Therapeutics

• The different functions of the kidneys include filtering blood, regulating blood pressure, and producing hormones.
• Methods to measure renal function include blood urea nitrogen (BUN), serum creatinine (SCr), and urine output.
• Acute kidney injury (AKI) is defined as an abrupt decrease in kidney function.
• Chronic kidney disease (CKD) is characterized by a slow decline in kidney function over time.
• End stage renal disease (ESRD) is the final stage of CKD, requiring renal replacement therapy.
• Drug-induced kidney disease (DIKD) is an adverse functional or structural change to the kidney after administration of a drug, chemical or biological product.
• Risk factors for drug-induced kidney injury include pre-existing kidney disease, certain medications, and medical conditions.
• Potential role for a pharmacist in CKD screening includes using screening tools such as those available in Ontario, Alberta, Manitoba, BC Renal Agency, Saskatchewan, and others.
• A CKD Checklist includes controlling blood pressure and managing CVD (ACEi/ARB, statin, ASA), reducing albuminuria (ACEi/ARB, SGLT2i, controlling blood glucose, weight loss, lowering dietary sodium intake), managing diabetes (individualizing A1C targets, adjusting medication doses as renal function declines), limiting nephrotoxins and adjusting medication doses (sick-day medication management, avoiding/limiting NSAID use, reviewing use of over-the-counter medications and herbals), and monitoring for and managing CKD complications (PTH, serum phosphorus, calcium, vitamin D, hemoglobin, iron st
• The major mechanisms by which drugs can cause kidney injury include nephrotoxicity, tubular toxicity, and interstitial toxicity.
• Common drugs that can cause kidney injury include acetaminophen, aminoglycosides, cisplatin, and cyclosporine, tacrolimus.
• Drug dosing regimens for patients with renal impairment should be designed appropriately.
• Drug-induced kidney disease can often be reversible.
• The presentation of drug-induced kidney disease can include metabolic acidosis, changes to serum electrolytes, proteinuria, pyuria, hematuria, rise in SCr (or reduced eGFR), decreased (or increased) urine output, symptoms of malaise, anorexia, nausea, vomiting, volume overload, and symptoms of kidney failure.
• Examples of drug-induced kidney disease include acute tubular necrosis, acute interstitial nephritis, glomerulonephritis, obstructive uropathy, and others.
• The mechanisms of drug-induced nephrotoxicity can include:

  • changes to renal blood flow (pre-renal)
  • direct kidney injury/damage (intra-renal)
  • acute tubular necrosis
  • interstitial nephritis
  • glomerulonephritis
  • obstructive uropathy (post-renal)
  • and others.
• Changes to renal blood flow (pre-renal) can be hemodynamically mediated, changes to renal blood flow can be acute decreases in GFR, and risk factors for changes to renal blood flow include heart failure, renal artery stenosis, volume depletion, CKD, and other nephrotoxins.
• Management of changes to renal blood flow (pre-renal) includes recognizing and addressing other risk factors, starting low, going slow, monitoring serum drug concentrations (where applicable), monitoring SCr, BUN, electrolytes, watching for concurrent diuretics, hypotensive agents, and managing concurrent medical conditions.
• Management of Acute tubular necrosis (ATN) includes discontinuing the nephrotoxin, maintaining adequate hydration, and monitoring SCr, BUN, and electrolytes.
• Obstructive Nephropathy is a type of direct kidney injury/damage (intra-renal) caused by blockage with precipitated drug crystals, tissue-degradation products released by drug, or precipitated calcium phosphate.
• Management of Obstructive Nephropathy includes high urine volume and urinary alkalinization.
• Osmotic nephropathy is a type of direct kidney injury/damage (intra-renal) caused by osmotic agents such as mannitol, IV immunoglobulins, and drug vehicles such as PEG or sucrose.
• Pre-existing CKD, older patients, and multiple nephrotoxic drugs are at risk for developing direct kidney injury/damage (intra-renal).
• Drug dosing in renal impairment is a crucial aspect of managing direct kidney injury/damage (intra-renal).
• Acute Interstitial Nephritis is a type of direct kidney injury/damage (intra-renal) associated with immune-mediated kidney injury and is generally idiosyncratic and inflammatory.
• Management of direct kidney injury/damage (intra-renal) includes discontinuing the nephrotoxin, maintaining adequate hydration, and monitoring SCr, BUN, and electrolytes.
• Chronic Interstitial Nephritis is a type of direct kidney injury/damage (intra-renal) that is progressive and irreversible.
• Management of Acute Interstitial Nephritis includes discontinuing the nephrotoxin, providing corticosteroids, and monitoring SCr, BUN, and symptoms of AIN for improvement.
• Nephrotoxic drugs that can cause direct kidney injury/damage (intra-renal) include Aminoglycosides, Radiographic contrast media, Cisplatin, Amphotericin B, Calcineurin inhibitors (cyclosporine, tacrolimus), Adefovir, cidofovir, tenofovir, Zoledronate.
• Direct kidney injury/damage (intra-renal) includes Acute tubular necrosis, Interstitial nephritis, and Glomerulonephritis.
• Renal vasculitis or thrombosis is a type of direct kidney injury/damage (intra-renal) caused by drugs such as hydralazine, allopurinol, and propylthiouracil.
• Glomerular disease is a type of direct kidney injury/damage (intra-renal) caused by drugs such as lithium and interferon-α and β.
• Acute tubular necrosis (ATN) is a type of direct kidney injury/damage (intra-renal) caused by ischemic or toxic cellular injury to renal tubules and is generally dose-dependent.
• Drug dosing in renal impairment should not be based solely on drug volume of distribution by the kidney after correction for creatinine (VdkC).
• Drug dosing in renal impairment should not be based solely on drug clearance by the kidney after correction for creatinine (ClkC).
• Changes in drug distribution and reduced elimination have the most clinical relevance.
• Drug dosing in renal impairment should be based on the individual patient's CrCl.
• Drug dosing in renal impairment should not be based solely on drug half-life by the kidney after correction for creatinine (t1/2kC).
• Drug accumulation of clinical relevance generally occurs if > 50% of drug (or active metabolite) are eliminated by the kidney.
• Generally if CrCl is ≥60mL/min, empiric dose adjustments are not required.