Talk:Renal System - Abnormalities

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Cite this page: Hill, M.A. (2024, June 21) Embryology Renal System - Abnormalities. Retrieved from


Avanoglu A & Tiryaki S. (2020). Embryology and Morphological (Mal)Development of UPJ. Front Pediatr , 8, 137. PMID: 32318525 DOI.

Embryology and Morphological (Mal)Development of Ureteropelvic Junction

Kidney parenchyma and collecting system arise from two different embryologic units as a result of a close interaction between them. Therefore, their congenital abnormalities are classified together under the same heading named CAKUT (congenital abnormalities of the kidney and urinary tract). The pathogenesis of CAKUT is thought to be multifactorial. Ureteropelvic junction obstruction (UPJO) is the most common and most investigated form of CAKUT. Despite years of experimental and clinical research, and the information gained on the embryogenesis of the kidney; its etiopathogenesis is still unclear. It involves both genetic and environmental factors. Failure in development of the renal pelvis, failure in the recanalization of ureteropelvic junction, abnormal pyeloureteral innervation, and impaired smooth muscle differentiation are the main proposed mechanisms for the occurrence of UPJO. There are also single gene mutations like AGTR2, BMP4, Id2 proposed in the etiopathogenesis of UPJO. Copyright © 2020 Avanoglu and Tiryaki. KEYWORDS: BMP4; congenital anomalies of the kidney and urinary tract; embryology; genetics; ureteropelvic junction obstruction PMID: 32318525 PMCID: PMC7154125 DOI: 10.3389/fped.2020.00137


Ectopias of the kidney, urinary tract organs, and male genitalia

Pathologe. 2018 Nov 16. doi: 10.1007/s00292-018-0505-z. [Epub ahead of print]

Mikuz G1. Author information Abstract The most frequent anomaly of the urogenital tract is a simple renal ectopia with one organ lying in the pelvis. Crossed renal ectopia is a less common condition in which the ectopic kidney is located on the opposite side of the midline from the ureteral insertion in the urinary bladder. The cause of both types of renal ectopia is the arrest or failure of the kidney ascent from the pelvic to the lumbar position. Whereas an accelerated ascent leads to a subdiaphragmal or intrathoracic ectopic position, an ectopic ureter can be defined as one that does not drain into the trigonum vesicae. The ectopic orificium can be located situated in the bladder neck and urethra as well as somewhere in the genital area.Exstrophy of the urinary bladder is not a complete ectopia. Because the abdominal wall and the anterior part of the bladder wall are lacking, the bladder mucosa grows directly into the skin. The complex exstrophy of the bladder and intestine corresponds to a cloacal exstrophy, in which the bladder is split in two halves on either side of the gut portion. Testicular ectopia refers to the location of the testis in a position outside of its normal course of descent.Prostatic ectopia does not refer to the wrong location of the entire organ, but to a scattered group of prostate glands, which are mostly found in the submucosal part of the urinary bladder or proximal urethra. Other described locations are the intestinal wall, anus, pericolic fat tissue, spleen, seminal vesicle, testis, and cervix uteri.The associated ectopic penis, scrotum, and penoscrotal transposition are the least common and probably the absolutely most unknown malformations of the male genitalia. The ectopic penis and scrotum are located in the perineum, whereas in the transposition the penis lies above the scrotum. KEYWORDS: Bladder exstrophy; Choristoma; Cloaca; Embryology; Penoscrotal transposition PMID: 30446779


Outcome after prenatal diagnosis of congenital anomalies of the kidney and urinary tract

Eur J Pediatr. 2016 May;175(5):667-76. doi: 10.1007/s00431-015-2687-1. Epub 2016 Jan 25.

Nef S1, Neuhaus TJ2, Spartà G3, Weitz M3, Buder K3, Wisser J4, Gobet R3, Willi U3, Laube GF3.


