first hour correlated significantly with the clearances of IS and pC. The significant correlation was observed between stimulated TScr and IS clearance (p=0.005) and pC clearance (p=0.003 (Figure 2A - 2B)

Conclusion

The urinary clearance of IS and pC is associated and directly correlated with the secretory response of the organic transporters of the proximal tubule