{"id":110,"date":"2019-04-24T12:39:34","date_gmt":"2019-04-24T12:39:34","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=110"},"modified":"2020-09-04T03:21:20","modified_gmt":"2020-09-04T03:21:20","slug":"renalclearance","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/renalclearance\/","title":{"rendered":"Renal Clearance"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\"> &#8220;Part of the total clearance due to renal excretion&#8221; <\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p>Renal clearance mainly reflects the <a href=\"\/pharmacology\/renal-excretion\">excretion<\/a> of drug into the urine by the kidneys. <a href=\"\/pharmacology\/renal-excretion\">Renal excretion<\/a>\n of the drug is the neat result of glomerular filtration, active tubular\n secretion and tubular reabsorption. Rare drugs may undergo renal \nmetabolism (e.g. insulin).\n<\/p>\n\n\n\n<figure class=\"wp-block-video aligncenter\"><video height=\"346\" style=\"aspect-ratio: 346 \/ 346;\" width=\"346\" controls src=\"https:\/\/sepia2.unil.ch\/pharmacology\/wp-content\/uploads\/2019\/06\/renalclearance_Trim.mp4\"><\/video><\/figure>\n\n\n\n<p>The value of renal clearance is often used to \nidentify the main mechanism involved in the renal excretion of the drug.\n Usually, if the renal clearance approximates the product of glomerular \nfiltration rate by the unbound fraction of the drug, then filtration is \nthought to be the prominent mechanism. When renal clearance is less than\n the product of glomerular filtration rate by the unbound fraction, then\n renal reabsorption is assumed. When renal clearance is greater than the\n product of glomerular filtration rate by the unbound fraction, then \nsecretion is thought to be present. However, all mechanisms may be \noperating, but one or two may dominate over the other masking their \ncontribution.\n<\/p>\n\n\n\n<p>Variation of renal blood flow or of the unbound \nplasma drug concentration may more or less affect renal clearance, \ndepending on the drug&#8217;s renal <a href=\"\/pharmacology\/extractionratio\">extraction ratio<\/a>.\n The drug&#8217;s renal clearance can also be influenced by variation of its \ntubular secretion through a competitive or non-competitive inhibition or\n by a change in its passive reabsorption rate, e.g. through change of \nthe urine pH (e.g. through <a href=\"\/pharmacology\/renal-excretion\">ion trapping<\/a>).\n Furthermore, an increase of urine flow diminishes the time available \nfor tubular reabsorption and therefore, can increase renal excretion of \ndrugs.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical implications<\/h3>\n\n\n\n<p>Usually, a drug&#8217;s renal clearance is proportional\n to the patient&#8217;s renal function. Whether a drug&#8217;s dosing rate needs to \nbe modified in patients with renal dysfunction depends on whether the \ndrug is primarily excreted through the kidneys and whether increased \ndrug levels are associated with adverse effects.\n<\/p>\n\n\n\n<p>In some cases, renal clearance may be artificially \nreduced by inhibiting the renal tubular secretion of the drug. This \nprolongs the drugs half-life and may produce undesired accumulation. But\n is can also allow spacing of the doses (e.g. co-administration of \nprobenecid with penicillin). Likewise, renal clearance of a weak acid or\n base may be artificially increased by acidification or alkalization of \nthe urine and therefore increasing the <a href=\"\/pharmacology\/renal-excretion\">ion trapping<\/a> of the drug in the urine.<\/p>\n\n\n\n<p><p class=\"hiddenTitle\">Chart Pharmacokinetics<\/p>\n<div>\n\n    <div id=\"chartContainer\">\n        <canvas id=\"chart\"><\/canvas>\n        <div class=\"\" id=\"divSliderContainer\"><\/div>\n    <\/div>\n\n    <script>\n\n        let chart;\n        let baseDataChartValues = [];\n        let dataChart = [];\n        let dataChartStoredValues = [];\n        let labelsChart = [];\n\n        let dose = 1000;\n        let baseDose = 1000;\n\n        let mDose = 1000;\n        let baseMDose = 1000;\n\n        let tau = 6;\n        let baseTau = 6;\n\n        let vd = 50;\n        let baseVd = 50;\n\n        let cl = 10;\n        let baseCl = 10;\n\n        let f = 0.7;\n        let baseF = 0.7;\n        \n        let e = 0.3;\n        \n        let q = 1;\n        \n        let otherCl = 1.5;\n\n        let ka = 1.5;\n        let tH;\n\n        const maxTime = 100;\n\n        function getPlasmaConcentration(h) {\n            let formulaPlasmaConcentration = (dose*f*ka\/(vd*(ka-cl\/vd))*(Math.exp(-cl\/vd*h)));\n            \n            formulaPlasmaConcentration = (dose*(1-e)*ka\/(vd*(ka-q*e\/vd))*(Math.exp(-1*(q+otherCl)*h\/vd)-Math.exp(-ka*h)));\n\n            return formulaPlasmaConcentration;\n        }\n\n        \/*\n         *\n         * t1\/2 = ln(2) * (volume of distribution \/ clearance)\n         *\n         *\/\n        function getHalfLife() {\n            tH = Math.log(2)*(vd\/cl);\n            return (Math.round(tH * 100) \/ 100);\n        }\n\n        function updateSlider(updateStored = false) {\n            dataChart = [];\n            if(updateStored) dataChartStoredValues = [];\n\n            for(let i = 0; i <= maxTime; i++) {\n                let concentration = getPlasmaConcentration(i);\n                dataChart.push(concentration);\n                if(updateStored) dataChartStoredValues.push(concentration);\n            }\n\n            chart.data.datasets[0].data = dataChart;\n            chart.data.datasets[1].data = dataChartStoredValues;\n\n            $( \"#slider-q\" ).slider( \"option\", \"value\", q);\n            $( \"#slider-e\" ).slider( \"option\", \"value\", e);\n            chart.update();\n        }\n\n        let sliderQ = '<div id=\"slider-q\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-q\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">Q<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainer').append(sliderQ);\n\nlet sliderE = '<div id=\"slider-e\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-e\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">E<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainer').append(sliderE);\n\n\n   \n\n        $(function() {\n\n            let handleQ = $('#custom-handle-q');\n\n            $( \"#slider-q\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0.1,\n                max: 2,\n                step: 0.1,\n                value: q,\n                create: function() {\n                    handleQ.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    q = ui.value;\n                    handleQ.text( ui.value );\n                    updateSlider();\n                }\n            });\n\n            let handleE = $('#custom-handle-e');\n\n            $( \"#slider-e\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0.01,\n                max: 1,\n                step: 0.01,\n                value: e,\n                create: function() {\n                    handleE.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    e = ui.value;\n                    handleE.text( ui.value );\n                    updateSlider();\n                }\n            });\n\n        });\n\n        Chart.pluginService.register({\n            beforeInit: function(chart) {\n\n                for(let i = 0; i <= maxTime; i++) {\n                    labelsChart.push(i);\n                    dataChart.push(getPlasmaConcentration(i));\n\n                    dataChartStoredValues = dataChart;\n                    baseDataChartValues = dataChart;\n                }\n\n            }\n        });\n\n        chart = new Chart(document.getElementById(\"chart\"), {\n            type: 'line',\n            data: {\n                labels: labelsChart,\n                datasets: [{\n                    label: \"Plasma Concentration\",\n                    data: dataChart,\n                    borderColor: colorDatasetMain.borderColor,\n                    fillColor: colorDatasetMain.fillColor,\n                    strokeColor: colorDatasetMain.strokeColor,\n                    highlightFill: colorDatasetMain.highlightFill,\n                    highlightStroke: colorDatasetMain.highlightStroke,\n                    borderWidth: \"1\",\n                    pointRadius: 0,\n                    fill: false\n                }, {\n                    label: \"Plasma Concentration\",\n                    data: dataChartStoredValues,\n                    borderColor: colorDatasetStored.borderColor,\n                    fillColor: colorDatasetStored.fillColor,\n                    strokeColor: colorDatasetStored.strokeColor,\n                    highlightFill: colorDatasetStored.highlightFill,\n                    highlightStroke: colorDatasetStored.highlightStroke,\n                    borderWidth: \"1\",\n                    pointRadius: 0,\n                    fill: false\n                }]\n            },\n            options: {\n                scales: {\n                    xAxes: [{\n                        scaleLabel: {\n                            display: true,\n                            labelString: 'H [hour]'\n                        }\n                    }],\n                    yAxes: [{\n                        scaleLabel: {\n                            display: true,\n                            labelString: 'C [mg\/l]'\n                        }\n                    }]\n                },\n                responsive: true,\n                maintainAspectRatio: false\n            }\n        });\n\n    <\/script>\n\n<\/div><\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Related terms<\/h3>\n\n\n\n<p>Excreted fraction (fe): fraction of the drug that is excreted unchanged in the urine.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Assessment<\/h3>\n\n\n\n<p>Renal clearance estimation from urine and plasma drug concentration:\n<\/p>\n\n\n\n<div class=\"wp-block-blocks-latex-block-latex\"><script type=\"text\/x-mathjax-config\">   MathJax.Hub.Config({tex2jax: {inlineMath: [['$','$'], ['\\\\(','\\\\)']]}}); <\/script> <p class=\"formula\">$$CL_{renal} = {\\text{urine flow} * \\text{urine concentration} \\over \\text{plasma concentration}}$$<\/p><p class=\"formula\"><\/div>\n\n\n\n<p>Renal clearance estimation from the renal <a href=\"\/pharmacology\/extractionratio\">extraction ratio<\/a> and renal perfusion:\n<\/p>\n\n\n\n<div class=\"wp-block-blocks-latex-block-latex\"><script type=\"text\/x-mathjax-config\">   MathJax.Hub.Config({tex2jax: {inlineMath: [['$','$'], ['\\\\(','\\\\)']]}}); <\/script> <p class=\"formula\">$$CL_{renal} = Q * E$$<\/p><p class=\"formula\"><\/div>\n\n\n\n<div class=\"wp-block-blocks-latex-block-latex\"><script type=\"text\/x-mathjax-config\">   MathJax.Hub.Config({tex2jax: {inlineMath: [['$','$'], ['\\\\(','\\\\)']]}}); <\/script> <p class=\"formula\">$$fe = {CL_{renal} \\over CL_{total}}$$<\/p><p class=\"formula\"><\/div>\n\n\n\n<p><strong>CL renal<\/strong> = renal clearance <\/p>\n\n\n\n<p><strong>CL total<\/strong> = total clearance <\/p>\n\n\n\n<p><strong>Q<\/strong> = renal perfusion <\/p>\n\n\n\n<p><strong>E<\/strong> = extraction ratio <\/p>\n\n\n\n<p><strong>fe<\/strong> = the excreted fraction<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;Part of the total clearance due to renal excretion&#8221; Description Renal clearance mainly reflects the excretion of drug into the urine by the kidneys. Renal excretion of the drug is the neat result of glomerular filtration, active tubular secretion and tubular reabsorption. Rare drugs may undergo renal metabolism (e.g. insulin). The value of renal clearance &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/parameters\/renalclearance\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Renal Clearance&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":7,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-110","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/110","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/comments?post=110"}],"version-history":[{"count":17,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/110\/revisions"}],"predecessor-version":[{"id":1301,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/110\/revisions\/1301"}],"up":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/7"}],"wp:attachment":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/media?parent=110"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}