renal excretion

腎排泄

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1. 〈U〉排泄,排泄作用 / 〈U〉〈C〉排泄物,分泌物
2. 腎臓の

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/10/25 06:22:25」(JST)

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In pharmacology, the clearance is a pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time; the usual units are mL/min. The quantity reflects the rate of drug elimination divided by plasma concentration.

The total body clearance will be equal to the renal clearance + hepatic clearance + lung clearance. Although for many drugs the clearance is simply considered as the renal excretion ability, that is, the rate at which waste substances are cleared from the blood by the kidney. In these cases clearance is almost synonymous with renal clearance or renal plasma clearance. Each substance has a specific clearance that depends on its filtration characteristics. Clearance is a function of glomerular filtration, secretion from the peritubular capillaries to the nephron, and re-absorption from the nephron back to the peritubular capillaries. Clearance is variable in zero-order kinetics because a constant amount of the drug is eliminated per unit time, but it is constant in first-order kinetics, because the amount of drug eliminated per unit time changes with the concentration of drug in the blood. The concept of clearance was described by Thomas Addis, a graduate of the University of Edinburgh Medical School.

It can refer to the amount of drug removed from the whole body per unit time, or in some cases the inter-compartmental clearances can be discussed referring to redistribution between body compartments such as plasma, muscle, fat.

Definition

Diagram showing the basic physiologic mechanisms of the kidney

When referring to the function of the kidney, clearance is considered to be the amount of liquid filtered out of the blood that gets processed by the kidneys or the amount of blood cleaned per time because it has the units of a volumetric flow rate [ volume / time ]. However, it does not refer to a real value; "the kidney does not completely remove a substance from the total renal plasma flow." From a mass transfer perspective and physiologically, volumetric blood flow (to the dialysis machine and/or kidney) is only one of several factors that determine blood concentration and removal of a substance from the body. Other factors include the mass transfer coefficient, dialysate flow and dialysate recirculation flow for hemodialysis, and the glomerular filtration rate and the tubular reabsorption rate, for the kidney. A physiologic interpretation of clearance (at steady-state) is that clearance is a ratio of the mass generation and blood (or plasma) concentration.

Its definition follows from the differential equation that describes exponential decay and is used to model kidney function and hemodialysis machine function:

$V{\frac {dC}{dt}}=-K\cdot C+{\dot {m}}\qquad (1)$

Where:

• ${\dot {m}}$ is the mass generation rate of the substance - assumed to be a constant, i.e. not a function of time (equal to zero for foreign substances/drugs) [mmol/min] or [mol/s]
• t is dialysis time or time since injection of the substance/drug [min] or [s]
• V is the volume of distribution or total body water [L] or [m³]
• K is the clearance [mL/min] or [m³/s]
• C is the concentration [mmol/L] or [mol/m³] (in the United States often [mg/mL])

From the above definitions it follows that ${\frac {dC}{dt}}$ is the first derivative of concentration with respect to time, i.e. the change in concentration with time.

It is derived from a mass balance.

Clearance of a substance is sometimes expressed as the inverse of the time constant that describes its removal rate from the body divided by its volume of distribution (or total body water).

In steady-state, it is defined as the mass generation rate of a substance (which equals the mass removal rate) divided by its concentration in the blood.

Effect of plasma protein binding

For substances that exhibit substantial plasma protein binding, clearance is generally defined as the total concentration (free + protein-bound) and not the free concentration.

Most plasma substances have primarily their free concentrations regulated, which thus remains the same, so extensive protein binding increases total plasma concentration (free + protein-bound). This decreases clearance compared to what would have been the case if the substance did not bind to protein. However, the mass removal rate is the same, because it depends only on concentration of free substance, and is independent on plasma protein binding, even with the fact that plasma proteins increase in concentration in the distal renal glomerulus as plasma is filtered into Bowman's capsule, because the relative increases in concentrations of substance-protein and non-occupied protein are equal and therefore give no net binding or dissociation of substances from plasma proteins, thus giving a constant plasma concentration of free substance throughout the glomerulus, which also would have been the case without any plasma protein binding.

In other sites than the kidneys, however, where clearance is made by membrane transport proteins rather than filtration, extensive plasma protein binding may increase clearance by keeping concentration of free substance fairly constant throughout the capillary bed, inhibiting a decrease in clearance caused by decreased concentration of free substance through the capillary.

Derivation of equation

Equation 1 is derived from a mass balance:

$\Delta m_{body}=(-{\dot {m}}_{out}+{\dot {m}}_{in}+{\dot {m}}_{gen.})\Delta t\qquad (2)$

where:

• $\Delta t$ is a period of time
• $\Delta m_{body}$ the change in mass of the toxin in the body during $\Delta t$
• ${\dot {m}}_{in}$ is the toxin intake rate
• ${\dot {m}}_{out}$ is the toxin removal rate
• ${\dot {m}}_{gen.}$ is the toxin generation rate

In words, the above equation states:

The change in the mass of a toxin within the body ($\Delta m$) during some time $\Delta t$ is equal to the toxin intake plus the toxin generation minus the toxin removal.

