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Kidney Week

Abstract: TH-PO947

Altering Body Temperatures Response to Heat Modulates Kidney Injury

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Sato, Yuka, University of Colorado Denver, Aurora, Colorado, United States
  • Roncal-jimenez, Carlos Alberto, University of Colorado Denver, Aurora, Colorado, United States
  • Andres-hernando, Ana, University of Colorado Denver, Aurora, Colorado, United States
  • Garcia, Gabriela E., University of Colorado Denver, Aurora, Colorado, United States
  • Lanaspa, Miguel A., University of Colorado Denver, Aurora, Colorado, United States
  • Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
Background

Hispanic Americans may be at more risk than African Americans for kidney damage from heat stress due to greater mitochondrial uncoupling because of genetic polymorphisms. Indeed, mitochondrial uncoupling proteins (UCP) dissipate the proton gradient in the mitochondria, resulting in more heat generation instead of ATP synthesis. We therefore hypothesized that the administration of a drug that could induce a mitochondrial uncoupling might result in a greater increase in body temperature following heat exposure, and that this might lead to greater renal damage.

Methods

To test this hypothesis C57BL/6 mice were exposed to 39.5°C for 30 minutes with subcutaneous injection of the chemical uncoupler; 2,4-dinitrophenol (DNP). After heat exposure, mice were returned to room temperature, and received access to water and food freely for one hour to avoid dehydration. The heat exposure was repeated twice per day for 10 days. Body temperature was evaluated with rectal probes.

Results

Body temperature immediately after the heat exposure was increased by heat and DNP (Table1). Albuminuria (uAlb) and BUN were increased in DNP+Heat group (Table1). uAlb correlated with body temperature (R=0.6, p<0.038). CPK was not increased in any groups,indicating an absence of rhabdomyolysis. Renal pathology showed greater tubular cell proliferation (proliferating cell nuclear antigen (PCNA) positive), tubular injury and interstitial macrophage infiltration (F4/80 positive) in the DNP+Heat group (Table1). HSP 70 expression was increased in Heat group and much more in Heat+DNP group.

Conclusion

Increasing body temperature for the same level of heat stress is associated with greater renal injury. Studies should evaluate whether individual temperature responses can predict renal injury in high risk subjects such as sugarcane workers.

Table1
 Non TreatDNPHeatDNP+Heat
Body temperature (°C)37.5±0.3638.6±0.11*40.9±0.27*42.1±0.44**
Urine albumin/creatinine (mg/gCr)62±1741±1680±33246±87 †
BUN (mg/dL)24.7±4.325.6±4.023.7±2.036.8±1.9**
PCNA (positive area %)8.456.156.0015.23‡
F4/80 (positive area %)2.491.991.388.22**

*p<0.001 vs NT, **p<0.001 vs NT, DNP, Heat, †p<0.001 vs NT, DNP, p<0.01 vs Heat, ‡p<0.05 vs NT, p<0.001 vs DNP, Heat,

Funding

  • NIDDK Support