PHM 411 MOST 1 Fall 2024 Lecture Notes PDF

PHM 411 MOST 1 Fall 2024 PH411–Modular Organ System Therapeutics (MOST 1) Kidney (AKI, DIKD, CKD & D...

PHM 411 MOST 1 Fall 2024 PH411–Modular Organ System Therapeutics (MOST 1) Kidney (AKI, DIKD, CKD & Dialysis) Timothy Nguyen, PharmD, MBA, BCPS, CCP, FASCP Professor of Pharmacy Practice Arnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University (LIU PHARMACY) Clinical Pharmacotherapy Specialist, Nephrology & Dialysis Fall 2024 © 2024 Prof. Nguyen 1 Copyright: © 2024 Prof. Timothy Nguyen. All rights reserved. Copyright: © 2024 Prof. Timothy Nguyen. All rights reserved. Unless otherwise indicated, all materials for this presentation are intellectual property. No part of this presentation, either recording, text or image may be used for any purpose other than personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission. © 2024 Prof. Nguyen 2 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Overview  Active Reading & Learning (Cases, Q&As, Quizzes, Think-out-loud, etc… throughout…) © 2024 Prof. Nguyen 3 Chapters & LOs Please notes… -Some items (fyi) are posting via Blackboard only in order to decrease printing & unnecessary wastes. © 2024 Prof. Nguyen 4 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 ANATOMY & PHYSIOLOGY © 2024 Prof. Nguyen 5 Anatomy © 2024 Prof. Nguyen 6 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 © 2024 Prof. Nguyen 7 The Nephron Functional unit of kidney 1 million per kidney Kidney disease (↓ # of nephrons) Nephron Anatomy Glomerulus Proximal tubule Loop of Henle Distal Tubule Collecting duct © 2024 Prof. Nguyen 8 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 9 © 2024 Prof. Nguyen 9 Glomerulus © 2024 Prof. Nguyen 10 http://www.health.bcu.ac.uk/physiology/glomerulus3.jpg © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 At the nephron (fyi) Passing of anions & cations Active & passive diffusion Na, K, Cl, HCO3, H2O Reabsorption – denotes transport from the urine back to the blood Secretion – movement of solutes or H2O from the blood to the nephron tubule lumen © 2024 Prof. Nguyen 11 Fundamental excretory renal processes Excretory Functions  Filtration  Secretion  Reabsorption Endocrine Functions  Renin  Erythropoietin (EPO) Metabolic Functions  Vitamin D3 activation  Insulin metabolism © 2024 Prof. Nguyen 12 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Glomerular Filtration Occurs at the glomerulus Pressure gradient across glomerulus Determinant of a drug capacity to be filtered Dependent on:  Water solubility  Surface area  Particle size & charge © 2024 Prof. Nguyen 13 Glomerular Filtration Most drugs are small enough for filter except for high molecular weight drugs Protein Binding Displace of highly bound drugs Only free drug can pass through the glomerulus © 2024 Prof. Nguyen 14 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Measurement of GFR © 2024 Prof. Nguyen 15  Kidney  CLcr (Filtration process) (~GFR) (Substances) Markers: Creatinine, Inulin, Radio-isotopes, © 2024 Prof. Nguyen Urea, Cystatin 16 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Measurement of GFR GFR = flow rate of filtered fluid through the kidney CLcr = Volume of blood plasma that is cleared of creatinine across the glomerulus per unit time (mL/min) – A useful measure for approximating the GFR Normal GFR ~120 mL/min ↓ ~ 1 mL/min/1.73 m2 >30 years old © 2024 Prof. Nguyen 17 Measurement of GFR Application: Quantify kidney function Determine ability to eliminate drugs © 2024 Prof. Nguyen 18 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Markers… Creatinine (~0.5 – 1.5 mg/dL) Product of metabolism on muscle mass Dependent on: Age, Sex, Weigh, & Muscle mass May vary, NOT 100% reliable Do NOT round Scr for older patients. Avoid use as the sole assessment of KF Standardized Cr traceable to IDMS (isotope dilution mass spectrometry) © 2024 Prof. Nguyen 19 Markers… Inulin Fructose polysacharide Radio-isotopes labeled: Iothlamate, Iohexol Intermittent availability, high cost, invasiveness Limited use in clinical settings © 2024 Prof. Nguyen 20 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Markers Cystatin C A low-molecular-weight protein Marker of kidney insufficiency May improve detection of early CKD Preliminary studies – superior eGFR in children, transplant patients & cirrhotic patients © 2024 Prof. Nguyen 21 Blood Urea Nitrogen (BUN) ~5 – 20 mg/dL Measures the amount of nitrogen in the blood From waste product urea Urea is made when protein is broken down Urea is clear via the urine ↑ BUN =~ kidney failure BUN:Cr ratio >20:1  ~dehydration © 2024 Prof. Nguyen 22 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 24 Hr CLcr 24 Hr CLcr = (Ucr x urine Volume) / Scr x 1,440 min [Ucr = urinary Cr (mg/dL), urine Volume = urinary rate (mL/min), Scr = plasma Cr (mg/dL)] Cr measured in blood & urine Cr is secreted, therefore CLcr is usually > GFR Subject to error Useful: vegetarians, low muscle mass, amputations © 2024 Prof. Nguyen 23 Active Learning 24 hr urine collection = 1800 mL, urinary Cr = 100 mg/dL, Scr 1 mg/dL Calculate 24hr-CLcr 24 © 2024 Prof. Nguyen 24 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Cockcroft and Gault (CG) Calculate CLcr (CG-CLcr) Male: CLcr = (140 – age) (wt) / (Scr) (72) Female: Male’s CLcr x 0.85 Weight (kg) Use Actual BW unless BMI>40 kg/m2 (Please note there are conflicting information. Use best clinical assessment/judgement. It is an estimation) © 2024 Prof. Nguyen 25 Cockcroft and Gault (CG) Study Hospitalized patients Primarily white males Age: 18 – 92 yrs Compared to collected CLcr Assume SS Not adjusted for BSA © 2024 Prof. Nguyen 26 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Weight Ideal Body Weight: Male: IBW (kg) = 50 + 2.3 (ht in inches >5 ft) Female: IBW (kg) = 45.5 + 2.3 (ht in inches >5 ft) Adjusted body weight (>30% above IBW): AdjBW = IBW + [0.4 (actual wt – IBW)] © 2024 Prof. Nguyen 27 Active Learning By the way, How do you know whether or not ABW is >30% above IBW? 1) ABW = 100 kg, IBW = 70 kg 2) ABW = 90 kg, IBW = 70 kg 28 © 2024 Prof. Nguyen 28 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Active Learning Determining the percentage of ABW over IBW: % over = (ABW – IBW) / (IBW) 29 © 2024 Prof. Nguyen 29 Modification of Diet in Renal Disease (MDRD) Estimates GFR (eGFR) GFR (mL/min/1.73m2) = 170 x [Pcr] –0.999 x [Age] – 0.176 x SUN-0.017 x Albumin+0.318 x 0.762 if female x 1.180 if Black “Four-variable” abbreviated MDRD GFR (mL/min/1.73m2) = 186 x [Scr] –1.154 x [Age] – 0.203 x [0.742 if female] x [1.210 if AA] © 2024 Prof. Nguyen 30 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Modification of Diet in Renal Disease (MDRD) Study 88% Caucasian, 6% diabetic Compared to I-othalamate measured GFR Does not require weight May underestimate