TY  - JOUR
T1  - Developmental and Genetic Foundations of Kidney and Urinary Tract Anomalies: An Anatomical and Clinical Exploration of CAKUT
TT  - Böbrek ve İdrar Yolu Anomalilerinin Gelişimsel ve Genetik Temelleri: CAKUT'un Anatomik ve Klinik İncelemesi
AU  - Toy, Şeyma
AU  - Yasin, Rida Zahiraldin İbrahim
AU  - Şahin, Necati Emre
PY  - 2025
DA  - April
Y2  - 2024
JF  - Unika Sağlık Bilimleri Dergisi
JO  - Unika. Sag. Bil. Derg.
PB  - Karabük Üniversitesi
WT  - DergiPark
SN  - 2757-6817
SP  - 103
EP  - 114
VL  - 5
IS  - 1
LA  - en
AB  - Congenital anomalies of the kidney and urinary tract (CAKUT) describe a broad spectrum of diseases resulting from aberrant development of the renal parenchyma, urinary collecting system, lower urinary tract, or kidneys during embryonic stages. Higher percentages of patients with CAKUT have lower urinary abnormalities, such as vesicoureteral reflux (25%), ureterovesical junction obstruction (11%), and ureteropelvic junction obstruction (25%). Kidney abnormalities are known to be prevalent throughout the prenatal period, making up roughly 20–30% of all detected anomalies. The term "CAKUT" refers to a group of diseases that include multiple cystic dysplastic kidneys and mild unilateral hydronephrosis. The prognosis of those with CAKUT can differ significantly; while some individuals may have ideal kidney function, others may experience chronic kidney disease requiring dialysis and kidney transplantation. There are still negative opinions about the etiology of CAKUT. Although familial clustering is common, many CAKUT instances are sporadic, indicating that genetic variables may influence CAKUT characteristics. Numerous studies focusing on embryology have shed light on the genetic components of CAKUT, but research in this area is ongoing. This study comprehensively explores the critical stages of embryonic kidney development and different types of CAKUT. Additionally, it examines long-term monitoring and treatment modalities for CAKUT patients It also examines the long-term monitoring and treatment methods of CAKUT patients in the literature.
KW  - Congenital kidney anomalies
KW  - Urinary tract developmental disorders
KW  - CAKUT
KW  - Kidney development.
N2  - Konjenital böbrek ve idrar yolu anomalileri (CAKUT), embriyonik dönemlerde böbrek parankiminin, idrar toplama sisteminin, alt idrar yollarının veya böbreklerin anormal gelişiminden kaynaklanan geniş bir hastalık yelpazesini tanımlar. CAKUT hastalarının yüksek yüzdeleri, vesikoureteral reflü (%25), üreterovesikal bileşke tıkanıklığı (%11) ve üreteropelvik bileşke tıkanıklığı (%25) gibi alt idrar yolu anomalilerine sahiptir. Böbrek anomalileri, prenatal dönem boyunca yaygın olarak görülmekte olup, tüm tespit edilen anomalilerin yaklaşık %20-30'unu oluşturur. CAKUT terimi, birden fazla kistik displastik böbrek ve hafif unilateral hidronefroz gibi hastalıkları içeren bir grup hastalığı tanımlar. CAKUT olanların prognozu önemli ölçüde farklılık gösterebilir; bazı kişiler ideal böbrek fonksiyonuna sahip olabilirken, diğerleri kronik böbrek hastalığı yaşayabilir ve sonunda diyaliz ve böbrek nakli gerekebilir. CAKUT etiyolojisi hakkında hala olumsuz görüşler mevcuttur. Ailevi kümelenme yaygın olsa da birçok CAKUT örneği sporadik olduğundan, genetik değişkenlerin CAKUT özelliklerini etkileyebileceği düşünülmektedir. Embriyolojiyi içeren birçok çalışma CAKUT'un genetik bileşenleri üzerine ışık tutmuş, ancak bu alandaki araştırmalar devam etmektedir. Bu çalışma, CAKUT'un embriyonik böbrek gelişimindeki kritik aşamaları ve farklı CAKUT tiplerini detaylı bir şekilde ele almaktadır. Ayrıca, literatürdeki CAKUT hastalarının uzun vadeli izleme ve tedavi yöntemlerini de incelemektedir.
CR  - Ahram, D. F., Lim, T. Y., Ke, J., Jin, G., Verbitsky, M., Bodria, M., Kil, B. H., Chatterjee, D., Piva, S. E., Marasa, M., Zhang, J. Y., Cocchi, E., Caridi, G., Gucev, Z., Lozanovski, V. J., Pisani, I., Izzi, C., Savoldi, G., Gnutti, B., … Sanna-Cherchi, S. (2023). Rare single nucleotide and copy number variants and the etiology of congenital obstructive uropathy: Implications for genetic diagnosis. Journal of the American Society of Nephrology, 34(6), 1105–1119. https://doi.org/10.1681/ASN.0000000000000132
CR  - Avanoglu, A., & Tiryaki, S. (2020). Embryology and Morphological (Mal)Development of UPJ. Frontiers in Pediatrics, 8, 137. https://doi.org/10.3389/fped.2020.00137
CR  - Bates, C., Ho, J., & Sims-Lucas, S. (2016). Embryonic Development of the Kidney. In E. D. Avner, W. E. Harmon, P. Niaudet, N. Yoshikawa, F. Emma, & S. L. Goldstein (Eds.), Pediatric Nephrology (pp. 3–36). Springer. https://doi.org/10.1007/978-3-662-43596-0_1
CR  - Bingham, G., & Rentea, R. (2021). Posterior Urethral Valve. StatPearls. Retrieved from: https://scholarlyexchange.childrensmercy.org/papers/3289
CR  - Chapman, A. B. (2007). Autosomal Dominant polycystic kidney disease: Time for a change? Journal of the American Society of Nephrology, 18(5), 1399–1407. https://doi.org/10.1681/ASN.2007020155
CR  - Chen, F. (2009). Genetic and developmental basis for urinary tract obstruction. Pediatric Nephrology, 24(9), 1621–1632. https://doi.org/10.1007/s00467-008-1072-y
CR  - Chevalier, R. L. (2004). Perinatal obstructive nephropathy. Seminars in Perinatology, 28(2), 124–131. https://doi.org/10.1053/j.semperi.2003.11.009
CR  - Chow, J. S., Benson, C. B., & Lebowitz, R. L. (2005). The clinical significance of an empty renal fossa on prenatal sonography. Journal of Ultrasound in Medicine, 24(8), 1049–1054. https://doi.org/10.7863/jum.2005.24.8.1049
CR  - Churchill, D. N., Bear, J. C., Morgan, J., Payne, R. H., McManamon, P. J., & Gault, M. H. (1984). Prognosis of adult onset polycystic kidney disease re-evaluated. Kidney International, 26(2), 190–193. https://doi.org/10.1038/ki.1984.154
CR  - Cleveland, R. H., Kushner, D. C., Herman, T. E., & Kim, S. H. (1986). Acquired ureteropelvic junction obstruction in childhood. Pediatric Radiology, 16(1), 76–78. https://doi.org/10.1007/BF02387516
CR  - Dabra, A., Gupta, R., Singh, J., & Kochhar, S. (2003). Prenatal diagnosis of familial ureteropelvic junction obstruction: A case report and review of the literature. Journal of Diagnostic Medical Sonography, 19(5), 316–319. https://doi.org/10.1177/8756479303256084
CR  - Di Fabrizio, D., Tavolario, I., Rossi, L., Nino, F., Bindi, E., & Cobellis, G. (2024). Combined minimally ınvasive treatment of pyeloureteral junction obstruction and primary obstructive megaureter in children: Case report and literature review. Children, 11(4), 407. https://doi.org/10.3390/children11040407
CR  - Dos Santos Junior, A. C. S., De Miranda, D. M., & Simões E Silva, A. C. (2014). Congenital anomalies of the kidney and urinary tract: An embryogenetic review. Birth Defects Research Part C: Embryo Today: Reviews, 102(4), 374–381. https://doi.org/10.1002/bdrc.21084
