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Published on: August 9, 2013
Opioids induce renal abnormalities in tumor-bearing mice
Ramya Arerangaiah1, Nagamala Chalasani, Aaron M Udager
1Division of Hematology, Oncology and Transplantation, University of Minnesota, MN 55455, USA.
Background/Aims:
The etiology of renal dysfunction in cancer patients is likely to be multifactorial. A large proportion of these patients receive opioid analgesics, but whether opioids contribute to renal dysfunction remains uncertain. In a murine cancer model, we examined the effects of chronic opioid administration on renal function and pathology, and the molecular mechanisms involved.
Methods:
C3H/HeJ mice implanted with 2472 tumor cells were treated with either morphine or hydromorphone in clinically relevant doses, or PBS (controls). Renal function was assessed by blood and urine chemistry as well as by measuring mean arterial pressure (MAP) and kidney perfusion. Pathological changes in the kidneys were examined by routine histology. Molecular changes were examined by assessing eNOS, iNOS, HO-1 and COX-2 expression in whole-kidney lysates by Western immunoblotting, and cellular colocalization of these enzymes was determined using immunofluorescence microscopy.
Results:
Three weeks of opioid treatment resulted in increased kidney weight, elevated BUN and proteinuria, and decreased MAP. This was accompanied by histological abnormalities including glomerular enlargement, hypercellularity, peritubular congestion, vasodilatation and tubular casts. The vasoregulatory molecules iNOS, eNOS, HO-1 and COX-2 were upregulated in the kidneys. The NOS inhibitor L-NAME prevented the morphine-induced increase in perfusion and kidney weight.
Conclusions:
The chronic use of clinically relevant doses of opioidsleads to structural kidney abnormalities, upregulates NOS, COX-2 and HO-1, and results in renal dysfunction in a murine model of cancer.
Insights
Chronic opioid use in cancer patients may cause kidney dysfunction. This study found that morphine and hydromorphone led to structural kidney abnormalities and impaired function in a mouse cancer model.
Area of Science:
- Nephrology
- Oncology
- Pharmacology
Background:
- Renal dysfunction is common in cancer patients, with multifactorial causes.
- The role of opioid analgesics, widely used in cancer care, in renal dysfunction is unclear.
Purpose of the Study:
- To investigate the effects of chronic opioid administration on renal function and pathology.
- To explore the underlying molecular mechanisms in a murine cancer model.
Main Methods:
- Murine cancer model treated with morphine, hydromorphone, or PBS.
- Assessment of renal function via blood/urine chemistry, mean arterial pressure (MAP), and kidney perfusion.
- Histological examination and molecular analysis (eNOS, iNOS, HO-1, COX-2) of kidney tissues.
Main Results:
- Opioid treatment increased kidney weight, BUN, and proteinuria, while decreasing MAP.
- Histological abnormalities included glomerular enlargement, hypercellularity, and tubular casts.
- Upregulation of vasoregulatory molecules (iNOS, eNOS, HO-1, COX-2) was observed; NOS inhibition mitigated some effects.
Conclusions:
- Clinically relevant opioid doses induce structural kidney abnormalities and renal dysfunction in a cancer model.
- Opioid administration upregulates nitric oxide synthase (NOS), COX-2, and HO-1.
- These findings suggest a direct link between chronic opioid use and kidney damage in cancer patients.
