Cardiorenal Syndrome is Present in Human Fetuses with Severe, Isolated Urinary Tract Malformations

Abstract

ObjectiveWe analyzed the association between renal and cardiovascular parameters in fetuses with isolated severe urinary tract malformations.Methods39 fetuses at a mean gestational age of 23.6 weeks with nephropathies or urinary tract malformations and markedly impaired or absent renal function were prospectively examined. Fetal echocardiography was performed, and thicknesses of the interventricular septum, and left and right ventricular wall were measured. Blood flow velocity waveforms of the umbilical artery, middle cerebral artery, and ductus venosus were obtained by color Doppler ultrasound. Concentrations of circulating n-terminal pro-B-type natriuretic peptide (nt-proBNP), cystatin C, ß2-microglobulin, and hemoglobin were determined from fetal blood samples.ResultsMalformations included 21 cases of obstructive uropathy, 10 fetuses with bilateral nephropathy, and 8 cases of bilateral renal agenesis. Marked biventricular myocardial hypertrophy was present in all cases. The ratio between measured and gestational age-adjusted normal values was 2.01 (interventricular septum), 1.85, and 1.78 (right and left ventricular wall, respectively). Compared to controls, levels of circulating nt-proBNP were significantly increased (median (IQR) 5035 ng/L (5936 ng/L) vs. 1874 ng/L (1092 ng/L); p<0.001). Cystatin C and ß2-microglobulin concentrations were elevated as follows (mean ± SD) 1.85±0.391 mg/L and 8.44±2.423 mg/L, respectively (normal range 1.66±0.202 mg/L and 4.25±0.734 mg/L, respectively). No correlation was detected between cardiovascular parameters and urinary tract morphology and function. Despite increased levels of nt-proBNP cardiovascular function was preserved, with normal fetal Doppler indices in 90.2% of cases.ConclusionUrinary tract malformations resulting in severe renal impairment are associated with biventricular myocardial hypertrophy and elevated concentrations of circulating nt-proBNP during fetal life. Cardiovascular findings do not correlate with kidney function or morphology.

The expanded spectrum of human disease associated with GREB1L likely includes complex congenital heart disease

“…Additionally, left ventricular hypertrophy may represent fetal cardio renal syndrome caused by increased systemic vascular resistance in the setting of bilateral renal agenesis. 37 Interestingly, the GREB1L variants associated with complex CHD lie in exons 24 and 26, near previously described variants associated with aortic stenosis and left ventricular hypertrophy in exons 26 and 27. 1,12 This region in GREB1L is highly -347 homologous to a region in GREB1, which includes a putative glycosyltransferase domain.…”

“…Hypertrophy of the LV could be attributable to undetected outflow tract obstructions, or alternatively could represent fetal cardiorenal syndrome related to renal agenesis. 37 Determining the full spectrum of GREB1L-associated disease has been limited by several factors. As demonstrated by our literature review, human studies of GREB1L have focused predominantly on anomalies of the kidney, uterus, vagina, and sensorineural hearing loss.…”

Neonatal mortality in dogs: Prognostic value of Doppler ductus venosus waveform evaluation - Preliminary results

“…However, in human fetuses with severe urinary tract malformations, a cardiorenal syndrome characterized by a bilateral ventricular hypertrophy (caused by an increased afterload) was described by Merz et al . [ 22 ] and it is known that a reverse DV a-wave (tDVw) can be a consequence of an increase afterload [ 7 ].…”

Old tool – new application: NT‐proBNP in fetal medicine

“…Extending findings of left ventricular dysfunction in pediatric cases of chronic kidney disease, Merz et al . investigated fetuses with severe, isolated urinary tract malformations (bilateral renal agenesis, bilateral nephropathies, obstructive uropathies).…”