Congenital anomalies of the kidney and urinary tract are common findings on fetal ultrasound. The aim of this prospective observational study was to describe outcome and risk factors in 115 patients born 1995-2001. All prenatally diagnosed children were stratified into low- and high-risk group and followed postnatally clinically and by imaging at defined endpoints. Risk factors were evaluated using odds ratios. Neonatal diagnosis included pelvi-ureteric junction obstruction (n = 33), vesicoureteral reflux (n = 27), solitary mild pelvic dilatation (postnatal anteroposterior diameter 5-10 mm; n = 25), and further diagnosis as primary obstructive megaureter, unilateral multicystic dysplastic kidney, renal dysplasia and posterior urethral valves. In 38 children with prenatal isolated hydronephrosis, ultrasound normalized at median age of 1.2 years (range 0.1-9). Surgery was performed in 34 children at median age of 0.4 years (0.1-10.8). Persistent renal anomalies without surgery were present in 43 children and followed in 36 for median time of 16 years (12.2-18). Oligohydramnios and postnatal bilateral anomalies were significantly associated with surgery and impaired renal function. CONCLUSION: The majority of children had a favourable postnatal outcome, in particular children with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis. Oligohydramnios and postnatal bilateral anomalies were risk factors for non-favourable outcome. WHAT IS KNOWN: • In congenital anomalies of the kidney and urinary tract significantly poorer outcome is known in patients with bilateral renal hypoplasia or solitary kidney associated with posterior urethral valves. • Other factors as proteinuria and vesicoureteral reflux were associated with a higher risk of progression to chronic renal failure in these patients. What is New: • Unlike other studies giving us above-mentioned information, we included all patients with any kind of prenatally diagnosed congenital anomalies of the kidney and urinary tract. Our study shows long-term follow up (median 16 years, range 12.2-18 years), especially in patients not needing surgery, but with persistent anomalies. • During postnatal long-term follow up (median 2.2 years, range 0.1-18 years) one third each showed normalization, need of surgery or persistence of anomalies without need of surgery. Our study revealed a good prognosis in the majority of these children, in particular with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis, and revealed oligohydramnios and postnatal bilateral anomalies as risk factors for a non-favourable outcome, defined as need of surgery, persistent anomalies with impaired renal function, end stage renal failure or death. KEYWORDS: Congenital anomalies of the kidney and urinary tract (CAKUT); Outcome; Postnatal; Prenatal; Risk factors PMID: 26805407 DOI: 10.1007/s00431-015-2687-1


Prenatal Diagnosis and Perinatal Outcomes of Congenital Megalourethra: A Multicenter Cohort Study and Systematic Review of the Literature

J Ultrasound Med. 2015 Nov;34(11):2057-64. doi: 10.7863/ultra.14.12064. Epub 2015 Oct 7.

Moaddab A1, Sananes N1, Hernandez-Ruano S1, Werneck Britto IS1, Blumenfeld Y1, Stoll F1, Favre R1, Ruano R2.


OBJECTIVES: The purpose of this study was to evaluate the prenatal findings and postnatal outcomes in fetuses with congenital megalourethra. METHODS: This retrospective study reviewed our experience and the literature between 1989 and 2014. Prenatal findings were evaluated and compared with postnatal findings, including neonatal mortality and abnormal renal function (need for dialysis or renal transplantation). RESULTS: Fifty fetuses with congenital megalourethra were analyzed, including 6 cases diagnosed in our centers. Most cases (n = 43 [86.0%]) were diagnosed in the second trimester. Only 1 case was diagnosed in the first trimester, whereas 6 cases (12.0%) were diagnosed in the third trimester. Thirty-five fetuses (70.0%) survived. Bilateral hydroureters were associated with perinatal death (P= .024). Among the survivors, 41.9% of the neonates had renal impairment. The following factors were associated with postnatal renal impairment: presence of severe oligohydramnios/anhydramnios (P = .033), bilateral hydronephrosis (P = .008), and earlier gestational age at delivery (P = .022). CONCLUSIONS: In fetal megalourethra, bilateral hydroureters, bilateral hydronephrosis, and severe oligohydramnios/anhydramnios are associated with neonatal mortality and renal impairment. © 2015 by the American Institute of Ultrasound in Medicine. KEYWORDS: anterior urethral valves; congenital megalourethra; fetal surgery; lower urinary tract obstruction; obstetric ultrasound; posterior urethral valves; urethral atresia PMID 26446816

See also PMID 25197200

WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish

Hum Mol Genet. 2015 Sep 15;24(18):5069-78. doi: 10.1093/hmg/ddv225. Epub 2015 Jun 23.

