Tauhid Ahmed Bhuiyan, PharmD presented a document on drug-induced acute kidney injury. The document discussed the background, epidemiology and overview of acute kidney injury. It reviewed the pathogenic mechanisms and prevention strategies of drug-induced acute kidney injury. It also evaluated the implications of computerized clinical decision support systems for medication dosing in patients with renal insufficiency.
This document discusses drug-induced acute kidney injury (AKI). It notes that AKI is characterized by an abrupt reduction in kidney function over 48 hours, shown by decreased urine output and increased creatinine levels. Between 5-20% of AKI cases are caused by medications, as kidneys excrete many water-soluble drugs and metabolites. Common culprits include contrast media, ACE inhibitors, NSAIDs, diuretics, and ARBs. Other "red flag" drugs mentioned are aminoglycosides, anticoagulants, anticonvulsants, antivirals, digoxin, immunosuppressants, and hypoglycemic medicines. Treatment focuses on supportive care like fluid management
In this presentation i have tried to thoroughly discuss about the concept of Drug induced kidney disease or injury, the mechanism behind it, its classification and how to access it.
The document discusses Drug Induced Kidney Disease (DIKD), specifically drug induced nephrotoxicity. It notes that DIKD is a common complication of various therapeutic agents that can cause abnormalities in acid-base balance, electrolytes, urine sediment, decline in glomerular filtration rate, and increased creatinine and BUN. It identifies several classes of drugs that commonly cause nephrotoxicity like aminoglycosides, amphotericin B, and cisplatin. It also discusses risk factors, clinical presentation, prevention, and various pathological mechanisms of nephrotoxicity including tubular epithelial cell damage, acute tubular necrosis, osmotic nephrosis, and hemodynamically mediated kidney
This document discusses drug dosing considerations in renal failure. It notes that dosage refers to the prescribed administration of a drug over time, while dose refers to a single amount. Patients with renal disease are more vulnerable to drug effects, which may increase or decrease. Assessment of renal function includes serum creatinine and BUN levels. Estimating glomerular filtration rate (eGFR) accounts for average body size. Many drugs require dosage adjustments or alternative choices in renal failure, especially those excreted renally. Loading doses do not typically change, while maintenance doses depend on drug clearance. Some antibiotics do not require adjustment.
Methotrexate is an anti-folate drug used to treat cancer and autoimmune diseases. It works by inhibiting dihydrofolate reductase. The document discusses methotrexate's mode of action, uses and doses for low-dose and high-dose regimens, side effects, drug interactions, pharmacokinetic parameters including bioavailability, volume of distribution, half-life, clearance, therapeutic drug monitoring goals, and the use of leucovorin rescue to treat methotrexate toxicity. Key points covered include the saturable absorption of high-dose methotrexate, its multi-compartment pharmacokinetics, and the importance of monitoring methotrexate levels to ensure adequate le
1) Sirolimus is an immunosuppressant that was first investigated as an antifungal agent in the 1970s and was found to have immunosuppressive properties in 1971. It was approved by the FDA for immunosuppression in 1999.
2) Sirolimus works by binding to FKBP and inhibiting the mTOR pathway, which leads to inhibition of lymphocyte proliferation. This results in reduced T and B cell proliferation.
3) Therapeutic drug monitoring is recommended for sirolimus and everolimus, as trough levels correlate well with efficacy and toxicity. The target trough range is generally 5-15 ng/mL for sirolimus and 3-8 ng/mL for ever
This document provides an overview of drug-induced liver disease (DILD). It defines DILD and discusses its epidemiology and risk factors. Two main mechanisms of hepatotoxicity are described - intrinsic and idiosyncratic. Various types of DILD are outlined including hepatocellular necrosis, steatosis, cholestasis, granulomatous hepatitis, and fibrosis/cirrhosis. Clinical manifestations, investigations, and treatment approaches are summarized. Assessment involves a patient history, liver enzyme levels, biopsy, and nutritional status evaluation. Treatment focuses on diagnosis, drug withdrawal, supportive care, and use of antidotes/corticosteroids if needed.
The kidney maintains the vital functions of clearing excess body fluid and removing metabolic and exogenous toxins from the blood
The kidney is particularly vulnerable to drugs and other agents that cause renal damage
The heart pumps approximately 25% of cardiac output into the kidneys
Any drug in the blood will eventually reach the highly vascularized kidneys
It may potentially cause drug induced renal failure
If the drug is primarily cleared by the kidney, the drug will become increasingly concentrated as it moves from the renal artery into the smaller vasculature of the kidney
The drug may be filtered or secreted into the lumen of the renal tubules
The concentrated drug exposes the kidney tissue to far greater drug concentration per surface area
Drug-induced kidney disease or nephrotoxicity (DIN) is a relatively common complication of several diagnostic and therapeutic agents.
This document discusses drug-induced acute kidney injury (AKI). It notes that AKI is characterized by an abrupt reduction in kidney function over 48 hours, shown by decreased urine output and increased creatinine levels. Between 5-20% of AKI cases are caused by medications, as kidneys excrete many water-soluble drugs and metabolites. Common culprits include contrast media, ACE inhibitors, NSAIDs, diuretics, and ARBs. Other "red flag" drugs mentioned are aminoglycosides, anticoagulants, anticonvulsants, antivirals, digoxin, immunosuppressants, and hypoglycemic medicines. Treatment focuses on supportive care like fluid management
In this presentation i have tried to thoroughly discuss about the concept of Drug induced kidney disease or injury, the mechanism behind it, its classification and how to access it.
The document discusses Drug Induced Kidney Disease (DIKD), specifically drug induced nephrotoxicity. It notes that DIKD is a common complication of various therapeutic agents that can cause abnormalities in acid-base balance, electrolytes, urine sediment, decline in glomerular filtration rate, and increased creatinine and BUN. It identifies several classes of drugs that commonly cause nephrotoxicity like aminoglycosides, amphotericin B, and cisplatin. It also discusses risk factors, clinical presentation, prevention, and various pathological mechanisms of nephrotoxicity including tubular epithelial cell damage, acute tubular necrosis, osmotic nephrosis, and hemodynamically mediated kidney
This document discusses drug dosing considerations in renal failure. It notes that dosage refers to the prescribed administration of a drug over time, while dose refers to a single amount. Patients with renal disease are more vulnerable to drug effects, which may increase or decrease. Assessment of renal function includes serum creatinine and BUN levels. Estimating glomerular filtration rate (eGFR) accounts for average body size. Many drugs require dosage adjustments or alternative choices in renal failure, especially those excreted renally. Loading doses do not typically change, while maintenance doses depend on drug clearance. Some antibiotics do not require adjustment.
Methotrexate is an anti-folate drug used to treat cancer and autoimmune diseases. It works by inhibiting dihydrofolate reductase. The document discusses methotrexate's mode of action, uses and doses for low-dose and high-dose regimens, side effects, drug interactions, pharmacokinetic parameters including bioavailability, volume of distribution, half-life, clearance, therapeutic drug monitoring goals, and the use of leucovorin rescue to treat methotrexate toxicity. Key points covered include the saturable absorption of high-dose methotrexate, its multi-compartment pharmacokinetics, and the importance of monitoring methotrexate levels to ensure adequate le
1) Sirolimus is an immunosuppressant that was first investigated as an antifungal agent in the 1970s and was found to have immunosuppressive properties in 1971. It was approved by the FDA for immunosuppression in 1999.
2) Sirolimus works by binding to FKBP and inhibiting the mTOR pathway, which leads to inhibition of lymphocyte proliferation. This results in reduced T and B cell proliferation.
3) Therapeutic drug monitoring is recommended for sirolimus and everolimus, as trough levels correlate well with efficacy and toxicity. The target trough range is generally 5-15 ng/mL for sirolimus and 3-8 ng/mL for ever
This document provides an overview of drug-induced liver disease (DILD). It defines DILD and discusses its epidemiology and risk factors. Two main mechanisms of hepatotoxicity are described - intrinsic and idiosyncratic. Various types of DILD are outlined including hepatocellular necrosis, steatosis, cholestasis, granulomatous hepatitis, and fibrosis/cirrhosis. Clinical manifestations, investigations, and treatment approaches are summarized. Assessment involves a patient history, liver enzyme levels, biopsy, and nutritional status evaluation. Treatment focuses on diagnosis, drug withdrawal, supportive care, and use of antidotes/corticosteroids if needed.
The kidney maintains the vital functions of clearing excess body fluid and removing metabolic and exogenous toxins from the blood
The kidney is particularly vulnerable to drugs and other agents that cause renal damage
The heart pumps approximately 25% of cardiac output into the kidneys
Any drug in the blood will eventually reach the highly vascularized kidneys
It may potentially cause drug induced renal failure
If the drug is primarily cleared by the kidney, the drug will become increasingly concentrated as it moves from the renal artery into the smaller vasculature of the kidney
The drug may be filtered or secreted into the lumen of the renal tubules
The concentrated drug exposes the kidney tissue to far greater drug concentration per surface area
Drug-induced kidney disease or nephrotoxicity (DIN) is a relatively common complication of several diagnostic and therapeutic agents.
Drug induced kidney disease (DIKD) is caused by drugs and characterized by increased serum creatinine and blood urea nitrogen levels that are temporally related to drug exposure. Acute tubular necrosis is the most common cause of DIKD in hospitalized patients. Risk factors include increased age, pre-existing kidney disease, use of multiple nephrotoxic drugs, and critical illness. Common culprit drugs are aminoglycosides, radiographic contrast media, nonsteroidal anti-inflammatory drugs, and antiviral drugs. Symptoms include decreased urine output, edema, and increased creatinine and BUN levels. Treatment involves discontinuing the offending drug, maintaining hydration, and renal replacement therapy for severe cases.
This document discusses challenging cases of acute heart failure involving diuretic resistance. It begins by defining diuretic resistance as a poor response to diuretic therapy, characterized by persistent signs and symptoms despite treatment. The pathophysiology of diuretic resistance is incompletely understood but may involve factors like RAAS activation, decreased renal function and blood flow, and distal tubular sodium reabsorption. The document reviews potential treatments for diuretic resistance including increasing and switching diuretic medications, adding mineralocorticoid receptor antagonists or thiazides, intravenous diuretic administration, and in select cases ultrafiltration. Early identification of diuretic resistance is important and associated with worse patient outcomes.
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.
A complete drug profile of Tacrolimus an immunosuppressant used for organ transplant. It consist of PK/PD, MOA, Indication & Uses, Contraindications, Warnings & Precautions, Drug-interaction, Doses & Administration, Dosage forms, Chemical Formula, Side-Effects, Adverse Drug Reactions, Therapeutic Drug Monitoring (TDM).
Drug induced liver injury (DILI) and HepatotoxicityDr. Ankit Gaur
In this presentation I have tried to explain the defination, Mechanism of drug induced liver injury (DILI) and hepatotoxicity with the help of few examples.
Diuretic resistance is defined as failure to achieve therapeutic reduction in edema even with maximal diuretic dosing. It can be caused by conditions like congestive heart failure, renal insufficiency, nephrotic syndrome, liver cirrhosis, and NSAID use. Mechanisms contributing to resistance include the braking phenomenon of increased sodium reabsorption in response to volume reduction, post-diuretic sodium retention due to RAAS activation, and renal adaptation like distal tubule hypertrophy. Combination diuretic therapy using drugs with different mechanisms of action can help overcome resistance.
mTOR inhibitors like sirolimus and everolimus are immunosuppressants that provide an alternative to calcineurin inhibitors for renal transplant patients. They have antiproliferative properties, cause less nephrotoxicity than CNIs, and are associated with lower rates of malignancy, viral infections, and improved renal function when used to convert patients from a CNI-based regimen. However, mTOR inhibitors are less effective at preventing acute rejection when used without a CNI in de novo transplants.
DILI is possible consequence of ingestion of OTC drugs like PCM.
so it require careful clinical knowledge before taking drugs without doctors prescriptions...
Renal replacement therapy encompasses life-supporting treatments for renal failure such as hemodialysis, peritoneal dialysis, and continuous renal replacement therapy. Hemodialysis uses diffusion and filtration across a semi-permeable membrane to remove waste and fluid. Peritoneal dialysis infuses dialysate into the peritoneal cavity. Continuous renal replacement therapy provides 24-hour treatment through diffusion, convection, or a combination. These therapies aim to replace normal kidney functions of waste removal and fluid balance.
This document discusses dose adjustment in patients with renal impairment. It covers several key topics:
1. The kidney's role in regulating fluids, electrolytes, waste removal, and drug excretion. Impaired kidney function affects drug pharmacokinetics.
2. Approaches for dose adjustment based on estimating remaining renal function and drug clearance. Dose, dosing interval, or both may be adjusted to maintain therapeutic drug levels.
3. Methods for estimating glomerular filtration rate and measuring kidney function using markers like inulin, creatinine, and urea. Creatinine clearance is commonly used in clinical practice.
4. Considerations for dose adjustment in patients on dialysis, as
The document discusses drugs and their effects on the kidney. It covers normal kidney function, methods of assessing renal function, how drugs are processed by the kidneys, diuretics, nephrotoxic drugs, and prescribing considerations for patients with kidney disease. Key points include how different drug classes like loop diuretics and thiazides work at different sites in the nephron to cause diuresis, risks of nephrotoxicity from NSAIDs, aminoglycosides and contrast agents, and dosing adjustments needed in renal impairment.
Febuxostat for treatment of chronic goutChoying Chen
Febuxostat is a xanthine oxidase inhibitor approved for the treatment of chronic gout. It has been shown in clinical trials to be more effective at lowering uric acid levels compared to allopurinol and is generally well-tolerated. However, febuxostat has been associated with increased rates of liver function abnormalities and cardiovascular events compared to allopurinol. It is recommended that liver function and symptoms of cardiovascular events be monitored in patients taking febuxostat. Febuxostat provides an alternative treatment option for patients who do not achieve target uric acid levels or experience adverse effects with allopurinol.
This document defines acute kidney injury (AKI) and describes its staging, risk factors, types, epidemiology, etiology, clinical presentation, diagnosis, and management. AKI is defined as a rapid decrease in kidney function shown by changes in serum creatinine, BUN, and urine output. It stages AKI severity based on changes in serum creatinine and urine output. Common causes of AKI include reduced renal perfusion, intrinsic kidney damage, and urinary obstruction. Treatment involves fluid hydration, electrolyte management, avoiding nephrotoxins, and considering diuretics or renal replacement therapy in severe cases.
The kidney plays an important role in regulating fluids, electrolytes, and removing waste from the body. Impairment of kidney function affects drug pharmacokinetics. Common causes of kidney failure include disease, injury, drug toxicity, infections, diabetes, toxins, and reduced blood flow. Acute kidney problems or trauma can lead to uremia where filtration is impaired, causing excess fluid and waste to accumulate. Uremic patients may have changes in drug absorption, distribution, and clearance. Dosage adjustments are often needed based on a patient's kidney function and drug properties to safely treat uremic patients.
Acute kidney injury (AKI), previously called acute renal failure, is a reversible increase in blood creatinine and nitrogenous waste products due to the kidney's inability to regulate fluids and electrolytes. AKI is classified using RIFLE and AKIN criteria and can have pre-renal, intrinsic renal, or post-renal causes. Common causes in children include sepsis, cardiac surgery, organ transplantation, hemolytic uremic syndrome, and acute glomerulonephritis. Diagnosis involves physical exam, lab tests of kidney function and urine analysis, and imaging studies may be needed to identify obstruction. Kidney biopsy may be required to determine etiology or prognosis when cause is unknown.