CR  - Enrique, K.-K., & Raquel, C.-S. (2021). Bilateral hydronephrosis as a consequence of vesicoureteral reflux in a 6-year-old male patient. Clinical Medical Reviews and Case Reports, 8(5). https://doi.org/10.23937/2378-3656/1410350
CR  - Feldenberg, L. R., & Siegel, N. J. (2000). Clinical course and outcome for children with multicystic dysplastic kidneys. Pediatric Nephrology, 14(12), 1098–1101. https://doi.org/10.1007/s004670000391
CR  - Fletcher, J., McDonald, S., & Alexander, S. I. (2013). Prevalence of genetic renal disease in children. Pediatric Nephrology, 28(2), 251–256. https://doi.org/10.1007/s00467-012-2306-6
CR  - Gonzalez, E., Gutierrez, E., Morales, E., Hernandez, E., Andres, A., Bello, I., Diaz-gonzalez, R., Leiva, O., & Praga, M. (2005). Factors influencing the progression of renal damage in patients with unilateral renal agenesis and remnant kidney. Kidney International, 68(1), 263–270. https://doi.org/10.1111/j.1523-1755.2005.00401.x
CR  - Grinsell, M. M., Butz, K., Gurka, M. J., Gurka, K. K., & Norwood, V. (2012). Sport-related kidney ınjury among high school athletes. Pediatrics, 130(1), e40–e45. https://doi.org/10.1542/peds.2011-2082
CR  - Guarino, N., Tadini, B., Camardi, P., Silvestro, L., Lace, R., & Bianchi, M. (2004). The incidence of associated urological abnormalities in children with renal ectopia. Journal of Urology, 172(4 Part 2), 1757–1759. https://doi.org/10.1097/01.ju.0000138376.93343.74
CR  - Halvorson, C. R., Bremmer, M. S., & Jacobs, S. C. (2010). Polycystic kidney disease: Inheritance, pathophysiology, prognosis, and treatment. International Journal of Nephrology and Renovascular Disease, 3, 69–83. https://doi.org/10.2147/ijnrd.s6939
CR  - Kajbafzadeh, A.-M., Payabvash, S., Salmasi, A. H., Monajemzadeh, M., & Tavangar, S. M. (2006). Smooth muscle cell apoptosis and defective neural development in congenital ureteropelvic junction obstruction. Journal of Urology, 176(2), 718–723. https://doi.org/10.1016/j.juro.2006.03.041
CR  - Klein, J., Gonzalez, J., Miravete, M., Caubet, C., Chaaya, R., Decramer, S., Bandin, F., Bascands, J.-L., Buffin-Meyer, B., & Schanstra, J. P. (2011). Congenital ureteropelvic junction obstruction: Human disease and animal models: Congenital UPJ obstruction. International Journal of Experimental Pathology, 92(3), 168–192. https://doi.org/10.1111/j.1365-2613.2010.00727.x
CR  - Kovesdy, C. P., Furth, S. L., Zoccali, C., & on behalf of the World Kidney Day Steering Committee. (2017). Obesity and kidney disease: Hidden consequences of the epidemic. Canadian Journal of Kidney Health and Disease, 4, 205435811769866. https://doi.org/10.1177/2054358117698669
CR  - Liu, B., & Fu, D. (2014). Low compliance bladder plays a role in hydronephrosis in lupus cystitis: A case report. Lupus, 23(8), 829–832. https://doi.org/10.1177/0961203314526440
CR  - Malekshahabi, T., Khoshdel Rad, N., Serra, A. L., & Moghadasali, R. (2019). Autosomal dominant polycystic kidney disease: Disrupted pathways and potential therapeutic interventions. Journal of Cellular Physiology, 234(8), 12451–12470. https://doi.org/10.1002/jcp.28094
CR  - Malhotra, G., Dhale, A., & Dharamshi, J. D. (2022). Horseshoe kidney with a documented giant calculi: A case report. Cureus. https://doi.org/10.7759/cureus.29144
