RGD Reference Report - Kidney pathology precedes and predicts the pathological cascade of cerebrovascular lesions in stroke prone rats. - Rat Genome Database

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Kidney pathology precedes and predicts the pathological cascade of cerebrovascular lesions in stroke prone rats.

Authors: Schreiber, Stefanie  Bueche, Celine Z  Garz, Cornelia  Kropf, Siegfried  Kuester, Doerthe  Amann, Kerstin  Heinze, Hans-Jochen  Goertler, Michael  Reymann, Klaus G  Braun, Holger 
Citation: Schreiber S, etal., PLoS One. 2011;6(10):e26287. doi: 10.1371/journal.pone.0026287. Epub 2011 Oct 21.
RGD ID: 30296658
Pubmed: PMID:22031827   (View Abstract at PubMed)
PMCID: PMC3198774   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0026287   (Journal Full-text)


INTRODUCTION: Human cerebral small vessel disease (CSVD) has been hypothesized to be an age-dependent disease accompanied by similar vascular changes in other organs. SHRSP feature numerous vascular risk factors and may be a valid model of some aspects of human CSVD. Here we compare renal histopathological changes with the brain pathology of spontaneously hypertensive stroke-prone rats (SHRSP).
MATERIAL AND METHODS: We histologically investigated the brains and kidneys of 61 SHRSP at different stages of age (12 to 44 weeks). The brain pathology (aggregated erythrocytes in capillaries and arterioles, microbleeds, microthromboses) and the kidney pathology (aggregated erythrocytes within peritubular capillaries, tubular protein cylinders, glomerulosclerosis) were quantified separately. The prediction of the brain pathology by the kidney pathology was assessed by creating ROC-curves integrating the degree of kidney pathology and age of SHRSP.
RESULTS: Both, brain and kidney pathology, show an age-dependency and proceed in definite stages whereas an aggregation of erythrocytes in capillaries and arterioles, we parsimoniously interpreted as stases, represent the initial finding in both organs. Thus, early renal tubulointerstitial damage characterized by rather few intravasal erythrocyte aggregations and tubular protein cylinders predicts the initial step of SHRSPs' cerebral vascular pathology marked by accumulated erythrocytes. The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by glomerulosclerosis and thrombotic renal microangiopathy in kidneys of older SHRSP predicts the final stages of SHRSPs' cerebrovascular lesions marked by microbleeds and thrombotic infarcts.
CONCLUSION: Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology. Further, an improved joined nephrologic and neurologic diagnostic may help to identify patients with CSVD at an early stage.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Glycosuria disease_progressionIAGP 30296658compared to Crl:WI Wistar ratsRGD 
Hematuria disease_progressionIAGP 30296658compared to Crl:WI Wistar ratsRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased erythrocyte aggregation disease_progressionIAGP 30296658compared to Crl:WI Wistar rat renal cortexRGD 
renal cast disease_progressionIAGP 30296658compared to Crl:WI Wistar rat renal cortexRGD 

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Objects Annotated

Strains
SHRSP/A3NCrl  (Stroke Prone Rats)


Additional Information