This document summarizes the clinical pharmacology of oral anticoagulants including warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in patients with kidney disease. It discusses the pharmacokinetics, dosing adjustments, and safety considerations for each drug in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). While newer oral anticoagulants have been shown to be more effective than warfarin in the general population, their use in patients with CKD and ESKD remains limited due to a lack of clinical trial data in these groups. Warfarin remains the most widely used oral anticoagulant for
This document discusses various renal function tests used to evaluate different aspects of kidney function. It describes tests of glomerular filtration rate (GFR) including clearance tests using substances like creatinine, inulin, and radioactive tracers. It also discusses tubular function tests like urine concentration tests, osmolarity measurements, and tests of the kidney's response to vasopressin. Formulas for calculating clearance, osmolarity, and free water clearance are provided. The significance of GFR measurements and estimated GFR formulas like Cockcroft-Gault and MDRD are summarized.
Renal function tests can help screen and monitor patients for kidney disease. The creatinine and BUN can be elevated by factors other than kidney disease, such as increased protein intake or muscle breakdown. To determine if acute renal failure is prerenal or renal (ATN), fractional excretion of sodium and urea are used, with prerenal azotemia having FENa <1% and FEUrea <35%. Estimating glomerular filtration rate (GFR) stages chronic kidney disease.
The document provides information on kidney function tests and renal assessment. It discusses the anatomy and function of the kidneys and urinary system. Various tests for evaluating glomerular filtration rate (GFR) and renal tubular function are described, including creatinine clearance, urea, uric acid, and beta-2 microglobulin. Urinalysis tests like specific gravity, pH, protein, glucose, and sediment examination are also covered. The document emphasizes the importance of renal function testing in conditions like diabetes, hypertension, and kidney disease.
The document discusses kidney function testing and the urinary system. It provides information on various tests used to evaluate kidney function, including clearance tests to measure glomerular filtration rate (GFR) using creatinine, urea, and uric acid. Clearance tests determine the rate at which the kidneys filter these waste products from the blood into urine. The document also discusses factors that affect interpretation of test results and when assessment of renal function is recommended.
rft is described in detail . function of kidney, objectives of doing the test. the various test available for assessing the renal function with clinical interpretation is available.
This document discusses renal function tests and their importance in assessing kidney function and detecting impairment. It describes various tests including urine analysis, blood tests of creatinine and urea, and glomerular function tests. Common indications for evaluating renal function are listed, such as older age, diabetes, and hypertension. The document also outlines approaches to interpreting test results and diagnosing different kidney conditions like acute injury, nephritic syndrome, and nephrotic syndrome.
This document discusses renal function tests and their use in assessing kidney function. It covers tests that measure glomerular filtration rate like creatinine clearance and urea clearance. Creatinine clearance is considered the best measure of glomerular filtration as creatinine is filtered at the glomerulus and neither reabsorbed nor secreted. Stages of kidney disease are defined based on glomerular filtration rate. Tubular function tests like urine concentration are also discussed. Biochemical changes in blood that occur with impaired kidney function are outlined.
This document discusses renal function tests (RFTs). It begins by describing the functions of the kidney including formation of urine, excretion of waste products, and regulation of water, electrolytes and acid-base balance.
It then explains that RFTs are used to assess renal damage, monitor progression of renal disease, and adjust dosing of nephrotoxic drugs. RFTs provide information on renal blood flow, glomerular filtration rate, tubular function, and urine output. Tests include urine analysis, measurements of glomerular function like creatinine clearance, and tests of tubular function like concentration and dilution tests. The document describes several RFTs in detail.
This document discusses various renal function tests used to evaluate different aspects of kidney function. It describes tests of glomerular filtration rate (GFR) including clearance tests using substances like creatinine, inulin, and radioactive tracers. It also discusses tubular function tests like urine concentration tests, osmolarity measurements, and tests of the kidney's response to vasopressin. Formulas for calculating clearance, osmolarity, and free water clearance are provided. The significance of GFR measurements and estimated GFR formulas like Cockcroft-Gault and MDRD are summarized.
Renal function tests can help screen and monitor patients for kidney disease. The creatinine and BUN can be elevated by factors other than kidney disease, such as increased protein intake or muscle breakdown. To determine if acute renal failure is prerenal or renal (ATN), fractional excretion of sodium and urea are used, with prerenal azotemia having FENa <1% and FEUrea <35%. Estimating glomerular filtration rate (GFR) stages chronic kidney disease.
The document provides information on kidney function tests and renal assessment. It discusses the anatomy and function of the kidneys and urinary system. Various tests for evaluating glomerular filtration rate (GFR) and renal tubular function are described, including creatinine clearance, urea, uric acid, and beta-2 microglobulin. Urinalysis tests like specific gravity, pH, protein, glucose, and sediment examination are also covered. The document emphasizes the importance of renal function testing in conditions like diabetes, hypertension, and kidney disease.
The document discusses kidney function testing and the urinary system. It provides information on various tests used to evaluate kidney function, including clearance tests to measure glomerular filtration rate (GFR) using creatinine, urea, and uric acid. Clearance tests determine the rate at which the kidneys filter these waste products from the blood into urine. The document also discusses factors that affect interpretation of test results and when assessment of renal function is recommended.
rft is described in detail . function of kidney, objectives of doing the test. the various test available for assessing the renal function with clinical interpretation is available.
This document discusses renal function tests and their importance in assessing kidney function and detecting impairment. It describes various tests including urine analysis, blood tests of creatinine and urea, and glomerular function tests. Common indications for evaluating renal function are listed, such as older age, diabetes, and hypertension. The document also outlines approaches to interpreting test results and diagnosing different kidney conditions like acute injury, nephritic syndrome, and nephrotic syndrome.
This document discusses renal function tests and their use in assessing kidney function. It covers tests that measure glomerular filtration rate like creatinine clearance and urea clearance. Creatinine clearance is considered the best measure of glomerular filtration as creatinine is filtered at the glomerulus and neither reabsorbed nor secreted. Stages of kidney disease are defined based on glomerular filtration rate. Tubular function tests like urine concentration are also discussed. Biochemical changes in blood that occur with impaired kidney function are outlined.
This document discusses renal function tests (RFTs). It begins by describing the functions of the kidney including formation of urine, excretion of waste products, and regulation of water, electrolytes and acid-base balance.
It then explains that RFTs are used to assess renal damage, monitor progression of renal disease, and adjust dosing of nephrotoxic drugs. RFTs provide information on renal blood flow, glomerular filtration rate, tubular function, and urine output. Tests include urine analysis, measurements of glomerular function like creatinine clearance, and tests of tubular function like concentration and dilution tests. The document describes several RFTs in detail.
This document summarizes renal function tests and urine analysis. It describes the anatomy and function of the nephron, steps in urine formation, and normal ranges for physical and chemical urine tests including volume, color, odor, specific gravity, pH, creatinine, BUN, electrolytes, glucose, protein, and ketones. It discusses clinical implications of abnormal test values and interfering factors. Macroscopic urine examination for casts and cells is also covered, in addition to exogenous markers of glomerular filtration rate like inulin and iothalamate clearance tests.
This document discusses renal function tests and their clinical implications. It begins by outlining the general anatomy and functions of the kidney. It then classifies renal function tests into urine analysis, blood tests, and tests of glomerular and tubular function. Specific tests are described, including creatinine clearance for glomerular function and urine concentration tests for tubular function. The document discusses how renal function tests can help in assessing and monitoring kidney damage and adjusting drug dosages. Clinical conditions that can be indicated by renal function tests include diabetic nephropathy, acute kidney injury, glomerular diseases, and chronic kidney disease.
This document discusses renal function tests and their use in evaluating kidney function. It describes the key functions of the kidney including fluid balance, waste excretion, blood pressure regulation, vitamin D and erythropoietin production. Tests are classified as evaluating glomerular function like glomerular filtration rate (GFR) tests or tubular function. GFR is best measured by creatinine clearance or equations using creatinine, age, and other factors. Urine and blood tests can indicate glomerular or tubular dysfunction. Clearance tests measure the removal of substances from blood by the kidneys. Renal biopsy may be used to diagnose kidney disease when function tests are unclear.
Approach to laboraratory diagnosis of acute and chronic renal failurepathakadrija
This document discusses the laboratory approach for diagnosis of acute and chronic renal failure. It describes how to determine if renal failure is acute or chronic, the routine tests performed, and how to estimate glomerular filtration rate (GFR) which is the best indicator of kidney function. It also details specific findings on urinalysis that provide clues to the underlying causes of renal disease such as different types of casts and cells.
This document provides an overview of renal function tests. It discusses the anatomy and physiology of the kidney and nephron. It describes various tests used to evaluate glomerular filtration rate (GFR) including creatinine clearance, urea clearance, insulin clearance, and inulin clearance tests. It also covers tests of tubular function like dilution and acidification tests. Normal ranges for urine and blood parameters are provided.
Hyperkalemia can be caused by increased potassium intake, redistribution of potassium from cells into the bloodstream, or decreased excretion of potassium by the kidneys. Clinical manifestations range from weakness to cardiac arrhythmias. Treatment involves membrane stabilization with calcium, shifting potassium into cells with insulin and glucose or sodium bicarbonate, and removing potassium from the body with loop diuretics, potassium-binding resins, or hemodialysis. Glucose should be given with insulin to treat hyperkalemia only if blood sugar is below 175 mg/dL.
The document discusses renal function tests and kidney function. It covers:
1. The kidney's main functions including waste removal, electrolyte balance, and vitamin D activation.
2. Glomerular filtration rate (GFR) is measured using clearance tests for urea, creatinine, inulin, and other substances. Creatinine clearance is commonly used to estimate GFR and diagnose chronic kidney disease.
3. Tubular function is assessed using concentration, dilution and excretion tests to identify impaired reabsorption or secretion.
GFR and tubular function tests provide information on filtration and reabsorption rates to evaluate kidney health and diagnose disease.
This document discusses renal function tests which are divided into three groups: glomerular function tests, tubular function tests, and urine analysis.
Glomerular function tests include clearance tests such as creatinine clearance test which measures glomerular filtration rate (GFR). Tubular function tests assess kidney's concentrating and diluting abilities through urine concentration and dilution tests. Urine analysis examines physical properties, chemical components, and microscopic contents of urine to detect abnormalities.
The document provides information on renal function tests. It discusses the anatomy and functions of the kidneys. There are several reasons to test renal function, including to assess functional capacity, detect impairment, monitor treatment response, and ensure safe drug use. Tests can evaluate glomerular function, renal plasma flow, and tubular function. Common tests include urine analysis, creatinine clearance, urea clearance, inulin clearance, para-amino hippurate clearance, and tests of urine concentration, acidification, and dilution abilities.
The document discusses renal function tests and evaluation of kidney function. It describes the key functions of the kidneys which include regulation of fluid balance, electrolytes, acid-base balance, and excretion of waste. It outlines tests to evaluate glomerular filtration rate (GFR) including creatinine clearance, inulin clearance, and prediction equations. Elevated creatinine and BUN are indicators of reduced GFR but have limitations. Urine analysis and clearance of exogenous filtration markers provide detailed information on kidney function and disease staging.
This document discusses various kidney function tests, including their purpose, methodology, and normal ranges. It describes tests of glomerular function like serum urea, serum creatinine, urea clearance, and creatinine clearance. It also covers tests of tubular function such as phenolsulphonephthalein excretion, concentration test, and dilution test. Less common tests like serum cystatin C and inulin clearance are also summarized. The document emphasizes interpreting results in light of clinical findings and notes factors that can influence certain test outcomes.
This document discusses renal function tests (RFTs) which are used to assess kidney function. It outlines the key functions of the kidney including excretion of waste, regulation of acid-base balance and electrolyte levels. RFTs evaluate parameters like glomerular filtration rate, renal blood flow, and tubular function. There are four main types of RFTs: urine analysis, concentration/dilution tests, blood chemistry tests, and renal clearance tests. Blood chemistry tests measure waste products like creatinine and urea to indicate kidney excretion ability, while urine tests examine physical/chemical properties and sediment to identify abnormalities. RFTs are used to diagnose and monitor kidney disease as well as drug toxicity.
This document provides information on renal function and tests used to evaluate kidney function. It discusses the key functions of the kidney including regulation of homeostasis, excretion of waste, and endocrine functions. Laboratory tests that can detect and monitor renal damage include glomerular filtration rate (GFR), plasma creatinine, plasma urea, urine protein, and urine analysis. The document outlines how the kidney can become damaged at the pre-renal, renal, or post-renal levels and describes tests and normal ranges used to evaluate kidney function.
Renal function tests are very useful for effective clinical evaluation of renal failure for effective management. So it is useful for medical and allied professional students and clinical practitioners.
Kidney function tests are used to identify impaired renal function, diagnose renal disease, monitor the course of renal disease and treatment response, and plan dialysis or transplantation. Tests of glomerular function include clearance tests measuring glomerular filtration rate (GFR) using creatinine, urea, inulin or radiolabeled substances. GFR declines with age. Tests of tubular function assess the proximal and distal tubules. The glomerular filtration rate (GFR) is the best measure of kidney excretory function and can be estimated using prediction equations or directly measured using clearance tests. Urine analysis provides additional information on renal function by examining the urine's physical, chemical, and microscopic properties.
Renal function tests assess kidney function and detect impairment. They include tests of glomerular filtration rate (GFR) using creatinine, urea and inulin clearance. GFR is calculated using creatinine levels and equations factoring age, weight and sex. Other tests evaluate tubular function through urine concentration, osmolality, and checking for proteins, glucose and amino acids in urine. Together these tests provide valuable information about both glomerular and tubular integrity and kidney health.
