Response to ‘Hypertensive nephrosclerosis: Pathogenesis and prevalence’

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Dr Luke presents briefly here and more extensively in his paper1.Luke R.G. Hypertensive nephrosclerosis: pathogenesis and prevalence.Nephrol Dial Transplant. 1999; 14: 2271-2278Crossref PubMed Scopus (79) Google Scholarthe hypothesis that inappropriate vasoconstriction to some glomeruli (in a sense a form of loss of autoregulation) leads to ischemic glomerulosclerosis and that the remaining nephrons undergo compensatory hypertrophy with proteinuria and focal segmental glomerulosclerosis. However, in our normal aging kidneys,2.Hill G.S. Heudes D. Bariety J. Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation.Kidney Int. 2003; 63: 1027-1036Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholarhypertrophic/focal segmental glomerulosclerosis-type glomeruli were much more common than ischemic ones, the reverse of what Dr Luke's hypothesis might predict. In this study,3.Hill G.S. Heudes D. Jacquot C. et al.Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension.Kidney Int. 2006; 69: 823-831Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholarwe specifically pointed out that loss of autoregulation likely accounts for at most 20–60% of progression of hypertensive lesions, depending on the race, ischemic glomerulosclerosis being more frequent than the focal segmental glomerulosclerosis type of glomerulosclerosis in whites, blacks having equal frequencies of the two types. We are thus in agreement with Dr Luke that there are two basic mechanisms at work, but think they more likely operate pari passu. Regarding the marked proteinuria in our patients, we clearly indicated that they represent the far end of the spectrum of hypertension in terms of proteinuria.3.Hill G.S. Heudes D. Jacquot C. et al.Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension.Kidney Int. 2006; 69: 823-831Abstract Full Text Full Text PDF PubMed Scopus (75) Google ScholarPatients with lower levels, such as those in the African American Study of Kidney Disease and Hypertension study, would not ordinarily be biopsied. This does not detract from the validity of our observations. The study4.Wright Jr, J.T. Bakris G. Greene T. et al.African American Study of Kidney Disease and Hypertension Study Group Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.JAMA. 2002; 288: 2421-2431Crossref PubMed Scopus (1632) Google Scholarcited showing increased glomerular filtration rate in response to amlodopine in subjects with <300 mg/dl proteinuria, but not over >300 mg/dl, can actually be interpreted to support our hypothesis of loss of autoregulation in hypertrophic, proteinuric glomeruli. Subjects with greater proteinuria would be anticipated to have a higher percentage of glomeruli with already dilated arterioles, with less capacity to respond to vasodilators.