The protective arm of the renin–angiotensin system may counteract the intense inflammatory process in fetuses with posterior urethral valves

Abstract

Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve.

Myocardial function in fetuses with lower urinary tract obstruction: Is there a cardiac remodeling effect due to renal damage?

“…Alterations of RV e’/a’ ratio in LUTO fetuses can be interpreted as sign of diastolic dysfunction leading to intrauterine cardiac remodeling as in TTTS recipients . Regarding the hypothesis of RAS activation in fetal LUTO with its potential consequences for cardiovascular remodeling, the positive correlation between RV e’/a’ ratio and β‐2‐microglobulin, α‐1‐microglobulin, and potassium may demonstrate the association between renal and cardiac (especially RV diastolic) dysfunction.…”

“…This may lead to an altered flow to the low‐resistance placental circulation, with the consequence of an increasing overall afterload on the fetal heart following cardiac remodeling like ventricular hypertrophy . As we know from experimental data, LUTO fetuses present increased urinary levels of RAS molecules like angiotensin (Ang) I, Ang‐(1‐7), and angiotensin‐converting enzyme 2 in comparison with controls . This may be a regulatory response to an inflammatory process, which is triggered by LUTO .…”

“…However, increased urinary levels of RAS components like angiotensin (Ang) I, angiotensin‐converting enzyme (ACE) 2, and Ang‐(1‐7) were reported in fetuses with posterior urethral valves. Furthermore, it has been shown that ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valves in comparison with controls . Therefore, it is assumed that there might be a link between RAS and LUTO .…”

“…Fetal lower urinary tract obstruction (LUTO) can lead to progressive renal dysfunction and postnatal end‐stage renal disease . The outcome of LUTO fetuses appears to be dependent on the severity of prenatal kidney damage . Renal ultrasound markers as well as analysis of fetal urine biochemistry can provide valuable information about the severity of LUTO and the prognosis for renal function …”

“…Some authors assume that megacystis and the associated compression of the iliac arteries lead to an increased afterload with potential hemodynamic consequences . However, recent data on fetal urine biochemistry showed that fetuses with LUTO present increased levels of renin‐angiotensin system (RAS) components, which lead to the hypothesis of a linked pathophysiology between RAS and LUTO . Experimental evidence that the classical RAS arm contributes to tubulointerstitial scarring in LUTO was already provided …”