Renal function in angiotensinogen gene-mutated renal tubular dysgenesis with glomerular cysts

Hibino, Satoshi; Sasaki, Hiroshi; Abe, Yoshifusa; Hojo, Akira; Uematsu, Mitsugu; Sekine, Takashi; Itabashi, Kazuo

doi:10.1007/s00467-014-3007-0

Cited by 7 publications

(11 citation statements)

References 16 publications

(37 reference statements)

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“…Furthermore, the patient reported here was not anuric or severely oligouric after birth. Lastly, the kidney biopsy did not show full-blown RTD: proximal tubules were mostly normal, in agreement with other available kidney histology reports from survivors [5,11,27], and although arterioles showed hypertrophic changes, arteries did not show evident wall thickening, in contrast to reports from both survivors and nonsurvivors [3-5, 11, 14, 30]. We hypothesize that the perinatal preservation of glomerular filtration and urine production might have protected our patient from severe complications such as pulmonary hypoplasia and the damaging effects of kidney failure itself, which, together with adequate supportive care, allowed our patient to survive the perinatal period.…”

Section: Discussionsupporting

confidence: 91%

“…In 2014, when approximately 150 cases of RTD had been reported, data on only ten long-term survivors was available (reviewed in [1]) [1,4,7,14,[26][27][28]. Since then, only seven more survivors have been described [5,6,[10][11][12]. The patient we present here is the only reported long-term survivor with biallelic variants in AGTR1.…”

Section: Discussionmentioning

confidence: 99%

“…Children with pathogenic variants in a RAS component typically die in utero or in the first days of life and develop stage 5 chronic kidney disease (CKD 5) at a young age [3,4]. Salt-wasting and hyperkalemia have been reported in several cases [5][6][7]. Biallelic pathogenic variants have been described in four essential genes of the RAS: angiotensinogen (AGT), renin (REN), angiotensin-converting enzyme (ACE) and the angiotensin II receptor (AGTR1) [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Survival without the need for kidney replacement therapy has been described in patients with biallelic pathogenic variants in ACE, AGT or REN [4][5][6][7][10][11][12][13][14]. Nevertheless, several questions remain unanswered.…”

Section: Introductionmentioning

confidence: 99%

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Functional tests to guide management in an adult with loss of function of type-1 angiotensin II receptor

et al. 2021

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Background Genetic loss of function of AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), or AGTR1 (type-1 angiotensin II receptor) leads to renal tubular dysgenesis (RTD). This syndrome is almost invariably lethal. Most surviving patients reach stage 5 chronic kidney disease at a young age. Methods Here, we report a 28-year-old male with a homozygous truncating mutation in AGTR1 (p.Arg216*), who survived the perinatal period with a mildly impaired kidney function. In contrast to classic RTD, kidney biopsy showed proximal tubules that were mostly normal. During the subsequent three decades, we observed evidence of both tubular dysfunction (hyperkalemia, metabolic acidosis, salt-wasting and a urinary concentrating defect) and glomerular dysfunction (reduced glomerular filtration rate, currently ~30 mL/min/1.73 m2, accompanied by proteinuria). To investigate the recurrent and severe hyperkalemia, we performed a patient-tailored functional test and showed that high doses of fludrocortisone induced renal potassium excretion by 155%. Furthermore, fludrocortisone lowered renal sodium excretion by 39%, which would have a mitigating effect on salt-wasting. In addition, urinary pH decreased in response to fludrocortisone. Opposite effects on urinary potassium and pH occurred with administration of amiloride, further supporting the notion that a collecting duct is present and able to react to fludrocortisone. Conclusions This report provides living proof that even truncating loss-of-function mutations in AGTR1 are compatible with life and relatively good GFR and provides evidence for the prescription of fludrocortisone to treat hyperkalemia and salt-wasting in such patients.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Functional tests to guide management in an adult with loss of function of type-1 angiotensin II receptor

et al. 2021

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“…Because the management of arterial hypotension and anuria influences the survival of an infant with RTD, early diagnosis of an anuric fetus with insufficient concrete findings on a fetal renal ultrasound is critical. Although RTD has typically been known as a fatal disease, several cases of survival after the neonatal period have recently been reported (Uematsu et al 2006(Uematsu et al , 2009Zingg-Schenk et al 2008;Danilov et al 2010;Schreiber et al 2010;Kim et al 2012;Hibino et al 2015;Richer et al 2015;Ruf et al 2018). We report here a case of an extremely preterm infant (among preterm infants, those born less than 28 weeks of gestation) with RTD managed without renal replacement therapy and discuss the most appropriate management of RTD based on the course of treatment (for this case) and a review of the literature.…”

