Providing Home Infusion for the Patient with Compromised Renal Function Carol J. Rollins, MS, PharmD, BCNSP Assistant Director, Clinical Pharmacy Services University Medical Center, Tucson, Arizona Top 5 Things to Know for CE: 1. Make sure your BADGE IS SCANNED each time you enter a session, to record your attendance. 2. Carry the Evaluation Packet you received on registration with you to EVERY session. 3. If you re not applying for CE, we still want to hear from you! Your opinions about our conference are very valuable. 4. Pharmacists and Nurses need to track their hours on the Statement of Continuing Education Certificate form as they go. 5. FOR CE: At your last session, total the hours and sign your Statement of Continuing Education Certificate form. Keep the PINK copy for your records. Place the YELLOW and WHITE copies in your Evaluation packet Make sure an evaluation form from each session you attended is completed and in your Evaluation packet Put your name on the outside of the packet, seal it, and drop it in the drop boxes in the NHIA registration area at the convention center Conflict of Interest I have no conflict of interest to declare related to this presentation. 1
Objec1ves Discuss the continuum of renal impairment from insufficiency to failure. Describe the impact of renal function on management of home infusion therapies. List the home infusion therapies with the potential to impact renal function. Compromised Renal Func1on When is renal function compromised? How should renal compromise be measured? Estimated CrCl (Cockcroft-Gault) Overestimates true GFR by 10-20% Active tubular secretion of Cr inhibited by trimethoprim Greater overestimation with poor GFR Measured CrCl (24 hr urine) Glomerular Filtration Rate (GFR) Equation from Modification of Diet in Renal Disease (MDRD) Estimated GFR (egfr) Used to quantify GFR and detect or stage chronic kidney dz Compromised Renal Func1on How long has renal function been compromised? Was it present on admission to home care? Did it develop while on home care? Did it develop or worsen because of the infusion therapy? Was the change in renal function predictable? What is the degree of renal compromise? Is this stable? How rapidly are changes occurring? Is adjustment to therapy required? Dose or frequency of dosing for the current therapy? Change to a different therapy? 2
Efferent Arteriole: Blood leaves the kidney Renal Physiology Afferent Arteriole: Blood enters the glomerulus to be filtered U R I N E 3 Glomerular Filtra1on Efferent Arteriole: Blood leaves glomerulus Hydrostatic pressure within the glomerulus pushes (filters) waste across the capillary 2 filtering system 1 Hydrostatic pressure Afferent Arteriole: Blood enters glomerulus 4 Bowman s Capsule Ultrafiltrate enters proximal renal tubule The Con1nuum of Renal Impairment: Acute Failure Incidence ~ 25% in ICU ~ 2-5% in general medicine Less than 1% occurs at home High morbidity Contributing factors may be modified Have you identified potential contributing factors? Have these factors been addressed? Patient vs physician Is monitoring adequate? 3
ARF in the Home SeEng 75% is prerenal azotemia Inadequate blood flow to kidneys Low intravascular volume: dehydration, diuresis Low effective circulating volume: ascites, CHF Medications affecting renal blood flow Generally reversible Correct the underlying problem quickly 25% from other causes Acute tubular necrosis (ATN) Acute interstitial nephritis Glomerulonephritis Obstruction ARF in the Home SeEng ATN Prolonged renal ischemia Direct toxicity to renal tubular cells Aminoglycosides, amphotericin B, cisplatin, pentamidine Acute interstitial nephritis (AIN) Hypersensitivity reaction; idiopathic BUN, SCr rise 3-5 days after 2 nd exposure Systemic s/sx may be present: fever, rash, eosinophilia Tubular basement membrane affected Medications implicated: NSAIDs, β-lactam abx, rifampin, ciprofloxacin, diuretics (loop and thiazide) ARF in the Home SeEng Glomerulonephritis Rare, idiopathic; presents as nephrotic syndrome Immune complex formation or autoantibodies Vasculitis damages glomerular capillaries Medications implicated: Gold, NSAIDs, rifampin, lithium Obstruction due to nephrolithiasis Crystals form due to supersaturation of urine Urine ph may be a contributing factor Factors increasing drug concentration in urine Medications implicated: Sulfonamides, acyclovir, amoxicillin, ciprofloxacin, foscarnet, methotrexate, triamterene, indinavir 4
Drug Crystals in Urine Acyclovir Amoxicillin (Bright Field) Drug Crystals in Urine Indinavir Sulfonamide Drug Crystals in Urine Sulphadiazine Sulphadiazine (Polarized Light) 5
Crystals in Urine Ascorbic Acid (Vitamin C) (Polarized Light) Calcium Oxalate Risk Factors for Drug- Induced Acute Renal Compromise Pre-existing chronic kidney disease Advanced age Diabetes Hypoperfusion Evaluate fluid intake and hydration status Dose and/or duration of therapy High doses Long duration often seen for home infusion Signs of Declining Renal Func1on Weight gain Fluid retention Reduced urine output Increased lab values Serum Creatinine in ARF: Increase > 0.5 mg/dl if Cr < 2.5 or > 1 mg/dl if Cr > 2.5 SCr vs GFR BUN K +, Phos, Mag Drug levels aminoglycosides, vancomycin 6
The Con1nuum of Renal Impairment: Insufficiency Less than optimal renal function May be in recovery from recent ARF Early to mid stage of chronic kidney disease (CKD) Not ESRD Requires careful evaluation of therapy Is the drug eliminated through the kidneys? Adjust the dosing regimen dose, frequency Are metabolites eliminated through the kidneys? Potential for toxicity The Con1nuum of Renal Impairment: CKD Progressive decline in renal function Kidney damage is present Proteinuria, albuminuria or microalbuminuria A continuum leading to irreversible damage of the nephrons resulting in no effective renal function Stages are based on egfr Stages 1 and 2: Normal to mild decrease in egfr Stages 3 to 4: egfr < 60 ml/minute/1.73 m 2 > 3 mo. Stages 4 to 5: egfr < 30 ml/minute/1.73 m 2 The Con1nuum of Renal Impairment: CKD ESRD CKD Stage 4 to 5 egfr < 30 ml/minute/1.73 m 2 Most medications will require dosage adjustment Few antibiotics do NOT require adjustment Nafcillin, cefriaxone Progresses to ESRD ESRD = Failure Renal replacement therapies Type of RRT: Peritoneal? Home HD? Intermittent HD? How frequent? Continues until kidney transplant or death 7
Disease Processes Contribu1ng to Altered Renal Func1on What is the patient s medical history? Causes of CKD and ESRD Diabetes (44%) Hypertension (27%) Kidney disease chronic glomerulonephritis (8%) Other causes Polycystic kidney disease, AIDS nephropathy, SLE, Urological conditions, Multiple myeloma Medica1ons Contribu1ng to Altered Renal Func1on Medication history All medications and dietary supplements Chronic medications OTC and Rx Analgesics Analgesic nephropathy Chronic ingestion of APAP or ASA with caffeine or codeine Cumulative dose of 1-2 kg APAP NSAIDs Medications affecting renal blood flow Decreased Glomerular Filtra1on Efferent Arteriole Vasodilation decreases hydrostatic pressure ACE inhibitors ARBs Most CCB Glomerulus Hydrostatic Pressure Afferent Arteriole Ultrafiltrate to proximal tubule Bowman scapsule Vasoconstriction decreases blood flow NSAIDs (PGE 2, PGI 2 vasodilation) CSA, tacrolimus Amphotericin B Vasopressors: phenylephrine, NE 8
Site of Diure1c Ac1on Physiology DCT = Distal Convoluted Tubules PCT = Proximal Convoluted Tubules TAL = Thick Ascending Loop Impact of Renal Compromise: Adjustment of Medica1on Accumulation of the parent drug Many medications are eliminated via the kidneys Adjust dose and/or dosing frequency Toxic metabolites may accumulate Use a therapeutic alternative Toxic carrier molecule Check the entire dosage form Use a therapeutic alternative Impact of Renal Compromise: Fluid and Electrolytes Impact depends on degree of renal compromise Increased risk of fluid retention May require restriction of fluid volume Increased risk of electrolyte abnormalities Increased K+, phos, mag Decreased sodium, bicarb Acid-base alterations 9
Impact of Renal Compromise: Monitoring Renal function Baseline Periodically during therapy How often? Clinical indicators Urine output Lab values- SCr, BUN, drug levels Risk factors Hydration status OTC medications Therapies Impac1ng Renal Func1on An important distinction Therapies causing altered renal function ARF drug vs pt condition (dehydration) CKD generally require longer term therapy Therapies requiring adjustment for renal function Many medications are eliminated via the kidneys Adjust dose and/or dosing frequency High risk therapies vs High risk patient Therapy: Amphotericin B, Cyclosporin, Tacrolimus Patient: Older, pre-existing renal compromise, at risk of reduced intravascular volume Summary Carefully assess baseline renal function prior to initiation of infusion therapy in the home Assess risk of renal complications and monitor accordingly ARF can occur in the home not common Monitor for S/Sx changing renal function CKD in the home infusion pt Dosage adjustment of many infusion drugs OTC and Rx drugs may alter egfr or SCr Monitor pt for S/Sx drug accumulation/toxicity 10
Case: 79 y.o. F w/ Ovarian Ca S/P Chemotherapy 7 days prior to D/C home Carboplatin and paclitaxel Vancomycin for GPC in blood, suspect Staph Received 2 doses of 1 gm Q 12h prior to discharge Objective data Ht: 62 inches Wt: 35kg (70% IBW) BMI: 14 SCr: 1 mg/dl (admit); 1.4 mg/dl (1 day before D/C) Other data I/O: 1510/2425 (1975 stool) 3 days before D/C home 1675/2195 (1865 stool) 2 days before D/C home 2400/1100 (500 stool) 1 day before D/C home Case: 79 y.o. F w/ Ovarian Ca What are the pt risks for renal compromise? Age Medications Vancomycin dose too high Hydration status Other medications not given Is the pt s renal function compromised? SCr = 1 mg/dl baseline What would you expect given age and BMI? SCr = 1.4 mg/dl 1 day before D/C (no labs D/C date) Outcome: pt readmitted 2 days after D/C home SCr 2.9 mg/dl and no urine output x 24 hr CE Ques1ons 1. True-False Renal adjustment of medication doses is based on estimated creatinine clearance using Cockcroft-Gault, not on the equation for GFR. 2. Which of the following increase the risk of acute renal failure? a. Short-term use of a β-lactam antibiotic b. Age range 1-5 years c. Low blood pressure from hypoperfusion d. Male gender 11
CE Ques1ons 3. Which of the following will reduce the risk of acute renal failure in the home setting? a. Adequate hydration b. Sequential administration of medications c. Dilution of IV medications in D5W d. Using the oral dosage form rather than IV 4. True-False Most antibiotics require dosage adjustment based on renal function. CE Ques1ons 5. Signs of declining renal function in your patient would include which of the following: a. Weight gain b. Decreased urinary output c. Increased serum Creatinine d. All of the above Answers to CE Ques1ons 1. True 2. C 3. A 4. True 5. D 12