Baranowska Körberg I1, Hofmeister W2, Markljung E3, Cao J3, Nilsson D4, Ludwig M5, Draaken M6, Holmdahl G7, Barker G8, Reutter H9, Vukojević V10, Clementson Kockum C11, Lundin J1, Lindstrand A12, Nordenskjöld A13.


Bladder exstrophy, a severe congenital urological malformation when a child is born with an open urinary bladder, is the most common form of bladder exstrophy-epispadias complex (BEEC) with an incidence of 1:30,000 children of Caucasian descent. Recent studies suggest that WNT genes may contribute to the etiology of bladder exstrophy. Here, we evaluated WNT-pathway genes in 20 bladder exstrophy patients using massively parallel sequencing. In total 13 variants were identified in WNT3, WNT6, WNT7A, WNT8B, WNT10A, WNT11, WNT16, FZD5, LRP1 and LRP10 genes and predicted as potentially disease causing, of which seven variants were novel. One variant, identified in a patient with a de novo nonsynonymous substitution in WNT3 (p.Cys91Arg), was further evaluated in zebrafish. Knock down of wnt3 in zebrafish showed cloaca malformations, including disorganization of the cloaca epithelium and expansion of the cloaca lumen. Our study suggests that the function of the WNT3 p.Cys91Arg variant was altered, since RNA overexpression of mutant Wnt3 RNA does not result in embryonic lethality as seen with wild-type WNT3 mRNA. Finally, we also mutation screened the WNT3 gene further in 410 DNA samples from BEEC cases and identified one additional mutation c.638G>A (p.Gly213Asp), which was paternally inherited. In aggregate our data support the involvement of WNT-pathway genes in BEEC and suggest that WNT3 in itself is a rare cause of BEEC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:

PMID 26105184

Urothelial Defects from Targeted Inactivation of Exocyst Sec10 in Mice Cause Ureteropelvic Junction Obstructions

PLoS One. 2015 Jun 5;10(6):e0129346. doi: 10.1371/journal.pone.0129346.

Fogelgren B1, Polgar N1, Lui VH1, Lee AJ1, Tamashiro KK1, Napoli JA1, Walton CB2, Zuo X3, Lipschutz JH4.


Most cases of congenital obstructive nephropathy are the result of ureteropelvic junction obstructions, and despite their high prevalence, we have a poor understanding of their etiology and scarcity of genetic models. The eight-protein exocyst complex regulates polarized exocytosis of intracellular vesicles in a large variety of cell types. Here we report generation of a conditional knockout mouse for Sec10, a central component of the exocyst, which is the first conditional allele for any exocyst gene. Inactivation of Sec10 in ureteric bud-derived cells using Ksp1.3-Cre mice resulted in severe bilateral hydronephrosis and complete anuria in newborns, with death occurring 6-14 hours after birth. Sec10FL/FL;Ksp-Cre embryos developed ureteropelvic junction obstructions between E17.5 and E18.5 as a result of degeneration of the urothelium and subsequent overgrowth by surrounding mesenchymal cells. The urothelial cell layer that lines the urinary tract must maintain a hydrophobic luminal barrier again urine while remaining highly stretchable. This barrier is largely established by production of uroplakin proteins that are transported to the apical surface to establish large plaques. By E16.5, Sec10FL/FL;Ksp-Cre ureter and pelvic urothelium showed decreased uroplakin-3 protein at the luminal surface, and complete absence of uroplakin-3 by E17.5. Affected urothelium at the UPJ showed irregular barriers that exposed the smooth muscle layer to urine, suggesting this may trigger the surrounding mesenchymal cells to overgrow the lumen. Findings from this novel mouse model show Sec10 is critical for the development of the urothelium in ureters, and provides experimental evidence that failure of this urothelial barrier may contribute to human congenital urinary tract obstructions.

PMID 26046524

The long-term management and outcomes of cloacal anomalies

Pediatr Nephrol. 2015 May;30(5):759-65. doi: 10.1007/s00467-014-2875-7. Epub 2014 Sep 13.

Fernando MA1, Creighton SM, Wood D.


Cloacal anomalies occur when failure of the urogenital septum to separate the cloacal membrane results in the urethra, vagina, rectum and anus opening into a single common channel. The reported incidence is 1:50,000 live births. Short-term paediatric outcomes of surgery are well reported and survival into adulthood is now usual, but long-term outcome data are less comprehensive. Chronic renal failure is reported to occur in 50 % of patients with cloacal anomalies, and 26-72 % (dependant on the length of the common channel) of patients experience urinary incontinence in adult life. Defaecation is normal in 53 % of patients, with some managed by methods other than surgery, including medication, washouts, stoma and antegrade continent enema. Gynaecological anomalies are common and can necessitate reconstructive surgery at adolescence for menstrual obstruction. No data are currently available on sexual function and little on the quality of life. Pregnancy is extremely rare and highly risky. Patient care should be provided by a multidisciplinary team with experience in managing these and other related complex congenital malformations. However, there is an urgent need for a well-planned, collaborative multicentre prospective study on the urological, gastrointestinal and gynaecological aspects of this rare group of complex conditions.

PMID 25217327


Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system)

J Pediatr Urol. 2014 Dec;10(6):982-98. doi: 10.1016/j.jpurol.2014.10.002. Epub 2014 Nov 15.

Nguyen HT1, Benson CB2, Bromley B3, Campbell JB4, Chow J5, Coleman B6, Cooper C4, Crino J7, Darge K5, Herndon CD4, Odibo AO7, Somers MJ8, Stein DR8.


OBJECTIVE: Urinary tract (UT) dilation is sonographically identified in 1-2% of fetuses and reflects a spectrum of possible uropathies. There is significant variability in the clinical management of individuals with prenatal UT dilation that stems from a paucity of evidence-based information correlating the severity of prenatal UT dilation to postnatal urological pathologies. The lack of correlation between prenatal and postnatal US findings and final urologic diagnosis has been problematic, in large measure because of a lack of consensus and uniformity in defining and classifying UT dilation. Consequently, there is a need for a unified classification system with an accepted standard terminology for the diagnosis and management of prenatal and postnatal UT dilation. METHODS: A consensus meeting was convened on March 14-15, 2014, in Linthicum, Maryland, USA to propose: 1) a unified description of UT dilation that could be applied both prenatally and postnatally; and 2) a standardized scheme for the perinatal evaluation of these patients based on sonographic criteria (i.e. the classification system). The participating societies included American College of Radiology, the American Institute of Ultrasound in Medicine, the American Society of Pediatric Nephrology, the Society for Fetal Urology, the Society for Maternal-Fetal Medicine, the Society for Pediatric Urology, the Society for Pediatric Radiology and the Society of Radiologists in Ultrasounds. RESULTS: The recommendations proposed in this consensus statement are based on a detailed analysis of the current literature and expert opinion representing common clinical practice. The proposed UTD Classification System (and hence the severity of the UT dilation) is based on six categories in US findings: 1) anterior-posterior renal pelvic diameter (APRPD); 2) calyceal dilation; 3) renal parenchymal thickness; 4) renal parenchymal appearance; 5) bladder abnormalities; and 6) ureteral abnormalities. The classification system is stratified based on gestational age and whether the UT dilation is detected prenatally or postnatally. The panel also proposed a follow-up scheme based on the UTD classification. CONCLUSION: The proposed grading classification system will require extensive evaluation to assess its utility in predicting clinical outcomes. Currently, the grading system is correlated with the risk of postnatal uropathies. Future research will help to further refine the classification system to one that correlates with other clinical outcomes such as the need for surgical intervention or renal function. Copyright © 2014. Published by Elsevier Ltd. KEYWORDS: Classification; Evaluation; Hydronephrosis; Postnatal; Prenatal; Ultrasonography Comment in Commentary to 'Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system)'. [J Pediatr Urol. 2014]

PMID 25435247


Bilateral intravesical ureterocele associated with unilateral partial duplication of the ureter and other anomalies: proposal of a new variant to the classification of ureterocles based on a perinatal autopsy, review of the literature and embryology

APMIS. 2010 Oct;118(10):809-14. doi: 10.1111/j.1600-0463.2010.02666.x. Epub 2010 Aug 17.

Jaiman S, Ulhøj BP. Department of Pathology, Randers Regional Hospital, Randers NØ, Denmark. Abstract The aims of this study were to demonstrate a case of bilateral intravesical ureterocele associated with megacystis and mega-ureters, unilateral partial duplication of the ureter and unilateral segmental renal dysplasia of the upper pole and an accessory spleen and to propose an addition of the new variant to the classification of ureteroceles. A perinatal necropsy was conducted on the 21-week fetus by employing the Rokitansky procedure with evisceration performed in blocks. The autopsy revealed the aforementioned abnormalities without cardiac or neural anomalies. The amniocentesis report was normal. Ureterocele is a saccular expansion of the distal ureter. It is most commonly observed in females and children and usually affects the upper moiety of a complete pyeloureteral duplication. Four types of ureteroceles are described: (A) ureterocele with single ureter (10%); (B) ureterocele with total duplication and intravesical development (10%); (C) ureterocele with total duplication and extravesical development (62%); and (D) ureterocele with ectopic ureter (3%). One case in a new born with bilateral intravesical ureterocele associated with hydrouretero-nephrosis and hyperechogenic spots in kidneys has been reported, but bilateral intravesical ureterocele with unilateral incomplete pyeloureteral duplication has never been described in the literature. © 2010 The Authors. Journal Compilation © 2010 APMIS.

PMID: 20854476


Increased prevalence of renal and urinary tract anomalies in children with Down syndrome

Pediatrics. 2009 Oct;124(4):e615-21. Epub 2009 Sep 14.

Kupferman JC, Druschel CM, Kupchik GS. Source Divisions of Pediatric Nephrology and Hypertension, Maimonides Infants and Children's Hospital, Brooklyn, New York 11219, USA. Abstract OBJECTIVE: The goal was to investigate the prevalence of renal and urinary tract anomalies (RUTAs) in a Down syndrome (DS) population.

METHODS: Data were obtained from the New York State Congenital Malformation Registry (NYS-CMR) in this retrospective cohort study. The occurrence of RUTAs was assessed for children with and without DS who were born in NYS between 1992 and 2004. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each malformation.

RESULTS: Between 1992 and 2004, 3832 children with DS and 3 411 833 without DS were born in NYS. The prevalence of RUTAs in the DS population was 3.2%, compared with 0.7% in the NYS population (OR: 4.5 [95% CI: 3.8 -5.4]). Children with DS had significantly increased risks of anterior urethral obstruction (OR: 29.7 [95% CI: 4.0 -217.7]), cystic dysplastic kidney (OR: 4.5 [95% CI: 1.5-14.1]), hydronephrosis (OR: 8.7 [95% CI: 6.8 -11.0]), hydroureter (OR: 8.5 [95% CI: 3.5-20.4]), hypospadias (OR: 2.0 [95% CI: 1.4 -2.9]), posterior urethral valves (OR: 7.1 [95% CI: 1.8 -28.8]), prune belly syndrome (OR: 11.9 [95% CI: 1.6 - 85.4]), and renal agenesis (OR: 5.4 [95% CI: 2.8 -10.4]). There was no significantly increased risk of ectopic kidney (OR: 1.6 [95% CI: 0.2-11.2]) or ureteropelvic junction obstruction (OR: 1.4 [95% CI: 0.2-9.9]) in the DS population.

CONCLUSION: Children with DS have significantly increased risks of RUTAs.

PMID: 19752083

Bardet-Biedl syndrome, renal transplant and percutaneous nephrolithotomy: a case report and review of the literature

Cases J. 2009 Jul 7;2:6771.

Middela S, Polizois K, Bradley AJ, Rao PN. Source Department of Urology, University Hospital of South Manchester Foundation NHS trust, Wythenshawe Hospital Southmoor Road, Manchester, M13 0DP UK.


Bardet-Biedl syndrome is an autosomal recessive disorder with obesity, polydactly, retinitis pigmentosa, hypogenitalism, intellectual impairment and varying degree of renal abnormalities. Fewer than ten cases of paediatric renal transplantation for BBS have been reported in literature so far. This is the only case report of BBS transplant urolithiasis which was dealt with percutaneous nephrolithotomy and has been stone free for seven years. This is a complex case with a rare genetic disorder, renal transplant, renal stone, ileal conduit, long loop and inversely placed kidney. This case exemplifies the need for multidisciplinary management of complex cases and emphasises PCNL as the safe method.

PMID: 19829857


Ambulatory blood pressure monitoring and renal functions in children with a solitary kidney

Pediatr Nephrol. 2007 Apr;22(4):559-64. Epub 2007 Jan 10.

Dursun H, Bayazit AK, Cengiz N, Seydaoglu G, Buyukcelik M, Soran M, Noyan A, Anarat A. Source Department of Pediatric Nephrology, Cukurova University School of Medicine, 01330 Balcali, Adana, Turkey.


The aim of this study is to investigate the blood pressure (BP) profile, microalbuminuria, renal functions, and relations with remaining normal kidney size in children with unilateral functioning solitary kidney (UFSK). Sixty-six children with UFSK were equally divided into three groups: unilateral renal agenesis (URA), unilateral atrophic kidney (UAK), and unilateral nephrectomy (UNP). Twenty-two age-, weight-, and height-matched healthy children were considered as a control group. The serum creatinine level and first-morning urine microalbumin and creatinine concentrations were determined by the standard methods. Also, the BP profile was determined by ambulatory blood pressure monitoring (ABPM). We found that the serum creatinine level was higher and creatinine clearance was lower in each patient groups compared to those of the control group (p < 0.05). Compared with the controls, each group of patients had mean office, 24-h, daytime, and night-time systolic and diastolic BP values similar to those of the controls (p > 0.05). An inverse correlation was found between the renal size standard deviation scores (SDS) of normal kidneys and 24-h systolic and diastolic BP load SDS in all of the patients (p < 0.05; r = -0.372, r = -0.295, respectively). The observed relationship between renal size SDS and 24-h mean arterial pressure (MAP), systolic and diastolic BP load SDS suggests that children with UFSK should be evaluated by using ABPM for the risk of hypertension.

PMID: 17216255


Congenital Megacalyces

his 10-month old male had a large left kidney, thought to be due to tumour. A CT of the renal tracts was performed, which shows no tumour, but confirms enlargement of the left kidney. The image shown is a posterior view from a 3D reconstruction of the excretory phase of the examination (click image for frontal MIP, a virtual IVP). There are more than the usual number of calyces, and they have a bizarre polygonal, faceted shape. Congenital megacalyces are thought to be due to developmental hypoplasia of the medullary pyramids. The enlarged, floppy calyces predispose to statis, infection and calculus formation. There is an association with congenital megaureter.

  • Renal ectopy
  • Renal fusion
  • asymptomatic renal ectopia


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