GFR in early CKD  More accurate if GFR 60 mL/min/1.73 m2 Pooled data from multiple studies Better performance, less bias, greater accuracy Preferred! © 2024 Prof. Nguyen 32 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Children (Schwartz) eGFR = [height (cm) x k] / Scr Infant (1 – 52 wks), k = 0.45 Child (1 – 13 yrs), k = 0.55 Adolescent male, k = 0.7; female 0.55 © 2024 Prof. Nguyen 33 Endocrine & Metabolic Functions © 2024 Prof. Nguyen 34 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Endocrine Functions Renin Prostaglandins & Bradykinins Erythropoietin (EPO) © 2024 Prof. Nguyen 35 The Kidneys Produces Renin (response to a ↓ in BP) (reacts with angiotensinogen) Angiotensin I (ACEI) (by angiotensin converting enzyme, ACE) Angiotensin II (ACE II) Stimulates the adrenal cortex to release Causes Vasoconstriction Aldosterone (↑ BP) (A mineralcorticoid, ↑ the reabsorption of Na+ & H2O by the kidneys, thereby ↑ blood Volume & BP) 36 © 2024 Prof. Nguyen 36 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Metabolic Functions Activation of vitamin D  Secondary hyperparathyroidism  Renal osteodystrophy Insulin metabolism Cytochrom P450, N-acetyltransferase, glutathione, etc… © 2024 Prof. Nguyen 37 38 © 2024 Prof. Nguyen 38 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 iPTH iPTH Ca++ Systemic Toxicity Cardiac Bone Disease Cutaneous Renal Osteodystrophy Vit D PO4 Renal Failure 39 © 2024 Prof. Nguyen 39 Active Learning 1) A 60 yo female, 6’, 165 lbs, Scr 1 mg/dL. Calculate CLcr using CG-equation 2) A 59 yo male foot ball player, 6’4”, 210 lbs, Scr 1 mg/dL. Calculate CLcr using CG-equation © 2024 Prof. Nguyen 40 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Active Learning Select ALL that apply: which of the following statements is/are TRUE about the kidneys? __Filter, secrete and reabsorb __Maintain water and electrolytes homeostasis __Drugs do not process through the kidneys __Produce and secrete erythropoietin © 2024 Prof. Nguyen 41 ACUTE KIDNEY DISEASE (AKI) © 2024 Prof. Nguyen 42 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Kidney failure Renal failure Acute renal failure Acute Kidney Injury Acute kidney failure (AKI) © 2024 Prof. Nguyen 43 National Kidney Foundation Acute Kidney Injury (AKI) Acute ↓ in KF ↑ waste products & volume Complications Fluid overload Acid-base abnormalities Electrolytes abnormalities Hospital acquired ICU-acquired Incidence 2-5% 6-23% Survival rate 30-50% 10-30% © 2024 Prof. Nguyen 44 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 AKI: Definitions ↑ Scr 0.5 mg/dL or > Or a 25% ↓ GFR or > Or UO < 0.5 mL/kg/h x6 hrs The Acute Kidney Network (AKIN)  Abrupt Scr ↑ >0.3 mg/dL Or 50% ↑ from baseline Or UO 6 hrs © 2024 Prof. Nguyen 45 AKI: RIFLE ↑ed SCr x1.5 or GFR Risk ↓ >25% UO 50% UO < 0.5 ml/kg/hr x 12h ↑ed SCr x3, GFR ↓ by 75%, or Failure SCr >4 mg/dL UO 4 weeks ESKD For > 3 months © 2024 Prof. Nguyen 46 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 AKI: UO Classification Anuric: 500 mL/24 hr Estimation GFR/CLcr during AKI NOT reliable © 2024 Prof. Nguyen 47 AKI: Risk Factors -CKD -Volume depletion -Elderly -Urinary tract obstruction -Nephrotoxic agents  Radiographic contrast  Aminoglycosides  Amphotericin B  NSAIDs  ACEIs & ARBs  Cyclosporine & tacrolimus © 2024 Prof. Nguyen 48 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 AKI: Classifications Pre-renal azotemia (Functional) Intrinsic