This document discusses nephrotoxic drugs and their impact on kidney function. It begins by explaining how renal damage from drugs can cause significant health issues like acute kidney injury and chronic kidney disease, as well as increasing medical costs. It then identifies several common classes of drugs that can cause nephrotoxicity, such as antibiotics, chemotherapy agents, antihypertensives, and NSAIDs. The document discusses mechanisms of nephrotoxicity for different drug classes and regions of the kidney. It also examines renal biomarkers that can help identify kidney injury earlier than serum creatinine. Finally, it provides examples of renal protective strategies like dose adjustments, monitoring, and hydration that can reduce the nephrotoxic risks of certain
This document discusses the pharmacotherapy of inflammatory bowel disease (IBD). IBD includes two major subtypes, ulcerative colitis and Crohn's disease, which are characterized by chronic inflammation of the intestinal tract. Treatment aims to induce and maintain remission of symptoms. First-line therapies include 5-aminosalicylic acid drugs and glucocorticoids. For cases that are steroid-dependent or resistant, immunosuppressants like azathioprine and anti-TNFα antibodies such as infliximab are used. Supportive care involves nutritional supplementation, antidiarrheals, and in severe cases of Crohn's, total parenteral nutrition may be given.
Elderly patients are often defined as those over 65 years old, but aging affects individuals differently. Physiologic changes that occur with aging can impact how drugs are absorbed, distributed, metabolized, and excreted from the body. Absorption and distribution may be altered due to changes in gastrointestinal function and decreases in muscle mass. Metabolism and excretion are often decreased due to reduced liver and kidney function. These changes can affect drug efficacy, safety, and risk of interactions and adverse events. When dosing elderly patients, their multiple medical conditions, polypharmacy, and risk for non-compliance must be considered. Pharmacists can help by counseling patients and monitoring their medication therapy.
Pharmacokinetic changes in renal impairment and dosage considerationsDr Htet
The kidneys play a key role in drug elimination from the body. Renal impairment can affect the pharmacokinetics of many drugs by reducing their excretion, increasing their bioavailability and toxicity. Dosage regimens must be adapted based on a patient's level of renal function and whether the drug or its metabolites are renally excreted. Drugs that are nephrotoxic or have a narrow therapeutic index require especially close monitoring and dosage adjustment according to glomerular filtration rate in patients with renal impairment.
This document discusses the diagnosis and management of acute kidney injury (AKI) in the intensive care unit (ICU). It defines AKI and outlines biomarkers that can help identify it earlier than creatinine. Common causes of AKI in the ICU include sepsis, major surgery, low cardiac output, and medications. The document reviews risk factors for developing AKI and strategies for preventing it, such as fluid management and avoiding nephrotoxins. It discusses general management of established AKI including nutrition, anticoagulation, and dialysis. The impact of renal replacement therapy on outcomes is also addressed.
Drug induced kidney disease (DIKD) is caused by drugs and characterized by increased serum creatinine and blood urea nitrogen levels that are temporally related to drug exposure. Acute tubular necrosis is the most common cause of DIKD in hospitalized patients. Risk factors include increased age, pre-existing kidney disease, use of multiple nephrotoxic drugs, and critical illness. Common culprit drugs are aminoglycosides, radiographic contrast media, nonsteroidal anti-inflammatory drugs, and antiviral drugs. Symptoms include decreased urine output, edema, and increased creatinine and BUN levels. Treatment involves discontinuing the offending drug, maintaining hydration, and renal replacement therapy for severe cases.
This document discusses challenging cases of acute heart failure involving diuretic resistance. It begins by defining diuretic resistance as a poor response to diuretic therapy, characterized by persistent signs and symptoms despite treatment. The pathophysiology of diuretic resistance is incompletely understood but may involve factors like RAAS activation, decreased renal function and blood flow, and distal tubular sodium reabsorption. The document reviews potential treatments for diuretic resistance including increasing and switching diuretic medications, adding mineralocorticoid receptor antagonists or thiazides, intravenous diuretic administration, and in select cases ultrafiltration. Early identification of diuretic resistance is important and associated with worse patient outcomes.
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.
A complete drug profile of Tacrolimus an immunosuppressant used for organ transplant. It consist of PK/PD, MOA, Indication & Uses, Contraindications, Warnings & Precautions, Drug-interaction, Doses & Administration, Dosage forms, Chemical Formula, Side-Effects, Adverse Drug Reactions, Therapeutic Drug Monitoring (TDM).
Drug induced liver injury (DILI) and HepatotoxicityDr. Ankit Gaur
In this presentation I have tried to explain the defination, Mechanism of drug induced liver injury (DILI) and hepatotoxicity with the help of few examples.
Diuretic resistance is defined as failure to achieve therapeutic reduction in edema even with maximal diuretic dosing. It can be caused by conditions like congestive heart failure, renal insufficiency, nephrotic syndrome, liver cirrhosis, and NSAID use. Mechanisms contributing to resistance include the braking phenomenon of increased sodium reabsorption in response to volume reduction, post-diuretic sodium retention due to RAAS activation, and renal adaptation like distal tubule hypertrophy. Combination diuretic therapy using drugs with different mechanisms of action can help overcome resistance.
mTOR inhibitors like sirolimus and everolimus are immunosuppressants that provide an alternative to calcineurin inhibitors for renal transplant patients. They have antiproliferative properties, cause less nephrotoxicity than CNIs, and are associated with lower rates of malignancy, viral infections, and improved renal function when used to convert patients from a CNI-based regimen. However, mTOR inhibitors are less effective at preventing acute rejection when used without a CNI in de novo transplants.
DILI is possible consequence of ingestion of OTC drugs like PCM.
so it require careful clinical knowledge before taking drugs without doctors prescriptions...
Renal replacement therapy encompasses life-supporting treatments for renal failure such as hemodialysis, peritoneal dialysis, and continuous renal replacement therapy. Hemodialysis uses diffusion and filtration across a semi-permeable membrane to remove waste and fluid. Peritoneal dialysis infuses dialysate into the peritoneal cavity. Continuous renal replacement therapy provides 24-hour treatment through diffusion, convection, or a combination. These therapies aim to replace normal kidney functions of waste removal and fluid balance.
This document discusses dose adjustment in patients with renal impairment. It covers several key topics:
1. The kidney's role in regulating fluids, electrolytes, waste removal, and drug excretion. Impaired kidney function affects drug pharmacokinetics.
2. Approaches for dose adjustment based on estimating remaining renal function and drug clearance. Dose, dosing interval, or both may be adjusted to maintain therapeutic drug levels.
3. Methods for estimating glomerular filtration rate and measuring kidney function using markers like inulin, creatinine, and urea. Creatinine clearance is commonly used in clinical practice.
4. Considerations for dose adjustment in patients on dialysis, as
The document discusses drugs and their effects on the kidney. It covers normal kidney function, methods of assessing renal function, how drugs are processed by the kidneys, diuretics, nephrotoxic drugs, and prescribing considerations for patients with kidney disease. Key points include how different drug classes like loop diuretics and thiazides work at different sites in the nephron to cause diuresis, risks of nephrotoxicity from NSAIDs, aminoglycosides and contrast agents, and dosing adjustments needed in renal impairment.
Febuxostat for treatment of chronic goutChoying Chen
Febuxostat is a xanthine oxidase inhibitor approved for the treatment of chronic gout. It has been shown in clinical trials to be more effective at lowering uric acid levels compared to allopurinol and is generally well-tolerated. However, febuxostat has been associated with increased rates of liver function abnormalities and cardiovascular events compared to allopurinol. It is recommended that liver function and symptoms of cardiovascular events be monitored in patients taking febuxostat. Febuxostat provides an alternative treatment option for patients who do not achieve target uric acid levels or experience adverse effects with allopurinol.
This document defines acute kidney injury (AKI) and describes its staging, risk factors, types, epidemiology, etiology, clinical presentation, diagnosis, and management. AKI is defined as a rapid decrease in kidney function shown by changes in serum creatinine, BUN, and urine output. It stages AKI severity based on changes in serum creatinine and urine output. Common causes of AKI include reduced renal perfusion, intrinsic kidney damage, and urinary obstruction. Treatment involves fluid hydration, electrolyte management, avoiding nephrotoxins, and considering diuretics or renal replacement therapy in severe cases.