CR  - Mehrazma, M., Tanzifi, P., & Rakhshani, N. (2014). Changes in structure, interstitial cajal-like cells and apoptosis of smooth muscle cells in congenital ureteropelvic junction obstruction. Pathology, 46, S134. https://doi.org/10.1097/01.pat.0000454556.77877.27
CR  - Nasir, A. A., Ameh, E. A., Abdur-Rahman, L. O., Adeniran, J. O., & Abraham, M. K. (2011). Posterior urethral valve. World Journal of Pediatrics, 7(3), 205–216. https://doi.org/10.1007/s12519-011-0289-1
CR  - N’Guessen, G., Douglas Stephens, F., & Pick, J. (1984). Congenital superior ectopic (Thoracic) kidney. Urology, 24(3), 219–228. https://doi.org/10.1016/0090-4295(84)90346-7
CR  - Özel, Ş. K., Emir, H., Dervişoğlu, S., Akpolat, N., Şenel, B., Kazez, A., Söylet, Y., Çetin, G., Danişmend, N., & Büyükünal, S. N. C. (2010). The roles of extracellular matrix proteins, apoptosis and c-kit positive cells in the pathogenesis of ureteropelvic junction obstruction. Journal of Pediatric Urology, 6(2), 125–129. https://doi.org/10.1016/j.jpurol.2009.07.011
CR  - Petrović, M., Andrejević, V., Djurasić, L., Stamenković, V., Acimović, M., Pejcić, T., Dragoslav, B., & Hadzi-Djokić, J. (2012). Tumors of the horseshoe kidney—Characteristics and literature review. Acta Chirurgica Iugoslavica, 59(1), 53–55.
CR  - Rabani, S. M., & Mousavizadeh, A. (2017). The dilemma of ureterovesical junction obstruction. Nephro-Urology Monthly, 9(5). https://doi.org/10.5812/numonthly.57201
CR  - Rasouly, H. M., & Lu, W. (2013). Lower urinary tract development and disease. WIREs Systems Biology and Medicine, 5(3), 307–342. https://doi.org/10.1002/wsbm.1212
CR  - Raviv, G., Leibovitch, L., Shenfeld, O., Mor, Y., Jonas, P., & Goldwasser, B. (1994). Ureteropelvic junction obstruction: Relation of etiology and age at surgical repair to clinical outcome. Urologia Internationalis, 52(3), 135–139. https://doi.org/10.1159/000282592
CR  - Rudnik-Schöneborn, S., John, U., Deget, F., Ehrich, J. H. H., Misselwitz, J., & Zerres, K. (1998). Clinical features of unilateral multicystic renal dysplasia in children. European Journal of Pediatrics, 157(8), 666–672. https://doi.org/10.1007/s004310050908
CR  - Sagi-Dain, L., Maya, I., Peleg, A., Reches, A., Banne, E., Baris, H. N., Tenne, T., Singer, A., & Ben-Shachar, S. (2018). Microarray analysis in pregnancies with isolated unilateral kidney agenesis. Pediatric Research, 83(4), 825–828. https://doi.org/10.1038/pr.2018.3
CR  - Seely, J. C. (2017). A brief review of kidney development, maturation, developmental abnormalities, and drug toxicity: Juvenile animal relevancy. Journal of Toxicologic Pathology, 30(2), 125–133. https://doi.org/10.1293/tox.2017-0006
CR  - Seikaly, M. G., Ho, P. L., Emmett, L., Fine, R. N., & Tejani, A. (2003). Chronic renal insufficiency in children: The 2001 Annual Report of the NAPRTCS. Pediatric Nephrology, 18(8), 796–804. https://doi.org/10.1007/s00467-003-1158-5
CR  - Shin, Y. B., & Park, J. H. (2016). Recent Trends in ADPKD Research. In J. H. Park & C. Ahn (Eds.), Cystogenesis (Vol. 933, pp. 3–11). Springer Singapore. https://doi.org/10.1007/978-981-10-2041-4_1