Since

$m_{body}=C\cdot V\qquad (3)$

and

${\dot {m}}_{out}=K\cdot C\qquad (4)$

Equation A1 can be rewritten as:

$\Delta (C\cdot V)=(-K\cdot C+{\dot {m}}_{in}+{\dot {m}}_{gen.})\Delta t\qquad (5)$

If one lumps the in and gen. terms together, i.e. ${\dot {m}}={\dot {m}}_{in}+{\dot {m}}_{gen.}$ and divides by $\Delta t$ the result is a difference equation:

${\frac {\Delta (C\cdot V)}{\Delta t}}=-K\cdot C+{\dot {m}}\qquad (6)$

If one applies the limit $\Delta t\rightarrow 0$ one obtains a differential equation:

${\frac {d(C\cdot V)}{dt}}=-K\cdot C+{\dot {m}}\qquad (7)$

Using the Product Rule this can be rewritten as:

$C{\frac {dV}{dt}}+V{\frac {dC}{dt}}=-K\cdot C+{\dot {m}}\qquad (8)$

If one assumes that the volume change is not significant, i.e. $C{\frac {dV}{dt}}=0$, the result is Equation 1:

$V{\frac {dC}{dt}}=-K\cdot C+{\dot {m}}\qquad (1)$

Solution to the differential equation

The general solution of the above differential equation (1) is:

$C={\frac {\dot {m}}{K}}+\left(C_{o}-{\frac {\dot {m}}{K}}\right)e^{-{\frac {K\cdot t}{V}}}\qquad (9)$

Where:

• C_o is the concentration at the beginning of dialysis or the initial concentration of the substance/drug (after it has distributed) [mmol/L] or [mol/m³]
• e is the base of the natural logarithm

Steady-state solution

The solution to the above differential equation (9) at time infinity (steady state) is:

$C_{\infty }={\frac {\dot {m}}{K}}\qquad (10a)$

The above equation (10a) can be rewritten as:

$K={\frac {\dot {m}}{C_{\infty }}}\qquad (10b)$

The above equation (10b) makes clear the relationship between mass removal and clearance. It states that (with a constant mass generation) the concentration and clearance vary inversely with one another. If applied to creatinine (i.e. creatinine clearance), it follows from the equation that if the serum creatinine doubles the clearance halves and that if the serum creatinine quadruples the clearance is quartered.

Measurement of renal clearance

Renal clearance can be measured with a timed collection of urine and an analysis of its composition with the aid of the following equation (which follows directly from the derivation of (10b)):

$K={\frac {C_{U}\cdot Q}{C_{B}}}\qquad (11)$

Where:

• K is the clearance [mL/min]
• C_U is the urine concentration [mmol/L] (in the USA often [mg/mL])
• Q is the urine flow (volume/time) [mL/min] (often [mL/24 h])
• C_B is the plasma concentration [mmol/L] (in the USA often [mg/mL])

When the substance "C" is creatinine, an endogenous chemical that is excreted only by filtration, the calculated clearance is equivalent to the glomerular filtration rate. Inulin clearance is also used to estimate glomerular filtration rate.

Note - the above equation (11) is valid only for the steady-state condition. If the substance being cleared is not at a constant plasma concentration (i.e. not at steady-state) K must be obtained from the (full) solution of the differential equation (9).

See also

• Creatinine clearance
• Kt/V
• Pharmacokinetics
• Renal clearance ratio
• Sieving coefficient
• Standardized Kt/V
• Table of medication secreted in kidney
• Urea reduction ratio

Further reading

• Also, for clearance via bile please see: Estimation of Biliary Excretion of Foreign Compounds Using Properties of Molecular Structure. 2014. Sharifi M., Ghafourian T. AAPS J. 16(1) 65-78.

UpToDate Contents

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• 1. 急性腎障害（急性腎不全）におけるナトリウム（FENa）、尿素（FEUrea）、およびその他分子の排泄率 fractional excretion of sodium urea and other molecules in acute kidney injury acute renal failure
• 2. 成人における尿蛋白排泄量の評価および非ネフローゼ域蛋白尿のみの評価 assessment of urinary protein excretion and evaluation of isolated non nephrotic proteinuria in adults
• 3. 腎尿細管性アシドーシスの概要と病態生理、およびカリウムバランスへの影響 overview and pathophysiology of renal tubular acidosis and the effect on potassium balance
• 4. ドーパミンの腎臓作用 renal actions of dopamine
• 5. 低カリウム血症誘発性腎機能障害 hypokalemia induced renal dysfunction

English Journal

• Applications of urinary proteomics in renal disease research using animal models.

• Lv Y1, Cai G, Chen X.
• Advances in experimental medicine and biology.Adv Exp Med Biol.2015;845:145-50. doi: 10.1007/978-94-017-9523-4_14.
• Animal models of renal disease are essential tools in research on kidney disease and have provided valuable insights into pathogenesis. Use of animal models minimises inter-individual differences, allows specific pathological changes to be examined, and facilitates collection of tissue samples. Thus
• PMID 25355577

• Sugar-sweetened beverage consumption: a risk factor for prevalent gout with SLC2A9 genotype-specific effects on serum urate and risk of gout.

