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

Schreiber S, Bueche CZ, Garz C, Kropf S, Kuester D, Amann K, Heinze HJ, Goertler M, Reymann KG, Braun H - PLoS ONE (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany. stefanie.schreiber@med.ovgu.de

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

Quantification of tubular protein cylinders and of erythrocyte aggregations within peritubular capillaries.Kidney medulla. A: tubular protein cylinders in <5% per field of view ( = 1), B: tubular protein cylinders in >5% per field of view ( = 2), C: tubular protein cylinders in >30% per field of view ( = 3), D: peritubular aggregated erythrocytes in <5% per field of view ( = 1), E: peritubular aggregated erythrocytes in >5% per field of view ( = 2), F: peritubular aggregated erythrocytes in >30% per field of view ( = 3).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3198774&req=5

pone-0026287-g001: Quantification of tubular protein cylinders and of erythrocyte aggregations within peritubular capillaries.Kidney medulla. A: tubular protein cylinders in <5% per field of view ( = 1), B: tubular protein cylinders in >5% per field of view ( = 2), C: tubular protein cylinders in >30% per field of view ( = 3), D: peritubular aggregated erythrocytes in <5% per field of view ( = 1), E: peritubular aggregated erythrocytes in >5% per field of view ( = 2), F: peritubular aggregated erythrocytes in >30% per field of view ( = 3).

Mentions: For all SHRSP and controls we separately assessed the occurrence of aggregated erythrocytes within peritubular capillaries and the occurrence of tubular protein cylinders in 6 HE slices per animal at all stages of age in a semiquantitative manner: aggregated erythrocytes or tubular protein cylinders per field of view (FOV) 0 = none, 1 =  <5%, 2 =  >5%, 3 =  >30% (Figure 1). We investigated 5 FOV (magnification 150x) per slice for kidney cortex and medulla each.


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

Schreiber S, Bueche CZ, Garz C, Kropf S, Kuester D, Amann K, Heinze HJ, Goertler M, Reymann KG, Braun H - PLoS ONE (2011)

Quantification of tubular protein cylinders and of erythrocyte aggregations within peritubular capillaries.Kidney medulla. A: tubular protein cylinders in <5% per field of view ( = 1), B: tubular protein cylinders in >5% per field of view ( = 2), C: tubular protein cylinders in >30% per field of view ( = 3), D: peritubular aggregated erythrocytes in <5% per field of view ( = 1), E: peritubular aggregated erythrocytes in >5% per field of view ( = 2), F: peritubular aggregated erythrocytes in >30% per field of view ( = 3).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198774&req=5

pone-0026287-g001: Quantification of tubular protein cylinders and of erythrocyte aggregations within peritubular capillaries.Kidney medulla. A: tubular protein cylinders in <5% per field of view ( = 1), B: tubular protein cylinders in >5% per field of view ( = 2), C: tubular protein cylinders in >30% per field of view ( = 3), D: peritubular aggregated erythrocytes in <5% per field of view ( = 1), E: peritubular aggregated erythrocytes in >5% per field of view ( = 2), F: peritubular aggregated erythrocytes in >30% per field of view ( = 3).
Mentions: For all SHRSP and controls we separately assessed the occurrence of aggregated erythrocytes within peritubular capillaries and the occurrence of tubular protein cylinders in 6 HE slices per animal at all stages of age in a semiquantitative manner: aggregated erythrocytes or tubular protein cylinders per field of view (FOV) 0 = none, 1 =  <5%, 2 =  >5%, 3 =  >30% (Figure 1). We investigated 5 FOV (magnification 150x) per slice for kidney cortex and medulla each.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany. stefanie.schreiber@med.ovgu.de

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus