View source for Biology:Mammalian kidney

{{Short description|Paired organ in the urinary system of mammals}}
{{Infobox anatomy
| Name        = Mammalian kidney
| Image       = Camel kidney (longitudinal cut).- FMVZ USP-30.jpg
| Caption     = Unipapillary, multilobar, smooth, bean-shaped camel kidney, in which the renal papillae are completely fused into the renal crest.{{sfn|Abdalla|2020|loc=Abstract|p=1}}
| System      = Urinary system and endocrine system
| Artery      = Renal artery
| Vein        = Renal vein
| Nerve       = Renal plexus
| Lymph       = Collecting lymphatic vessels
| Precursor   = Ureteric bud, [[Biology:Metanephrogenic blastema|metanephrogenic blastema]]
}}
The '''mammalian kidneys''' are a pair of excretory organs of the urinary system of [[Biology:Mammal|mammal]]s. They are a type of metanephric kidney.{{sfn|Withers, Cooper, Maloney et al.|2016|p=25|loc=1.2.8 Excretion}} The kidneys in mammals are usually bean-shaped{{Sfn|Keogh, Kilroy, Bhattacharjee|2020|loc=7.3. Mammals|p=8}} and located behind the peritoneum (retroperitoneally){{sfn|Eurell, Frappier|2006|loc=Kidney : General Organisation}} on the back (dorsal) wall of the body.{{sfn|Withers, Cooper, Maloney et al.|2016|loc=3.6.3 The Kidney|p=250}} Each kidney consists of a renal capsule, peripheral cortex, internal medulla, calices, and renal pelvis, although the calices or renal pelvis may be absent in some [[Biology:Species|species]]. [[Biology:Urine|Urine]] is excreted from the kidney through the ureter.{{sfn|Withers, Cooper, Maloney et al.|2016|loc=3.6.3 The Kidney|p=250}} [[Chemistry:Nitrogen|Nitrogen]]-containing waste products are excreted by the kidneys in mammals mainly in the form of [[Chemistry:Urea|urea]].{{Sfn|Fenton, Knepper|2007|loc=Abstract|p=679}}

The structure of the kidney may differ between species.<ref name=":33">{{Cite Q|Q117034134}}</ref> The kidneys can be unilobar (single lobe) or multilobar, unipapillary (single papilla), with several papillae or multipapillary,{{sfn|WHO|1991|loc=3.4 Species, strain, and sex differences in renal structure and function|p=49}} may be smooth-surfaced or lobulated,{{sfn|Abdalla|2020|loc=Abstract|p=1}}{{sfn|Breshears, Confer|2017|loc=Structure|p=617}} also the kidneys may be [[Biology:Reniculate kidney|reniculate]], which are found mainly in [[Biology:Marine mammal|marine mammal]]s.{{sfn|Ortiz|2001|loc=Kidney structure|p=1832}} The simplest type of kidney in mammals is the unipapillary kidney with single lobe.{{sfn|Kriz, Kaissling|2012|p=595|loc=Renal vasculature}}{{sfn|Eurell, Frappier|2006|loc=Kidney : General Organisation}} Differences in kidney structure are the result of adaptations during evolution to variations in body mass and habitats (in particular, habital [[Earth:Aridity|aridity]]) between species{{sfn|Zhou, Rong, Guo et al.|2023|loc=Introduction|p=2}}{{sfn|Zhou, Rong, Guo et al.|2023|loc=The Evolution of Renal Structures Was Driven by Body Size and Habitats in Mammals|p=6}}<ref name=":33" />. The human kidney is an example of the mammalian kidney.

The cortex and medulla of the kidney contain nephrons.{{Sfn|Davidson|2009|loc=Figure 1. Structure of the mammalian kidney}} The cortex contains glomeruli and is responsible for filtering the [[Biology:Blood|blood]].{{sfn|Withers, Cooper, Maloney et al.|2016|loc=3.6.3 The Kidney|p=250}} In mammals, the nephrons can be classified into the nephrons with a short loop and a long loop of Henle,{{Sfn|Dantzler|2016}} and the loop of Henle is responsible for urine concentration.{{Sfn|Casotti, Lindberg, Braun|2000|p=R1723}} Amongst the vertebrates, only mammals and [[Biology:Bird|bird]]s have kidneys that can produce urine more concentrated ([[Biology:Tonicity#Hypertonic solution|hypertonic]]) than the [[Biology:Blood plasma|blood plasma]],{{sfn|Withers, Cooper, Maloney et al.|2016|loc=3.6.3 The Kidney|p=250}} but only in mammals do all nephrons have the loop of Henle.{{Sfn|Casotti, Lindberg, Braun|2000|p=R1722-R1723}}

The kidneys of mammals are vital organs{{sfn|Little, McMahon|2012|loc=Summary|p=1}} that maintain water, [[Physics:Electrolyte|electrolyte]] and [[Chemistry:Acid–base homeostasis|acid-base]] balance in the body, excrete nitrogenous waste products, regulate [[Physics:Blood pressure|blood pressure]], participate in bone formation{{sfn|Little, McMahon|2012|loc=An Overview of Cell Players and Cellular Processes in Metanephric Kidney Development|p=2}}<ref>{{Cite Q|Q30419294}}</ref><ref name=":8" /> and in regulation of glucose levels.<ref name=":31" /> The processes of blood plasma filtration, tubular reabsorption and tubular secretion occur in the kidneys, and urine formation is a result of these processes.<ref>{{Cite Q|Q117041834|url=https://books.google.com/books?id=Ugq5BgAAQBAJ&pg=PA198|p=198}}</ref> The kidneys produce [[Biology:Renin|renin]]<ref name="auto1">{{Cite Q|Q30431545}}</ref> and [[Biology:Erythropoietin|erythropoietin]]<ref name="auto">{{Cite Q|Q89620015|doi-access=free}}</ref> [[Biology:Hormone|hormone]]s, and are involved in the conversion of [[Chemistry:Vitamin D|vitamin D]] to its active form.<ref name=":5">{{Cite Q|Q33783519}}</ref> Mammals are the only [[Biology:Class|class]] of vertebrates in which only the kidneys are responsible for maintaining the [[Homeostasis|homeostasis]] of the [[Biology:Extracellular fluid|extracellular fluid]] in the body.<ref>{{Cite Q|Q117043359|url=https://books.google.com/books?id=1zP4bYDWq_wC&pg=PA506|p=506}}</ref> The function of the kidneys is regulated by the autonomic nervous system and hormones.<ref>{{Cite Q|Q117043609|url=https://books.google.com/books?id=5aZHEAAAQBAJ&pg=PA5|p=5}}</ref>

The kidneys can have noninfectious and [[Medicine:Infectious disease|infectious]] diseases; in rare cases, [[Medicine:Birth defect|congenital]] and [[Medicine:Genetic disorder|hereditary]] anomalies occur in the kidneys of mammals.<ref name=":23" /> [[Medicine:Pyelonephritis|Pyelonephritis]] is usually caused by bacterial infections.<ref name=":24" /><ref name=":26" /> Some diseases may be species specific,<ref name=":27" /> and parasitic kidney diseases are common in some species.<ref name=":19" /><ref name=":28" /> The structural characteristics of the mammalian kidneys make them vulnerable to ischemic and [[Medicine:Toxic injury|toxic]] injuries.<ref name=":29" /> The potential for regeneration in mature kidneys is limited{{sfn|Little, McMahon|2012|loc=7 Reassessing Renal Disease, Repair, and Regeneration Using Developmental Biology|p=12}}{{sfn|Kumar|2018|loc=Figure 1 Schematic illustration highlighting patchy regenerative/reparative processes after mammalian acute kidney injury|p=28}} because new nephrons cannot be formed,{{sfn|Davidson|2011|loc=Introduction|p=1435}} but in cases of limited injury, renal function can be restored through compensatory mechanisms.{{sfn|Davidson|2011|loc=Postnatal regenerative response of the mammalian kidney|p=1437-1439}} Permanent damage can lead to [[Medicine:Chronic kidney disease|chronic kidney disease]].<ref name=":30" /><ref name=":2" /> Ageing of the kidneys also causes changes in them, and the number of functioning nephrons decreases with age.{{sfn|Breshears, Confer|2017|loc=Aging of the Kidney|p=637}}

== Structure ==

=== Gross anatomy ===
[[File:Didactic model of a mammal Kidney with numbered parts.png|thumb|Didactic model of the multilobar mammalian kidney:<ref>{{Cite Q|Q117050923|doi-access=free}}</ref> {{hlist
 |1. Fibrous capsule
 |2. Cortex
 |3. Renal pyramid of the medulla
 |4. Renal column of the cortex
 |5. Nephron
 |6. Renal papilla
 |7. Minor renal calyx
 |8. Major renal calyx
 |9. Renal pelvis
 |10. Ureter
 |11. Renal artery
 |12. Renal vein
 |13. Interlobar artery
 |14. Renal lobe
 |15. Arcuate artery
 |16. Interlobular artery.
}}]]

==== Location and shape ====
In mammals, kidneys are usually bean-shaped;{{Sfn|Keogh, Kilroy, Bhattacharjee|2020|loc=7.3. Mammals|p=8}} the shape is unique to mammals ([[Biology:Fish|fish]], for example, has elongated kidneys).<ref>{{Cite Q|Q117048829|p=569|url=https://books.google.com/books?id=BR8KAAAAQBAJ&pg=PA569}}</ref> Kidneys are located retroperitoneally{{sfn|Eurell, Frappier|2006|loc=Kidney : General Organisation}} on the back (dorsal) wall of the body.{{sfn|Withers, Cooper, Maloney et al.|2016|loc=3.6.3 The Kidney|p=250}} One of the key factors that determine the shape and [[Biology:Morphology|morphology]] of the kidneys in mammals is their mass.<ref>{{Cite Q|Q117048961}}</ref> The concave part of the bean-shaped kidneys is called the renal hilum, through which the renal artery and [[Biology:Nerve|nerve]]s enter the kidney. The renal vein, collecting lymphatic vessels and ureter exit the kidney through the renal hilum.{{sfn|Eurell, Frappier|2006|loc=Kidney : General Organisation}}<ref name=":0">{{Cite Q|Q117048995|p=319|url=https://books.google.com/books?id=qpQ9y-vXovoC&pg=PA319}}</ref> In the body, the kidney is surrounded by a mass of adipose tissue.<ref>{{Cite Q|Q117050154|last1=De Martino|first1=Cesare|last2=Allen|first2=Delmas|last3=Accinni|first3=Lidia|chapter=Microscopic structure of the kidney|url=https://doi.org/10.1007/978-1-4613-2575-8_4|pages=53–82}}</ref>

==== General structure ====
The outer layer of each kidney is made up of a fibrous sheath called a renal capsule. The peripheral layer of the kidney is called the cortex, and the inner layer is called the medulla. The medulla consists of pyramids (also called malpighian pyramids), ascending with their base to the cortex and forming together with it the renal lobe.{{Sfn|Davidson|2009|loc=Figure 1 Structure of the mammalian kidney}} The pyramids are separated from each other by renal columns (Bertin's columns) formed by cortical tissue.<ref>{{Cite Q|Q117051109|pages=16-18}}</ref> The tips of the pyramids end with the renal papillae, from which urine is excreted into the calyces, pelvis, ureter, and, in most species, directly into the [[Biology:Urinary bladder|bladder]],{{Sfn|Davidson|2009|loc=Figure 1 Structure of the mammalian kidney}}<ref name=":1">{{Britannica|id=497964|title=Renal pyramid}}</ref> after which it is excreted through the urethra.<ref>{{Cite web |title=Excretion - Mammals |url=https://www.britannica.com/science/excretion/Mammals |access-date=2023-03-11 |website=Encyclopædia Britannica |language=en |archive-date=3 June 2022 |archive-url=https://web.archive.org/web/20220603205956/https://www.britannica.com/science/excretion/Mammals |url-status=live }}</ref>

=== Parenchyma ===
[[File:Simplified structure of the mammalian kidney lobe.svg|thumb|left|Simplified structure of the mammalian kidney lobe:{{Sfn|Davidson|2009|loc=Figure 1. Structure of the mammalian kidney}}{{sfn|Kriz, Kaissling|2012|p=602|loc=Figure 20.9 Schematic of nephrons and collecting duct}}<br>
{{hlist
 |1.&nbsp;Cortex
 |2.&nbsp;Outer medulla
 |3.&nbsp;Inner medulla
 |4.&nbsp;Inner stripe
 |5.&nbsp;Outer stripe
 |6.&nbsp;Juxtamedullary nephron
 |7.&nbsp;Medullary ray
 |8.&nbsp;Renal capsule
 |9.&nbsp;Renal papilla.
}}
----
{{legend|#2ab924|Podocytes}}
{{legend|#dda330|Proximal convoluted tubule}}
{{legend|#e7dc2e|Proximal straight tubule}}
{{legend|#c3c3bc|Intermediate tubule (loop of Henle)}}
{{legend|#134ef7|Distal straight tubule}}
{{legend|#000000|Macula densa}}
{{legend|#8cabf8|Distal convoluted tubule}}
{{legend|#00f6e9|Connecting tubule}}
{{legend|#9d18ec|Collecting duct}}
<!-- TODO: Example of short nephron is missing;a source with colored parts of the nephron is needed  to draw the short nephron. -->]]
The [[Biology:Parenchyma|parenchyma]], being the functional part of the kidneys, is visually divided into cortex and medulla.<ref>{{Cite web |title=Anatomy of the Kidney & Ureter |url=https://training.seer.cancer.gov/kidney/anatomy/ |access-date=2023-03-11 |website=SEER Training |publisher=U. S. National Cancer Institute |archive-date=11 March 2023 |archive-url=https://web.archive.org/web/20230311111627/https://training.seer.cancer.gov/kidney/anatomy/ |url-status=live }}</ref><ref>{{Cite Q|Q117066071|url=https://books.google.com/books?id=Hb1BXjgb0McC&pg=PA177|p=177}}</ref> The cortex and medulla are based on nephrons{{Sfn|Davidson|2009|loc=Figure 1. Structure of the mammalian kidney|p=2}}<ref>{{Cite Q|Q28388052}}</ref> together with an extensive network of [[Biology:Blood vessel|blood vessel]]s and [[Biology:Capillary|capillaries]], as well as collecting ducts, into which nephrons empty, and renal interstitium.{{sfn|Grant Maxie|2015|loc=Anatomy|p=379}} There is a blood-filtering part of the nephron in the cortex — the renal corpuscle, from which the renal tubule extends to the medulla into the loop of Henle, then the tubule returns back to the cortex and with its distal end flows into its collecting duct that is common to several nephrons. The collecting ducts descend again into the medulla and fuse to wider collecting ducts which pass through the inner medulla.{{Sfn|Sands, Layton|2012|p=1464|loc=Kidney Structure}}{{sfn|Sands, Verlander|2004|loc=Figure 1.1 A long-looped and short-looped nephron together with the collecting system|p=4-5}}

Based on the location of the renal corpuscle, nephrons are classified into 3 types: superficial (closer to the renal capsule), midcortical (in the middle part of the cortex) and juxtamedullary (closer to the medulla) nephrons. According to the length of the loop of Henle, nephrons are classified into nephrons with a long loop and with a short loop of Henle.{{sfn|Kriz, Kaissling|2012|p=600|loc=Nephrons and Collecting Duct System}}

==== Cortex ====
Structurally, the cortex consists of cortical labyrinth and medullary rays.{{sfn|Kriz, Kaissling|2012|loc=Kidney Types and Renal Pelvis|p=595}} The cortical labyrinth contains interlobular arteries, vascular networks formed by afferent and efferent arterioles, renal corpuscles, proximal convoluted tubules, macula densa, distal convoluted tubules, connecting tubules and the initial parts of the collecting ducts.{{sfn|Sands, Verlander|2004|loc=Cortex|p=6}} The proximal convoluted tubules predominate in the cortical labyrinth.<ref name=":20">{{Cite Q|Q117066851|url=https://books.google.com/books?id=25_cDQAAQBAJ&pg=PA19|pages=19}}</ref> The continuous layer of the cortex lying above the medullary rays is called the cortex corticis.{{sfn|Kriz, Kaissling|2012|loc=Kidney Types and Renal Pelvis|p=595}} Some mammals have nephrons whose loops of Henle do not reach the medulla; such nephrons are called cortical nephrons.{{Sfn|Sands, Layton|2012|loc=Kidney Structure|p=1464}} The medullary rays of the cortex contain the proximal straight tubules, the cortical part of the thick ascending limb of the loops of Henle, and the cortical part of the collecting ducts.{{sfn|Sands, Verlander|2004|loc=Cortex|p=6}} The cortex is divided into lobules, each of which is a medullary ray in conjunction with connected to it nephrons, and interlobular arteries that pass between the lobules.{{sfn|Grant Maxie|2015|loc=Anatomy|p=378}} The ratio of cortex to medulla varies between species, in domesticated animals the cortex usually occupies a third or fourth part of the parenchyma, while in desert animals with long loops of Henle it is only a fifth part.{{sfn|Breshears, Confer|2017|loc=Structure|p=617}}

==== Medulla ====
The medulla in mammals is divided into outer and inner regions. The outer region consists of short loops of Henle and collecting ducts, while the inner region consists of long loops and collecting ducts.{{Sfn|Davidson|2009|loc=Overview of kidney structure and embryonic development}} The outer region is also subdivided into outer<ref name=":14">{{Cite Q|Q117068124|url = https://books.google.com/books?id=dW6eBQAAQBAJ&pg=PA357|pages=357}}</ref> (lying directly under the cortex){{sfn|Sands, Verlander|2004|loc=Outer Medulla|p=8}} and inner stripes.<ref name=":14" /> The stripes differ in that the outer stripe contain proximal straight tubules, while the inner strite contain thin descending limbs of the loop of Henle (a section of the nephron following the proximal straight tubule).{{sfn|Sands, Verlander|2004|loc=Outer Medulla|p=8}}

==== The ratio of the outer and inner medulla ====
Most mammalian species have nephrons with both short and long loops of Henle, while some species may have only one type. For example, mountain beavers have only nephrons with a short loop, and, accordingly, there is no inner medulla in the kidney. [[Biology:Dog|Dog]]s and [[Biology:Cat|cat]]s, on the other hand, have only long-loop nephrons. The ratio of nephrons with short loops of Henle to those with long loops also varies between species.<ref>{{Cite Q|Q117072065|chapter-url=https://link.springer.com/chapter/10.1007/978-3-642-69863-7_1|author=W. Kriz|chapter=Structure and Function of the Renal Medulla|pages=3–10|doi=10.1007/978-3-642-69863-7_1}}</ref>

=== Structural differences between species ===
[[File:Variation of the mammalian kidney between domestic animal species in English.jpg|thumb|Variation of the kidney between domestic mammalian species:{{sfn|Keogh, Kilroy, Bhattacharjee|2020|loc=7.3.1. Mammalian kidneys: overall morphology|p=9}}{{hlist|(A) Equine kidneys with heart-shaped right kidney|(B) Bovine kidneys with lobulated cortex and fused medulla|(C) Canine bean-shaped kidneys.}}]]
Structurally, kidneys vary between mammals.{{sfn|Casotti, Lindberg, Braun|2000|p=R1722}} What structural type a particular species will have depends generally on the body mass of the animals.{{Sfn|Dantzler|2016|loc=2.2.6 Mammals|p=20}} Small mammals have unilobar kidneys with a compact structure and a single renal papilla,{{sfn|Casotti, Lindberg, Braun|2000|p=R1722}}{{sfn|WHO|1991|loc=3.4 Species, strain, and sex differences in renal structure and function|p=49}} while larger animals have multilobar kidneys, such as those of bovines,{{sfn|Casotti, Lindberg, Braun|2000|p=R1722}}{{sfn|WHO|1991|loc=3.4 Species, strain, and sex differences in renal structure and function|p=49}} but [[Biology:Bovinae|bovine]] kidneys are also externally lobulated (visually divided into lobes).{{sfn|Breshears, Confer|2017|loc=Structure|p=617}} By itself, the lobe is equivalent to a simple unipapillary kidney, as in [[Biology:Rat|rat]]s or [[Biology:Mouse|mice]].<ref name=":20" /> Bovine kidneys also lack renal pelvis, urine from the major calices is excreted directly into the ureter.{{sfn|Abdalla|2020|loc=3. Results and discussion|p=3}}

Kidneys can be unipapillary,{{sfn|WHO|1991|loc=3.4 Species, strain, and sex differences in renal structure and function|p=49}} as in [[Biology:Rat|rat]]s and [[Biology:Mouse|mice]],<ref>{{Cite Q|Q48636042}}</ref> with few renal papillae, as in [[Biology:Spider monkey|spider monkey]]s, or with many, as in pigs and [[Biology:Human|human]]s.{{sfn|WHO|1991|loc=3.4 Species, strain, and sex differences in renal structure and function|p=49}} Most animals have single renal papilla.{{sfn|WHO|1991|loc=3.4 Species, strain, and sex differences in renal structure and function|p=49}} In some animals, such as [[Biology:Horse|horse]]s, the tips of the renal pyramids fuse with each other to form a common renal papilla, called the renal crest.<ref>{{Cite Q|Q117074872|url=https://books.google.com/books?id=0rDhBwAAQBAJ&pg=PA286|pages=286}}</ref> The renal crest usually appears in animals larger than the [[Biology:Rabbit|rabbit]].{{Sfn|Dantzler|2016|loc=2.2.6 Mammals|p=19—20}}

[[File:Authors drawing of a dolphin reniculate kidney.png|thumb|left|120px|Author's drawing of a [[Biology:Dolphin|dolphin]] reniculate kidney:<ref>{{Cite Q|Q54957107}}</ref> {{hlist|1. Renal artery|2. Renal vein|3. Common collecting duct that becomes the ureter.}}]]
In [[Biology:Marine mammal|marine mammal]]s, [[Biology:Otter|otter]]s and bears, the kidneys are [[Biology:Reniculate kidney|reniculate]], consisting of small reniculi,{{sfn|Ortiz|2001|loc=Kidney structure|p=1832}} each of which is comparable to a simple unilobar kidney.{{sfn|Kriz, Kaissling|2012|loc=Kidney Types and Renal Pelvis|p=595}} Marine mammal kidneys can have hundreds{{sfn|Ortiz|2001|loc=Kidney structure|p=1832}} or thousands<ref name=":2">{{Cite Q|Q43573882}}</ref> of reniculi, each with its own cortex, medulla, and calyx.{{sfn|Ortiz|2001|loc=Kidney structure|p=1832}} For example, each [[Biology:Whale|whale]] kidney consist of about {{Num|7000}} renculi which join a common collective system.<ref name=":2" /> In [[Biology:Manatee|manatee]]s, which are also marine mammals, the kidneys are actually multilobar, since the cortex is continuous.{{sfn|Ortiz|2001|loc=Kidney structure|p=1832}}

The size of the kidneys increases with the mass of mammals, and the number of nephrons in the kidneys between mammals increases [[Biology:Allometry|allometrically]].{{sfn|Keogh, Kilroy, Bhattacharjee|2020|loc=7.3.1. Mammalian kidneys: overall morphology|p=8}} In mice, the kidneys are approximately {{convert|1|cm|1|abbr=on}} long, weighing 400&nbsp;mg, with 16,000&nbsp;nephrons, while in the [[Biology:Killer whale|killer whale]], the kidney length exceeds {{convert|25|cm|0|abbr=on}}, the mass is approximately {{convert|4.5|kg|0|abbr=on}}, with the number of nephrons of the order of 10,000,000. At the same time, killer whale kidneys are reniculate, and each reniculus is comparable to the kidney of mice.<ref name=":22">{{Cite Q|Q104492546}}</ref>

=== Microanatomy ===
By microanatomic structure, the kidney can be divided into several main elements: [[Biology:Interstitium|interstitium]], renal corpuscles, tubules, and vasculature.{{sfn|Breshears, Confer|2017|loc=Structure|p=617}} The interstitium is the [[Biology:Cell|cells]] and [[Biology:Extracellular matrix|extracellular matrix]] in the space between the glomeruli, vessels, tubules, and collecting ducts.{{sfn|Russell, Hong, Windsor et al.|2019|loc=Detailed Features of Human and Mammalian Renal Lymphatic Anatomy : Renal Interstitium|p=6}}{{Sfn|Kriz, Kaissling|2012|loc=Interstitium : Definition|p=602}} The interstitial space surrounding cells is filled with [[Biology:Interstitial fluid|interstitial fluid]].<ref name=":13">{{Cite Q|Q36123584}}</ref> The interstitium between the tubules contains fibroblasts, [[Biology:Dendritic cell|dendritic cell]]s, [[Biology:Macrophage|macrophage]]s and [[Biology:Lymphocyte|lymphocyte]]s. Cortical interstitium also includes the endothelial cells of the lymphatic capillaries,<ref name=":13" /> which are considered part of the interstitium due to the lack of a [[Biology:Basement membrane|basement membrane]].{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Detailed Features of Human and Mammalian Renal Lymphatic Anatomy : Morphology of Renal Lymph Vessels|p=6}} Interstitial fibroblasts form the tissue skeleton of the kidney.{{sfn|Kriz, Kaissling|2012|loc=Interstitial Fibroblasts|p=602}} [[Biology:Blood vessel|Blood vessel]]s, [[Biology:Nerve|nerve]]s and lymphatic vessels run through the interstitium.{{sfn|Breshears, Confer|2017|loc=Interstitium|p=622}} The nephron, together with the collecting duct into which it empties, is called the uriniferous tubule. Each uriniferous tubule, along with the vasculature supplying it, is embedded in the interstitium.{{sfn|Breshears, Confer|2017|loc=Structure|p=617}}

Approximately 18–26 different [[Biology:Cell type|cell type]]s have been described in mammalian kidneys, with a large variation in the range due to a lack of consensus on what counts as a particular cell type, and likely to species differences.<ref>{{Cite Q|Q117085458}}</ref> Renal corpuscles are composed of 4 cell types: fenestrated [[Biology:Endothelium|endothelium]], [[Biology:Mesangial cell|mesangial cell]]s, [[Biology:Podocyte|podocyte]]s and parietal epithelial cells of Bowman's capsule.<ref>{{Cite Q|Q34434949}}</ref> At least 16 different cell types make up the renal tubules.<ref name=":25">{{Cite Q|Q93115184}}</ref> The tubules themselves are divided into at least 14 segments,<ref name=":25" /> which differ in cell types and functions.<ref>{{Cite Q|Q35589079}}</ref> The normal functioning of the kidneys is provided by the complex of [[Biology:Epithelium|epithelial]], [[Biology:Endothelium|endothelial]], interstitial and immune cells.{{Sfn|Balzer, Rohacs, Susztak|2022|loc=Introduction|p=1}}

=== Blood supply ===
[[File:Equine kidney 02-FMVZ USP-3.jpeg|thumb|Equine kidney blood supply]]
Blood enters the kidney through the renal artery,<ref name=":0" /> which in the multilobar kidney branches in the area of the renal pelvis into large interlobar arteries that pass through the renal columns.<ref name=":1" />{{sfn|Grant Maxie|2015|loc=Vascular supply|p=379}} The interlobar arteries branch at the base of the pyramid, giving rise to arcuate arteries, from which the interlobular arteries extend into the cortex.{{sfn|Grant Maxie|2015|loc=Vascular supply|p=379}} The interlobar arteries supply the pyramids and the adjacent cortex with an extensive network of blood vessels.<ref name=":1"/> The cortex itself is heavily permeated with arteries, while there are no arteries in the medulla.{{sfn|Kriz, Kaissling|2012|p=595|loc=Renal vasculature}} The [[Medicine:Vein|venous]] flow of blood runs back parallel to the arteries.{{sfn|Grant Maxie|2015|loc=Vascular supply|p=379}} In some species, in the cortex there are veins isolated from the arteries under the capsule, which in humans are called stellate veins. These veins flow into the interlobular veins.{{sfn|Kriz, Kaissling|2012|p=596|loc=Renal vasculature}} The [[Biology:Renal portal system|renal portal system]] is absent in mammals,<ref>{{Cite Q|Q117088499}}</ref> with the exception of [[Biology:Monotreme|monotreme]]s.<ref>{{Cite Q|Q117088647|url=https://books.google.com/books?id=m-eQUEUjG2UC&pg=PA782|pages=782}}</ref> Mammals are the only class of vertebrates (with exception of some species) that does not have a renal portal system.{{sfn|Keogh, Kilroy, Bhattacharjee|2020|loc=6. Renal portal system|p=6}}

The vascular glomeruli of nephrons receive blood from afferent arterioles, which originate in the interlobular arteries with intermediate formation of prearterioles. Each afferent arteriole divides into several renal glomeruli. Then these glomeruli join into the efferent arteriole, into which filtered blood goes from the nephrons. In nephrons with a long loop of Henle, the efferent arterioles branch, forming straight vessels called vasa recta, descending into the medulla. The descending vasa recta, ascending vasa recta vessels, and the loop of Henle together form the countercurrent system of the kidney. In the afferent arteriole, blood is supplied at high pressure, which promotes filtration, and in the efferent arteriole, it is at low pressure, which promotes reabsorption.{{sfn|Grant Maxie|2015|loc=Vascular supply|p=379}}

Despite their small size, the kidneys of mammals account for a significant part of the minute volume of blood circulation.<ref>{{Cite Q|Q117089453|url=https://books.google.com/books?id=hcw2AAAAQBAJ&pg=PA371|pages=371}}</ref> It is believed that in land mammals, about a fifth of the volume of blood that passes through the [[Biology:Heart|heart]] passes through the kidneys.<ref>{{Cite Q|Q117089734|url=https://books.google.com/books?id=lKVqBgAAQBAJ&pg=PT299|pages=299}}</ref> In adult [[Biology:Mouse|mice]], for example, minute volume is about 9%–22%.<ref>{{Cite Q|Q42177011}}</ref>

=== Lymphatic system ===
The kidney is well supplied with lymphatic vessels,{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Introduction|p=1}} which remove excess fluid with substances and [[Biology:Macromolecule|macromolecule]]s dissolved in it from the [[Biology:Interstitium|interstitium]] that fills the space between the tubules and blood vessels.<ref>{{Cite Q|Q100995658}}</ref>{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Renal Lymphatic Physiology under Normal Conditions : Formation of Renal Lymph|p=7}} The [[Biology:Anatomy|anatomy]] of the [[Biology:Lymphatic system|lymphatic system]] of the kidney is similar between mammals.<ref name=":3">{{Cite Q|Q84203623}}</ref> Lymphatics basically follow the path of blood vessels.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Anatomy of Renal Lymphatics : Renal Vascular Anatomy|p=2}}

The lymphatic system of the kidneys begins in the cortex with the initial blind-end intralobular lymphatic capillaries passing near the tubules and renal corpuscles, but the lymphatic vessels do not go inside the renal corpuscles. The intralobular lymphatic capillaries are connected to the arcuate lymphatics.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Comparative Renal Lymphatic Anatomy : Mammalian Renal Lymphatic Anatomy|p=3}} The arcuate lymphatics pass into the interlobar lymphatics, which pass near the interlobar arteries.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Comparative Renal Lymphatic Anatomy : Mammalian Renal Lymphatic Anatomy|p=3}}<ref name=":3" /> The arcuate and interlobar lymphatics are lymphatic precollectors.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Detailed Features of Human and Mammalian Renal Lymphatic Anatomy : Morphology of Renal Lymph Vessels|p=6}} Finally, the interlobar lymphatics join the collecting hilar lymphatics leaving the kidney through renal hilum.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Comparative Renal Lymphatic Anatomy : Mammalian Renal Lymphatic Anatomy|p=3}} Lymphatic vessels are usually absent in the medulla of the mammalian kidneys, and the role of lymphatic vessels is assumed to be performed by vasa recta.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Renal Lymphatic Physiology under Normal Conditions : Interstitial Fluid and Protein Drainage in the Medulla|p=9}}{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Detailed Features of Human and Mammalian Renal Lymphatic Anatomy : Medullary Lymphatics|p=5}}

In some species, there may be differences in the anatomy of the lymphatic system of the kidney. For example, [[Biology:Sheep|sheep]] lack lymphatics in the renal capsule, and [[Biology:Rabbit|rabbit]]s lack interlobular lymphatics.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Comparative Renal Lymphatic Anatomy : Mammalian Renal Lymphatic Anatomy|p=3}} Most [[Research|studies]] fail to detect lymphatic vessels in the renal medulla of [[Biology:Animal|animal]]s, in particular, they are not found in sheep and [[Biology:Rat|rat]]s. But some studies have found lymphatic vessels in the renal medulla of pigs and rabbits.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Detailed Features of Human and Mammalian Renal Lymphatic Anatomy : Medullary Lymphatics|p=5}} Depending on the species, there may or may not also be a connection between the lymphatics of the renal capsule and the internal renal lymphatic system.{{Sfn|Russell, Hong, Windsor et al.|2019|loc=Table 1. Comparison of renal lymphatic anatomy between species|p=5}}

=== Nerve supply ===
The innervation of the kidney is provided by [[Medicine:Efferent nerve fiber|efferent]] sympathetic nerve fibers entering the kidney through the renal hilum,<ref name=":0" /> originating in the celiac plexus,{{sfn|Kopp|2018|loc=2.2 Intrarenal Distribution of Efferent Renal Sympathetic Nerves|p=6}} and [[Biology:Afferent nerve fiber|afferent]], leaving the kidney to the spinal ganglion.{{sfn|Kopp|2018|loc=2.2 Intrarenal Distribution of Efferent Renal Sympathetic Nerves|p=6}} There is no reliable evidence for the innervation of the kidney by parasympathetic nerves,{{sfn|Kopp|2018|loc=2.2 Intrarenal Distribution of Efferent Renal Sympathetic Nerves|p=6}} while the existing evidence is controversial.<ref>{{Cite Q|Q101322955}}</ref> Efferent sympathetic nerve fibers reach the renal vasculature, renal tubules, [[Biology:Juxtaglomerular cell|juxtaglomerular cell]]s, and the wall of the renal pelvis,{{sfn|Kopp|2011|loc=Abstract}} all parts of the nephron are innervated by sympathetic nerves.{{sfn|Kopp|2018|loc=2.2 Intrarenal Distribution of Efferent Renal Sympathetic Nerves|p=6}} Nerve fibers pass through the connective tissue around the [[Biology:Artery|arteries]] and [[Biology:Arteriole|arteriole]]s. In the medulla, the descending vasa recta are innervated as long as they contain [[Biology:Smooth muscle|smooth muscle]] cells.{{sfn|Kriz, Kaissling|2012|p=610|loc=Nerves}} Most afferent nerve fibers are located in the renal pelvis.{{sfn|Kopp|2011c|loc=7.1. Kidney}} The vast majority of nerves in the kidneys are [[Biology:Myelin|unmyelinated]].{{sfn|Kopp|2011b|loc=2.1. Neural Pathways}}

Normal physiological stimulation of the efferent sympathetic nerves of the kidney is involved in maintaining the balance of water and [[Chemistry:Sodium|sodium]] in the body. Activation of the efferent sympathetic nerves of the kidney reduces its blood flow, and respectively, filtration and excretion of sodium in the urine, and also increases the rate of [[Medicine:Renin–angiotensin system|renin secretion]].{{sfn|Kopp|2018|loc=Introduction|p=1}} The afferent nerves in the kidney are also involved in maintaining balance. Mechanosensory nerves of the kidney are activated by stretching of the tissue of the renal pelvis, which can occur with an increase in the rate of urine flow from the kidney, resulting in a [[Biology:Reflex|reflex]] decrease in the activity of efferent sympathetic nerves. That is, activation of the afferent nerves in the kidney suppresses the activity of the efferent nerves.{{sfn|Kopp|2011|loc=8.1. Activation of Afferent Renal Sensory Nerves by Physiological Stimuli}}

== Functions ==

=== Excretory function ===
In mammals, [[Chemistry:Nitrogen|nitrogen]]ous [[Biology:Metabolism|metabolic]] products are excreted predominantly in the form of [[Chemistry:Urea|urea]],{{Sfn|Fenton, Knepper|2007|loc=Abstract|p=679}} which is the end by-product of mammalian [[Biology:Protein metabolism|protein metabolism]]<ref name=":4">{{Cite Q|Q39762062}}</ref><ref>{{Cite Q|Q28284934}}</ref> and is highly [[Chemistry:Solubility|soluble]] in water.<ref>{{Cite web |title=Excretion - General features of excretory structures and functions |website=Britannica |url=https://www.britannica.com/science/excretion/General-features-of-excretory-structures-and-functions |access-date=2023-03-14 |archive-date=4 June 2022 |archive-url=https://web.archive.org/web/20220604161313/https://www.britannica.com/science/excretion/General-features-of-excretory-structures-and-functions |url-status=live}}</ref> Most of the urea is excreted by the kidneys.<ref name=":4" /> [[Biology:Blood|Blood]] filtration, as in other [[Biology:Vertebrate|vertebrate]]s, occurs in the renal glomeruli, where pressurized blood passes through a [[Medicine:Vascular permeability|permeable]] barrier that filters out [[Biology:Blood cell|blood cell]]s and large protein molecules, forming primary urine. Filtered primary urine is [[Biology:Osmoregulation|osmotically]] and ionically the same as blood plasma. In the tubules of the nephron, substances useful for the body, dissolved in the primary urine, are subsequently reabsorbed, as the urine is being concentrated.{{sfn|Bradley|2009|loc=8.4 Terrestrial vertebrates|p=121}}

=== Osmoregulation ===
Mammalian kidneys maintain an almost constant level of plasma osmolarity. The main component of [[Biology:Blood plasma|blood plasma]], which determines its osmolarity, is [[Chemistry:Sodium|sodium]] and its anions.{{sfn|Sands, Layton|2009|loc=Introduction}} The key role in maintaining a constant level of osmolarity is managed by the control of the ratio of sodium and water in the blood.{{sfn|Sands, Layton|2009|loc=Introduction}}<ref>{{Cite Q|Q57865766}}</ref> Drinking large amounts of water can dilute the blood plasma, in which case the kidneys produce more dilute urine than the plasma to keep the [[Chemistry:Salt|salt]] in the blood but to remove the excess water. If too little water is consumed, then urine is excreted more concentrated than blood plasma.{{sfn|Sands, Layton|2009|loc=Introduction}} The concentration of urine is provided by an osmotic gradient that increases from the border between the cortex and medulla to the top of the pyramid of the medulla.{{sfn|Sands, Layton|2009|loc=Introduction}}

In addition to the kidneys, the [[Biology:Hypothalamus|hypothalamus]] and neurohypophysis are involved in the regulation of water balance through a [[Feedback|feedback]] system. The [[Biology:Osmoreceptor|osmoreceptor]]s of the hypothalamus respond to an increase in the osmolarity of the blood plasma, as a result of which the secretion of [[Biology:Vasopressin|vasopressin]] by the posterior pituitary gland is stimulated, and [[Medicine:Thirst|thirst]] also arises. The kidneys respond via [[Biology:Receptor (biochemistry)|receptors]] to increased levels of vasopressin by increasing water reabsorption, resulting in a decrease in plasma osmolarity due to its dilution with water.<ref>{{Cite Q|Q38399100}}</ref>

Variation in the rate of water excretion is an important survival function for mammals that have limited access to water.{{sfn|Sands, Layton|2009|loc=Introduction}} The most prominent feature of the mammalian kidneys are the loops of Henle, they are the most efficient way to reabsorb water and create concentrated urine, which allows you to save water in the body.{{Sfn|Schulte, Kunter, Moeller|2014|loc=Adapting to living on dry land: the water-retaining kidney was invented twice|p=718}} After passing through the loop of Henle, the fluid becomes hypertonic relative to the blood plasma.<ref>{{Cite Q|Q117104227 |chapter=The loop of Henle, distal tubule and collecting duct |chapter-url=https://link.springer.com/chapter/10.1007/978-94-011-4086-7_6 |pages=70–85 |access-date=2023-03-14}}</ref> Mammalian kidneys combine nephrons with short and long loops of Henle.<ref>{{Cite Q|Q43688352}}</ref> The ability to concentrate urine is determined mainly by the structure of the medulla and the length of the loops of Henle.{{sfn|Abdalla|2020|loc=1. Introduction|p=1—2}}

=== Endocrine function ===
In addition to excretory, the kidneys also perform an endocrine function, they produce certain [[Biology:Hormone|hormone]]s. The [[Biology:Juxtaglomerular cell|juxtaglomerular cell]]s of the kidneys produce [[Biology:Renin|renin]], which is a key regulator of the [[Medicine:Renin–angiotensin system|renin–angiotensin system]], which is responsible for blood pressure regulation.<ref name="auto1"/>

The production of [[Biology:Erythropoietin|erythropoietin]] by the kidneys is responsible for the differentiation of erythroid progenitor cells in the [[Biology:Bone marrow|bone marrow]] into erythrocytes and is induced by [[Medicine:Hypoxia (medical)|hypoxia]]. Thus, with a lack of [[Chemistry:Oxygen|oxygen]], the number of [[Biology:Red blood cell|red blood cell]]s in the blood increases, and they are responsible for transporting oxygen.<ref name="auto"/>

The kidneys are involved in the [[Biology:Metabolism|metabolism]] of [[Chemistry:Vitamin D|vitamin D]]. In the [[Biology:Liver|liver]], vitamin D is converted to [[Chemistry:Calcifediol|calcifediol]] (25OHD), while the kidneys convert calcifediol to [[Chemistry:Calcitriol|calcitriol]] (1,25(OH)<sub>2</sub>D), which is the active form of the vitamin and is essentially a [[Biology:Hormone|hormone]]. Vitamin D is involved in the formation of [[Biology:Bone|bone]]s and [[Biology:Cartilage|cartilage]], and also performs a number of other functions, for example, it is involved in the functioning of the [[Biology:Immune system|immune system]].<ref name=":5" />

=== Blood pressure regulation ===
Some mammalian internal organs, including the kidneys and [[Medicine:Lung|lung]], are designed to function within normal [[Physics:Blood pressure|blood pressure]] levels and normal [[Medicine:Blood volume|blood volume]] levels, and blood pressure itself is also affected by changes in blood volume levels. Therefore, maintaining a constant blood volume for mammals is a very important function of the body.{{sfn|Bradley|2009|loc=11.5 The mammalian kidney|p=164}} The stable level of blood volume is influenced by the [[Medicine:Glomerular filtration rate|glomerular filtration rate]], the function of individual parts of the nephron, the sympathetic nervous system and the renin-angiotensin-aldosterone system.<ref>{{Cite Q|Q28729911}}</ref>

In the walls of the afferent arterioles at the entrance to the renal glomeruli, there are [[Biology:Juxtaglomerular cell|juxtaglomerular cell]]s. These cells are sensitive to changes in the minute volume of blood circulation, and to the composition and volume of the [[Biology:Extracellular fluid|extracellular fluid]], producing [[Biology:Renin|renin]] in response to changes in their level.<ref name=":6">{{Cite journal |last1=Sequeira-Lopez |first1=Maria Luisa S. |last2=Gomez |first2=R. Ariel |date=2021-04-02 |title=Renin Cells, the Kidney, and Hypertension |journal=Circulation Research |language=en |volume=128 |issue=7 |pages=887–907 |doi=10.1161/CIRCRESAHA.121.318064 |issn=0009-7330 |pmc=8023763 |pmid=33793334}}</ref> Once in the bloodstream, renin converts [[Biology:Angiotensinogen|angiotensinogen]] to angiotensin I. Angiotensin I is further cleaved by the [[Biology:Angiotensin-converting enzyme|angiotensin-converting enzyme]] to angiotensin II, which is a potent [[Chemistry:Vasoconstriction|vasoconstrictor]] that increases blood pressure.<ref name=":6" /> In addition to angiotensin II, other biologically active substances can be formed in mammals. Angiotensin II can be cleaved to angiotensin III, angiotensin IV and angiotensin (1–7).<ref>{{Cite Q|Q117104121 |url=https://books.google.com/books?id=JeTwCAAAQBAJ&pg=PA153 |pages=153}}</ref>

=== Acid-base balance ===
Maintaining acid-base balance is vital because changes in [[Chemistry:PH|pH]] levels affect virtually every biological process in the body.{{Sfn|Eladari|2014|loc=Introduction|p=1623}} In a typical mammal, a normal average pH level is around 7.4.<ref>{{Cite Q|Q117048829|url=https://books.google.com/books?id=BR8KAAAAQBAJ&pg=PA637|pages=637}}</ref> As in the case of other [[Biology:Vertebrate|vertebrate]]s in mammals, the acid-base balance is maintained mainly by the [[Chemistry:Bicarbonate buffer system|bicarbonate buffer system]] (HCO<sub>3</sub><sup>-</sup>/CO<sub>2</sub>), which allows maintaining a constant pH level of the blood and extracellular fluid.<ref name=":42">{{Cite Q|Q117190520|url=https://books.google.com/books?id=f5sACAAAQBAJ&pg=PA64|pages=66}}</ref> This buffer system is described by the following equation:<ref name=":12">{{Citation|lang=en|url=https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/acid-base-regulation|title=Acid-Base Regulation|author=James L. Lewis III|work=MSD Manuals - Medical Professional Version|date=Jul 2021|access-date=2023-03-17|archive-url=https://web.archive.org/web/20230317174120/https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/acid-base-regulation|archive-date=2023-03-17}}</ref>

:<chem>HCO_3^- + H+ <=> H2CO3 <=> CO2 + H2O</chem>

The regulation of the acid-base balance through the bicarbonate buffer system is provided by the lungs and kidneys.<ref name=":42" /> The lungs regulate CO<sub>2</sub> ([[Chemistry:Carbon dioxide|carbon dioxide]]) level, while the kidneys regulate HCO<sub>3</sub><sup>-</sup> and H<sup>+</sup> ([[Chemistry:Bicarbonate|bicarbonate]] and [[Chemistry:Hydrogen|hydrogen]] [[Physics:Ion|ion]]s).<ref name=":12" /> The kidneys play a key role in maintaining a constant level of acid-base balance in mammals.<ref name=":8">{{Cite Q|Q28972309}}</ref> In the glomeruli, HCO<sub>3</sub><sup>-</sup> is completely filtered into primary urine.<ref name=":12" /> To maintain a constant pH, the kidneys reabsorb almost all of the HCO<sub>3</sub><sup>-</sup> from primary urine back into the bloodstream and [[Biology:Secretion|secrete]] H<sup>+</sup> into the urine, oxidizing the urine.{{Sfn|Eladari, Hasler, Féraille|2012|loc=Bicarbonate Absorption|p=84}}

Reabsorption of HCO<sub>3</sub><sup>-</sup> occurs in the proximal tubule, in the ascending limb of the loop of Henle, and to a lesser extent in the distal convoluted tubule of the nephron. H<sup>+</sup> secretion is carried out mainly through Na<sup>+</sup>/H<sup>+</sup> exchangers in the tubules of the nephron.{{Sfn|Eladari, Hasler, Féraille|2012|loc=Bicarbonate Absorption|p=84}} The collecting ducts are involved in the energy-dependent secretion of H<sup>+</sup>.{{Sfn|Eladari|2014|loc=Renal ammonia handling : Fig. 3|p=1629}} When H<sup>+</sup> ions enter the urine, they can combine with filtered HCO<sub>3</sub><sup>-</sup> to form [[Chemistry:Carbonic acid|carbonic acid]] H<sub>2</sub>CO<sub>3</sub>, which is being converted into CO<sub>2</sub> and H<sub>2</sub>O (water) by the luminal carbonic anhydrase. The formed CO<sub>2</sub> diffuses into the cells of the tubules, where it combines with H<sub>2</sub>O with the help of [[Biology:Cytosol|cytosol]]ic [[Biology:Carbonic anhydrase|carbonic anhydrase]] and forms HCO<sub>3</sub><sup>-</sup>, which then returns to the bloodstream, and the formed H<sup>+</sup> ion is secreted into the urine. Some of the H<sup>+</sup> ions are secreted at an energy cost through an [[Chemistry:Adenosine triphosphate|ATP]]-dependent mechanism.{{Sfn|Eladari, Hasler, Féraille|2012|loc=Bicarbonate Absorption|p=84}}

The excreted urine is slightly acidic. The excretion of H<sup>+</sup> together with urine also occurs through buffer systems, in particular, NH<sub>4</sub><sup>+</sup> ([[Chemistry:Ammonium|ammonium]]).{{Sfn|Eladari|2014|loc=Renal ammonia handling|p=1627}} Only a small amount of NH<sub>4</sub><sup>+</sup> is filtered through the glomerulus; {{Sfn|Eladari|2014|loc=Renal ammonia handling|p=1627}} most of the ammonium excreted is the result of H<sup>+</sup> ion oxidation of NH<sub>3</sub> ([[Chemistry:Ammonia|ammonia]]) formed in the cells of the proximal convoluted tubule, which is secreted into the lumen of the tubule either as NH<sub>3</sub> or as NH<sub>4</sub><sup>+</sup>.{{Sfn|Eladari|2014|loc=Renal ammonia handling|p=1627-1628}} The formation of ammonia is also accompanied by the formation of new HCO<sub>3</sub><sup>-</sup>, which replenishes the extracellular buffer system.{{Sfn|Eladari|2014|loc=Renal ammonia handling|p=1627-1628}} In the thick ascending tubule of the loop of Henle, on the contrary, NH<sub>4</sub><sup>+</sup> is absorbed, which causes its accumulation in the interstitium.{{Sfn|Eladari|2014|loc=Renal ammonia handling : Fig.2|p=1628}} The final stage of urine oxidation occurs in the collecting ducts, where H<sup>+</sup> ions are secreted with the involvement of ATP, and NH<sub>3</sub> is transported from the interstitium and secreted into the urine, where NH<sub>3</sub> is oxidized by H<sup>+</sup> to form NH<sub>4</sub><sup>+</sup>.{{Sfn|Eladari|2014|loc=Renal ammonia handling : Fig. 3|p=1629}} By regulating HCO<sub>3</sub><sup>-</sup> reabsorption and H<sup>+</sup> secretion, the kidneys help maintain blood pH [[Homeostasis|homeostasis]].<ref name=":12" />

=== Glucose homeostasis ===
Together with the [[Biology:Liver|liver]],<ref>{{Cite Q|Q123236759 |url=https://books.google.com/books?id=4Ab8CAAAQBAJ&pg=PA534 |pages=534}}</ref> the kidneys are involved in maintaining glucose homeostasis in the body of mammals.<ref name=":31">{{Cite Q|Q57012122}}</ref><ref name=":32">{{Cite Q|Q123237143 |url=https://books.google.com/books?id=Dw3vfMM3wiIC&pg=PA77 |pages=77-78}}</ref> The processes of [[Chemistry:Filtration|filtration]], reabsorption and consumption of glucose, as well as the production of glucose through [[Biology:Gluconeogenesis|gluconeogenesis]], occur in the kidneys.<ref name=":31" /><ref name=":32" /> Glucose consumption ([[Biology:Glycolysis|glycolysis]]) occurs primarily in the medulla, while gluconeogenesis occurs in the cortex. [[Biology:Hormone|Hormonally]], the process of gluconeogenesis in the kidneys is regulated by [[Biology:Insulin|insulin]] and [[Biology:Catecholamine|catecholamine]]s.<ref name=":31" />

== Evolution ==

=== Definitive mammalian kidney ===
The first mammals are believed to have appeared during the Permian period, which was characterized by cold nights in arid [[Earth:Desert|desert]]s and a strong seasonality with long, cold winters. It is likely that cold and [[Earth:Aridity|aridity]] were significant factors of [[Biology:Evolutionary pressure|evolutionary pressure]] at that time. The development of warm-bloodedness in protomammals could lead to an increase in the intensity of blood circulation, and, accordingly, to an increase in [[Physics:Blood pressure|blood pressure]], which, in turn, increased the [[Medicine:Glomerular filtration rate|glomerular filtration rate]] of the kidneys. However, an increase in the glomerular filtration rate would also lead to an increase in the removal rate of water from the body.{{sfn|Vize, Smith|2004|p=352}} All mammals have a thin segment of the tubule that is part of the loop of Henle. This segment is responsible for the concentration of urine and the reabsorption of water.{{sfn|Vize, Smith|2004|p=351}} It can be assumed that the development of a water reabsorption mechanism could be part of the evolution of warm-bloodedness, rather than a direct [[Biology:Adaptation|adaptation]] to aridity.{{sfn|Vize, Smith|2004|p=352}}

=== Adaptations to aridity ===
The ability to produce more concentrated urine is inversely dependent on the body mass of the mammals, that is, the smaller the mass of the animal, the more concentrated urine relative to animals with a larger mass its kidneys could produce during adaptation to an [[Earth:Aridity|arid]] environment.<ref name=":21">{{Cite Q|Q112795614}}</ref> Some desert animals have evolved greater ability to concentrate urine than other animals.<ref>{{Cite Q|Q121096094}}</ref> The most concentrated urine among the studied species is produced by the Australian [[Biology:Hopping mouse|hopping mouse]] Notomys alexis,<ref name=":21" /> whose kidneys have longer loops of Henley and an elongated renal papilla compared to the kidneys of other mammals.<ref>{{Cite Q|Q122965291}}</ref> The longer loops of Henley in the Australian hopping mouse make it possible to produce very concentrated urine{{Sfn|Schulte, Kunter, Moeller|2014|loc=Adapting to living on dry land: the water-retaining kidney was invented twice|p=718}} and survive in conditions of water scarcity.<ref name=":21" />

=== Adaptations to body mass ===
The simplest type of kidney in mammals is the unipapillary kidney, consisting of a cortex, medulla, and renal pelvis.{{sfn|Zhou, Rong, Guo et al.|2023|loc=Introduction|p=1}} But the unipapillary kidney is limited by the number of nephrons at which it functions optimally.{{sfn|Zhou, Rong, Guo et al.|2023|loc=The Evolution of Renal Structures Was Driven by Body Size and Habitats in Mammals|p=6}} It is assumed that unipapillary kidney was the original kidney structure in mammals, from which multilobar kidneys.{{sfn|Zhou, Rong, Guo et al.|2023|loc=Introduction|p=2}}

More complex multilobar kidneys likely emerged as an adaptation to the increased body mass of mammals and the corresponding need for an increase in the number of nephrons in the kidneys.{{sfn|Zhou, Rong, Guo et al.|2023|loc=The Evolution of Renal Structures Was Driven by Body Size and Habitats in Mammals|p=6}} A further adaptation mechanism is an increase in the size of the renal glomeruli in large mammals (and, accordingly, an increase in the length of the tubules), as in [[Biology:Elephant|elephant]]s, in which the diameter of the glomerulus can be 2 times larger than in killer whales.<ref name=":22" />

The appearance of [[Biology:Reniculate kidney|reniculate kidney]]s was probably the result of adaptation to both an increase in body mass and [[Earth:Habitat|habitat]]s.{{sfn|Zhou, Rong, Guo et al.|2023|loc=Introduction|p=2}}{{sfn|Zhou, Rong, Guo et al.|2023|loc=The Evolution of Renal Structures Was Driven by Body Size and Habitats in Mammals|p=6}} Reniculate kidneys probably allow the number of nephrons to be increased by adding renculi without the need to increase tubule length as the organ size increases.<ref name=":22" />

=== Reniculate kidneys ===
{{Main|Biology:Reniculate kidney}}
Reniculate kidneys are typical mainly for [[Biology:Marine mammal|marine mammal]]s. They are believed to be an adaptation both to the large body mass, allowing the number of nephrons to increase by increasing the number of renculi, and to a diet with large amounts of [[Chemistry:Saline water|saline water]], as well as an adaptation for long term diving. Consumption of excess [[Chemistry:Salt|salt]] leads to intracellular [[Medicine:Dehydration|dehydration]], resulting in a need for rapid removal of excess salt from the body, which in the case of reniculate kidneys is facilitated by an increase in the total surface area between the cortex and medulla.{{sfn|Zhou, Rong, Guo et al.|2023|loc=Introduction|p=2}} The need to dive for long periods of time requires a reduction in the body's [[Chemistry:Oxygen|oxygen]] consumption,{{Sfn|Ortiz|2001|loc=Apnea/simulated diving|p=1838}} while the kidneys are an energy-consuming organ,<ref>{{Cite Q|Q33683963}}</ref> so the glomerular filtration rate decreases during diving.{{Sfn|Ortiz|2001|loc=Apnea/simulated diving|p=1838}} In contrast, the glomerular filtration rate is very high between dives.{{sfn|Zhou, Rong, Guo et al.|2023|loc=Introduction|p=2}}

== Development ==

=== Stages of kidney development ===
In mammals, the final kidney is the metanephric kidney, but kidneys development occurs in three stages with the development of three different types of kidney during [[Biology:Embryo|embryo]]nic period: pronephros, mesonephros and metanephros.{{Sfn|Bush, Sakurai, Nigam|2012|loc=Overview|p=859}}<ref name=":7">{{Cite Q|Q117156103}}</ref> All three types develop from the [[Biology:Intermediate mesoderm|intermediate mesoderm]] sequentially in the cranio-caudal direction (in the direction from the side of the head to the tail of the body).{{Sfn|Davidson|2009|p=|loc=1. Overview of kidney structure and embryonic development}}<ref name=":7" /> First, the pronephros is formed, in mammals it is considered rudimentary, that is, it does not function.{{Sfn|Bush, Sakurai, Nigam|2012|loc=Overview|p=859}} Then, caudal to the pronephros, the mesonephros develops, which is the functioning kidney of the [[Biology:Embryo|embryo]].{{Sfn|Bush, Sakurai, Nigam|2012|loc=Overview|p=859}}<ref name=":7" /> Subsequently, the mesonephros degrades in females, and in males it participates in the development of the [[Biology:Reproductive system|reproductive system]]. The third stage is the formation of a metanephros in the caudal part of the embryo, which is a permanent kidney.{{Sfn|Bush, Sakurai, Nigam|2012|loc=Overview|p=859}}

=== Metanephros development ===
[[File:Schematic representation of nephrogenesis in English.webp|thumb|Schematic representation of nephrogenesis during embryologic development following induction of cap mesenchyme by the ureteric bud.<ref>{{Cite Q|Q117085458 |url=https://www.nature.com/articles/s41536-021-00156-w/figures/1}}</ref>]]
The metanephros develops from the ureteric bud, which is an outgrowth on the caudal part of the nephric duct,<ref>{{Cite Q|Q50792365}}</ref><ref>{{Cite Q|Q100943416}}</ref> and the [[Biology:Metanephrogenic blastema|metanephrogenic blastema]], which is part of the [[Biology:Intermediate mesoderm|intermediate mesoderm]] surrounding the ureteral bud.{{Sfn|Bush, Sakurai, Nigam|2012|loc=Overview|pp=859-860}}<ref name=":10">{{Cite Q|Q41006079}}</ref> The development of metanephros begins with the induction of a metanephrogenic blastema by the ureteric bud.<ref name=":10" />{{Sfn|Bush, Sakurai, Nigam|2012|loc=Overview|p=859}} While the kidney develops, the metanephrogenic blastema and ureteric bud reciprocally induce each other.{{Sfn|Bush, Sakurai, Nigam|2012|loc=Overview|p=859}} Growing into the mesoderm, the ureteric bud branches and transforms into a tree structure that will eventually become the ureter, renal pelvis, major and minor calyces, renal papillae, and collecting ducts.{{Sfn|Bush, Sakurai, Nigam|2012|loc=Development of the Metanephros|p=861-862}} At the same time, at the tips of the collecting ducts, the mesoderm differentiates into epithelial cells that form nephron tubules{{Sfn|Bush, Sakurai, Nigam|2012|loc=Development of the Metanephros|p=860}} (processes of epithelialization and tubulogenesis occur).{{Sfn|Bush, Sakurai, Nigam|2012|loc=Development of the Metanephros|p=861}} Vascular system of the kidney is also developed with the development of nephrons, with large vessels branching from the dorsal aorta.{{Sfn|Bush, Sakurai, Nigam|2012|loc=Development of the Metanephros|p=861}}

In some mammals, kidney [[Biology:Organogenesis|organogenesis]] ends before birth, while in others it may continue for some time into the [[Medicine:Postpartum period|postpartum period]]{{Sfn|Bush, Sakurai, Nigam|2012|loc=Termination of the Kidney Development|p=882}} (for example, in [[Biology:Rodent|rodent]]s it ends about a week after birth).<ref>{{Cite Q|Q42235704}}</ref> When the formation of new nephrons (nephrogenesis) ends, the number of nephrons in the kidney becomes final.{{Sfn|Bush, Sakurai, Nigam|2012|loc=Termination of the Kidney Development|p=882}}

=== Postnatal maturation ===
After birth and in the postnatal period, the kidneys are functionally immature; functional development of the kidneys in all mammals lags behind the anatomical development.<ref name=":9">{{Cite Q|Q33607543}}</ref> In the postnatal period, the mass of the tubules is not large enough, so the ability to reabsorb fluids is reduced compared to the kidneys of adult mammals.<ref>{{Cite Q|Q88659637}}</ref> During this period, [[Medicine:Hypertrophy|hypertrophy]] and [[Medicine:Hyperplasia|hyperplasia]] of the tubules occurs, and the kidneys increase in size. The period during which fully functional kidneys form varies significantly between mammalian species. In [[Biology:Rat|rat]]s, the kidneys quickly become fully functional, while in [[Biology:Monkey|monkey]]s it takes 5 months.<ref name=":9" />

== Injury and diseases ==
Kidney [[Disease|disease]]s or disorders may be [[Medicine:Birth defect|congenital]], [[Medicine:Genetic disorder|inherited]], non-infectious, and [[Medicine:Infection|infectious]].<ref name=":23">{{Cite web |title=Urinary System |url=https://www.msdvetmanual.com/urinary-system |url-status=live |archive-url=https://web.archive.org/web/20230927143854/https://www.msdvetmanual.com/urinary-system |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref> Diseases vary between mammalian species. Some diseases may be specific only to some species, while the others may be more common in one species and less common in another.<ref name=":27">{{Cite Q|Q122870348|pages=231-232}}</ref> For example, chronic progressive nephropathy is common in [[Biology:Mouse|mice]], [[Biology:Rat|rat]]s and [[Biology:Naked mole-rat|naked mole-rat]]s,<ref>{{Cite Q|Q122849312|url=https://books.google.com/books?id=rUwADQAAQBAJ&pg=PA503|page=503}}</ref> but at the same time there is no analogous disease in [[Biology:Human|human]]s.<ref>{{Cite Q|Q37514291}}</ref>

=== Congenital and inherited anomalies ===
Congenital anomalies and hereditary disorders of the kidneys among mammals are rare, but can have a significant impact on kidney function,<ref>{{Cite web |title=Overview of Congenital and Inherited Anomalies of the Urinary System |url=https://www.msdvetmanual.com/urinary-system/congenital-and-inherited-anomalies-of-the-urinary-system/overview-of-congenital-and-inherited-anomalies-of-the-urinary-system |url-status=live |archive-url=https://web.archive.org/web/20230927150324/https://www.msdvetmanual.com/urinary-system/congenital-and-inherited-anomalies-of-the-urinary-system/overview-of-congenital-and-inherited-anomalies-of-the-urinary-systemcongenital-and-inherited-anomalies-of-the-urinary-system |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref> in some cases they can cause death in the early neonatal period.<ref name=":16">{{Cite web |title=Renal Anomalies |url=https://www.merckvetmanual.com/urinary-system/congenital-and-inherited-anomalies-of-the-urinary-system/renal-anomalies |url-status=live |archive-url=https://web.archive.org/web/20230927153234/https://www.merckvetmanual.com/urinary-system/congenital-and-inherited-anomalies-of-the-urinary-system/renal-anomalies |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref> Among the anomalies of kidney development are [[Medicine:Hypoplasia|hypoplasia]] and [[Biology:Dysplasia|dysplasia]] of the kidneys (dysplasia can be unilateral or bilateral), [[Medicine:Agenesis|agenesis]] (absence) of one or both kidneys, [[Medicine:Polycystic kidney disease|polycystic kidney disease]], simple [[Medicine:Renal cyst|renal cyst]]s, perirenal pseudocysts, doubled or tripled renal arteries, malposition of the kidneys, [[Medicine:Horseshoe kidney|horseshoe kidney]] and nephroblastoma.<ref name=":16" />

=== Non-infectious diseases ===
Non-infectious diseases of the kidney include [[Medicine:Acute kidney injury|acute kidney injury]], [[Medicine:Chronic kidney disease|chronic kidney disease]],<ref name=":17">{{Cite web |title=Renal Dysfunction in Small Animals |url=https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/renal-dysfunction-in-small-animals |url-status=live |archive-url=https://web.archive.org/web/20230927153459/https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/renal-dysfunction-in-small-animals |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref> glomerular diseases<ref>{{Cite web |title=Glomerular Disease in Small Animals |url=https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/glomerular-disease-in-small-animals |url-status=live |archive-url=https://web.archive.org/web/20230927153615/https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/glomerular-disease-in-small-animals |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref> and tubular diseases ([[Medicine:Renal tubular acidosis|renal tubular acidosis]], [[Medicine:Fanconi syndrome|Fanconi syndrome]] and renal glycosuria).<ref>{{Cite web |title=Renal Tubular Defects in Small Animals |url=https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/renal-tubular-defects-in-small-animals |url-status=live |archive-url=https://web.archive.org/web/20230927153624/https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/renal-tubular-defects-in-small-animals |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref> In small mammals, renal [[Medicine:Neoplasm|neoplasm]]s are rare but usually are not benign.<ref>{{Cite web |title=Neoplasia of the Urinary System in Small Animals |url=https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/neoplasia-of-the-urinary-system-in-small-animals |url-status=live |archive-url=https://web.archive.org/web/20230927153901/https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/neoplasia-of-the-urinary-system-in-small-animals |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref> Renal neoplasms and [[Medicine:Abscess|abscess]]es are rare in [[Biology:Ruminant|ruminant]]s.<ref>{{Cite Q|Q122886585|url=https://books.google.com/books?id=H3DkAwAAQBAJ&pg=PA768|page=768}}</ref> [[Medicine:Obstructive uropathy|Obstructive uropathy]] (obstruction of [[Biology:Urine|urine]] flow from one or both kidneys) can lead to [[Medicine:Hydronephrosis|hydronephrosis]] with dilatation of the renal pelvis.<ref>{{Cite web |title=Obstructive Uropathy in Small Animals |url=https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/obstructive-uropathy-in-small-animals |url-status=live |archive-url=https://web.archive.org/web/20230927154101/https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/obstructive-uropathy-in-small-animals |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref> Kidney stones can also be formed in the kidneys (nephrolithiasis).<ref>{{Cite web |title=Urolithiasis in Small Animals |url=https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/urolithiasis-in-small-animals |url-status=live |archive-url=https://web.archive.org/web/20230927154227/https://www.merckvetmanual.com/urinary-system/noninfectious-diseases-of-the-urinary-system-in-small-animals/urolithiasis-in-small-animals |archive-date=2023-09-27 |access-date=2023-09-29 |website=Merck Veterinary Manual |language=en}}</ref>

The cause of acute kidney injury in most cases is ischemic or [[Medicine:Toxic injury|toxic]] injury. Mammalian kidneys are susceptible to ischemic injury because mammals lack a [[Biology:Renal portal system|renal-portal system]], and as a result, vascular [[Chemistry:Vasoconstriction|vasoconstriction]] in the glomeruli can lead to decreased blood supply to the entire kidney. The kidneys are susceptible to toxic injury, since [[Biology:Toxin|toxin]]s are reabsorbed in the tubules along with most of the filtered substances.<ref name=":29">{{Cite Q|Q38248788}}</ref> The kidneys are able to restore their functionality after acute injury, but it also can progress into [[Medicine:Chronic kidney disease|chronic kidney disease]]. Chronic kidney disease is characterised by loss of function of the kidney tissues, and the disease is usually progressive.<ref name=":17" />

=== Infectious diseases ===
Kidney infections in small mammals are usually caused by aerobic bacteria, including ''[[Biology:Escherichia coli|Escherichia coli]]'', [[Biology:Staphylococcus|staphylococci]], [[Biology:Enterococcus|enterococci]], and [[Biology:Streptococcus|streptococci]].<ref name=":18">{{Cite web |title=Overview of Infectious Diseases of the Urinary System in Small Animals |url=https://www.merckvetmanual.com/urinary-system/infectious-diseases-of-the-urinary-system-in-small-animals/overview-of-infectious-diseases-of-the-urinary-system-in-small-animals |url-status=live |archive-url=https://web.archive.org/web/20230927154622/https://www.merckvetmanual.com/urinary-system/infectious-diseases-of-the-urinary-system-in-small-animals/overview-of-infectious-diseases-of-the-urinary-system-in-small-animals |archive-date=2023-09-27 |access-date=2023-09-30 |website=Merck Veterinary Manual |language=en}}</ref> [[Medicine:Fungal infection|Fungal]] and parasitic infections of the kidney are rare in small mammals.<ref name=":18" /> [[Medicine:Pyelonephritis|Pyelonephritis]] is usually caused by [[Biology:Bacteria|bacteria]] that enter the kidney through the ascending route from the lower parts of the urinary system, in rare cases through the [[Biology:Blood|blood]] (descending [[Medicine:Bloodstream infections|hematogenous route]]).<ref name=":24">{{Cite web |title=Pyelonephritis in Small Animals |url=https://www.merckvetmanual.com/urinary-system/infectious-diseases-of-the-urinary-system-in-small-animals/pyelonephritis-in-small-animals |url-status=live |archive-url=https://web.archive.org/web/20230927155512/https://www.merckvetmanual.com/urinary-system/infectious-diseases-of-the-urinary-system-in-small-animals/pyelonephritis-in-small-animals |archive-date=2023-09-27 |access-date=2023-09-30 |website=Merck Veterinary Manual |language=en}}</ref> In [[Biology:Ruminant|ruminant]]s, pyelonephritis is most often caused by the bacteria ''[[Biology:Corynebacterium renale|Corynebacterium renale]]'' and ''[[Biology:Escherichia coli|Escherichia coli]]''.<ref name=":26">{{Cite Q|Q38959395}}</ref> Fish-eating mammals (such as [[Biology:Mink|mink]]s and [[Biology:Dog|dog]]s) can become infected with the giant kidney worm ''[[Biology:Dioctophyme renale|Dioctophyme renale]]''.<ref name=":19">{{Cite Q|Q122851992|url=https://books.google.com/books?id=Jpg1ysgVn-AC&pg=PA1532|page=1532}}</ref> Pigs can become infected with the ''Stephanurus dentatus'' worm, which is found throughout the world, but is more common in the tropics and [[Earth:Subtropics|subtropics]].<ref name=":28">{{Cite web |title=Swine Kidney Worm Infection |url=https://www.merckvetmanual.com/urinary-system/infectious-diseases-of-the-urinary-system-in-large-animals/swine-kidney-worm-infection |url-status=live |archive-url=https://web.archive.org/web/20230604172201/https://www.merckvetmanual.com/urinary-system/infectious-diseases-of-the-urinary-system-in-large-animals/swine-kidney-worm-infection |archive-date=2023-06-04 |access-date=2023-09-30 |website=Merck Veterinary Manual |language=en}}</ref><ref name=":19" /> Kidney infections are considered rare among marine mammals.<ref>{{Cite Q|Q122880668|url=https://books.google.com/books?id=srxHDwAAQBAJ&pg=PA30-IA35|page=30}}</ref>

=== Ageing ===
After maturation, the kidneys slowly begin to undergo ageing processes, which are characterized by changes in [[Biology:Anatomy|anatomy]], [[Biology:Physiology|physiology]], function and regenerative capabilities. During the life of mammals, glomerulosclerosis affects glomeruli, the [[Biology:Basement membrane|basement membrane]] thickens, the tubules undergo atrophic changes, and the renal interstitium [[Medicine:Fibrosis|fibrosis]] increases. The number of functioning nephrons gradually decreases throughout the life. In terms of function, the [[Medicine:Glomerular filtration rate|glomerular filtration rate]] decreases and the ability to concentrate urine decreases, too. Age-related changes themselves may not be noticeable and may not lead to [[Medicine:Kidney failure|kidney failure]] or disease, but are a risk factor for kidney or urinary tract diseases.{{sfn|Breshears, Confer|2017|loc=Aging of the Kidney|p=637}}

== Repair and regeneration ==
Unlike more primitive [[Biology:Vertebrate|vertebrate]]s such as [[Biology:Fish|fish]], in mammals nephrogenesis ends before or some time after birth,{{sfn|Davidson|2011|loc=Introduction|p=1435}} caused by the loss of the condensed mesenchyme of the [[Biology:Metanephrogenic blastema|metanephrogenic blastema]].{{sfn|Davidson|2011|loc=Cessation of mammalian nephrogenesis|p=1436}} As a result, new nephrons cannot form in adults,{{sfn|Davidson|2011|loc=Introduction|p=1435}} and after [[Biology:Injury|injuries]], the kidneys of adult mammals cannot [[Biology:Regeneration|regenerate]] through the formation of new nephrons.{{sfn|Little, McMahon|2012|loc=7 Reassessing Renal Disease, Repair, and Regeneration Using Developmental Biology|p=12}} However, kidneys have other [[Biology:Compensatory growth (organ)|compensatory]] and regenerative mechanisms for restoring their function.{{sfn|Davidson|2011|loc=Postnatal regenerative response of the mammalian kidney|pp=1437-1439}}

=== Compensatory capabilities ===
In the case of unilateral [[Medicine:Nephrectomy|nephrectomy]], the load on the remaining kidney increases, increasing the rate of [[Medicine:Glomerular filtration rate|filtration]] and reabsorption and leading to changes in the nephrons themselves. The renal glomerulus may double or triple in diameter. These compensatory changes are similar to the changes in nephrons that occur after birth as the kidney grows.{{sfn|Davidson|2011|loc=Postnatal regenerative response of the mammalian kidney|p=1437}} Resection of kidney tissue also does not cause kidney regeneration,<ref>{{Cite Q|Q37728655}}</ref> however, compensatory changes can also occur after kidney damage if it leads to a significant decrease in the number of nephrons in the kidneys.{{sfn|Davidson|2011|loc=Conclusions and perspectives|p=1441}}

=== Nephron regeneration ===
Within a single nephron, regenerative abilities differ between its parts.{{sfn|Yang, Liu, Fogo|2014|loc=What Is Kidney Regeneration?}} In acute [[Medicine:Toxic injury|toxic]] and ischemic injuries, the tubules are able to regenerate and restore the function of the nephron.{{sfn|Davidson|2011|loc=Postnatal regenerative response of the mammalian kidney|p=1437}} In particular, the proximal part of the nephron, through which up to two-thirds of the primary [[Biology:Urine|urine]] is absorbed,<ref name=":15">{{Cite Q|Q118136559|chapter=Nephron Repair in Mammals and Fish|url=https://books.google.com/books?id=gv9PCwAAQBAJ&pg=997|pages=997}}</ref> has the ability to regenerate.<ref name=":11">{{Cite Q|Q55210136}}</ref> This part of the nephron in mammals is most at risk of ischemic or toxic damage.<ref name=":15" /> In addition, the repair of nephrons occurs in the course of normal physiological activity throughout the life due to the shedding of tubular epithelial cells.{{sfn|Davidson|2011|loc=Postnatal regenerative response of the mammalian kidney|p=1438}} The glomerulus has a complex structure, and its ability to recover after injury is limited.{{sfn|Yang, Liu, Fogo|2014|loc=Introduction}} [[Biology:Mesangial cell|Mesangial]] and endothelial cells are able to [[Biology:Cell proliferation|proliferate]] and restore their population after injury. On the contrary, [[Biology:Podocyte|podocyte]]s do not proliferate under normal conditions.{{sfn|Yang, Liu, Fogo|2014|loc=Mechanisms of Kidney Regeneration}}

=== Healing after injury ===
If minor damage to the nephron tubules occurs, the lost cells are replaced by new ones, and the [[Biology:Epithelium|epithelium]] regenerates, restoring its structure and function. In moderate to severe [[Biology:Injury|injuries]] with large [[Biology:Cell|cell]] loss, the chances of regeneration of the tubular epithelium are reduced.{{sfn|Kumar|2018|loc=Figure 1 Schematic illustration highlighting patchy regenerative/reparative processes after mammalian acute kidney injury|p=28}} In such cases, damage leads to [[Medicine:Inflammation|inflammatory]] and [[Medicine:Fibrosis|fibrotic]] responses, and regenerative tissue repair is impaired.{{sfn|Kumar|2018|loc=Figure 1 Schematic illustration highlighting patchy regenerative/reparative processes after mammalian acute kidney injury|p=28}} Such a reaction is typical for [[Medicine:Acute kidney injury|acute kidney injury]].<ref name=":2" /> Fibrosis is the second line of body defences,<ref>{{Cite Q|Q38453872}}</ref> which was supposed to reduce possible hemorrhage and fight possible [[Medicine:Infection|infection]] during the [[Biology:Evolution|evolution]] of mammals.<ref name=":2" /> Renal fibrosis is the result of failed kidney healing and associated with renal dysfunction,{{sfn|Nogueira, Pires, Oliveira|2017|loc=Impact of Renal Fibrosis on Human Health|p=3}} but it was suggested that it might support survival of non-injured and partially injured nephrons.{{sfn|Nogueira, Pires, Oliveira|2017|loc=Renal Fibrosis: Aetiology and Pathophysiology|p=2}} Chronic kidney injury is characterized by fibrosis, scarring, and loss of tissue function.<ref name=":30">{{Cite Q|Q118139734|url=https://books.google.com/books?id=Xc1SHo0EHfYC&pg=PA811|pages=811|chapter=Chapter 34 - Kidney|author1=H. Haller|author2=S. Sorrentino}}</ref>

== References ==
{{reflist}}

== Bibliography ==
'''Books'''
{{refbegin}}
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** {{Cite Q|Q114595502
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* {{Cite Q|Q115690208
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 |pages = 121, 164
 |ref = {{harvid|Bradley|2009}}
}}
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}}
* {{Cite Q|Q95000300
 |ref = {{harvid|Davidson|2009}}
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* {{Cite Q|Q117066151
 |author1 = Jeff M. Sands
 |author2 = Jill W. Verlander
 |chapter = 1 Anatomy and Physiology of the Kidneys
 |chapter-url = https://books.google.com/books?id=_3mmDwAAQBAJ&pg=PT18
 |pages = 3-54
 |ref = {{harvid|Sands, Verlander|2004}}
}}
{{refend}}

'''Article in scientific journals'''
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* {{Cite Q|Q37845213|ref={{harvid|Davidson|2011}}}}
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* {{Cite Q|Q37705263
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* {{Cite Q|Q48664600
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* {{Cite Q|Q122181216
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}}
{{refend}}

==External links==

[[Category:Mammal anatomy]]

{{Sourceattribution|Mammalian kidney}}