The kidney plays an important role in regulating fluids, electrolytes, and removing waste from the body. Impairment of kidney function affects drug pharmacokinetics. Common causes of kidney failure include disease, injury, drug toxicity, infections, diabetes, toxins, and reduced blood flow. Acute kidney problems or trauma can lead to uremia where filtration is impaired, causing excess fluid and waste to accumulate. Uremic patients may have changes in drug absorption, distribution, and clearance. Dosage adjustments are often needed based on a patient's kidney function and drug properties to safely treat uremic patients.
Acute kidney injury (AKI), previously called acute renal failure, is a reversible increase in blood creatinine and nitrogenous waste products due to the kidney's inability to regulate fluids and electrolytes. AKI is classified using RIFLE and AKIN criteria and can have pre-renal, intrinsic renal, or post-renal causes. Common causes in children include sepsis, cardiac surgery, organ transplantation, hemolytic uremic syndrome, and acute glomerulonephritis. Diagnosis involves physical exam, lab tests of kidney function and urine analysis, and imaging studies may be needed to identify obstruction. Kidney biopsy may be required to determine etiology or prognosis when cause is unknown.
This document discusses nephrotoxic drugs and their impact on kidney function. It begins by explaining how renal damage from drugs can cause significant health issues like acute kidney injury and chronic kidney disease, as well as increasing medical costs. It then identifies several common classes of drugs that can cause nephrotoxicity, such as antibiotics, chemotherapy agents, antihypertensives, and NSAIDs. The document discusses mechanisms of nephrotoxicity for different drug classes and regions of the kidney. It also examines renal biomarkers that can help identify kidney injury earlier than serum creatinine. Finally, it provides examples of renal protective strategies like dose adjustments, monitoring, and hydration that can reduce the nephrotoxic risks of certain
This document discusses the pharmacotherapy of inflammatory bowel disease (IBD). IBD includes two major subtypes, ulcerative colitis and Crohn's disease, which are characterized by chronic inflammation of the intestinal tract. Treatment aims to induce and maintain remission of symptoms. First-line therapies include 5-aminosalicylic acid drugs and glucocorticoids. For cases that are steroid-dependent or resistant, immunosuppressants like azathioprine and anti-TNFα antibodies such as infliximab are used. Supportive care involves nutritional supplementation, antidiarrheals, and in severe cases of Crohn's, total parenteral nutrition may be given.
Elderly patients are often defined as those over 65 years old, but aging affects individuals differently. Physiologic changes that occur with aging can impact how drugs are absorbed, distributed, metabolized, and excreted from the body. Absorption and distribution may be altered due to changes in gastrointestinal function and decreases in muscle mass. Metabolism and excretion are often decreased due to reduced liver and kidney function. These changes can affect drug efficacy, safety, and risk of interactions and adverse events. When dosing elderly patients, their multiple medical conditions, polypharmacy, and risk for non-compliance must be considered. Pharmacists can help by counseling patients and monitoring their medication therapy.
Pharmacokinetic changes in renal impairment and dosage considerationsDr Htet
The kidneys play a key role in drug elimination from the body. Renal impairment can affect the pharmacokinetics of many drugs by reducing their excretion, increasing their bioavailability and toxicity. Dosage regimens must be adapted based on a patient's level of renal function and whether the drug or its metabolites are renally excreted. Drugs that are nephrotoxic or have a narrow therapeutic index require especially close monitoring and dosage adjustment according to glomerular filtration rate in patients with renal impairment.
This document discusses the diagnosis and management of acute kidney injury (AKI) in the intensive care unit (ICU). It defines AKI and outlines biomarkers that can help identify it earlier than creatinine. Common causes of AKI in the ICU include sepsis, major surgery, low cardiac output, and medications. The document reviews risk factors for developing AKI and strategies for preventing it, such as fluid management and avoiding nephrotoxins. It discusses general management of established AKI including nutrition, anticoagulation, and dialysis. The impact of renal replacement therapy on outcomes is also addressed.
This document discusses acute kidney injury (AKI). It provides definitions of AKI from various clinical practice guidelines. AKI can be prerenal, intrinsic, or postrenal based on its etiology. Common causes are listed. Diagnosis involves medical history, physical exam, lab tests of blood and urine. Staging systems like RIFLE and KDIGO use changes in serum creatinine and urine output to stage AKI severity. Prevention focuses on identifying at-risk patients and implementing strategies like intravenous fluids. Treatment aims to support kidney function through fluid management, electrolyte monitoring, and potentially renal replacement therapy like hemodialysis.
<SUMMARY>
The document provides an overview of acute kidney injury (AKI), including definitions, classification, epidemiology, etiology, diagnosis, management, and prevention strategies. It defines AKI according to the KDIGO criteria and discusses the RIFLE and AKIN classification systems. Prerenal, intrinsic, and postrenal causes of AKI are outlined. Diagnosis involves establishing baseline kidney function, identifying potential causes, and evaluating volume status, laboratory tests, and imaging studies. Management focuses on treating the underlying cause, optimizing hemodynamics, and preventing complications. Prevention emphasizes recognizing risk factors and avoiding nephrotoxic exposures.
</SUMMARY>
This document discusses acute kidney injury (AKI), including its definition, classification systems, causes, biomarkers, treatment, and management. It provides a brief history of terms used to describe AKI and summarizes current classification systems. It also outlines causes of AKI, the advantages of various biomarkers for early detection, and general principles and indications for renal replacement therapy (RRT). Modalities of RRT including peritoneal dialysis, intermittent hemodialysis, slow low-efficiency dialysis, and continuous renal replacement therapy are compared.
Dr. Manan B. Shah presented on biomarkers for acute kidney injury. The presentation discussed the need for biomarkers to detect AKI earlier than serum creatinine, as creatinine levels typically rise only after 50% kidney function is lost. Several promising urinary biomarkers were described, including NGAL, KIM-1, IL-18, and cystatin C, which can indicate kidney injury earlier. The presentation proposed that a panel of biomarkers may help guide whether renal replacement therapy is needed for patients with AKI. Early detection and treatment of AKI using biomarkers could potentially improve outcomes by preventing or minimizing kidney injury.
Acute kidney injury (AKI) is common in hospitalized patients, occurring in 5-7% of hospitalized patients and up to 30% of ICU patients. Common causes include decreased renal perfusion due to factors like sepsis, surgery, heart or liver failure, nephrotoxic medications, or urinary tract obstruction. The definition of AKI involves an increase in serum creatinine of ≥0.3 mg/dL within 48 hours or ≥1.5 times baseline within 7 days. Management involves identifying and treating the underlying cause, maintaining fluid and electrolyte balance, and initiating renal replacement therapy in severe cases to prevent complications.
Acute kidney injury (AKI) is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days.It's most common in those who are critically ill and already hospitalized.
Acute kidney injury (AKI) is a growing problem with increasing incidence and mortality. The presentation defines AKI based on increases in serum creatinine and outlines guidelines for prevention and treatment including fluid management, glycemic control, nutrition, and initiation of renal replacement therapy. Long-term outcomes of AKI include increased risk of mortality, myocardial infarction, and chronic kidney disease. Common causes of AKI include sepsis, circulatory shock, nephrotoxic drugs, and surgery, while risk factors include advanced age, chronic diseases, and pre-existing kidney impairment.
The document discusses acute renal failure (ARF), also known as acute kidney injury (AKI). It defines ARF as the deterioration of renal function over hours to days, resulting in the kidneys' inability to excrete waste and maintain fluid/electrolyte homeostasis. The diagnostic criteria for ARF include a rapid rise in creatinine or reduction in urine output. ARF is classified based on urine output and can be prerenal, intrinsic renal, or postrenal in etiology. Anesthetic management of patients with ARF requires special considerations for fluid balance, electrolytes, drugs, and prevention of further kidney injury.
This document discusses acute kidney injury (AKI), including:
1. Definitions and classifications of AKI including RIFLE and AKIN criteria.
2. Biomarkers that can help detect AKI earlier than creatinine such as NGAL and cystatin C.
3. Treatment of AKI including conservative management, indications for renal replacement therapy (RRT), and modalities of RRT such as intermittent hemodialysis, continuous RRT, and peritoneal dialysis.
Acute kidney injury (AKI) is a common condition characterized by a sudden decline in kidney function. It affects 5-7% of hospital admissions and 30% of intensive care unit admissions. The top causes of AKI in India are diarrheal diseases, sepsis, malaria, drug toxicity, and hospital-acquired injuries. Treatment focuses on optimizing fluid status and hemodynamics, removing nephrotoxins if possible, and initiating renal replacement therapy as needed based on the underlying cause and severity of AKI.
1) A study examined the relationship between renal oxygen supply and demand in patients with and without acute kidney injury (AKI) after cardiac surgery.
2) The study found that patients with AKI had a higher slope in the relationship between renal oxygen consumption and glomerular filtration rate compared to controls, indicating impaired oxygen supply relative to demand.
3) This challenges the previous view that acute renal failure represents an "acute renal success" by reducing renal workload and preserving oxygen supply, and suggests AKI may actually involve renal hypoxic injury due to inadequate oxygen supply relative to demand.
This document discusses diuretics and their use in acute kidney injury (AKI). It begins with definitions of AKI and how it is measured. AKI, formerly called acute renal failure, is a clinical syndrome involving a decline in glomerular filtration rate and the accumulation of waste products. Measurement of renal function typically involves serum creatinine, though it has limitations.
The document then discusses the epidemiology of AKI, noting it occurs in 1-7% of hospitalized patients and carries high mortality, especially those requiring renal replacement therapy. High risk factors for AKI are discussed.
The bulk of the document focuses on diuretics - their definitions, classes including loop diuretics and mechanisms of
The document discusses acute kidney dysfunction (AKD) in intensive care unit patients. It defines AKD and describes the RIFLE criteria for classifying its severity. Common risk factors for AKD include hypovolemia, hypotension, and exposure to nephrotoxins. The document outlines prevention and treatment strategies and notes that mortality is high for patients requiring renal replacement therapy for AKD.
1. AKI (acute kidney injury) is defined as an acute decrease in kidney function over hours to days, previously known as acute renal failure. Biomarkers can help detect AKI earlier than creatinine.
2. Causes of AKI include decreased blood flow to the kidneys (pre-renal), direct injury to the kidneys (intrinsic renal), and urinary tract obstruction (post-renal). The most common causes are decreased blood flow due to shock, sepsis, or surgery.
3. Early nephrology consultation and avoiding nephrotoxins may help reduce mortality in AKI. Biomarkers, fluid management, and considering renal replacement therapy are important
This document discusses how drugs are eliminated by the kidneys and the mechanisms of renal injury caused by various drugs. It notes that many drugs can injure the kidneys through a few common mechanisms, such as altering renal blood flow or causing direct tubular toxicity. It provides examples of specific drugs that can cause these types of renal injuries. The document also discusses factors that influence drug dosing in patients with renal impairment and principles for safely prescribing drugs in such patients.
This document discusses the prevention and treatment of acute kidney injury (AKI) in intensive care units. It covers the pathophysiology and risk factors for AKI, current diagnostic criteria and biomarkers for early detection, and strategies for prevention including maintaining renal perfusion and avoiding nephrotoxins. The document also reviews renal replacement therapy modalities for AKI treatment, such as intermittent hemodialysis, slow low efficiency dialysis, hemofiltration and hemodiafiltration, and their definitions and comparisons. It concludes that prevention of AKI is better than treatment and emphasizes maintaining renal perfusion status and prompt treatment of sepsis.
IMPORTANCE: Optimal timing of initiation of renal replacement therapy (RRT) for severe acute kidney injury (AKI) but without life-threatening indications is still unknown.
OBJECTIVE: To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day all-cause mortality.
-AKI occurs in ≈ 7% of hospitalized patients , 36 – 67% of critically ill patients
-Causes of AKI were frequently categorized as prerenal, intrinsic renal, and postrenal.
This 12-year retrospective study from a single center evaluated the efficacy and safety of octreotide for the treatment of post-cardiac surgery chylothorax in children. The study found that octreotide resulted in complete resolution of chylothorax in 62% of patients and partial resolution in 34% of patients. Adverse effects were minor and transient. The authors concluded that octreotide is a promising therapeutic option for post-cardiac surgery chylothorax in children based on its efficacy and safety profile.
This study assessed the safety and efficacy of octreotide in treating post-cardiac surgery chylothorax in pediatric patients over 12 years. The study found that octreotide resolved chylothorax in 62% of patients, with complete resolution in 28% and partial resolution in 34%. Octreotide failed to resolve chylothorax in 38% who required thoracic duct ligation. Common minor side effects included transient hyperglycemia, abdominal distension, and tachycardia, but no patients discontinued octreotide due to side effects. The study concludes that octreotide shows promising benefits for treating post-cardiac surgery chylothorax with an acceptable safety profile.
This document provides an overview of Clostridium difficile infection (CDI) including its background, epidemiology, diagnosis, and management. CDI is caused by the bacterium C. difficile and is a common cause of infectious diarrhea, especially in healthcare settings. Diagnosis involves stool testing for toxins produced by C. difficile. Treatment depends on severity and includes metronidazole, vancomycin, or newer agents like fidaxomicin. Recurrent CDI may be treated with probiotics, rifaximin, or fecal microbiota transplantation.
Focal segmental glomerulosclerosis (FSGS) is a kidney disease characterized by scarring in the glomeruli. It can be primary/idiopathic or secondary to other causes like viral infections, drugs, ischemia, etc. Patients often present with nephrotic syndrome. Treatment involves controlling blood pressure and proteinuria with ACE inhibitors/ARBs initially. For idiopathic FSGS with nephrotic syndrome, the first line treatment is corticosteroids. Mycophenolate mofetil or calcineurin inhibitors can be used as steroid-sparing alternatives. For steroid-resistant FSGS, calcineurin inhibitors like cyclosporine A are recommended.
Critical Appraisal High Dose Vs Low Dose Caffeine Citrate in PretermsTauhid Bhuiyan
The document discusses two studies that compared high dose vs low dose caffeine citrate for treatment of apnea of prematurity. The 2015 study found:
1) High dose caffeine (40/20 mg/kg loading/maintenance) was not associated with higher rates of extubation failure or more frequent apnea episodes compared to low dose (20/10 mg/kg).
2) Both doses were well-tolerated with no significant differences in adverse effects.
3) The authors concluded higher doses may reduce extubation failure and apnea frequency without increased side effects. However, the study had a small sample size.
An earlier 2004 study found similar results, with high dose (80/20 mg/kg loading
IDA is the most common form of anemia worldwide, affecting approximately 50% of anemia cases. It results from prolonged negative iron balance in the body due to factors like inadequate iron intake, decreased absorption, increased demand, or blood loss. Diagnosis involves a complete history, physical exam, and lab tests showing low indicators of iron stores like serum ferritin and iron, along with an elevated TIBC. Treatment aims to replenish iron stores and typically consists of oral iron supplementation of 200mg elemental iron per day for 3-6 months.
Gastroesophageal Reflux in Preterm NeonateTauhid Bhuiyan
Gastroesophageal reflux (GER) is common in preterm neonates due to immature esophageal motility and lower esophageal sphincter relaxation. Diagnosis is challenging as symptoms are nonspecific. Tests include pH probes and multiple intraluminal impedance monitoring. Management follows a step-wise approach starting with non-pharmacological measures like body positioning and feeding strategies. If symptoms persist, alginate formulations, H2 receptor blockers, and proton pump inhibitors may be used though evidence for their efficacy is limited in preterms. Further research is needed to develop optimal evidence-based treatment guidelines for GER in this population.
