RTD is a rare disorder, characterized by prematurity, oligo- or anhydramnios, severe arterial hypotension and neonatal renal failure. It is a hyterozygous inherited autosomal-recessive disease with over 50 reported mutations [2]. It affects angiotensinogen, angiotensinogen receptor 1, renin or angiotensin converting enzyme genes in the Renin angiotensin system (RAAS) without a predictive genotype-phenotype correlation so far. Similar clinical findings have been observed in children exposed to RAAS blockage during pregnancy [3], highlighting the importance of RAAS for kidney development. So far, about 150 cases of RTD have been published [2], however, only about 10 long-term survivors have been reported [2, 4]; in most cases RTD is fatal either in utero or shortly after birth [5]. Differentiated proximal tubules are significantly reduced or even absent [5] on histological examinations of the patients’ kidneys. Prenatal signs of RTD are oligo- or anhydramnios and lack of concrete findings in prenatal urinary tract ultrasound. After birth, hallmark signs are a varying degree of Potter sequence with facial abnormalities and pulmonary hypoplasia, hypocalvaria and contractures of joints [2]. Patients present with severe, therapy refractory arterial hypotension, anuria and usually need respiratory support [5].
Hypotension and anuria amongst reported survivors were refractory to the usual treatment of fluid boluses, furosemide, catecholamine therapy and hydrocortisone treatment. Nearly all patients required peritoneal dialysis for the first days or weeks of life until diuresis was established. In two reported cases the continuous infusion of Fresh Frozen Plasma helped to increase blood pressure but peritoneal dialysis was still necessary [6, 7]. Only one child is reported so far that did not need peritoneal dialysis. Richer et al. report a preterm infant (26 + 5 gestational age) developing adequate blood pressure and diuresis when started on continuous vasopressin infusion on day 8 of life [8]. Our patient is only the second one described without renal replacement therapy in the neonatal period and also the second one having received vasopressin.
The application of intravenous vasopressin increases arterial blood pressure by a direct vasoconstrictive effect via V1 receptors and a local inhibition of nitric oxide production. At the same time, renal blood flow is enhanced possibly through selective efferent arteriolar constriction and nitric oxide mediated afferent arteriolar vasodilatation [9]. Some studies have found vasopressin helpful in catecholamine refractory arterial hypotension in septic and cardiac shock although its role is not yet clear [10]. In these studies, vasopressin significantly raised mean arterial blood pressure and urinary output [9, 11].
In all reported survivors of RTD, blood pressure and diuresis normalized, hypoaldosteronism though, persisted in most cases, rendering a fludrocortisone therapy necessary [2, 4, 6,7,8].
Our patient suffered from spontaneous gastric perforation. The mechanism is unclear, a hypoperfusion of the intestines and some intraluminal pressure for example due to the gastric tube may be a likely explanation. Few reports exist on gastric perforation through nasogastric tubes in preterm infants as most perforations are seen in the esophagus [12]. The patient reported by Kim et al. developed an ileac perforation in the neonatal period [4] which may be related to arterial hypotension in RTD, the patient reported by Richer et al. suffered from necrotizing enterocolitis. Whether this is related to RTD or extreme prematurity remains uncertain [8]. Since the number of survivors reported is small, it is difficult to assess whether a certain percentage of these patients suffers from intestinal perforations; however, due to hypoperfusion of the intestines a causative relation seems possible. Whether intestinal hypoperfusion is the result of underlying disease or impaired microcirculation due to the use of vasopressors remains unclear. Also, the administration of hydrocortisone has been associated with spontaneous intestinal perforations in the past [13]. So far, these have not been described in secondary RTD caused by exposure to RAAS blockers during pregnancy [3]. In patients who developed intestinal perforations, peritoneal dialysis is not an option; all reported patients were born preterm and of very low birthweight making also hemodialysis impossible.
As the patient described by Kim et al. [4], the use of vasopressin may have prevented renal replacement therapy in our patient by establishing sufficient renal perfusion and consecutively urinary output.
In the few survivors reported, chronic or end-stage renal disease is present [2], in one case renal transplantation at the age of 4 was performed [14], another patient needed peritoneal dialysis [7]. However, as stated by the authors, all patients show normal cognitive development.