Section: Introductionmentioning

confidence: 96%

Management of a Preterm Infant with Renal Tubular Dysgenesis: A Case Report and Review of the Literature

Kondoh

Kawai

Matsumoto

et al. 2020

Tohoku J. Exp. Med.

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Renal tubular dysgenesis (RTD) is the absence or poor development of the renal proximal tubules caused by gene mutations in the renin-angiotensin system. Although RTD has been considered fatal, improving neonatal intensive care management has enhanced survival outcomes. However, little has been reported on the survival of extremely preterm infants. This study reports the survival of an extremely preterm infant with RTD and discusses the appropriate management of RTD by reviewing the literature. A female infant weighing 953 g was delivered at 27 weeks' gestation by Cesarean section because of oligohydramnios. She exhibited severe persistent pulmonary hypertension, severe systemic hypotension, and renal dysfunction shortly after birth. Respiratory management was successfully undertaken using nitric oxide inhalation and high-frequency oscillatory ventilation. Desmopressin was effective in maintaining her blood pressure and urinary output. She was diagnosed with RTD based on genetic testing, which revealed a compound heterozygous mutation in the angiotensin-converting enzyme gene in exon 18 (c.2689delC; p.Pro897fs) and exon 20 (c.3095dupT; p.Leu1032fs). At 2 years, she started receiving oral fludrocortisone for treating persistently high serum creatinine levels, which was attributed to nephrogenic diabetes insipidus caused by RTD. Subsequently, her urine output decreased, and renal function was successfully maintained. Currently, there is no established treatment for RTD. Considering cases reported to date, treatment with vasopressin and fludrocortisone appears to be most effective for survival and maintenance of renal function in patients with RTD. This study presents the successful management of RTD using this strategy in an extremely preterm infant.

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Expanding the clinical spectrum of autosomal‐recessive renal tubular dysgenesis: Two siblings with neonatal survival and review of the literature

Vincent

Alrajhi

Lazier

et al. 2022

Molec Gen & Gen Med

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Background Autosomal‐recessive renal tubular dysgenesis (AR‐RTD) is a rare genetic disorder caused by defects in the renin‐angiotensin system that manifests as fetal anuria leading to oligohydramnios and Potter sequence. Although the most common outcome is neonatal death from renal failure, pulmonary hypoplasia, and/or refractory arterial hypotension; several cases have been reported that describe survival past the neonatal period. Methods Herein, we report the first family with biallelic ACE variants and more than one affected child surviving past the neonatal period, as well as provide a review of the previously reported 18 cases with better outcomes. Results While both siblings with identical compound heterozygous ACE variants have received different treatments, neither required renal replacement therapy. We show that both vasopressin and fludrocortisone in the neonatal period may provide survival advantages, though outcomes may also be dependent on the type of gene variant, as well as other factors. Conclusion While AR‐RTD is most often a lethal disease in the neonatal period, it is not universally so. A better understanding of the factors affecting survival will help to guide prognostication and medical decision‐making.

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Renal function in angiotensinogen gene-mutated renal tubular dysgenesis with glomerular cysts

Cited by 7 publications

References 16 publications

Functional tests to guide management in an adult with loss of function of type-1 angiotensin II receptor

Functional tests to guide management in an adult with loss of function of type-1 angiotensin II receptor

Management of a Preterm Infant with Renal Tubular Dysgenesis: A Case Report and Review of the Literature

Expanding the clinical spectrum of autosomal‐recessive renal tubular dysgenesis: Two siblings with neonatal survival and review of the literature

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