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Chapter 1 - Normal Human Kidney Development and Congenital Anomalies of the Kidneys and Urinary Tract

from Section 1 - Normal and Abnormal Human Kidney Development

Published online by Cambridge University Press:  10 August 2023

Helen Liapis
Affiliation:
Ludwig Maximilian University, Nephrology Center, Munich, Adjunct Professor and Washington University St Louis, Department of Pathology and Immunology, Retired Professor
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Summary

We present the sequence of events leading to the permanent human kidney. Nephrogenesis begins around 22 days after fertilisation and completes around the 34–36th week of gestation. There are three pairs of kidneys in human development: the pronephros, mesonephros and metanephros, arising sequentially from intermediate mesoderm on the dorsal body wall. The first two pairs involute and are resorbed during fetal life, but they are essential precursors to the metanephros and normal adult kidneys do not develop if they are disrupted. Human metanephric kidney development begins around day 28 post conception when the ureteric bud arises as an outpouching of the distal mesonephric duct/Wolffian duct. Glomeruli form from 8–9 weeks and nephrogenesis continues in the outer rim of the cortex until 34 weeks. Perturbation of early pathways can lead to a range of phenotypes including renal agenesis, dysplasia and duplex kidneys, as well as malpositioning defects such as pelvic or horseshoe kidneys if they fail to ascend to their normal 12th thoracic to 3rd lumbar vertebral site during development.

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Publisher: Cambridge University Press
Print publication year: 2023

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References

Bertram, J. F., Douglas-Denton, R. N., Diouf, B., Hughson, M. D., Hoy, W. E.. Human nephron number: implications for health and disease. Pediatr Nephrol. 2011;26:1529–33.CrossRefGoogle ScholarPubMed
Sasaki, T., Tsuboi, N., Okabayashi, Y., Haruhara, K., Kanzaki, G., Koike, K., et al. Estimation of nephron number in living humans by combining unenhanced computed tomography with biopsy-based stereology. Sci Rep. 2019;9:14400.CrossRefGoogle ScholarPubMed
McMahon, A. P., Aronow, B. J., Davidson, D. R., Davies, J. A., Gaido, K. W., Grimmond, S., et al. GUDMAP: the genitourinary developmental molecular anatomy project. J Am Soc Nephrol. 2008;19:667–71.CrossRefGoogle ScholarPubMed
Ryan, D., Sutherland, M. R., Flores, T. J., Kent, A. L., Dahlstrom, J. E., Puelles, V. G., et al. Development of the human fetal kidney from mid to late gestation in male and female infants. EBioMedicine. 2018;27:275–83.Google Scholar
Chambers, J. M., Wingert, R. A.. Advances in understanding vertebrate nephrogenesis. Tissue Barriers. 2020;8:1832844.CrossRefGoogle ScholarPubMed
Kampmeier, O. F.. The metanephros or so-called permanent kidney in part provisional and vestigial. Anat Rec 1926;33:115–20.Google Scholar
Winyard, P. J. D., Nauta, J., Lirenman, D. S., Hardman, P., Sams, V. R., Risdon, R. A., et al. Deregulation of cell survival in cystic and dysplastic renal development. Kidney Int. 1996;49:135–46.CrossRefGoogle ScholarPubMed
Osathanondh, V., Potter, E. L.. Development of human kidney as shown by microdissection. III. Formation and interrelationship of collecting tubules and nephrons. Arch Pathol. 1963;76:290302.Google Scholar
Osathanondh, V., Potter, E. L.. Development of human kidney as shown by microdissection. II. Renal pelvis, calyces and papillae. Arch Pathol. 1963;76:277–89.Google ScholarPubMed
Potter, E. L.. Normal and Abnormal Development of the Kidney. Chicago: Year Book Medical Publishers; 1972.Google Scholar
Lindström, N. O., McMahon, J. A., Guo, J., Tran, T., Guo, Q., Rutledge, E., et al. Conserved and divergent features of human and mouse kidney organogenesis. J Am Soc Nephrol. 2018;29:785805.Google Scholar
Lindström, N. O., Tran, T., Guo, J., Rutledge, E., Parvez, R. K., Thornton, M. E., et al. Conserved and divergent molecular and anatomic features of human and mouse nephron patterning. J Am Soc Nephrol. 2018;29:825–40.Google ScholarPubMed
Kitazawa, H., Fujii, S., Ishiyama, H., Matsubayashi, J., Ishikawa, A., Yamada, S., et al. Nascent nephrons during human embryonic development: spatial distribution and relationship with urinary collecting system. J Anat. 2021;238:455–66.CrossRefGoogle ScholarPubMed
Ishiyama, H., Ishikawa, A., Kitazawa, H., Fujii, S., Matsubayashi, J., Yamada, S., et al. Branching morphogenesis of the urinary collecting system in the human embryonic metanephros. PLoS ONE. 2018;13(9):e0203623.CrossRefGoogle ScholarPubMed
Little, M. H., Kumar, S. V., Forbes, T.. Recapitulating kidney development: progress and challenges. Semin Cell Dev Biol. 2019;91:153–68.Google Scholar
Little, M. H., Quinlan, C.. Advances in our understanding of genetic kidney disease using kidney organoids. Pediatr Nephrol. 2020;35:915–26.CrossRefGoogle ScholarPubMed
Saxen, L.. Organogenesis of the Kidney. Cambridge: Cambridge University Press; 1987.Google Scholar
Weber, S., Taylor, J. C., Winyard, P., Baker, K. F., Sullivan-Brown, J., Schild, R., et al. SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol. 2008;19:891903.CrossRefGoogle ScholarPubMed
Self, M., Lagutin, O. V., Bowling, B., Hendrix, J., Cai, Y., Dressler, G. R., et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25:5214–28.CrossRefGoogle ScholarPubMed
Fetting, J. L., Guay, J. A., Karolak, M. J., Iozzo, R. V., Adams, D. C., Maridas, D. E., et al. FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney. Development. 2014;141:1727.CrossRefGoogle ScholarPubMed
Nigam, A., Knoers, N., Renkema, K. Y.. Impact of next generation sequencing on our understanding of CAKUT. Semin Cell Dev Biol. 2019;91:104–10.CrossRefGoogle ScholarPubMed
Lang, C., Conrad, L., Michos, O.. Mathematical approaches of branching morphogenesis. Front Genet. 2018;9:673.CrossRefGoogle ScholarPubMed
Davies, J. A., Hohenstein, P., Chang, C. H., Berry, R.. A self-avoidance mechanism in patterning of the urinary collecting duct tree. BMC Dev Biol. 2014;14:35.Google Scholar
Lindström, N. O., Chang, C. H., Valerius, M. T., Hohenstein, P., Davies, J. A.. Node retraction during patterning of the urinary collecting duct system. J Anat. 2015;226:1321.Google Scholar
Osathanondh, V., Potter, E. L.. Development of the human kidney as shown by microdissection. IV and V. Arch Pathol. 1966;82:391411.Google Scholar
Rowan, C. J., Sheybani-Deloui, S., Rosenblum, N. D.. Origin and function of the renal stroma in health and disease. In: Miller, R. K., editor. Kidney Development and Disease. Cham: Springer International Publishing; 2017. p. 205–29.Google Scholar
England, A. R., Chaney, C. P., Das, A., Patel, M., Malewska, A., Armendariz, D., et al. Identification and characterization of cellular heterogeneity within the developing renal interstitium. Development. 2020;147(15).dev190108.Google Scholar
Hum, S., Rymer, C., Schaefer, C., Bushnell, D., Sims-Lucas, S.. Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning. PLoS ONE. 2014;9:e88400.CrossRefGoogle ScholarPubMed
Mohamed, T., Sequeira-Lopez, M. L. S.. Development of the renal vasculature. Semin Cell Dev Biol. 2019;91:132–46.Google Scholar
Daniel, E., Azizoglu, D. B., Ryan, A. R., Walji, T. A., Chaney, C. P., Sutton, G. I., et al. Spatiotemporal heterogeneity and patterning of developing renal blood vessels. Angiogenesis. 2018;21:617–34.CrossRefGoogle ScholarPubMed
Munro, D. A. D., Hohenstein, P., Davies, J. A.. Cycles of vascular plexus formation within the nephrogenic zone of the developing mouse kidney. Sci Rep. 2017;7:3273.Google Scholar
Huang, J. L., Woolf, A. S., Kolatsi-Joannou, M., Baluk, P., Sandford, R. N., Peters, D. J., et al. Vascular endothelial growth factor C for polycystic kidney diseases. J Am Soc Nephrol. 2016;27:6977.Google Scholar
Jafree, D. J., Long, D. A.. Beyond a passive conduit: implications of lymphatic biology for kidney diseases. J Am Soc Nephrol. 2020;31:1178–90.CrossRefGoogle ScholarPubMed
Renkema, K. Y., Winyard, P. J., Skovorodkin, I. N., Levtchenko, E., Hindryckx, A., Jeanpierre, C., et al. Novel perspectives for investigating congenital anomalies of the kidney and urinary tract (CAKUT). Nephrol Dial Transplant. 2011;26:3843–51.CrossRefGoogle ScholarPubMed
Liapis, H., Winyard, P. J. D.. Cystic diseases and developmental kidney defects. In: Jennette, J. C., Olson, J. L., Silva, F. G., D’Agati, V. D., editors. Heptinstall’s Pathology of the Kidney. 7th ed. Philadelphia: Wolters Kluwer; 2015. p. 119–72.Google Scholar
Yulia, A., Napolitano, R., Aiman, A., Desai, D., Johal, N., Whitten, M., et al. Perinatal and infant outcome of fetuses with prenatally diagnosed hyperechogenic kidneys. Ultrasound in Obstetrics & Gynecology. 2021;57:9538.CrossRefGoogle Scholar
Yulia, A., Winyard, P.. Management of antenatally detected kidney malformations. Early Hum Dev. 2018;126:3846.CrossRefGoogle ScholarPubMed
Cardona-Grau, D., Kogan, B. A.. Update on multicystic dysplastic kidney. Curr Urol Rep. 2015;16:67.CrossRefGoogle ScholarPubMed
Sanna-Cherchi, S., Westland, R., Ghiggeri, G. M., Gharavi, A. G.. Genetic basis of human congenital anomalies of the kidney and urinary tract. J Clin Invest. 2018;128:415.CrossRefGoogle ScholarPubMed
Groopman, E. E., Povysil, G., Goldstein, D. B., Gharavi, A. G.. Rare genetic causes of complex kidney and urological diseases. Nat Rev Nephrol. 2020;16:641–56.Google Scholar
Bekheirnia, M. R., Bekheirnia, N., Bainbridge, M. N., Gu, S., Coban Akdemir, Z. H., Gambin, T., et al. Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene. Genet Med. 2017;19:412–20.CrossRefGoogle ScholarPubMed
Winyard, P., Chitty, L. S.. Dysplastic kidneys. Semin Fetal Neonatal Med. 2008;13:142–51.Google Scholar
Atiyeh, B., Husmann, D., Baum, M.. Contralateral renal abnormalities in patients with renal agenesis and noncystic renal dysplasia. Pediatrics. 1993;91:812–5.Google Scholar
Narchi, H.. Risk of Wilms’ tumour with multicystic kidney disease: a systematic review. Arch Dis Child. 2005;90:147–9.Google ScholarPubMed
Narchi, H.. Risk of hypertension with multicystic kidney disease: a systematic review. Arch Dis Child. 2005;90:921–4.Google ScholarPubMed
Decramer, S., Parant, O., Beaufils, S., Clauin, S., Guillou, C., Kessler, S., et al. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol. 2007;18:923–33.Google Scholar
Verhave, J. C., Bech, A. P., Wetzels, J. F., Nijenhuis, T.. Hepatocyte nuclear factor 1β-associated kidney disease: more than renal cysts and diabetes. J Am Soc Nephrol. 2016;27:345–53.CrossRefGoogle ScholarPubMed
Bonsib, S. M.. Renal hypoplasia, from grossly insufficient to not quite enough: consideration for expanded concepts based upon the author’s perspective with historical review. Adv Anat Pathol. 2020;27:311–30.CrossRefGoogle Scholar
Winyard, P. J. D., Risdon, R. A., Sams, V. R., Dressler, G., Woolf, A. S.. The PAX2 transcription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations. J Clin Invest. 1996;98:451–9.CrossRefGoogle ScholarPubMed
Wheway, G., Mitchison, H. M.. Opportunities and challenges for molecular understanding of ciliopathies-The 100,000 Genomes Project. Front Genet. 2019;10:127.CrossRefGoogle ScholarPubMed
Doery, A. J., Ang, E., Ditchfield, M. R.. Duplex kidney: not just a drooping lily. JMed Imaging Radiat Oncol. 2015;59:149–53.Google Scholar
Kozlov, V. M., Schedl, A.. Duplex kidney formation: developmental mechanisms and genetic predisposition. F1000Res. 2020;9.Google Scholar
Mackie, G. G., Stephens, F. D.. Duplex kidneys: a correlation of renal dysplasia with position of the ureteral orifice. J Urol. 1975;114:27480.CrossRefGoogle ScholarPubMed
Costantini, F., Kopan, R.. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell. 2010;18:698712.Google Scholar
Short, K. M., Smyth, I. M.. The contribution of branching morphogenesis to kidney development and disease. Nat Rev Nephrol. 2016;12:754–67.Google Scholar
Hwang, D. Y., Kohl, S., Fan, X., Vivante, A., Chan, S., Dworschak, G. C., et al. Mutations of the SLIT2-ROBO2 pathway genes SLIT2 and SRGAP1 confer risk for congenital anomalies of the kidney and urinary tract. Hum Genet. 2015;134:905–16.CrossRefGoogle ScholarPubMed
Bingham, G., Leslie, S. W.. Pelvic Kidney. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC.; 2020.Google Scholar
Kirkpatrick, J. J., Leslie, S. W.. Horseshoe Kidney. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC.; 2020.Google Scholar
Schiappacasse, G., Aguirre, J., Soffia, P., Silva, C. S., Zilleruelo, N.. CT findings of the main pathological conditions associated with horseshoe kidneys. Br J Radiol. 2015;88(1045):20140456.CrossRefGoogle ScholarPubMed
Ahn, Y. H., Lee, C., Kim, N. K. D., Park, E., Kang, H. G., Ha, I. S., et al. Targeted exome sequencing provided comprehensive genetic diagnosis of congenital anomalies of the kidney and urinary tract. J Clin Med. 2020;9(3):751.Google Scholar
van der Ven, A. T., Connaughton, D. M., Ityel, H., Mann, N., Nakayama, M., Chen, J., et al. Whole-exome sequencing identifies causative mutations in families with congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol. 2018;29:2348–61.Google Scholar
Verbitsky, M., Westland, R., Perez, A., Kiryluk, K., Liu, Q., Krithivasan, P., et al. The copy number variation landscape of congenital anomalies of the kidney and urinary tract. Nat Genet. 2019;51:117–27.Google ScholarPubMed
Penna, F. J., Elder, J. S.. CKD and bladder problems in children. Adv Chronic Kidney Dis. 2011;18:362–9.CrossRefGoogle ScholarPubMed
Pruthi, R., O’Brien, C., Casula, A., Braddon, F., Lewis, M., Maxwell, H., et al. UK Renal Registry 16th annual report: chapter 7 demography of the UK paediatric renal replacement therapy population in 2012. Nephron Clin Pract. 2013;125:127–38.Google Scholar
Yang, S. P., Woolf, A. S., Quinn, F., Winyard, P. J. D.. Deregulation of renal transforming growth factor-beta1 after experimental short-term ureteric obstruction in fetal sheep. Am J Pathol. 2001;159:109–17.CrossRefGoogle ScholarPubMed
Cao, K. X., Milmoe, N. J., Cuckow, P. M., Olsen, L. H., Johal, N. S., Winyard, P. J. D., et al. Antenatal biological models in the characterization and research of congenital lower urinary tract disorders. J Pediatr Urol. 2020;17:21–9.Google Scholar
Chevalier, R. L.. Evolution, kidney development, and chronic kidney disease. Semin Cell Dev Biol. 2019;91:11931.Google Scholar
Kolvenbach, C. M., Dworschak, G. C., Frese, S., Japp, A. S., Schuster, P., Wenzlitschke, N., et al. Rare variants in BNC2 are implicated in autosomal-dominant congenital lower urinary-tract obstruction. Am J Hum Genet. 2019;104(5):9941006.Google Scholar
Shepard, T. H.. Catalog of Teratogenic Agents. Baltimore: The Johns Hopkins University Press; 2010.Google Scholar
Nicolaou, N., Renkema, K. Y., Bongers, E. M., Giles, R. H., Knoers, N. V.. Genetic, environmental, and epigenetic factors involved in CAKUT. Nat Rev Nephrol. 2015;11:720–31.Google Scholar
Groen In ‘t Woud, S., Renkema, K. Y., Schreuder, M. F., Wijers, C. H., van der Zanden, L. F, Knoers, N. V., et al. Maternal risk factors involved in specific congenital anomalies of the kidney and urinary tract: a case-control study. Birth Defects Res A Clin Mol Teratol. 2016;106:596603.Google Scholar
Yosypiv, I. V.. Renin-angiotensin system in mammalian kidney development. Pediatr Nephrol. 2021;36:479–89.Google Scholar
Lee, L. M., Leung, C. Y., Tang, W. W., Choi, H. L., Leung, Y. C., McCaffery, P. J., et al. A paradoxical teratogenic mechanism for retinoic acid. Proc Natl Acad Sci U S A. 2012;109:13668–73.Google Scholar
Bhat, P. V., Manolescu, D. C.. Role of vitamin A in determining nephron mass and possible relationship to hypertension. J Nutr. 2008;138:1407–10.Google Scholar
Argeri, R., Thomazini, F., Lichtenecker, D. C. K., Thieme, K., do Carmo Franco, M., Gomes, G. N.. Programmed adult kidney disease: importance of fetal environment. Front Physiol. 2020;11:586290.Google Scholar
Woolf, A. S.. Environmental influences on renal tract development: a focus on maternal diet and the glucocorticoid hypothesis. Klin Padiatr. 2011;223 Suppl 1:S10–S7.CrossRefGoogle ScholarPubMed
Tran, S., Chen, Y. W., Chenier, I., Chan, J. S., Quaggin, S., Hébert, M. J., et al. Maternal diabetes modulates renal morphogenesis in offspring. J Am Soc Nephrol. 2008;19:943–52.Google Scholar
Macumber, I., Schwartz, S., Leca, N.. Maternal obesity is associated with congenital anomalies of the kidney and urinary tract in offspring. Pediatr Nephrol. 2017;32:635–42.CrossRefGoogle ScholarPubMed

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