This document discusses advanced non-small cell lung cancer and targeted therapies. It provides an overview of lung cancer epidemiology and risk factors like smoking. It also reviews molecular targets in NSCLC like EGFR, KRAS, and EML4-ALK and associated targeted therapies. The document outlines NSCLC diagnosis, staging, and management approaches including surgery, chemotherapy, and newer targeted therapies based on molecular profiling.
This document provides an overview of ST-elevation myocardial infarction (STEMI) including its epidemiology, etiology, pathophysiology, risk factors, diagnosis, and current guideline-directed management. It begins with definitions of STEMI and acute coronary syndrome. Key points include that STEMI accounts for 30-40% of myocardial infarctions in the US with a mortality rate of 8.8-18.4%. Risk factors include age, gender, family history, hypertension, diabetes, hyperlipidemia, and tobacco use. Diagnosis is made through ECG showing ST elevations and elevated cardiac biomarkers. Current treatment involves prompt reperfusion therapy with either primary percutaneous coronary intervention or fibrinolytic therapy to restore blood flow to the
1. Tauhid Ahmed Bhuiyan, PharmD
PGY-1 Resident
King Faisal Specialist Hospital & Research Center
Drug-Induced Acute Kidney Injury:
A Contemporary Overview and Prevention Strategies
King Faisal Specialist Hospital and Research Center (KFSHRC) is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing
pharmacy education. (UAN# 0833-0000-14-006-L01-P, 0833-0000-14-006-L01-T)
A Knowledge Based Activity
2. You have a heart murmur
and I’m starting to hear
your liver and kidneys
complain, too
3. Objectives
Familiarize with the background, epidemiology, and general
overview of acute kidney injury (AKI)
Recognize diagnostic criteria and laboratory parameters of AKI
Review pathogenic mechanisms and practical prevention
strategies of drug-induced AKI (DI-AKI)
Evaluate implications of computerized Clinical Decision Support
System (CDSS) for medication dosing in patients with renal
insufficiency
I do not have financial relationship and no actual or potential conflict of interest in relation to this activity
5. Renal System
Blood flow to
the glomeruli
Formation and processing
of ultrafiltrate
Excretion
Basic physiology:
Plasma filtration: 120
mL/min
http://patients.uroweb.org/kidney-ureteral-stones/symptoms
6. Epidemiology
In US, the reported incidence of AKI in all hospital admission:
1% (community-acquired)
7.1% (hospital-acquired)
About 5-20% of critically ill patients experience an episode of AKI
during the course of their illness
AKI receiving renal replacement therapy (RRT) has been reported in
4.9% of all admission to intensive-care unit (ICU)
Prognosis:
Mortality range ≈10%-80% depending on patient population
Lewington A., et al. Clinical practice guideline 2010; www.renal.org/guidelines
7. Definition
Clinical characterization:
Abrupt decrease in renal function
Accumulation of nitrogenous waste
products (azotemia)
Inability to maintain and regulate
fluid, electrolytes, and acid-base
balance
8. Clinical Course
Three distinct phases:
• Generally occurs over 1 to 2 days
• Characterized by progressive decrease in urine production
(UO <400mL/day)
• Lasts from days to weeks
• Worse prognosis than nonoliguric patients
• Strict fluid and electrolyte monitoring and management are
required
Oliguric
• Period of increased urine production over several days
immediately after oliguric phase
• Signals the initial repair of the kidney insult
• Patients may remain markedly azotemic for several days
Diuretic
• Occurs over several weeks to months depending on the
severity
• Signals the return to the patient’s baseline kidney function,
normalization of urine production
Recovery
10. Risk Factors
Age >75
Sepsis
Heart failure
Diabetes mellitus
Liver disease
Use of nephrotoxic agents/medications
Urinary tract obstruction
11. Objectives
Familiarize with the background, epidemiology, and general
overview of acute kidney injury (AKI)
Recognize diagnostic criteria and laboratory parameters of AKI
Review pathogenic mechanisms and practical prevention
strategies of drug-induced AKI (DI-AKI)
Evaluate implications of computerized Clinical Decision Support
System (CDSS) for medication dosing in patients with renal
insufficiency
12. Diagnosis
Clinical assessment
Comprehensive history and physical examination
Volume status
AKI risk factors
Assessment of kidney function
RIFLE vs. AKIN ?
Laboratory findings
13. Assessment of Kidney Function
Acute Kidney Injury Network
Stage Serum Creatinine (Scr)
Urine Output
(UO)
1
Scr increase 1.5 to 2 fold OR ≥26.5 µmol/L
from baseline
<0.5 mL/kg/h ≥6 hours
2 Scr increase >2 to 3 fold from baseline
<0.5 mL/kg/h ≥12
hours
3
Scr increase >3 fold from baseline OR
≥354 µmol/L with an acute rise of at least
>44 µmol/L OR on RRT
<0.3 mL/kg/h ≥24
hours OR anuria ≥12
hours
This staging system is accepted by Kidney Disease Improving Global Outcome
(KDIGO) clinical practice guideline of AKI
−Diagnosis
Kellum JA., et al. Kidney International Supplements 2012; 2:124-138
14. Assessment of Kidney Function
Risk, Injury, Failure, Loss, and ESRD
Serum Creatinine (Scr) Urine Output (UO)
R
Scr increase 1.5 fold OR GFR
decrease >25%
<0.5 mL/kg/h ≥6 hours
I
Scr increase 2 fold OR GFR
decrease >50%
<0.5 mL/kg/h ≥12 hours
F
Scr increase 3 fold OR GFR
decrease >75%; Scr >354 µmol/L
with an acute rise >44 µmol/L
<0.3 mL/kg/h ≥24 hours OR
anuria ≥12 hours
L
Persistent acute renal failure =
complete loss of kidney function
>4 weeks
E ESRD >3 months
−Diagnosis
Kellum JA., et al. Kidney International Supplements 2012; 2:124-138
15. Laboratory Evaluation
Quantitative measurements
Urine output: direct evaluation of kidney function
Measured over 24hrs as I/O’s
Glomerular Filtration Rate (GFR)
Cockcroft-Gault vs. MDRD (Modification of Diet in Renal Disease)
Qualitative measurements
Urinanalysis (UA): GOLD standard
Specific to differentiating AKF
−Diagnosis
16. Laboratory Evaluation Cont.
UA
Component
Prerenal
Azotemia
Acute Tubular
Necrosis
Postrenal
Obstruction
Urine
Na+(mEq/l)
<20 >40 >40
FENa+ <1% >2% >1%
Urine/plasma
creatinine
>40 <20 <20
Specific gravity >1.010 <1.010 Variable
Urine
osmolality
(mOsm/kg)
Up to 1200 <300 <300
[Urinary indices in acute kidney failure]
Donald FB. Acute Renal Failure. Applied Therapeutics: The Clinical Use Of Drugs. 2009;30:1-11
17. Objectives
Familiarize with the background, epidemiology, and general
overview of acute kidney injury (AKI)
Recognize diagnostic criteria and laboratory parameters of AKI
Review pathogenic mechanisms and practical prevention
strategies of drug-induced AKI (DI-AKI)
Evaluate implications of computerized Clinical Decision Support
System (CDSS) for medication dosing in patients with renal
insufficiency
19. Epidemiology
Drug-induced kidney injury causes
7% of all drug toxicities
18%—20% of AKI in hospitals
1%—5% of nonsteroidal anti-inflammatory drugs (NSAIDs) users in
community
Most implicated medications
Aminoglycosides (AG) Amphotericin B (Amp B) Radiocontrast media
Angiotensin Converting
Enzyme Inhibitor (ACEI)
Angiotensin Receptor
Blockers (ARBs)
NSAIDs
Howell HR., et al. US Pharm 2007;32(3): 45-50
Lewington A., et al. Clinical practice guideline 2010; www.renal.org/guidelines
21. Altered Intraglomerular
Hemodynamics
Pathogenesis is via reducing the
volume OR pressure OR both
of blood delivered to the kidney
Common medications
NSAIDs
ACEI, ARBs
Calcineurin inhibitors (e.g.
