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Nephrosclerosis: a term in quest of a disease
1Service de Néphrologie, AP-HP, Hôpital Georges Pompidou, Université Paris-Descartes, Paris, France.
Insights
Nephrosclerosis, previously linked to hypertension, is now understood as a genetic renovasculopathy, particularly in Black individuals. Research highlights APOL1 gene variants and metabolic factors, suggesting a need for precise pathological descriptions over the broad term "nephrosclerosis".
Area of Science:
- Nephrology
- Genetics
- Pathology
Background:
- Nephrosclerosis has historically been attributed to hypertension and aging, often considered a primary cause of end-stage renal failure (ESRD), especially in Black populations.
- The traditional view suggested hypertension caused nephrosclerosis, leading to a focus on blood pressure control for slowing renal decline.
- The term 'nephrosclerosis' is a broad classification that may obscure underlying nephropathies and genetic predispositions.
Purpose of the Study:
- To re-evaluate the etiology of nephrosclerosis, challenging the long-held belief that hypertension is the primary cause.
- To explore the genetic underpinnings of nephrosclerosis, particularly the role of APOL1 gene variants.
- To differentiate aging-related renal changes from those caused by hypertension and other metabolic factors.
Main Methods:
- Review of clinical and experimental evidence.
- Identification of coding region variants in the APOL1 gene.
- Histomorphometric analysis to distinguish between aging and hypertension-induced renal lesions.
Main Results:
- Evidence suggests nephrosclerosis, especially in Black individuals, is a genetic renovasculopathy that may precede hypertension.
- APOL1 gene variants are identified, opening new research avenues for nephroangiosclerosis and focal-segmental glomerulosclerosis (FSGS).
- Histomorphometric studies differentiate aging lesions from hypertension-induced ones, revealing glomerular changes like ischemic obsolescence, glomerulomegaly, and focal-segmental sclerosis due to autoregulation loss.
Conclusions:
- Hypertension control may not significantly slow renal function decline in nephrosclerosis as previously expected.
- Nephrosclerosis is a complex condition influenced by genetic (e.g., APOL1) and metabolic factors (obesity, oxidative stress, dyslipidemia, atherosclerosis).
- The term 'nephrosclerosis' is imprecise; 'arterionephrosclerosis' is preferred, necessitating elucidation of specific genetic and metabolic drivers for accurate diagnosis and treatment.
Abstract:
For a century, nephrosclerosis was ascribed to nonmalignant hypertension and aging. However, it was intuitively perceived that hypertension may follow rather than explain this nephrovasculopathy. Hypertensive nephrosclerosis was long considered a major cause of end-stage renal failure (ESRD). This is especially true in blacks of African descent but not in other ethnic populations. The term 'nephrosclerosis' is still an easy way out to classify a patient with renal insufficiency. This leads to neglect the possibility of an overlooked nephropathy complicated by hypertension and to believe that drastic blood pressure control may retard the progression to ESRD. Several clinical and experimental lines of evidence lead to the understanding that nephrosclerosis, especially in blacks, is a genetic renovasculopathy that precedes the rise in blood pressure. The identification of coding region variants in APOL1 encoding apolipoprotein L-1 in black but also white and Asians opens new lines of research on the genetics of nephroangiosclerosis and of FSGS. Metabolic derangements, such as obesity, oxidative stress, dyslipidemia and atherosclerosis may be considered confounding factors with regard to nephrosclerosis. Histomorphometric studies led to sorting out the lesions due to aging from those stemming from hypertension. They shed new light not only on glomerular lesions that comprise ischemic obsolescence but also on glomerulomegaly and focal-segmental sclerosis, the latter due to a loss of renal autoregulation. It appears that the control of hypertension is not credited with the expected benefit for slowing the decline of renal function. 'Nephrosclerosis' can be considered an umbrella term of poor significance that should be replaced by its pathologic description, that is, arterionephrosclerosis and incite to elucidate the various genetic and metabolic factors that lead to a lesion in quest of a specific disease.
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