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Survival over 2 years of autosomal-recessive renal tubular dysgenesis.

Kim SY, Kang HG, Kim EK, Choi JH, Choi Y, Cheong HI - Clin Kidney J (2012)

Bottom Line: Although AR-RTD has typically been known as a lethal disease due to refractory hypotension and renal failure immediately after birth, few cases have reported survival of the neonatal period.We report here an additional case of AR-RTD, who had novel ACE mutations and survived over 2 years and provide a review of the five previously reported surviving cases.In conclusion, AR-RTD is not a uniformly fatal disease, although factors affecting the survival remain unknown.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

ABSTRACT
Autosomal-recessive renal tubular dysgenesis (AR-RTD) is a rare disorder caused by a genetic defect in the renin-angiotensin system. Although AR-RTD has typically been known as a lethal disease due to refractory hypotension and renal failure immediately after birth, few cases have reported survival of the neonatal period. We report here an additional case of AR-RTD, who had novel ACE mutations and survived over 2 years and provide a review of the five previously reported surviving cases. In conclusion, AR-RTD is not a uniformly fatal disease, although factors affecting the survival remain unknown.

No MeSH data available.


Related in: MedlinePlus

Possible sequential changes in the renin–angiotensin–aldosterone system in the present case.  decreased or absent ACE activity due to genetic mutations,  compensatory overproduction of Angiotensin I, the substrate of ACE and  conversion of a small portion of Angiotensin I to Angiotensin II by minimally functioning mutant (p.R259H) ACE or via other proteolytic enzyme systems such as chymases and tissue plasminogen activators (t-PA).
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fig1: Possible sequential changes in the renin–angiotensin–aldosterone system in the present case. decreased or absent ACE activity due to genetic mutations, compensatory overproduction of Angiotensin I, the substrate of ACE and conversion of a small portion of Angiotensin I to Angiotensin II by minimally functioning mutant (p.R259H) ACE or via other proteolytic enzyme systems such as chymases and tissue plasminogen activators (t-PA).

Mentions: Renal hypoperfusion is probably the cardinal lesion leading to AR-RTD because the same tubular lesions can be produced secondarily by various fetal conditions associated with insufficient renal blood supply and consequent marked stimulation of the RAS, including renal artery stenosis and fetal exposure to RAS blockers [4]. Therefore, the presumed consequence of all mutations observed in AR-RTD is the absence of Angiotensin II production or function [4]. However, the profiles of RAS components vary according to the underlying genetic defect of individual patient [7]. A patient with ACE mutations revealed a high plasma renin activity, high active renin concentration and low ACE concentration [7], as shown in the present case. In addition, the present case revealed markedly increased Angiotensin I level with mildly increased Angiotensin II and aldosterone levels. The interpretation of the hormonal changes in the present case may be as follows: (i) production of Angiotensin I, the substrate of ACE, is markedly increased to overcome the defective ACE activity, (ii) the missense (p.R259H) mutant ACE has minimal residual function or other proteolytic enzyme systems are activated due to defective ACE function and (iii) a small portion of markedly increased Angiotensin I is converted to Angiotensin II by minimally functioning mutant ACE or via other proteolytic enzyme systems (Figure 1). The compensatory increase of Angiotensin II may be the cause of survival and milder course of the patient. Schreiber et al. [8] recommended an early trial of mineralocorticoids to overcome extreme hypotension and hyperkalemia in patients with RTD.


Survival over 2 years of autosomal-recessive renal tubular dysgenesis.

Kim SY, Kang HG, Kim EK, Choi JH, Choi Y, Cheong HI - Clin Kidney J (2012)

Possible sequential changes in the renin–angiotensin–aldosterone system in the present case.  decreased or absent ACE activity due to genetic mutations,  compensatory overproduction of Angiotensin I, the substrate of ACE and  conversion of a small portion of Angiotensin I to Angiotensin II by minimally functioning mutant (p.R259H) ACE or via other proteolytic enzyme systems such as chymases and tissue plasminogen activators (t-PA).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400456&req=5

fig1: Possible sequential changes in the renin–angiotensin–aldosterone system in the present case. decreased or absent ACE activity due to genetic mutations, compensatory overproduction of Angiotensin I, the substrate of ACE and conversion of a small portion of Angiotensin I to Angiotensin II by minimally functioning mutant (p.R259H) ACE or via other proteolytic enzyme systems such as chymases and tissue plasminogen activators (t-PA).
Mentions: Renal hypoperfusion is probably the cardinal lesion leading to AR-RTD because the same tubular lesions can be produced secondarily by various fetal conditions associated with insufficient renal blood supply and consequent marked stimulation of the RAS, including renal artery stenosis and fetal exposure to RAS blockers [4]. Therefore, the presumed consequence of all mutations observed in AR-RTD is the absence of Angiotensin II production or function [4]. However, the profiles of RAS components vary according to the underlying genetic defect of individual patient [7]. A patient with ACE mutations revealed a high plasma renin activity, high active renin concentration and low ACE concentration [7], as shown in the present case. In addition, the present case revealed markedly increased Angiotensin I level with mildly increased Angiotensin II and aldosterone levels. The interpretation of the hormonal changes in the present case may be as follows: (i) production of Angiotensin I, the substrate of ACE, is markedly increased to overcome the defective ACE activity, (ii) the missense (p.R259H) mutant ACE has minimal residual function or other proteolytic enzyme systems are activated due to defective ACE function and (iii) a small portion of markedly increased Angiotensin I is converted to Angiotensin II by minimally functioning mutant ACE or via other proteolytic enzyme systems (Figure 1). The compensatory increase of Angiotensin II may be the cause of survival and milder course of the patient. Schreiber et al. [8] recommended an early trial of mineralocorticoids to overcome extreme hypotension and hyperkalemia in patients with RTD.

Bottom Line: Although AR-RTD has typically been known as a lethal disease due to refractory hypotension and renal failure immediately after birth, few cases have reported survival of the neonatal period.We report here an additional case of AR-RTD, who had novel ACE mutations and survived over 2 years and provide a review of the five previously reported surviving cases.In conclusion, AR-RTD is not a uniformly fatal disease, although factors affecting the survival remain unknown.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

ABSTRACT
Autosomal-recessive renal tubular dysgenesis (AR-RTD) is a rare disorder caused by a genetic defect in the renin-angiotensin system. Although AR-RTD has typically been known as a lethal disease due to refractory hypotension and renal failure immediately after birth, few cases have reported survival of the neonatal period. We report here an additional case of AR-RTD, who had novel ACE mutations and survived over 2 years and provide a review of the five previously reported surviving cases. In conclusion, AR-RTD is not a uniformly fatal disease, although factors affecting the survival remain unknown.

No MeSH data available.


Related in: MedlinePlus