CR  - Stonebrook, E., Hoff, M., & Spencer, J. D. (2019). Congenital anomalies of the kidney and urinary tract: A clinical review. Current Treatment Options in Pediatrics, 5(3), 223–235. https://doi.org/10.1007/s40746-019-00166-3
CR  - Subramanian, S., & Ahmad, T. (2019). Polycystic kidney disease of childhood. Retrieved from: https://europepmc.org/article/nbk/nbk537137
CR  - Takeuchi, H., Koyanagi, T., Yoshizato, T., Takashima, T., Satoh, S., & Nakano, H. (1994). Fetal urine production at different gestational ages: Correlation to various compromised fetuses in utero. Early Human Development, 40(1), 1–11. https://doi.org/10.1016/0378-3782(94)90094-9
CR  - Tangri, N., Hougen, I., Alam, A., Perrone, R., McFarlane, P., & Pei, Y. (2017). Total kidney volume as a biomarker of disease progression in autosomal dominant polycystic kidney disease. Canadian Journal of Kidney Health and Disease, 4, 205435811769335. https://doi.org/10.1177/2054358117693355
CR  - Tkocz, M., & Kupajski, M. (2012). Tumour in horseshoe kidney – different surgical treatment shown in five example cases. Współczesna Onkologia, 3, 254–257. https://doi.org/10.5114/wo.2012.29295
CR  - Toka, H. R., Toka, O., Hariri, A., & Nguyen, H. T. (2010). Congenital anomalies of kidney and urinary tract. Seminars in Nephrology, 30(4), 374–386. https://doi.org/10.1016/j.semnephrol.2010.06.004
CR  - Torra, R. (2019). Recent advances in the clinical management of autosomal dominant polycystic kidney disease. F1000Research, 8, 116. https://doi.org/10.12688/f1000research.17109.1
CR  - Uberoi, J., Disick, G. I. S., & Munver, R. (2009). Minimally invasive surgical management of pelvic‐ureteric junction obstruction: Update on the current status of robotic‐assisted pyeloplasty. BJU International, 104(11), 1722–1729. https://doi.org/10.1111/j.1464-410X.2009.08682.x
CR  - Urisarri, A., Gil, M., Mandiá, N., Aldamiz-Echevarría, L., Iria, R., González-Lamuño, D., & Couce, M.-L. (2018). Retrospective study to identify risk factors for chronic kidney disease in children with congenital solitary functioning kidney detected by neonatal renal ultrasound screening. Medicine, 97(32), e11819. https://doi.org/10.1097/MD.0000000000011819
CR  - Van Den Bosch, C. M. A., Van Wijk, J. A. E., Beckers, G. M. A., Van Der Horst, H. J. R., Schreuder, M. F., & Bökenkamp, A. (2010). Urological and nephrological findings of renal ectopia. Journal of Urology, 183(4), 1574–1578. https://doi.org/10.1016/j.juro.2009.12.041
CR  - Walker, E. Y. X., Winyard, P., & Marlais, M. (2023). Congenital anomalies of the kidney and urinary tract: Antenatal diagnosis, management and counselling of families. Pediatric Nephrology. https://doi.org/10.1007/s00467-023-06137-z
CR  - Westland, R., & Schreuder, M. F. (2014). Gender differences in solitary functioning kidney: Do they affect renal outcome? Pediatric Nephrology, 29(11), 2243–2244. https://doi.org/10.1007/s00467-013-2473-0
CR  - Yecies, T., Turner Іi, R. M., Ferroni, M. C., Jacobs, B. L., & Davies, B. J. (2016). Partial and hemi-nephrectomy for renal malignancy in patients with horseshoe kidney. The Canadian Journal of Urology, 23(1), 8156–8159.
UR  - https://dergipark.org.tr/tr/pub/unikasaglik/issue//1480900
L1  - https://dergipark.org.tr/tr/download/article-file/3916413
ER  -