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[Nephropathy associated with arterial hypertension: genes and Barker's hypothesis]
1Divisione di Nefrologia, Azienda Ospedaliera di Reggio Calabria e Centro di Fisiologia Clinica CNR, Reggio Calabria.
Insights
Hypertension significantly increases renal failure risk, independent of other factors. Factors like genetics and intrauterine growth influence hypertension-related kidney damage.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Genetics
Context:
- Glomerular diseases have dominated nephrology research for decades.
- Increasing end-stage renal disease (ESRD) from hypertension has refocused attention on blood pressure's renal impact.
- High blood pressure is a confirmed, independent risk factor for renal failure.
Purpose:
- To explore the multifactorial nature of hypertension-related renal injury.
- To integrate genetic, intrauterine growth, and environmental factors in understanding kidney disease.
- To examine the interaction between genetic predisposition and developmental influences on renal health.
Summary:
- Hypertension is a major independent risk factor for renal failure.
- Disturbed intrauterine growth (e.g., due to malnutrition) impacts cardiovascular development, predisposing individuals to adult hypertension and related conditions (Barker's hypothesis).
- Reduced nephron number at birth, exacerbated by hypertension-induced vascular damage and genetic factors (ACE gene D allele), increases susceptibility to cardiovascular and renal diseases.
Impact:
- Highlights the critical role of hypertension in kidney disease progression.
- Emphasizes the long-term consequences of intrauterine growth on adult cardiovascular and renal health.
- Suggests a complex interplay between genetics, early development, and environmental factors in determining susceptibility to hypertension-related nephropathy.
Abstract:
For about three decades glomerular diseases have been the most intensively investigated research area in nephrology. The increasing proportion of patients with end-stage renal disease (ESRD) secondary to hypertension has now revived interest in hypertension. Prospective studies have firmly established that high blood pressure is associated with an increased risk of renal failure independent of other risk factors. Hypertension-related renal injury might be interpreted in a general context taking into account genes, intrauterine growth and environmental factors. Disturbed intrauterine growth (due to malnutrition or other factors) has a negative influence on the development of the cardiovascular system and favours the occurrence of hypertension, insulin resistance, hypercholesterolaemia and hyperuricaemia in adult life (Barker's hypothesis). Altered intrauterine growth has also been associated with a reduced number of nephrons at birth. Damage attributable to glomerular hyperperfusion in kidneys with a reduced number of nephrons is aggravated by vascular lesions in middle and small arterial vessels (secondary to hypertension, hyperlipidaemia and environmental risk factors such as smoking). The observation that subjects homozygous for the D allele of the ACE gene are predisposed to both cardiovascular complications and nephrosclerosis, suggests that genetic factors may interact with altered intrauterine growth in determining the risk of cardiovascular and renal diseases.