Invited Review: A Contemporary Overview of Chronic Progressive Nephropathy in the Laboratory Rat, and Its Significance for Human Risk Assessment
Abstract
CPN (chronic progressive nephropathy) is a spontaneous age-related disease that occurs in high incidence in the strains of rat commonly used in preclinical toxicology studies, exhibiting a male predisposition. Although increasing in incidence and severity with age, evidence indicates that CPN should be regarded as a specific disease entity and not just a manifestation of the aging process. A number of factors, mainly dietary manipulations, have been shown to modify the expression of CPN. Amongst these, restriction of caloric intake is the most effective for inhibiting the disease process. The precise etiology of CPN and the mechanism(s) underlying its pathogenesis remain unknown, but the long-standing assumption that glomerular dysfunction is the primary basis is challenged in the light of contemporary developments in understanding filtration and postglomerular cellular processing of albumin. CPN is not only a degenerative disease, but also has regenerative aspects with a high cell proliferative rate in affected tubules. Accordingly, evidence is emerging that advanced, particularly end-stage CPN, is a risk factor for a marginal increase in the background incidence of renal tubule tumors. Many chemicals are known to exacerbate the severity of CPN to an advanced stage, and this interaction between chemical and CPN can result in a small increase in the incidence of renal adenomas in 2-year carcinogenicity bioassays. Review of the pathological entities associated with chronic renal failure in man emphasizes that this rodent condition has no strict human counterpart. Because CPN is a rodent-specific entity, the finding of a small, statistically significant increase in renal tubule tumors, linked to exacerbation of CPN by a test chemical in a preclinical study for carcinogenicity, can be regarded as having no relevance for extrapolation in human risk assessment.
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Only elderly male rats are sensitive to chronic progressive nephropathies.
“As a matter of fact, only elderly male rats are sensitive to chronic progressive nephropathies (Hard and Khan, 2004).”
From RETRACTED: Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize (2012) · cites this paper as Hard and Khan, 2004
Only elderly male rats are sensitive to chronic progressive nephropathies.
“It is known that only elderly male rats are sensitive to chronic progressive nephropathies [37].”
From Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modified maize (2014) · cites this paper as [37]
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- Authors
- Hard, G. C., & Khan, K. N.
- Affiliations
- Tairua 2853, New Zealand,
- Pfizer (United States) (US)
- Venue
- Toxicologic Pathology
- Publisher
- SAGE Publications
- Published
- 2004-02
- Volume
- 32
- Issue
- 2
- Pages
- 171-180
- ISSN
- 0192-6233 (ISSN-L)
- 1533-1601
- OpenAlex
- W2099137078
- Cited by
- 167
- References
- 94
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 9 · 2015: 14 · 2014: 8 · 2013: 14 · 2012: 18
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicologic Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- chronic progressive nephropathy, laboratory rats, age-related kidney disease, caloric restriction, dietary intervention, glomerular dysfunction, renal adenoma, carcinogenicity bioassays, chronic kidney disease, human risk assessment
- MeSH terms
- Animals, Humans, Kidney Failure, Chronic, Species Specificity, Risk Assessment, Toxicity Tests, Rats
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