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


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.


CONCLUSIONS
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.
Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany. stefanie.schreiber@med.ovgu.de
Stefanie
S
Schreiber
Celine Z
CZ
Bueche
Cornelia
C
Garz
Siegfried
S
Kropf
Doerthe
D
Kuester
Kerstin
K
Amann
Hans-Jochen
HJ
Heinze
Michael
M
Goertler
Klaus G
KG
Reymann
Holger
H
Braun
D000818:Animals; D001921:Brain / Q000473:pathology; D059345:Cerebral Small Vessel Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR