Pathophysiology of Congenital Anomalies of the Kidney and Urinary Tract: A Comprehensive Review
Abstract
:1. Introduction
2. Background
3. CAKUT Diagnoses
3.1. Nephropathies
3.1.1. Aplasia and Dysplasia
Epidemiology
Clinical Presentation
Pathophysiology
3.1.2. Hypoplasia and Oligomeganephronia
Epidemiology
Clinical Presentation
Pathophysiology
3.1.3. Positional Anomalies of the Kidneys (Horseshoe Kidney, Ectopic Kidney, Pancake Kidney, Malrotation)
Epidemiology
Clinical Presentation
Pathophysiology
3.2. Uropathies
3.2.1. Multiple Ureters and Vesicoureteral Reflux
Epidemiology
Clinical Presentation
Pathophysiology
3.2.2. Bladder-Exstrophy-Epispadias-Complex
Epidemiology
Clinical Presentation
Pathophysiology
3.2.3. Obstructive Uropathy (Posterior Urethral Valves, Ureteropelvic Junction Obstruction)
Epidemiology
Clinical Presentation
Pathophysiology
3.2.4. Ureteroceles
Epidemiology
Clinical Presentation
Pathophysiology
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nephropathies | Uropathies |
---|---|
Unilateral renal agenesis | Multiple ureters |
Bilateral renal agenesis | Epispadias |
Multicystic dysplastic kidneys (MCDK) | Bladder exstrophy |
Simple renal hypoplasia | Cloacal exstrophy |
Oligomeganephronia | Posterior urethral valves (PUV) |
Horseshoe kidney | Ureteropelvic junction obstruction (UPJO) |
Ectopic kidney | Ureterocele |
Malrotated kidney |
Disease | Genetic Mutations | Mechanism | Symptoms/ Outcome | Associated Syndromes/Notes |
---|---|---|---|---|
Unilateral renal agenesis | CFTR *, ADGRG2 *, WT1 *, RET ^, CHD1L *, TRIM32 *, WNT, WNT4 ^, PAX8 * | Failure of the ureteric bud to induce metanephric mesenchyme | Frequently asymptomatic. Less often hypertension, compensatory hypertrophy of solitary kidney, CKD, UTI | Zinner syndrome, OHVIRA, VACTERL |
Bilateral renal agenesis | RET^, GDNF, WNT11, DSTYK, ITGA8, FGF20, GREB1L, WT1, ANOS1 *, EYA1 *, SIX1 *, SIX5 * | Developmental failure of both ureteric buds | Rapidly fatal, oligohydramnios, pulmonary hypoplasia, Potter phenotype | |
Multicystic dysplastic kidneys | PAX2, TCF2, calcineurin-NFAT, BMPER | Abnormal interaction between the ureteric bud and the metanephric mesenchyme | VUR, UTI, Potter phenotype, hypertension, progression to renal failure | VACTERL, renal coloboma, branchio-oto-renal syndrome, Mayer-Rokitansky |
Simple renal hypoplasia | BMP2, BMP4, ALK3 | An underdevelopment of renal tissue due to insufficient nephron formation in utero | Frequently asymptomatic. VUR, hypertension | |
Oligomeganephronia | PAX2 *, EAY1 *, SALL1 *, RET1, chromosome 4 * | Unknown, but hypothesized as reduced nephron number during renal development | Short stature, polyuria, polydipsia, proteinuria, progressive CKD, hypertension, glomerular hypertrophy | Renal-coloboma syndrome, branchio-oto-renal syndrome, Townes-Brocks syndrome, acrorenal syndrome, and Seckel syndrome, |
Horseshoe kidney | No known genetic etiology | Fusion of inferior poles of kidney | Frequently asymptomatic. VUR, nephrolithiasis, UTI, hydronephrosis | Turner Syndrome, Trisomy 18 |
Ectopic kidney | No known genetic etiology | Abnormal migration of the kidney during development | Frequently asymptomatic. VUR, nephrolithiasis, urinary incontinence, UTI, hydronephrosis. | Omphalocele–Exstrophy-Imperforate Anus–Spinal Defects Syndrome (OEIS), MCDK, Ureterocele |
Multiple ureters | RET, GDNF, GATA3, SLIT2/ROBO2, FOXC1, FOXC2, SOX11, GREM1, BMP4, beta-catenin | Premature bifurcation of the ureteric bud or two distinct ureteral buds. | VUR, UTI, hydronephrosis, ureteroceles, nephrolithiasis | Associated with ureteroceles |
Epispadias | WNT3, WNT9B, TP63, ISL1 | Failure of midline fusion of the genetic tubercle | Urinary incontinence, cosmetic concerns, sexual dysfunction | Frequently presents with bladder exstrophy |
Bladder exstrophy | WNT3, WNT9B, TP63, ISL1 | Improper closure of the mesoderm development between bladder and abdominal wall | Urinary incontinence, hydronephrosis, UTI, sexual dysfunction | Epispadias, pelvic floor defects |
Cloacal exstrophy | WNT3, WNT9B, TP63, ISL1 | Severe disruption in the closure of the ventral abdominal wall and cloacal membrane | Urinary + bowel incontinence, obstructive uropathy, renal failure, fistula formation | Spinal anomalies, genital malformation |
Posterior urethral valve | PCDH9, SALL1, BNC2, TBX5, PTK7 | Formed by remnants of the Wolffian duct or failure of the urogenital membrane to dissolve | Oligohydramnios, hydronephrosis, Potter phenotype, UTI, CKD | Exclusive to males |
Ureteropelvic junction obstruction | No known genetic etiology | Aperistalsis of ureteral segments due to hypertrophy or absence of ureteral smooth muscles | Oligohydramnios, hydronephrosis, Potter phenotype, renal failure | |
Ureteroceles | RET/GDNF, EYA1, PAX2, SALL1, FOXC1, FOXC2, SLIT2/ROBO2, AGTR1 | Failure of membrane at the distal ureter to completely dissolve and its subsequent dilation | Asymptomatic, bladder distension, urosepsis | Dual renal collecting systems |
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Brockwell, M.; Hergenrother, S.; Satariano, M.; Shah, R.; Raina, R. Pathophysiology of Congenital Anomalies of the Kidney and Urinary Tract: A Comprehensive Review. Cells 2024, 13, 1866. https://doi.org/10.3390/cells13221866
Brockwell M, Hergenrother S, Satariano M, Shah R, Raina R. Pathophysiology of Congenital Anomalies of the Kidney and Urinary Tract: A Comprehensive Review. Cells. 2024; 13(22):1866. https://doi.org/10.3390/cells13221866
Chicago/Turabian StyleBrockwell, Maximilian, Sean Hergenrother, Matthew Satariano, Raghav Shah, and Rupesh Raina. 2024. "Pathophysiology of Congenital Anomalies of the Kidney and Urinary Tract: A Comprehensive Review" Cells 13, no. 22: 1866. https://doi.org/10.3390/cells13221866