Hypertensive Nephropathy and the Gene for Angiotensin-Converting Enzyme

Kario, Kazuomi; Kanai, Nobuyuki; Nishiuma, Shinichi; Fujii, Takeshi; Saito, Ken; Matsuo, Takefumi; Matsuo, Masafumi; Shimada, Kazuyuki

doi:10.1161/01.atv.17.2.252

Cited by 39 publications

(20 citation statements)

References 31 publications

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“…Therefore, the absence of a demonstrated shift in the systolic BP threshold associated with increased albumin permeability does not contradict the premise that nephron loss impairs autoregulatory protection. In this heterogeneous clinical study population, other factors, such as genetic polymorphisms 25 and renal macrovascular disease, may modulate the relationship between systemic BP and glomerular permeability; in fact, a proportion of individuals with hypertension and CKD maintain a normal albumin permeability. Therefore, it would not be surprising if a remnant nephron effect resulted in an altered slope of the systolic BP-FE alb relationship without a defined shift in threshold.…”

Section: Discussionmentioning

confidence: 99%

Modification of the Relationship Between Blood Pressure and Renal Albumin Permeability by Impaired Excretory Function and Diabetes

et al. 2015

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H ypertension accelerates the progression of chronic kidney disease (CKD) and controlling blood pressure (BP) is the mainstay of general CKD management. 1,2 In animal models, a remnant nephron effect has been described, whereby a reduction in nephron mass results in increased transmission of systemic hydrostatic pressure to the glomerular microcirculation, accompanied by increased glomerular permeability, proteinuria, and progressive renal injury.3-5 Operation of a similar phenomenon in human CKD is implied by the fact that faster CKD progression is associated with BP increments that in isolation rarely initiate significant loss of excretory function.6 However, the relationship between nephron loss and vulnerability to hypertensive damage in humans is poorly defined; it is unknown whether there is a threshold level of excretory impairment at which BP increments are more likely to overcome renal autoregulation and induce further injury. Antihypertensive trials have not reported effects on hard renal end points stratified by baseline function and so guidelines do not differentiate CKD BP targets on the basis of estimated glomerular filtration rate (eGFR). 1Increased glomerular albumin leak is a feature of hypertensive renal end-organ damage, and there is some evidence that CKD patients with heavier proteinuria benefit from lower BP targets. 7,8 It is postulated that these observations reflect an increase in glomerular permeability caused by elevated glomerular capillary hydrostatic pressure. 9,10We sought evidence of a human remnant nephron effect increasing the transmission of BP to the glomerular microcirculation and modulating the relationship between increasing BP and albumin permeability. Specifically, we hypothesized that at lower levels of excretory function, a given BP increment would be associated with a greater relative increase in renal albumin permeability. This hypothesis was tested in a representative sample of the US population: the National Health and Nutrition Examination Survey (NHANES) 1999 to 2010. Fractional excretion of albumin (FE alb , relative to creatinine) was used as the primary measure of albumin permeability; because a given albumin leak occurring across a reduced nephron mass must indicate a greater degree of albumin permeability, 11 FE alb is a more logical measure of renal albumin permeability than the total urine albumin:creatinine ratio (ACR).Diabetes mellitus, like reduced nephron mass, is considered to increase the transmission of systemic pressure to the Abstract-In animal models, reduced nephron mass impairs renal arteriolar autoregulation, increasing vulnerability of the remaining nephrons to elevated systemic blood pressure (BP). A feature of the resulting glomerular capillary hypertension is an increase in glomerular permeability. We sought evidence of a similar remnant nephron effect in human chronic kidney disease. In participants from the United States National Health and Nutrition Examination Surveys 1999 to 2010 (N=23 710), we examined the effect of reduced estimated ...

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Section: Discussionmentioning

confidence: 99%

Modification of the Relationship Between Blood Pressure and Renal Albumin Permeability by Impaired Excretory Function and Diabetes

et al. 2015

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“…This polymorphism has been shown to be correlated with left ventricular hypertrophy [32] and myocardial infarction [3,29]. Several groups found the D allele of the ACE I/D polymorphism to be associated with micro-albuminuria, retinopathy and left ventricular hypertrophy in patients with essential hypertension [18,24]. Despite these contradictions further investigations of these polymorphisms seem reasonable because of the importance of detecting patients at elevated risk for arterial hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…The renin-angiotensin system plays a crucial role in blood pressure homeostasis and is involved in the pathogenesis of arterial hypertension. Genotypic variants of its major components angiotensinogen (AGT) and angiotensin I converting enzyme (ACE) have been reported to contribute to the development of arterial hypertension [7], other cardiovascular diseases like myocardial infarction [3] and development of target organ damage like micro-albuminuria, retinopathy and left ventricular hypertrophy [18,24]. A recent study has shown linkage of AGT gene locus (1q42-43) to essential hypertension [4].…”

Section: Introductionmentioning

confidence: 99%

Angiotensin I converting enzyme and angiotensinogen gene polymorphisms related to 24-h blood pressure in paediatric type I diabetes mellitus

Pavlović¹,

Holl

Haeberle

et al. 1999

European Journal of Pediatrics

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“…101 Interestingly, many patients with microalbuminuria may be genetically predisposed to abnormally high levels of angiotensin II, by virtue of being DD polymorphic for the ACE gene, 102,103 a condition that involves increased circulating (and perhaps also tissue) levels of converting enzyme. 104 Moreover, a greater frequency of unfavourable genotype combinations for key factors in the renin-angiotensin system (angiotensin II converting enzyme, angiotensinogen, the AT1 receptor for angiotensin II) has recently been documented in microalbuminuric patients.…”

Section: -99mentioning

confidence: 99%

Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension

et al. 2002

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This paper reviews the existing epidemiological and clinical evidence about the relationships of non-diabetic microalbuminuria with cardiovascular risk factors such as elevated blood pressure (BP), systolic particularly, cardiac hypertrophy, adverse metabolic status, smoking habits, elevated angiotensin II levels, endothelial dysfunction, acute and perhaps subclinical inflammation. Because of that unique property of reflecting the influence of so many clinically relevant parameters, microalbuminuria may legitimately be defined as an integrated marker of cardiovascular risk, an unique profile among the several prognostic predictors available to

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Hypertensive Nephropathy and the Gene for Angiotensin-Converting Enzyme

Cited by 39 publications

References 31 publications

Modification of the Relationship Between Blood Pressure and Renal Albumin Permeability by Impaired Excretory Function and Diabetes

Modification of the Relationship Between Blood Pressure and Renal Albumin Permeability by Impaired Excretory Function and Diabetes

Angiotensin I converting enzyme and angiotensinogen gene polymorphisms related to 24-h blood pressure in paediatric type I diabetes mellitus

Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension

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