• Batt C1, Phipps-Green AJ1, Black MA1, Cadzow M1, Merriman ME1, Topless R1, Gow P2, Harrison A3, Highton J4, Jones P5, Stamp L6, Dalbeth N5, Merriman TR1.
• Annals of the rheumatic diseases.Ann Rheum Dis.2014 Dec;73(12):2101-6. doi: 10.1136/annrheumdis-2013-203600. Epub 2013 Sep 11.
• OBJECTIVE: Consumption of high fructose corn syrup (HFCS)-sweetened beverages increases serum urate and risk of incident gout. Genetic variants in SLC2A9, that exchanges uric acid for glucose and fructose, associate with gout. We tested association between sugar (sucrose)-sweetened beverage (SSB) co
• PMID 24026676

• The serum uromodulin level is associated with kidney function.

• Risch L, Lhotta K, Meier D, Medina-Escobar P, Nydegger UE, Risch M.
• Clinical chemistry and laboratory medicine : CCLM / FESCC.Clin Chem Lab Med.2014 Dec 1;52(12):1755-61. doi: 10.1515/cclm-2014-0505.
• Abstract Background: In chronic kidney diseases of various etiologies, the urinary excretion of uromodulin is usually decreased in parallel with the glomerular filtration rate. This study aimed to investigate whether serum uromodulin is associated with kidney function.METHODS: Within the framework o
• PMID 24933630

Japanese Journal

• 〔研究ノート〕慢性腎臓病モデルラットの骨密度維持に対する食餌アルギニンあるいは大豆イソフラボン抽出物投与の有効性評価に関する基礎的研究

• 間野 琴子,宮内 智美,春宮 覚,海老沢 秀道
• 學苑 866, 47-55, 2012-12-01
• … The present study was carried out to determine whether dietary isoflavone and arginine could preserve the renal function and prevent renal injury and bone mineral density loss in the chronic kidney disease model rat. … Group CA still showed the symptoms of chronic kidney disease, such as renal swelling, a decreased CCr, elevated BUN and increased urinary NAG activity compared to the Intact rats that had not received adenine treatment. …
• NAID 110009491056

• N-type Calcium Channel Inhibition With Cilnidipine Elicits Glomerular Podocyte Protection Independent of Sympathetic Nerve Inhibition

• LEI Bai,NAKANO Daisuke,FUJISAWA Yoshihide,LIU Ya,HITOMI Hirofumi,KOBORI Hiroyuki,MORI Hirohito,MASAKI Tsutomu,ASANUMA Katsuhiko,TOMINO Yasuhiko,NISHIYAMA Akira
• Journal of pharmacological sciences 119(4), 359-367, 2012-08-20
• … Animals were divided into groups, as follows, and observed from 9 to 27 weeks of age: 1) vehicle (n = 14), 2) vehicle plus renal-denervation (n = 15), 3) cilnidipine (50 mg/kg per day, p.o.; … n = 10), and 4) cilnidipine plus renal-denervation (n = 15). … Renal denervation attenuated elevations in blood pressure, but failed to suppress urinary protein excretion and podocyte injury in HS-UNX-SHR. …
• NAID 10031071591

• GC療法後に著明な低ナトリウム血症を呈しRenal salt wasting syndromeが考えられた1例

• 松村 英理,大城 吉則,宮城 亮太 [他]
• 泌尿器科紀要 58(8), 425-429, 2012-08
• … Renal impairment with a decreased glomerular filtration rate is a classical nephrotoxicity associated with cisplatin (CDDP). … Renal salt wasting syndrome (RSWS), which is characterized by water and salt wasting, is a rare nephrotoxicity associated with CDDP. … Five days later, he developed nausea, dysorexia, delirium, hyponatremia (serum sodium level 115 mEq/l), and renal dysfunction. …
• NAID 40019387948

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★リンクテーブル★

リンク元	「腎排泄」
関連記事	「renal」「excretion」

「腎排泄」

　　[★]

英

renal excretion

関

肝排泄、薬物排泄

• 抗菌薬

• ペニシリン系抗菌薬：アンピシリン、メチシリン
• セフェム系抗菌薬：(セフォペラゾン、セフトリアキソン以外)
• アミノグリコシド系抗菌薬：ストレプトマイシン、カナマイシン、ゲンタマイシン
• バンコマイシン、テイコプラニン：血中モニタリングが好ましい。

• 抗結核薬：イソニアジド

• 抗不整脈薬：プロカインアミド、ジソピラミド

• 抗悪性腫瘍薬：ブレオマイシン

• 抗躁薬：炭酸リチウム

• アトロピン

• ジゴキシン：(おそらくもう使われていない)

国試

• 100G114

「renal」

　　[★]

• adj.

• 腎臓の、腎性の、腎の

関

kidney、renally

　

「excretion」

　　[★]

• n.

• 排泄、排泄物