A Premature Baby with Severe Oligohydramnios and Hypotension: a Case Report of Renal Tubular Dysgenesis

Min, Jeesu; Cho, Myung Hyun; Bae, Seong Phil; Shin, Seung Han; Ha, Il Soo; Cheong, Hae Il; Kang, Hee Gyung

doi:10.3346/jkms.2020.35.e283

Cited by 4 publications

(1 citation statement)

References 20 publications

(46 reference statements)

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“…In support of this mechanism, we show that H + excretion is also stimulated by the administration of fludrocortisone and that amiloride has the exact opposite effect on urinary K + and H + excretion. The use of fludrocortisone as a treatment in RTD patients has been suggested before [ 6 , 10 , 25 ]. However, the exact effects of fetal RAS dysfunction on the development of the different tubular segments are still largely unknown, as is the functionality of the different segments and molecular transporters.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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Patterns of differentiation of renin lineage cells during nephrogenesis

Kessel

Steglich

Hickmann

et al. 2021

American Journal of Physiology-Renal Physiology

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Developmentally heterogeneous renin expressing cells serve as progenitors for mural, glomerular and tubular cells during nephrogenesis and are collectively termed renin lineage cells (RLCs). In this study, we quantified different renal vascular and tubular cell types based on specific markers, assessed proliferation, and de-novo differentiation in the RLC population. We used kidney sections of mRenCre-mT/mG mice throughout nephrogenesis. Marker positivity was evaluated in whole digitalized sections. At embryonic day 16, RLCs appeared in the developing kidney, and expression of all stained markers in RLCs was observed. The proliferation rate of RLCs did not differ from the proliferation rate of non-RLCs. The RLCs expanded mainly by de-novo differentiation (neogenesis). The fractions of RLCs originating from the stromal progenitors of the metanephric mesenchyme (renin producing cells, vascular smooth muscle cells, mesangial cells) decreased during nephrogenesis. In contrast, aquaporin 2 positive RLCs in the collecting duct system that embryonically emerges almost exclusively from the ureteric bud, expanded postpartum. The cubilin positive RLC fraction in the proximal tubule, deriving from the cap mesenchyme, remained constant. During nephrogenesis, RLCs were continuously detectable in the vascular and tubular compartments of the kidney. Therein, various patterns of RLC differentiation that depend on the embryonic origin of the cells were identified.

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Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline

Wopperer,

Olinger,

Wiesener

et al. 2024

Hypertension

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BACKGROUND: Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the REN (renin)-angiotensin system. Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms. METHODS: Exome sequencing for a gene panel associated with renal disease was performed. The REN-angiotensin system was assessed by comprehensive biochemical analysis in blood. REN expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project. RESULTS: The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the AGT (angiotensinogen) gene. Blood AGT concentrations were low, but plasma REN concentration and gene expression in kidney biopsy, vascular, and tubular cells revealed strong upregulation of REN. Angiotensin II and aldosterone in blood were not abnormally elevated. CONCLUSIONS: Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the renin-angiotensin system in a patient with AGT mutation revealed novel insights regarding compensatory upregulation of REN in vascular and tubular cells of the kidney and in plasma in response to depletion of AGT substrate as a source of Ang II (similarly observed with hepatic AGT silencing for the treatment of hypertension).

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A Premature Baby with Severe Oligohydramnios and Hypotension: a Case Report of Renal Tubular Dysgenesis

Cited by 4 publications

References 20 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

Patterns of differentiation of renin lineage cells during nephrogenesis

Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline

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