Post-renal © 2024 Prof. Nguyen 49 AKI: Pre-Renal Azotemia Hypoperfusion Systemic: hemorrhage, volume depletion, drugs, CHF Afferent & efferent arterioles vasoconstriction E.g. of drugs that impaired physiologic response (↓ glomerular hydrostatic pressure) ACEIs & ARBs NSAIDs Cyclosporine, tacrolimus Isolated: renal artery stenosis, emboli © 2024 Prof. Nguyen 50 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Pre-Renal: Treatment Correct primary hemodynamics NS/Hydration if volume depleted Pressure management prn Blood products prn © 2024 Prof. Nguyen 51 AKI: Intrinsic Damaged kidney Small blood vessels Glomeruli Renal tubules Interstitium Acute Tubular Necrosis (ATN) Prolonged prerenal AKI Hypotension, vasoconstriction Drugs (contrast media, aminoglycosides, amphotericin B, heavy metals) © 2024 Prof. Nguyen 52 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 AKI: Intrinsic - Treatment Avoidance Stop additional insults Prevention & treat complications Maintain perfusion & UO Consider IV fluid bolus Diuretic Loop diuretics, IV bolus or infusion Consider add thiazide-like diuretic © 2024 Prof. Nguyen 53 AKI: Intrinsic - Treatment Prevention & treat complications (con’t)  Avoid Dopamine Renal dose 1 – 2 mcg/kg/min Causes renal & mesenteric vasodilation & can ↑ UO NOT proven to improve KF or survival NOT recommended  Acidosis NaHCO3 (HCO3 >15 mEq/L, pH >7.2)  Electrolyte & nutrition considerations © 2024 Prof. Nguyen 54 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 AKI: Post-Renal Bladder outlet obstruction Calculi History: trauma, BPH, Cancers, nephrolithiasis, fibrosis Drugs: anti-cholinergics (TCAs, antihistamine) Treatment Relieve obstruction © 2024 Prof. Nguyen 55 AKI: Renal Replacement Therapy Volume overload unresponsive to diuretics Uremia Life-threatening electrolytes disburbances Refractory acidosis [AEIOU (acidosis, electrolytes, intoxication, overload, uremia)] © 2024 Prof. Nguyen 56 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 AKI: Prevention Avoid nephrotoxin drugs Hydrations  IV NS is preferred Education Avoid dopamine, fenoldopam, diuretics Contrast-induced nephropathy (CIN) prevention © 2024 Prof. Nguyen 57 AKI: Fractional excretion of Na FeNa = (UNa x Scr x 100) / (Ucr x sNa) (The % of the Na is filtered & excreted in the urine) © 2024 Prof. Nguyen 58 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Classifications of Acute Kidney Injury (Differential Diagnosis of AKI) Prerenal & Functional Intrinsic (ATN) Postrenal Clinical Volume depletion Chronic renal hypoperfusion Kidney stones Renal artery stenosis Nephrotoxins (e.g. contrast, BPH CHF antibiotics) Cancers Hypercalcemia Vasculitis NSAID/ACEI Glomerulonephritis Cyclosporin Physical Hypotension Rash Distended bladder examination Dehydration Fever Enlarge prostate Petechia (round spots on skin) if thrombotic Ascites Serum BUN/Scr >20:1 15:1 15:1 ratio Urine Yes No No concentrated? Low urine Na (40 mEq/L Urine Na >40 mEq/L Low FeNa (2 FeNa >2 Low urine osmolarity Low urine osmolarity Urine sediment Normal Muddy-brown granular casts; Variable, may be normal tubular epithelial casts Urinary WBC Negative 2 – 4+ Variable Urinary RBC Negative 2 – 4+ 1+ Proteinuria Negative Positive Negative © 2024 Prof. Nguyen 59 AKI: Goals of Therapy Prevent AKI Avoid or minimize insult Prevent or ↓ extrarenal complications Maintain BP, fluid & electrolyte homeostasis Prevent RRT Restore pre-AKI renal function © 2024 Prof. Nguyen 60 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Active Learning Case – AKI #1: WR is a 70 yo White male with PMH of heart disease, HTN & DM. c/o CP & was admitted for further work up. He has a procedure done with contrast media to enhance view. Meds: enalapril 10 mg po bid, ASA 81 mg po daily, metoprolol XL 50 mg po daily, furosemide 40 mg po bid, metformin 500 mg bid, APAP prn, verapamil 61 © 2024 Prof. Nguyen 61 Active Learning Labs on admission (3 days ago): 140 105 35 4 22 2.3 110 Current Labs: BUN 55, Scr 3, UO 550 mL/day, FeNa 2.2 Dx: AKI 62 © 2024 Prof. Nguyen 62 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Active Learning 1) List risk factors associated with AKI: 2) Identify the type of AKI WR has: 63 © 2024 Prof. Nguyen 63 Active Learning Select ALL that apply: which of the following methods of KF assessment is appropriate for WR? __Cockcroft-Gault CLcr __MDRD-eGFR __Inulin label __None of the above 64 © 2024 Prof. Nguyen 64 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Active Learning Case – AKI #2: CC: LS is a 60 yo male, 5’8”, c/o nausea & vomiting x 4 days PMH: DM, HTN, back pain Meds PTA: ASA 81 mg po daily, lisinopril 5 mg po daily, ibuprofen 400 mg po q6h prn, torsemide 20 mg po daily, docusate 100 mg po bid prn 65 © 2024 Prof. Nguyen 65 Active Learning Labs: 138 105 60 5 22 1.8 230 PE: BP 96/60, HR 100, RR 22, UO 10 mL/hr, FeNa 0.8, pale appearance Dx: AKI 66 © 2024 Prof. Nguyen 66 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Active Learning Questions: 1) List risk factors for AKI 2) What type of AKI? 3) Describe management strategies 67 © 2024 Prof. Nguyen 67 DRUG-INDUCED KIDNEY DISEASE © 2024 Prof. Nguyen 68 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 DIKD: Epidemiology ↑ Scr 0.5 mg/dL or > Or ↓ 25% or > in GFR Risk factors: h/o CKD, ↑ age Epidemiology  7% of all drug toxicities  18 – 27% of AKI in hospitals  1 – 5 % of NSAIDs users in community  Drugs: Aminoglycosides, NSAIDs, ACEI/ARB, Contrast dye, amphotericin B © 2024 Prof. Nguyen 69 DIKD: Kidneys at Risk of toxicity High exposure to toxin Autoregulation & specialize BF through glomerulus High intrarenal drug metabolism Tubular transport processes Concentration of solutes in tubules Urine acidification © 2024 Prof. Nguyen 70 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 DIKD: Etiology Acute Tubular Necrosis (ATN)  Aminoglycosides  CIN  Cisplatin & carboplatin; Amphotericin B Hemodynamically mediated KD  ACEI/ARB  NSAIDs, Cyclosporin & tacrolimus Tubulointerstitial disease © 2024 Prof. Nguyen 71 (fyi) ATN: Aminoglycoside Toxicity (Gentamycin, tobramycin, amikacin, others) Incidence 1.7 – 58% Pathogenesis  Proximal damage  obstruction of the lumen  Cationic charge of drug leads to binding to tubular epithelial cells & uptake into the cells  Accumulation of phospholipids & toxicity Presentation Gradual ↑ Scr & ↓ GFR Nonoliguric KD © 2024 Prof. Nguyen 72 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 (fyi) ATN: Aminoglycoside Toxicity Risk Factors  Large drug dosing, prolonged therapy  Concurrent nephrotoxins  CKD, ↑ age, shock, liver disease, dehydration Prevention  Avoid in high-risk patients  Adequate hydration  Limit large dose  Avoid other nephrotoxins  Use extended dosing interval © 2024 Prof. Nguyen 73 ATN: Contrast-associated AKD (CA-AKI [CIN] Iso-osmolar (300 mOsm/kg) