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Physiology of the kidney

Last updated: February 23, 2021

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Nephrons are the functional units of the kidneys. They are composed of a renal corpuscle (the glomerulus and the Bowman capsule) and a renal tubule (the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, the collecting tubule, and the collecting ducts). The main functions of nephrons are urine production and excretion of waste products; regulation of electrolytes, serum osmolality, and acid-base balance; hormone production and secretion (e.g., erythropoietin, renin, calcitriol, prostaglandins); and maintenance of glucose homeostasis. Urine production involves filtration of the plasma in the renal corpuscle (a passive process), the secretion of substances to be eliminated (e.g., urea, hydrogen, potassium) into the lumen of the renal tubules, and the reabsorption of substances (e.g., glucose, urea, uric acid, potassium) within the renal tubules. These processes are regulated by a number of hormones that affect either renal blood flow or the function of the different transporters across the renal tubule. In addition, there are local mechanisms that regulate renal perfusion (e.g., myogenic regulation of the diameter of afferent arterioles) and urine osmolarity (e.g., tubuloglomerular feedback). The most commonly used measure of renal function is the glomerular filtration rate (GFR), which is the volume of primary ultrafiltrate filtered into the Bowman capsule per unit of time. In clinical settings, the GFR estimated using equations such as the modification of diet in renal disease (MDRD) study equation and the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. For more information on the kidney, see also “Kidneys.”

General information

Homeostasis [1]

Substance Site of reabsorption Site of secretion Transporters Clinical relevance
  • The same sites and percentages as for sodium
  • Na+-Ca2+ exchanger
  • Ca2+ ATPase
  • Competes with calcium
  • Urea transporters (e.g., urea transporter A1)
  • Symport with Na+
  • Maintains acid-base balance



Function Regulation Clinical relevance
Afferent arteriole
  • Regulation of blood flow
Proximal convoluted tubule
  • Brush border resorption of most of the ultrafiltrate
  • Forms NH3 and secretes it into lumen (facilitates H+ secretion)
Loop of Henle Thin descending limb of the loop of Henle
Thick ascending limb of the loop of Henle
Distal convoluted tubule (DCT)
  • Resorption of ions: Na+, Cl-, Mg2+and Ca2+
  • Impermeable to H2O
  • Decreases ultrafiltrate osmolality
Connecting tubule and collecting duct
Efferent arteriole
  • Regulation of blood flow

Countercurrent multiplication

  1. NaCl is actively transported from the tubular fluid in the ascending limb into the interstitial space.
  2. The interstitium becomes hypertonic. This allows water to follow a gradient and move passively from the tubular fluid with a lesser osmolarity to the interstitium with a higher osmolarity
  3. Continuous production of urine continuous movement of water from the tubular fluid into the interstitium steady increase of the osmotic gradient → significant increase in the amount of water reabsorbed in the descending limb.

Renal blood supply

Renal blood flow

Regulation of renal blood flow [1]

The kidney has multiple mechanisms to regulate its own blood flow. This allows for changing the rate of glomerular filtration if fluctuations in systemic blood pressure occur.

Myogenic autoregulation (Bayliss effect)


Tubuloglomerular feedback

Renin-angiotensin-aldosterone system (RAAS) [2]

ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II. ARBs inhibit the effect of angiotensin II. Both drug classes are used to treat arterial hypertension.

Besides their inhibitory effects on the heart (e.g., heart rate), β-blockers decrease blood pressure by inhibiting β1-receptors of the juxtaglomerular apparatus (JGA), which leads to decreased renin release.

Hormonal effects on the kidney

Autonomic regulation

Hypovolemic shock with severe hypotension activates the sympathetic nervous system. Subsequently, the hypovolemia and noradrenaline-induced vasoconstriction result in low renal blood flow → low GFR low urine production → acute renal injury.

This section focuses on fluid compartments, the basics of glomerular filtration, and tubular secretion. For more information on kidney function tests, see “Diagnostic evaluation of the kidney and urinary tract.”

Fluid compartments

The 60–40–20 rule refers to total body water (60% of body mass), ICF (40% of body mass), and ECF (20% of body mass).

Think of HIKIN to help you remember the main intracellular ion: HIgh K+ INtracellularly.

Renal clearance

  • Description: : the volume of plasma that is cleared of a certain substance per unit of time
  • Mechanism
    • Cx = Ux x V/Px
      • Px = Plasma concentration of substance X (mg/mL)
      • V = Urine flow rate (mL/min)
      • Ux = Urine concentration of substance X (mg/mL)
      • Cx = Clearance of substance X (mL/min)
    • If the clearance of substance X is:
      • > GFR: net tubular secretion of substance X
      • < GFR: net tubular reabsorption or substance X is not freely filtered in the glomerulus
      • = GFR: no net tubular secretion of reabsorption

Glomerular filtration rate [3]

The GFR is used to estimate kidney function and to stage chronic kidney disease.

Relative solute concentrations along proximal convoluted tubules

  • Mechanism
    • Water is absorbed along the PCT along with other solutes (e.g., creatinine, electrolytes, glucose)
    • At the beginning of the PCT, the concentration of all solutes within the glomerularly filtered tubular fluid (TF) is equivalent to the plasma concentration (P).
    • Compared to water, solutes can be reabsorbed along the PCT:
      • At the same rate →; no change in tubular fluid concentration compared to plasma concentration (TF/P = 1)
      • At a lower rate →; increased tubular fluid concentration compared to plasma concentration (TF/P > 1)
      • At a higher rate →; decreased tubular fluid concentration compared to plasma concentration (TF/P < 1)
    • Specific solutes
      • Sodium (Na+): reabsorbed at the same rate as water throughout the PCT → (TF/P)Sodium = 1
      • Inulin
        • Not reabsorbed, nor secreted along the PCT → (TF/P)Inulin > 1
        • Inulin is unique in that its amount does not change along the PCT but its tubular concentration is determined solely by water reabsorption.
      • PAH and creatinine: net tubular secretion along the PCT → (TF/P)PAH/Creat. /Creat. > (TF/P)Inulin > 1
      • Chloride (Cl): (TF/P)Chloride > 1 throughout the PCT
        • Initially reabsorbed at a slower rate than water and sodium → (TF/P)Chloride > 1 and rising
        • More distally in the PCT, reabsorbed at the same rate as water and sodium → still (TF/P)Chloride > 1 but no longer increasing (plateaued)
      • Glucose: reabsorbed at a higher rate than water → (TF/P)Glucose < 1

The increase in inulin concentration along the PCT is the result of a constant amount of inulin within the tubular fluid (no reabsorption or secretion) and the reabsorption of water. The increase in inulin concentration along the PCT is the result of water reabsorption and a constant amount of inulin within the tubular fluid (without tubular inulin secretion).

Water is reabsorbed along the PCT while the amount of inulin within the tubular fluid stays the same (no reabsorption or secretion of inulin). This leads to an increasing concentration of inulin along the PCT.

Inulin clearance

  • Description: used to assess the GFR
  • Mechanism
    • Inulin is freely filtered and neither reabsorbed nor secreted in the tubular system, i.e., the amount of inulin in the urine reflects the amount that is filtered by the kidneys.
    • Inulin clearance can be used to calculate GFR: GFR = Uinulin x V/Pinulin = Cinulin

Creatinine clearance

Para-aminohippuric acid (PAH) [2]

  • Description: used to estimate effective renal plasma flow
  • Mechanism
    • PAH is freely filtered in the glomerulus and secreted into the tubular lumen, but not reabsorbed. Hence, almost 100% of the PAH that enters the kidney is excreted.
    • Effective renal plasma flow (eRPF)
    • Clearance depends on the plasma concentration of PAH (∼ 650 mL/min)
      • If the plasma concentration of PAH is low, it gets completely excreted from the plasma through filtration and secretion.
      • Secretion is dependent on an organic anion transporter that is located on the basolateral membrane of the proximal convoluted tubule.
      • If concentration of PAH surpasses the transport capacity of the anion transporters (or if there is damage to the PCT; ), secretion is impaired, which reduces the total excreted amount of PAH. This leads to slight underestimation of renal plasma flow.

Glucose clearance

SGLT1 is located in the 1ntestine.
SGLT2 is located in the proximal 2bule.

Renal filtration

Filtration fraction (FF)

PDA - Prostaglandins Dilate Afferent arterioles

ACE - Angiotensin II Constricts Efferent arterioles

Filtered load

  • Description: the amount of a substance X that is filtered by the glomerulus per unit of time
  • Mechanism: filtered load (mg/min) = GFR (mL/min) x plasma concentration of substance X (mg/mL)
Changes in glomerular dynamics
Renal plasma flow Filtration fraction Possible cause
  • Unchanged
  • Unchanged
  • Unchanged
  • Unchanged
  • Unchanged

Renal excretion

Excretion rate

  • Description: the amount of substance X that is excreted into the urine per unit of time
  • Mechanism: excretion rate (mg/min) = urine flow rate (mL/min) x urine concentration of substance X (mg/mL)

Fractional excretion

  • Description: the proportion of the glomerular filtered substance X that is excreted in the urine
  • Mechanism
    • Fractional excretion = excreted load (urinary concentration of X)/filtered load (GFR × plasma concentration of X)
      • FE < 1: a large proportion of the filtered substance is reabsorbed in the tubules (e.g., water, glucose, amino acids, sodium chloride)
      • FE > 1: a small proportion of the filtered substance is reabsorbed or additional tubular secretion occurs (e.g., PAH, atropine)
    • Fractional excretion of sodium (FeNa): percentage of the glomerular filtered sodium that is excreted in the urine
    • Reabsorption rate = filtered load (GFR × plasma concentration of X) - excreted load (urine flow rate x urine concentration of X)
    • Secretion rate = excreted load - filtered load
  1. Woodcock T. Plasma volume, tissue oedema, and the steady-state Starling principle. BJA Education. 2017; 17 (2): p.74-78. doi: 10.1093/bjaed/mkw035 . | Open in Read by QxMD
  2. Corrigan G, Ramaswamy D, Kwon O, et al. PAH extraction and estimation of plasma flow in human postischemic acute renal failure. Am J Physiol Renal Physiol. 1999; 277 (2): p.F312-F318. doi: 10.1152/ajprenal.1999.277.2.f312 . | Open in Read by QxMD
  3. Hall JE. Guyton and Hall Textbook of Medical Physiology. Elsevier ; 2016
  4. Kumar, Clark. Kumar and Clark's Clinical Medicine, 9th edition. Elsevier ; 2016