The document discusses renal function tests and kidney function. It describes how the kidneys maintain homeostasis, excrete waste, and perform hormonal functions. Glomerular filtration rate (GFR) is the most important test of kidney function, and can be estimated by creatinine clearance or plasma creatinine level. Other tests include urinalysis to check for proteins, cells, and analytes like glucose. Renal tubular function is also important and can be assessed through concentration, dilution, and acidification tests. Interpreting these tests helps identify kidney dysfunction or disease and monitor treatment effectiveness.
This document provides information on renal function tests. It discusses the functions of the kidney including regulation of water, electrolytes and acid-base balance, and excretion of metabolic waste. Various indications for renal function testing are mentioned, including diagnosis and assessment of renal disease. Common tests discussed include urine analysis, blood tests of creatinine, electrolytes, and glomerular and tubular function tests such as creatinine clearance. Methods for urine collection and important parameters in urine and blood tests are outlined. Abnormal findings and their causes are described for several urine dipstick and microscopic tests.
This document provides an overview of applied renal physiology and renal function tests by Dr. Nilesh Kate. It discusses the pathophysiology of common renal disorders like renal failure and nephrotic syndrome. It also describes various renal function tests including analysis of urine and blood, clearance tests to measure GFR and RPF, and radiological tests. Diagnostic techniques like renal biopsy are also mentioned. The document concludes with an overview of dialysis methods like hemodialysis and peritoneal dialysis as well as renal transplantation.
This document discusses various biochemical and radiological tests used to evaluate renal function and diagnose renal disease. It describes tests that measure glomerular filtration rate (GFR) like creatinine clearance, urea clearance, and inulin clearance. It also discusses tubular function tests like urine analysis, concentration tests, and acid load tests. Biomarkers of renal injury like kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 are also summarized. Radiological investigations like ultrasound, CT, MRI, renal scans, biopsy and cystoscopy are also mentioned.
Newer Oral Anticoagulant in Chronic Kidney DiseaseAbdullah Ansari
Kidney specific mechanisms leading to atrial fibrillation
Possible mechanism of CKD progression in atrial fibrillation
Atherosclerosis Risk in Communities (ARIC) study
Guidelines
Pulmonary embolism & deep vein thrombosis
Nephrotic syndrome
Problems with Vit K antagonists in CKD
Non Vit K oral anticoagulants
Site of action of NOACs and VKAs
Pharmacology of Direct Oral Anticoagulants
Trials for NOACs
Dose NOACs according to renal function
Laboratory monitoring of NOACs
Anticoagulant reversal of NOACs
This document summarizes renal function tests and urine analysis. It describes the anatomy and function of the nephron, steps in urine formation, and normal ranges for physical and chemical urine tests including volume, color, odor, specific gravity, pH, creatinine, BUN, electrolytes, glucose, protein, and ketones. It discusses clinical implications of abnormal test values and interfering factors. Macroscopic urine examination for casts and cells is also covered, in addition to exogenous markers of glomerular filtration rate like inulin and iothalamate clearance tests.
This document discusses renal function tests and their clinical implications. It begins by outlining the general anatomy and functions of the kidney. It then classifies renal function tests into urine analysis, blood tests, and tests of glomerular and tubular function. Specific tests are described, including creatinine clearance for glomerular function and urine concentration tests for tubular function. The document discusses how renal function tests can help in assessing and monitoring kidney damage and adjusting drug dosages. Clinical conditions that can be indicated by renal function tests include diabetic nephropathy, acute kidney injury, glomerular diseases, and chronic kidney disease.
This document discusses renal function tests and their use in evaluating kidney function. It describes the key functions of the kidney including fluid balance, waste excretion, blood pressure regulation, vitamin D and erythropoietin production. Tests are classified as evaluating glomerular function like glomerular filtration rate (GFR) tests or tubular function. GFR is best measured by creatinine clearance or equations using creatinine, age, and other factors. Urine and blood tests can indicate glomerular or tubular dysfunction. Clearance tests measure the removal of substances from blood by the kidneys. Renal biopsy may be used to diagnose kidney disease when function tests are unclear.
Approach to laboraratory diagnosis of acute and chronic renal failurepathakadrija
This document discusses the laboratory approach for diagnosis of acute and chronic renal failure. It describes how to determine if renal failure is acute or chronic, the routine tests performed, and how to estimate glomerular filtration rate (GFR) which is the best indicator of kidney function. It also details specific findings on urinalysis that provide clues to the underlying causes of renal disease such as different types of casts and cells.
This document provides an overview of renal function tests. It discusses the anatomy and physiology of the kidney and nephron. It describes various tests used to evaluate glomerular filtration rate (GFR) including creatinine clearance, urea clearance, insulin clearance, and inulin clearance tests. It also covers tests of tubular function like dilution and acidification tests. Normal ranges for urine and blood parameters are provided.
Hyperkalemia can be caused by increased potassium intake, redistribution of potassium from cells into the bloodstream, or decreased excretion of potassium by the kidneys. Clinical manifestations range from weakness to cardiac arrhythmias. Treatment involves membrane stabilization with calcium, shifting potassium into cells with insulin and glucose or sodium bicarbonate, and removing potassium from the body with loop diuretics, potassium-binding resins, or hemodialysis. Glucose should be given with insulin to treat hyperkalemia only if blood sugar is below 175 mg/dL.
The document discusses renal function tests and kidney function. It covers:
1. The kidney's main functions including waste removal, electrolyte balance, and vitamin D activation.
2. Glomerular filtration rate (GFR) is measured using clearance tests for urea, creatinine, inulin, and other substances. Creatinine clearance is commonly used to estimate GFR and diagnose chronic kidney disease.
3. Tubular function is assessed using concentration, dilution and excretion tests to identify impaired reabsorption or secretion.
GFR and tubular function tests provide information on filtration and reabsorption rates to evaluate kidney health and diagnose disease.
This document discusses renal function tests which are divided into three groups: glomerular function tests, tubular function tests, and urine analysis.
Glomerular function tests include clearance tests such as creatinine clearance test which measures glomerular filtration rate (GFR). Tubular function tests assess kidney's concentrating and diluting abilities through urine concentration and dilution tests. Urine analysis examines physical properties, chemical components, and microscopic contents of urine to detect abnormalities.
The document provides information on renal function tests. It discusses the anatomy and functions of the kidneys. There are several reasons to test renal function, including to assess functional capacity, detect impairment, monitor treatment response, and ensure safe drug use. Tests can evaluate glomerular function, renal plasma flow, and tubular function. Common tests include urine analysis, creatinine clearance, urea clearance, inulin clearance, para-amino hippurate clearance, and tests of urine concentration, acidification, and dilution abilities.