cyclosporine, tacrolimus)
Prostaglandins (PGs) Angiotensin II
Vasodilation Vasoconstriction
http://biologigonz.blogspot.com/2010/02/mengenal-ginjal.html
−Functional
22. In most circumstances, do not pose significant risk to patients with
normal renal function
In patients with decreased renal perfusion
Inhibition of PGs vasoconstrictions ↓ blood flow & ischemic injury
Indomethacin poses the highest risk
Altered Intraglomerular
Hemodynamics−NSAIDs
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
23. Frequent cause of AKI in patient with
Severe renal artery stenosis
Chronic kidney disease (CKD)
Congestive heart failure
“Double-edged sword”
Exerts a predictable dose-related reduction in GFR
Nephrotoxicity is due to vasoconstrictive effect on efferent arteriole in
the absence of “absolute” or “effective” circulatory volume
Altered Intraglomerular
Hemodynamics−ACEI/ARBs
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
24. Altered Intraglomerular
Hemodynamics−Calcineurin inhibitors
Despite improved allograft half-life and patient survival
Nephrotoxicity often limits the clinical use
Severity
Acute (reversible)
Chronic (irreversible)
Mechanism of nephrotoxicity has not been clearly established
Experimental model
Exerts preglomerular vasoconstriction significant reduction of renal plasma
flow and GFR tissue ischemia
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
25. Prevention Strategies
Drugs Practical Prevention
NSAIDs,
ACEIs/ARBs
Use analgesics with lesser PG activity
(e.g. acetaminophen, aspirin)
Avoid ACEIs/ARBs in patients with
hypovolemia or bilateral renal artery
stenosis
Calcineurin
inhibitors
Use lowest effective dose
For cyclosporine
Use micronized form
Avoid strong CYP3A4 inhibitors
Calcium channel blockers may
ameliorate or provide early protection
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
Guo X., et al. CLEV CLIN J MED. 2002;69(4):289312
27. Acute Tubular Necrosis (ATN)
Most common drug-induced kidney disease in the inpatient settings
Proposed mechanisms of toxicity
Impairing mitochondrial function
Interfering with tubular transport
Increase oxidative stress or forming free radicals
Common medications
Antibiotics: Amp B, AGs , Vancomycin
Antivirals: Adefovir, Cidofovir, Tenofovir, Foscarnet
Antineoplastics: Cisplatin
Bisphosphonate: Zoledronate
Radiocontrast media
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
Naughton CA., et al. Am Fam Physician. 2008;78(6)743-50
−Intrinsic
28. Approximately 80% of patients experience some renal dysfunction with
amp B treatment (> 4g dose)
Proposed pathogenic mechanisms
Direct proximal and distal tubular toxicity
Afferent arterial vasoconstriction
Risk factors
Pre-existing renal insufficiency
Volume depletion
Hypokalemia
High average daily dose
Diuretic use
Concomitant nephrotoxin use
Rapid infusion
Acute Tubular Necrosis−Amp B
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
29. Variable incidence of nephrotoxicity
1.7%—58%
Proposed pathogenic mechanisms
Cationic charge binding and uptake
by tubular epithelial cells disrupt
normal cellular function cellular
death
Stimulate calcium sensing receptor
on the apical membrane induction
of cellular signaling and cell death
Risk factors
Prolonged therapy
Trough concentration >2 μg/mL
(except amikacin)
Previous AG therapy (recent)
Concurrent use of other
nephrotoxins
Patient related factors
Acute Tubular Necrosis−AGs
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
Relative toxicities (in descending order)
Neomycin > Gentamycin > Tobramicin > Amikacin > Streptomycin
30. Mostly contributed to the early
formulations
“Mississippi mud” (~70% pure)
Variable incidence of
nephrotoxicity
Monotherapy: 5-7%
Concomitant aminoglycoside:
7-35%
Proposed mechanisms
Stimulates oxygen consumption
and ATP in proximal tubule
Oxidative stress damages
glomeruli and proximal tubule
Independent risk factors
Concomitant nephrotoxins use
Age
Duration of therapy
Trough >15 μg/mL
Informative reading: “Vancomycin nephrotoxicity: myths and facts”
Acute Tubular Necrosis−Vancomycin
Rybak M, et al. Am J Health‐Syst Pharm. 2009;82-98
31. Third leading cause of inpatient AKI
Associated with a high (34%) inpatient mortality rate
Complex pathogenic mechanism
Started with renal vasodilation and an osmotic diuresis to intense
vasoconstriction ischemia
Risk factors
Underlying diabetic nephropathy or chronic renal insufficiency
Age >75 years
Congestive heart failure
Volume depletion
Patient receiving aggressive diuretic regimens
Acute Tubular Necrosis−Radiocontrast
media
Donald, Brophy F. Acute Renal Failure. Applied Therapeutics: The Clinical Use of Drugs. 2009; 30-41
32. Drugs Practical Prevention
Amp B
Use sodium loading before and after therapy initiation
Use lipid-based formulation
Consider alternate day administration or continuous
infusion over 24h
Consider alternative agents in high-risk patients with renal
impairment
AGs
Avoid use if possible in high-risk population
Limit prolonged therapy
Use extended interval dosing
Adjust dosage for renal function
Maintain trough levels ≤ 1 μg/mL
Prevention Strategies
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
Guo X., et al. CLEV CLIN J MED. 2002;69(4):289312
33. Prevention Strategies
Drugs Practical Prevention
Vancomycin
Avoid concomitant nephrotoxins
Monitor trough levels
Radiocontrast
media
Consider hydration with normal saline and sodium
bicarbonate before and after procedure
Administration of diuretics such as, mannitol and
furosemide should be avoided
Monitor renal function 24-48 h post-procedure
Consider N-acetylcysteine therapy before procedure
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
Guo X., et al. CLEV CLIN J MED. 2002;69(4):289312
35. Acute Interstitial Nephritis (AIN)
Cause of up to 3% of all AKI cases
Etiology
Drugs (antibiotics responsible for one-third of these cases) – 75%
Infections – 5%-10%
Tubulointerstitial nephritis and uveitis (TINU) syndrome – 5%-
10%
Autoimmune/Systemic disease (e.g. sarcoidosis, SLE) – 5%-10%
Inflammatory changes
Glomerulus, renal tubular cells, and the surrounding interstitium
Fibrosis and renal scarring
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
−Intrinsic
36. Acute Interstitial Nephritis (AIN)
Common medications
NSAIDs
Penicillin (methicillin) and cephalosporin
Lithium
Rifampin
Quinolones
Diuretics (loops, thiazides)
Hydralazine
Interferon-alfa
May need kidney biopsy to confirm diagnosis
Pannu N., et al. Crit Care Med. 2008;36(4):216-22
37. Prevention Strategies
Drugs Practical Prevention
NSAIDs
Avoid long term use, particularly of more than one analgesic
Use alternate agents in patients with chronic pain
Lithium
Avoid volume depletion
Monitor drug levels
Naughton CA., et al. Am Fam Physician. 2008;78(6)743-50
39. Crystal Nephropathy
Renal impairment results from
drugs that produce crystals
that are insoluble in human
urine
Pathogenic mechanism
Precipitation of crystals in distal
tubular lumen obstruct urine
flow and elicit interstitial
reaction
Common medications
Antibiotics: Ampicillin,
Ciprofloxacin, Sulfonamides
Antivirals: Acyclovir, Foscarnet,
Ganciclovir, Indinavir,
Methotrexate
Triamterene
Risk factors
Volume depletion
Underlying renal insufficiency
Excessive dose
Intravenous (IV) administration
Naughton CA., et al. Am Fam Physician. 2008;78(6)743-50
−Postrenal
40. Prevention Strategies
Drugs Practical Prevention
Acyclovir,
methotrexate, sulfa
antibiotics,
triamterene
Discontinue or reduce dose
Ensure adequate hydration
Establish high urine flow
Administer orally
Naughton CA., et al. Am Fam Physician. 2008;78(6)743-50
41. Goals
Short term: stop the progression of kidney damage
Long term: restore normal kidney function
In general
Stopping the offending agent
Avoid concomitant nephrotoxins
Maintain adequate hydration
RRT
Management of DI-AKI
42. General Preventative Measures
Assess baseline renal function using MDRD
Dose adjustment based on renal function
Correct modifiable risk factors of nephrotoxicity before
initiation of drug therapy
Ensure adequate hydration before and during therapy with
potential nephrotoxins
Use equally effective non-nephrotoxic drugs whenever possible
43. Objectives
Familiarize with the background, epidemiology, and general
overview of acute kidney injury (AKI)
Recognize diagnostic criteria and laboratory parameters of AKI
Review pathogenic mechanisms and practical prevention
strategies of drug-induced AKI (DI-AKI)
Evaluate implications of computerized Clinical Decision Support
System (CDSS) for medication dosing in patients with renal
insufficiency
44. Clinical Decision Support System
(CDSS)
First introduced in clinical practice in the 1970s
Designed to improve clinical decision making at the point
of care
Implementation provided
Improved medication related clinical outcomes, and
Reduced medication related errors and adverse events
45. Guided Medication Dosing for Inpatients
With Renal Insufficiency
Study objective
Incorporation of guided dosing algorithms for inpatients with renal
insufficiency into existing computerized physician order entry system
would result in:
Larger proportion of appropriate dosing and frequency orders
Shorter hospital length of stay (LOS)
Lower cost
Lower frequency of worsening renal function
Study design
Study population: all patients admitted to the medical, surgical, neurology,
and obstetrics and gynecology services at Brigham and Women’s Hospital
between September 1997 and April 1998
Study periods: 4 alternating 8-weeks blocks of intervention and control
subperiods
Chertow GM., et al. JAMA. 2001;286(22):2839-44
49. Authors’ Conclusion
“The application intervention led to a statistically
significant and clinically meaningful increase in the
proportion of prescriptions considered appropriate for
inpatients with renal insufficiency”
Chertow GM., et al. JAMA. 2001;286(22):2839-44
50. Pharmacist Role
Vigilance
Early intervention
Identify patient and drug related risk factors
Recommend specific dosing or safer alternatives
Suggest and help implement CDSS
51. Summary
AKI is an abrupt decrease in renal function that leads to azotemia, and
imbalance of fluid, acid-base, and electrolytes
Almost all cases of AKI are hospital-acquired and drug related
etiologies are being the most common
Diagnosis of AKI is based on clinical presentations, assessment of
kidney function, and laboratory findings especially UA
Pathogenic mechanisms of DI-AKI include altered intraglomerular
hemodynamics, ATN, AIN, and crystal nephropathy
52. Summary Cont.
Management of DI-AKI is common across all drugs:
Correcting volume and electrolyte depletion
Stopping the offending agents, and
Maintaining adequate hydration
Implementation of CDSS had shown to have clinically meaningful
appropriate dose and frequency of drug orders, and decrease length of
stay in patients with renal insufficiency
53.
54. References
Pannu N., Nadim MK. An overview of drug-induced acute kidney injury. Crit Care Med.
2008;36(4):216-223
Donald FB. Acute Renal Failure. In: Koda-kimble MA., Young LY., Alldredge BK., et al., ed. Applied
Therapeutics: The Clinical Use Of Drugs. Baltimore, Lippincott Williams & Wilkins; 2009: 30(1-11)
Guo X., Nzerue C. How to prevent, recognize, and treat drug-induced nephrotoxicity. Clev Clin J Med.
2002; 69(4):289-312
Lewington A., Kanagasundaram S. Module 5 - acute kidney injury clinical practice guideline. UK renal
association. www.renal.org/guidelines. Published March 08, 2011. Accessed January 12, 2014
Howell HR., Brundige ML. et al. Drug-Induced Acute Renal Failure. US Pharm. 2007;32(3):45-50
Schetz M., Dasta J., et al. Drug-induced acute kidney injury. Curr Opin Crit Care. 2005;11:555-65
Singh NP., Ganguli A., et al. Drug-induced Kidney Disease. JAPI. 2003; 51:970-79
Rybak M, Lomaestro B, Rotschafer JC., et al. Therapeutic monitoring of vancomycin in adult patients:
A consensus review of the American Society of Health-System Pharmacists, the Infectious Disease
Society of America, and the Society of Infectious Disease Pharmacists. Am J Health-Syst Pharm. 2009;
66: 82-98
Kellum JA., Aspelin P., Barsoum RS., et al. Clinical practice guideline for acute kidney injury. Kidney
International Supplements. 2012; 2:124-138
Chertow GM., Lee J., Kuperman GJ., et al. Guided medication dosing for inpatients with renal
insufficiency. JAMA 2001;286(22):2839-44
56. Question 1
What is the CORRECT sequence of clinical
course of AKI?
a) Recovery Diuretic Oliguric
b) Diuretic Recovery Oliguric
c) Oliguric Diuretic Recovery
d) None of the above
57. Question 2
How do NSAIDs alter intraglomerular
hemodynamics?
a) Vasoconstriction of afferent arteriole by blocking PG
activity
b) Vasodilation of efferent arteriole by blocking
Angiotnesin II
c) Vasoconstriction of efferent arteriole by blocking
Angiotnesin II
d) Vasodilation of afferent arteriole by blocking PG
activity
58. Question 3
Which of the following pharmacologic agents
has been shown to decrease radiocontrast media
induced AKI when given concurrently with other
fluid therapies?
a) N-acetylcysteine
b) Furosemide
c) Mannitol
d) Calcium channel blockers
59. Question 4
Which of the following aminoglycosides have
relatively the highest risk of nephrotoxicity?
a) Neomycin
b) Gentamycin
c) Amikacin
d) Streptomycin
60. Question 5
Prophylactic measures to reduce amphotericin B
induced nephrotoxicity include:
a) Ensure adequate hydration before and after therapy
initiation
b) Use lipid-based formulation
c) Consider alternate day administration or continuous
infusion over 24h
d) All of the above
Editor's Notes
Explain the reason for choosing this Topic
Forced me to learn about the topic since never presented before
One of the preventable medication related adverse event
Differntiate AKI vs. ARF (adaptation of AKI by nephrology)
Briefly talk about the anatomy of the kidney and nephron
Normally, Plasma filtration:120 ml/minute
Intraglomerular pressure autoregulation
Prostaglandin (PG)
Angiotensin II
Clearly explain each stage, link the UO to the clinical course described before
MDRD, currently the most widely used method for estimation of glomerular filtration rate (eGFR) provided by the MDRD. In patients with a GFR lower than 60 ml per minute per 1.73 m2, the MDRD method has been shown to be superior to the CG method
Know exactly the justification of the over and under estimation of CG equation
There’s a wonderful review article written by a clinical pharmacy in Am Fam Physician in 2008 differentiating the source or pathogenic mechanism of drug induced
There’s a wonderful review article written by a clinical pharmacy in Am Fam Physician in 2008 differentiating the source or pathogenic mechanism of drug induced
Proximal tubular cells (most vulnerable)
Role of concentrating and reabsorbing filtrate
Rybak
Excreted as unchanged form ~80%−90%
There’s a wonderful review article written by a clinical pharmacy in Am Fam Physician in 2008 differentiating the source or pathogenic mechanism of drug induced
From uptodate (acute interstitial nephritis)
There’s a wonderful review article written by a clinical pharmacy in Am Fam Physician in 2008 differentiating the source or pathogenic mechanism of drug induced
Emphasize modifiable risks of nephrotoxicity
Explain the Intervention and evaluation here in details…..