The document discusses renal function tests and evaluation of kidney function. It describes the key functions of the kidneys which include regulation of fluid balance, electrolytes, acid-base balance, and excretion of waste. It outlines tests to evaluate glomerular filtration rate (GFR) including creatinine clearance, inulin clearance, and prediction equations. Elevated creatinine and BUN are indicators of reduced GFR but have limitations. Urine analysis and clearance of exogenous filtration markers provide detailed information on kidney function and disease staging.
This document discusses various kidney function tests, including their purpose, methodology, and normal ranges. It describes tests of glomerular function like serum urea, serum creatinine, urea clearance, and creatinine clearance. It also covers tests of tubular function such as phenolsulphonephthalein excretion, concentration test, and dilution test. Less common tests like serum cystatin C and inulin clearance are also summarized. The document emphasizes interpreting results in light of clinical findings and notes factors that can influence certain test outcomes.
This document discusses renal function tests (RFTs) which are used to assess kidney function. It outlines the key functions of the kidney including excretion of waste, regulation of acid-base balance and electrolyte levels. RFTs evaluate parameters like glomerular filtration rate, renal blood flow, and tubular function. There are four main types of RFTs: urine analysis, concentration/dilution tests, blood chemistry tests, and renal clearance tests. Blood chemistry tests measure waste products like creatinine and urea to indicate kidney excretion ability, while urine tests examine physical/chemical properties and sediment to identify abnormalities. RFTs are used to diagnose and monitor kidney disease as well as drug toxicity.
This document provides information on renal function and tests used to evaluate kidney function. It discusses the key functions of the kidney including regulation of homeostasis, excretion of waste, and endocrine functions. Laboratory tests that can detect and monitor renal damage include glomerular filtration rate (GFR), plasma creatinine, plasma urea, urine protein, and urine analysis. The document outlines how the kidney can become damaged at the pre-renal, renal, or post-renal levels and describes tests and normal ranges used to evaluate kidney function.
Renal function tests are very useful for effective clinical evaluation of renal failure for effective management. So it is useful for medical and allied professional students and clinical practitioners.
Kidney function tests are used to identify impaired renal function, diagnose renal disease, monitor the course of renal disease and treatment response, and plan dialysis or transplantation. Tests of glomerular function include clearance tests measuring glomerular filtration rate (GFR) using creatinine, urea, inulin or radiolabeled substances. GFR declines with age. Tests of tubular function assess the proximal and distal tubules. The glomerular filtration rate (GFR) is the best measure of kidney excretory function and can be estimated using prediction equations or directly measured using clearance tests. Urine analysis provides additional information on renal function by examining the urine's physical, chemical, and microscopic properties.
Renal function tests assess kidney function and detect impairment. They include tests of glomerular filtration rate (GFR) using creatinine, urea and inulin clearance. GFR is calculated using creatinine levels and equations factoring age, weight and sex. Other tests evaluate tubular function through urine concentration, osmolality, and checking for proteins, glucose and amino acids in urine. Together these tests provide valuable information about both glomerular and tubular integrity and kidney health.
The document discusses renal function tests and kidney function. It describes how the kidneys maintain homeostasis, excrete waste, and perform hormonal functions. Glomerular filtration rate (GFR) is the most important test of kidney function, and can be estimated by creatinine clearance or plasma creatinine level. Other tests include urinalysis to check for proteins, cells, and analytes like glucose. Renal tubular function is also important and can be assessed through concentration, dilution, and acidification tests. Interpreting these tests helps identify kidney dysfunction or disease and monitor treatment effectiveness.
This document provides information on renal function tests. It discusses the functions of the kidney including regulation of water, electrolytes and acid-base balance, and excretion of metabolic waste. Various indications for renal function testing are mentioned, including diagnosis and assessment of renal disease. Common tests discussed include urine analysis, blood tests of creatinine, electrolytes, and glomerular and tubular function tests such as creatinine clearance. Methods for urine collection and important parameters in urine and blood tests are outlined. Abnormal findings and their causes are described for several urine dipstick and microscopic tests.
This document provides an overview of applied renal physiology and renal function tests by Dr. Nilesh Kate. It discusses the pathophysiology of common renal disorders like renal failure and nephrotic syndrome. It also describes various renal function tests including analysis of urine and blood, clearance tests to measure GFR and RPF, and radiological tests. Diagnostic techniques like renal biopsy are also mentioned. The document concludes with an overview of dialysis methods like hemodialysis and peritoneal dialysis as well as renal transplantation.
This document discusses various biochemical and radiological tests used to evaluate renal function and diagnose renal disease. It describes tests that measure glomerular filtration rate (GFR) like creatinine clearance, urea clearance, and inulin clearance. It also discusses tubular function tests like urine analysis, concentration tests, and acid load tests. Biomarkers of renal injury like kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 are also summarized. Radiological investigations like ultrasound, CT, MRI, renal scans, biopsy and cystoscopy are also mentioned.
Newer Oral Anticoagulant in Chronic Kidney DiseaseAbdullah Ansari
Kidney specific mechanisms leading to atrial fibrillation
Possible mechanism of CKD progression in atrial fibrillation
Atherosclerosis Risk in Communities (ARIC) study
Guidelines
Pulmonary embolism & deep vein thrombosis
Nephrotic syndrome
Problems with Vit K antagonists in CKD
Non Vit K oral anticoagulants
Site of action of NOACs and VKAs
Pharmacology of Direct Oral Anticoagulants
Trials for NOACs
Dose NOACs according to renal function
Laboratory monitoring of NOACs
Anticoagulant reversal of NOACs
The document discusses newer oral anticoagulants (NOACs) that are alternatives to vitamin K antagonists for treating and preventing blood clots. It describes several NOACs including dabigatran, rivaroxaban, apixaban, and edoxaban. For each drug, it provides information on indications, pharmacokinetics, dosing regimens, clinical trials results, and safety compared to warfarin. The document concludes that NOACs are as effective as warfarin with less monitoring requirements but may have a higher risk of gastrointestinal bleeding.
Anticoagulation expanding steadily over the past few decades.
In addition to Heparins and vitamin K antagonist, other anticoagulants that directly target the enzymatic activity of thrombin and factor Xa have been developed.
This document provides an outline for a presentation on newer oral anticoagulants (NOACs). It discusses the properties and advantages of various NOACs including dabigatran, rivaroxaban, apixaban, and edoxaban compared to vitamin K antagonists. It summarizes the results of major clinical trials that compared these drugs to warfarin for stroke prevention in atrial fibrillation and treatment of venous thromboembolism. It also provides dosing guidelines and management of side effects for the different NOACs.
The document summarizes several drug approvals and updates from the FDA in August 2017. Mavyret was approved for treating HCV genotypes 1-6 without cirrhosis or with compensated cirrhosis. Carospir received approval as an oral suspension for heart failure, hypertension, and hepatic edema. Duzallo was approved as a combination of lesinurad and allopurinol for treating gout in patients not at target uric acid levels on allopurinol alone. Vabomere was approved for complicated UTIs caused by designated bacteria. Other notable approvals included Idhifa for AML, Besponsa for ALL, and Benznidazole for Chagas disease in pediatric patients.
This document provides guidelines for dosing adjustments of various medications in patients with renal impairment. Key points discussed include:
- Dosages of renally eliminated drugs should be adjusted based on a patient's creatinine clearance or GFR. Initial doses may need to be reduced or dosing intervals lengthened.
- Herbal medicines and over-the-counter drugs should be assessed in patients with kidney disease to avoid nephrotoxic agents.
- Many antihypertensives, analgesics, antibiotics, statins and other commonly prescribed medications require dosage adjustments with impaired renal function.
- The Cockcroft-Gault and MDRD equations can estimate creatinine clearance and GFR to
Hepatic Considerations In Oral Surgery .pptxSudiptaBera9
This document provides an overview of considerations for oral surgery in patients with liver disease. It discusses the functional role of the liver and risks associated with dental care for patients with liver disease such as impaired hemostasis, drug interactions, and increased susceptibility to infection. It also covers preoperative evaluation including liver function tests and coagulation assessment. Guidelines are provided for preoperative management including vitamin K replacement, drug dosing adjustments based on liver function, and anesthesia considerations. Postoperative management focuses on hemostasis and infection control.
Direct oral anticoagulants (DOACs) have quickly become attractive alternatives to the long‐standing standard of care in anticoagulation, vitamin K antagonist. DOACs are indicated for prevention and treatment of several cardiovascular conditions. Since the first approval in 2010, DOACs have emerged as leading therapeutic alternatives that provide both clinicians and patients with more effective, safe, and convenient treatment options in thromboembolic settings. With the expanding role of DOACs, clinicians are faced with increasingly complex decisions relating to appropriate agent, duration of treatment, and use in special populations. This review will provide an overview of DOACs and act as a practical reference for clinicians to optimize DOAC use among common challenging scenarios. Topics addressed include (1) appropriate indications; (2) use in patients with specific comorbidities; (3) monitoring parameters; (4) transitioning between anticoagulant regimens; (5) major drug interactions; and (6) cost considerations.
Direct oral anticoagulants (DOACs)—dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa), and betrixaban (Bevyxxa) are anticoagulation pharmacotherapy used for the prevention of thrombosis in several cardiovascular contexts.1 DOACs are categorized into 2 main classes: oral direct factor Xa inhibitors (ie, rivaroxaban, apixaban, edoxaban, and betrixaban) and direct thrombin inhibitors (ie, dabigatran). In 2010, the US Food and Drug Administration (FDA) approved its first DOAC, dabigatran, followed by rivaroxaban, apixaban, edoxaban, and betrixaban in the following years. DOACs are relatively new agents demonstrating superiority or noninferiority to prior standards of care, anticoagulation with vitamin K antagonists (VKA; ie, warfarin), or low‐molecular‐weight heparins (LMWHs), in reducing risk of thromboembolic complications with similar or reduced bleeding risk.2, 3, 4, 5 Advantages of DOACs compared with VKAs include fewer monitoring requirements, less frequent follow‐up, more immediate drug onset and offset effects (important for periprocedural and acute bleeding management), and fewer drug and food interactions.6 As a result, DOAC prescriptions exceeded those for warfarin by 2013, with apixaban being the most frequently prescribed DOAC for patients with nonvalvular atrial fibrillation (NVAF).7
Over the past decade, DOACs have been the subject of extensive investigation in many clinical scenarios. Though guidelines and review articles have provided detailed and in‐depth analyses of the immense literature base, these can be too cumbersome and challenging to integrate into everyday clinical use
In general, FDA‐approved indications for each of the DOACs are comparable (see Table 1). Dabigatran, rivaroxaban, apixaban, and edoxaban are approved for the lowering the risk of stroke and embolism in NVAF as well as deep vein thrombosis and pulmonary embolism treatment/prophylaxis.8, 9, 10, 11 Unique indications
Dose Adjustment in renal and hepatic failurePallavi Kurra
This document discusses dosage adjustments for patients with renal or hepatic failure. It covers:
1) Causes, classification, and measurement of renal failure including glomerular filtration rate (GFR) and creatinine clearance. Dosage adjustments are recommended based on GFR for various drug classes.
2) Causes, classification, and liver function tests for hepatic failure. Considerations for dosage adjustments in patients with hepatic impairment include drug elimination pathways and protein binding.
3) Formulas for estimating creatinine clearance from serum creatinine levels, including the Cockcroft-Gault and modification of diet in renal disease (MDRD) methods.
1) The document discusses several oral anticoagulants including rivaroxaban, apixaban, and edoxaban. It provides details on their mechanisms of action, pharmacokinetics, clinical trials, FDA approvals, dosing, and considerations for transitioning between anticoagulants.
2) Rivaroxaban was shown to be non-inferior to warfarin in reducing strokes in AF patients in the ROCKET-AF trial and superior to warfarin for preventing recurrent VTE in the EINSTEIN-DVT trial.
3) Apixaban was found to significantly reduce strokes compared to aspirin in AF patients not suitable for warfarin in the A
This document provides an outline and overview of newer oral anticoagulants (NOACs). It discusses the types of NOACs including dabigatran, rivaroxaban, and apixaban. It describes the properties, indications, dosing, and results of clinical trials comparing each NOAC to warfarin for preventing strokes in atrial fibrillation and for treating deep vein thrombosis. The document concludes that NOACs have advantages over warfarin such as fewer drug interactions and no need for regular monitoring, though they have slightly higher risks of gastrointestinal bleeding.
This document summarizes current treatment guidelines for lupus nephritis. It defines lupus nephritis based on ACR criteria and recommends an early renal biopsy. For initial treatment of proliferative lupus nephritis (classes III/IV), guidelines differ on whether cyclophosphamide or mycophenolate mofetil is preferred. Maintenance therapy with mycophenolate mofetil or azathioprine with low-dose steroids is recommended, with mycophenolate mofetil showing better outcomes. Immunosuppression should be continued for at least one year after complete remission is achieved.
This document provides an outline on the topic of novel oral anticoagulants (NOACs) including:
1) An introduction to NOACs and their advantages over vitamin K antagonists.
2) Details on the properties, indications, dosing, and trial results of specific NOACs including Dabigatran, Rivaroxaban, Apixaban, and Edoxaban.
3) Guidance on switching between anticoagulant regimens, dealing with dosing errors, and follow-up of patients on NOACs.
This document discusses commonly used drugs that require dosage adjustment or caution in patients with chronic kidney disease (CKD). It notes that around 50% of patients with an estimated glomerular filtration rate (eGFR) below 60 mL/min experience drug-related adverse events, with risks increased in those who are non-white, older, have diabetes, or more advanced CKD. Common adverse events reported include hypoglycemia, falling, nausea, hyperkalemia, and confusion. Several classes of drugs like NSAIDs, sodium phosphate preparations, iodinated contrast, gadolinium, antibiotics, antihypertensives, and lipid-lowering drugs require caution or dosage adjustment in CKD. The document emphasizes reviewing medications for
This document discusses drug dosing considerations in patients with chronic kidney disease. It provides guidelines for estimating glomerular filtration rate (GFR) using creatinine-based equations like CKD-EPI and Cockcroft-Gault to guide drug dosing. For drugs that are renally cleared, doses may need to be reduced as kidney function declines. Drugs are classified by their fraction excreted unchanged to determine dosing adjustments needed. Examples of common drug classes like antihypertensives, hypoglycemics, and antimicrobials are outlined with dosing recommendations based on a patient's GFR and kidney function stage. Measuring drug levels can help optimize therapeutic regimens in patients with chronic kidney
Lapatinib is a tyrosine kinase inhibitor that reversibly binds to EGFR and HER2, blocking phosphorylation. It is used in combination with capecitabine for advanced/metastatic HER2+ breast cancer and with letrozole for HER2+/HR+ disease. It has good CNS penetration and may prevent brain metastases. Clinical trials showed combination with trastuzumab increased pCR rates over monotherapy. Common side effects include diarrhea, rash, fatigue. Dose reductions are needed for severe hepatic or cardiac toxicity.
This document discusses oral anticoagulants, including both older agents like warfarin and newer direct-acting anticoagulants. It provides details on the mechanisms of action, dosing, indications, clinical trials, and safety considerations for dabigatran, rivaroxaban, apixaban, and other oral anticoagulants. Key highlights include the mechanisms of thrombin and factor Xa inhibition by the newer agents, fixed dosing without monitoring for dabigatran and rivaroxaban, and results from major clinical trials demonstrating non-inferiority compared to warfarin for stroke prevention in atrial fibrillation.
Darbepoetin scientific information and comparisonHarsh shaH
Darbepoetin alfa is an erythropoiesis-stimulating agent used to treat anemia. It is created through recombinant DNA technology and has 5 sugar chains, whereas erythropoietin has 3 chains. This longer circulating half-life allows darbepoetin alfa to be administered less frequently than erythropoietin. Clinical studies have shown darbepoetin alfa is effective at maintaining hemoglobin levels in patients with chronic kidney disease on dialysis or not on dialysis when administered weekly or every two weeks. Darbepoetin alfa is generally well-tolerated, with hypertension and dyspnea being the most common adverse reactions.
Atrial fibrillation is common in the elderly and requires an individualized treatment approach balancing stroke and bleeding risks. Rate control is generally recommended for those over age 80, while rhythm control may be suitable for highly symptomatic or younger patients with few comorbidities. Anticoagulation reduces stroke risk but requires consideration of frailty, cognition, polypharmacy, nutrition, and life expectancy. Novel oral anticoagulants offer advantages over warfarin for the elderly due to fewer drug interactions and more predictable dosing.
The SPRINT trial examined the effects of more intensive vs standard blood pressure treatment in over 9,000 adults age 50 or older with high blood pressure. Participants were randomized to a systolic blood pressure goal of less than 120 mm Hg (intensive) or less than 140 mm Hg (standard). The trial found that the primary composite cardiovascular outcome occurred at a 25% lower rate in the intensive treatment group compared to standard treatment. All-cause mortality was also 27% lower with intensive treatment. Intensive treatment resulted in more frequent adverse events like hypotension but overall benefits were found to exceed potential harms.
The three key points are:
1. The kidneys develop from three successive sets - the pronephros, mesonephros, and metanephros. The pronephros is rudimentary and nonfunctional, while the mesonephros functions briefly in early fetal development. The metanephros forms the permanent kidneys.
2. The permanent kidneys develop from an interaction between the ureteric bud and metanephrogenic blastema. The ureteric bud induces the blastema to form nephrons.
3. Congenital anomalies can occur if development goes awry, such as renal agenesis, horseshoe kidney, ectopic or
Membranous nephropathy is characterized by thickening of the glomerular capillary wall and immune complex deposition beneath podocytes. It is a common cause of nephrotic syndrome in adults. Primary membranous nephropathy is often associated with antibodies against phospholipase A2 receptor (PLA2R) or thrombospondin type 1 domain-containing 7A. Secondary membranous nephropathy can be caused by infections, malignancies, autoimmune diseases or drugs. Treatment involves immunosuppression with corticosteroids and cytotoxic drugs like cyclophosphamide to induce remission and prevent relapse and progression to end-stage renal disease.
Minimal change disease (MCD) is a common cause of nephrotic syndrome characterized by intense proteinuria. In children, MCD accounts for 70-90% of nephrotic syndrome cases. The disease is caused by abnormalities of the immune system resulting in foot process effacement and proteinuria. Treatment typically involves steroid therapy, which induces remission in most children within 8 days. However, relapses are common and additional immunosuppressive agents are often needed for frequent relapsing or steroid-dependent cases.
Anti-GBM disease is a rare autoimmune disease characterized by antibodies against type IV collagen in the basement membrane of the glomeruli and lungs. It commonly presents as rapidly progressive glomerulonephritis and pulmonary hemorrhage. Treatment involves plasma exchange to remove antibodies combined with cyclophosphamide and corticosteroids to suppress antibody production. Prognosis depends on renal function at presentation, with most patients achieving remission if treated early before requiring dialysis. Relapse is rare but can occur if exposures like smoking continue.
FSGS is a pattern of scarring within the glomeruli that can be caused by various factors. It represents a major cause of end-stage renal disease. There are several variants of FSGS including classic, perihilar, cellular, collapsing, and tip variants. FSGS can be primary, secondary to things like adaptive responses, viruses, drugs, or genetic mutations. Treatment depends on the underlying cause but may include immunosuppressive therapies or managing underlying conditions. Distinguishing FSGS from minimal change disease can sometimes be challenging as they can appear similar or transition between each other.
This document provides information on lupus nephritis (LN), including its history, definition, epidemiology, pathogenesis, and renal biopsy. Some key points:
- LN is an immune complex glomerulonephritis that commonly affects patients with systemic lupus erythematosus (SLE). It can lead to serious morbidity and mortality.
- The pathogenesis of LN involves autoimmune responses against apoptotic nuclear material, defects in clearance of apoptotic debris, and activation of innate and adaptive immune cells like myeloid dendritic cells and plasmacytoid dendritic cells.
- A renal biopsy is still the gold standard for diagnosing LN, and the histologic findings were first characterized
This document discusses guidelines for glycemic control in patients with diabetes and chronic kidney disease. It recommends monitoring HbA1c levels twice per year and targeting levels between 6.5-8%. Clinical trials showed that intensive glycemic control can reduce kidney disease progression but may increase mortality risk if targets are too low. The document also discusses guidelines for blood pressure control and the renoprotective effects of blocking the renin-angiotensin system with ACE inhibitors or ARBs. Combination therapy with an ACE inhibitor and ARB or adding an MRA may provide additional benefits but also increase risks like hyperkalemia.
The document discusses the pathogenesis of lupus nephritis, including the loss of immune tolerance leading to autovaccination and persistent antinuclear antibodies, with a subset of patients developing lupus nephritis depending on additional genetic susceptibility factors; it also covers the classification, treatment approaches including immunosuppressive therapies, and clinical trials of lupus nephritis.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
3. INRODUCTION
• Heart failure, thrombotic cardiovascular events, and sudden cardiac
death are common in CKD and ESKD
• CKD pt are disproportionately at higher risk of nonvalvular atrial
fibrillation (AF) compared with the general population
• Prevalence of AF increases as kidney disease worsens, and it is close
to 15% of dialysis dependent CKD pt, which is three times that of
age-matched controls
• Warfarin is one of the most commonly prescribed oral anticoagulants
• Newer anticoagulants may be favored over warfarin in patients with
ESRD and calciphylaxis
4. WARFARIN
• Oral anticoagulant with which clinicians have the most experience
• Racemic mixture of two optically active isomers (R and S) in equal
proportion
• Polymorphisms in vitamin K epoxide reductase gene and cytochrome
P450 type 2C9 (CYP2C9) responsibility of variability in warfarin dosing
• Vitamin K epoxide reductase genotype may be the best predictor –
responsible for the conversion of vitamin K epoxide to vitamin K
• CYP2C9 alleles are poor metabolizers, leading to prolonged t1/2 -
when compared with the wild type
5. Type Prodrug
Pharmacokinetics Pharmacod
ynamics:
Binding to
Effector
Metabolism
Renal Dose
Adjustment
Dialyzable
Warfarin
Vitamin K–
dependent
factor
inhibitor
No
Extensive
metabolism
by CYP2C9
No No Irreversible
Cmax, h t1/2, h
Protein
binding, %
VD, L
Bioavailability,
%
Warfarin 2–6 42 97–99 10 99
Increase Anticoagulant
Effects
Decrease Anticoagulant
Effects
Warfarin
Amiodarone, fluconazole,
tigecycline, voriconazole,
fluoroquinolones, verapamil,
diltiazem, other anticoagulants,
antiplatelet drugs, NSAIDs, and
SSRIs
Rifampin, phenobarbital,
carbamazepine, cigarette smoking
7. • Clinical practice guidelines do not recommend dosage reduction for
CKD or ESKD .
• According Limdi et al. found that mean dose reductions of 10% and
19% were required in patients with eGFR 30–59 and ,30 ml/min
compared with individuals with eGFR60 ml/min to maintain
therapeutic warfarin dosing
• Single warfarin dose (0.75 mg/kg) in individuals with GFR of 30–59
had a shorter t1/2 at 29.9hrs versus 44.8hrs in healthy controls.
• An increase in warfarin clearance was observed from 2.6 ml/kg per
hour in healthy controls to 3.7 ml/kg per hour in CKD
8. • The American College of Chest Physicians guidelines recommend,
• For INR >9 and no bleed, a single oral 2.5- to 5-mg dose to bring the
INR down in 1–2 days
• For serious bleeding, regardless of INR value, 10 mg is administered
parentally, and it is supplemented by fresh frozen plasma, prothrombin
complex concentrate, or recombinant factor VIIa.
• These measures are repeated every 12 hours if the INR remains
elevated .
• Hemorrhagic effects can be prolonged in patients with CKD and
patients with ESKD for a given INR value compared with in non-CKD
individuals
9. • GFR<30 ml/min per 1.73 m2, or ESRD complicates warfarin therapy
• Lower doses are required to maintain therapeutic INR
• Greater fluctuations in INR values with lower individual time in the
therapeutic range and higher risks of major bleeding events for any
given INR value have been reported in lot of studies.
• In a retrospective study of patients with ESKD and AF, warfarin
doubled stroke risk, presumably hemorrhagic, compared with no
treatment
• But all these studies have selection bias.
10. • Increased vascular calcification and calciphylaxis with
warfarin given that it reduces function of vitamin K–
dependent vascular calcification inhibitors, such as matrix
Gla proteins
• AKI secondary to glomerular hemorrhage due to thrombin
depletion in patients on warfarin with INR>3 in whom there
is no other identifiable etiology of AKI
11. • The American Heart Association 2014 updated
guidelines for anticoagulation management in AF
recommend warfarin as the drug of choice in patients
with advanced CKD (creatinine clearance ,30 ml/min)
and patients with ESKD
12. Direct Thrombin Inhibitor—Dabigatran
• Dabigatran etexilate, 150 mg twice daily, is FDA approved to
prevent stroke or systemic embolism in patients with AF
• Lower doses (75 mg twice daily), with a creatinine clearance
of 15–30 ml/min
13. • Normal thrombin time has the best negative predictive value to
exclude the presence of dabigatran
• Ecarin-based assays, such as the ecarin clotting time, are highly
sensitive and correlate strongly with drug concentrations
(metalloproteinase, cleaves prothrombin to meizothrombin)
Both these test linearly correlated with drug concentration measured
by liquid chromatography tandem mass spectrometry
14. OAC Type Prodrug
Pharmacokinetics Pharmacodyn
amics:
Binding to
Effector
Metabolism
Renal Dose
Adjustment
Dialyzable
Dabigatran
Direct
thrombin
inhibitor
Yes
Metabolized
by esterases,
80% excreted
by kidney
Yes Yes Reversible
OAC Cmax, h t1/2, h
Protein
binding, %
VD, L
Bioavailability,
%
Dabigatran 1–2 12–14 38 50–70 3–7
Drug Increase Anticoagulant Effects Decrease Anticoagulant Effects
Dabigatran
Amiodarone, verapamil, ketoconazole, dronaderone,
clopidogrel, enoxaparin, other anticoagulants, antiplatelet
drugs
Rifampin
15. • Elimination t1/2 doubled in patients with CKD
• A single hemodialysis session removed 62%–68%
• Reversal of Antithrombotic Effects
• fresh frozen plasma and prothrombin complex concentrate
• factor VIII inhibitor bypass activity
• hemodialysis and continuous venovenous hemofiltration
• Idarucizumab
(humanized mAb fragment directed against dabigatran and its acyl-glucuronide metabolites, its
binding affinity to dabigatran is higher than dabigatran to thrombin, thus neutralizing the
anticoagulant effect immediately after a single 5-g intra-venous dose )
16. SAFETY OF DRUG
• Major bleeding were reported in frail elderly individuals, patients with
CKD, and patients with ESKD
• Dabigatran versus warfarin reduces risk of stroke or systemic
embolism and intracranial hemorrhage, with an increased risk of
gastrointestinal bleeding events
• The only study in patients on hemodialysis using the FMCNA
database; it reported a 1.5-fold higher risk of death or
hospitalization from bleeding with dabigatran versus warfarin
18. Rivaroxaban
• FDA approved in patients with AF to prevent stroke or systemic embolism
,deep venous thrombosis (DVT) and pulmonary embolism prophylaxis after
knee and hip replacement
• Not approved in patients with mechanical heart valves
• Oral bioavailability varies with dosing strength: 80%–100% with a 10-mg
dose and 66% with a 20-mg dose
• 20 mg/d for patients with a GFR>50 ml/min and 15 mg/d for patients
with a GFR 30–50 ml/min . Avoided in patients with GFR<15 ml/min
• For DVT and PE prophylaxis, dosage is 10 mg/d
• Started 6–10 hours after surgery for DVT/ PE prophylaxis, and it is
continued for 35 days after hip replacement and 12 days after knee
replacement
19. • Few study suggests that reduced rivaroxaban clearance with
worsening creatinine clearance resulted in increased drug exposure
• Rivaroxaban is likely to accumulate in patients with CKD and patients
with ESKD even at lower doses (10 or 15 mg/d),
• It is poorly cleared by hemodialysis.
20. Apixaban
• FDA approved for reduction of stroke or systemic embolism in
patients with AF at 5 mg twice daily .
• With any two of the following 1.serum creatinine >1.5 mg/dl,
2.age >80 years old, or
3.body weight >60 kg,
a reduced dose of 2.5 mg twice daily is recommended .
• Approved for DVT/PE prophylaxis after hip and knee replacement at
2.5 mg twice daily
• Treatment of DVT/PE at 10 mg twice daily for a week followed by 5
mg twice daily
• It is not approved for use with mechanical heart valves
21. • Because of its high degree of protein binding, dialysis clearance is low
• Elimination t1/2 was slightly increased in all subjects with CKD (17
hours) versus controls (15 hours).
• The AUC, Cmax, and Cmin all increased when measured at day 8
compared to day 1 suggesting accumulation of the drug.
• But at day 8 drug levels were still within the normal reference range.
• Drug levels comparing day 5 versus day 8 suggested that a steady
state had been reached.
22. Edoxaban
• Approved for patients with AF
• It is also approved for treatment of DVT/PE only after an initial 5- to
10-day treatment with parenteral anticoagulation
• It is recommended at 60 mg once daily for patients with GFR of 50–95
ml/min and 30 mg once daily for patients with GFR of 15–50 ml/min
• Although its molecular weight is 738 g/mol and it is only 55% protein
bound, it is poorly cleared by dialysis –possibly due to the large
volume of distribution
23. OAC Type Prodrug
Pharmacokinetics Pharmacody
namics:
Binding to
Effector
Metabolism
Renal Dose
Adjustment
Dialyzable
Apixaban
Free and clot-
bound Xa
inhibitor
No
Metabolized in
liver by CYP3A4,
then excreted in
feces and kidney
(25%), no active
metabolite
No Small Reversible
Rivaroxaban
Free and clot-
bound Xa
inhibitor
No
66% Excreted by
kidney, 36%
unchanged,
minimal in feces
Yes No Reversible
Edoxaban
Free Xa
inhibitor
No
50% Excreted
unchanged by the
kidney, 10%
hydrolyzed by
carboxyesterase 1
Yes No Reversible
24. OAC Cmax, h t1/2, h
Protein
binding, %
VD, L
Bioavailability,
%
Apixaban 3–4 12 87 21 50
Rivaroxaban 2–4 6–13 >90 50 66–100
Edoxaban 1–2 10–14 55 107 62
•
Drug Increase Anticoagulant Effects Decrease Anticoagulant Effects
Apixaban
Ketoconazole, other anticoagulants,
antiplatelet drugs
Rifampin
Rivaroxaban
Other anticoagulants, antiplatelet
drugs, fluconazole, ketoconazole,
erythromycin, and clarithromycin
Rifampin, phenytoin,
carbamazepine, St. John’s Wort
Edoxaban
Other anticoagulants, antiplatelet
drugs,
Rifampin
•
25. LAB MONITERING
• PT prolongation occurs to a greater degree than APTT prolongation
with factor Xa inhibitors
• Chromogenic anti-Xa activity assay (e.g., Rotachrom) may be more
reliable and accurate
26. Reversal modality Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban
Reversal by
antidotes
Prothrombin
complex concentrate
Yes doubtful Yes Yes Yes
Recombinant factor
VIIa
Yes No Yes Yes Yes
Fresh frozen plasma Yes doubtful Yes Yes Yes
Factor VIII inhibitor
bypass activity
Not reported Yes Yes Yes Yes
Specific antidote No Idaracizumab Investigational (andexanet alfa)
Dialysis as a
treatment option for
major bleeding
events
Hemodialysis No Yes No No No
27. • In the general population, newer oral anticoagulants (dabigatran,
rivaroxaban, or apixaban) compared with warfarin were more
effective in reducing stroke or systemic embolism without an
increased risk of intracranial hemorrhage and gastrointestinal
bleeding
• Patients with AF on chronic hemodialysis reported a 1.7-fold higher
risk of death or hospitalization from bleeding with rivaroxaban versus
warfarin
• Apixaban was superior to warfarin in reducing stroke or systemic
embolism rates and major bleeding among participants with kidney
dysfunction
28. • A recent Cochrane review reported reduced risk of stroke or systemic
embolism and similar risk of major bleeding among patients with AF
and CKD treated with factor Xa inhibitors versus warfarin
• But most of these studies did not include haemodialysis patient
29. GAP IN STUDIES
• Comparative efficacy and safety data remain limited to support use of
one oral anticoagulant over another in patients with CKD stages 4–5
or ESKD
• Lack of a standardized approach
30. CONCLUION
• GFR<30 ,including those on dialysis, were systematically excluded
from landmark trials
• Warfarin remains the most widely used oral anticoagulant
• If the individual time in therapeutic INR range is ,50% or if patients
experience complications, such as calciphylaxis, APIXABAN CAN BE
USED.
Editor's Notes
Carboxylation of vitamin K–dependent proteins requires the reduced form of vitamin K, γ-glutamyl carboxylase enzyme, molecular oxygen, and carbon dioxide. Because body stores of vitamin K are low, the oxidized (inactive) form of vitamin K is recycled to the reduced (active) form by vitamin K epoxide reductase, which is inhibited by warfarin. Inhibition results in reduced hepatic synthesis of these clotting factors and reduction in their activities by 40%–50%.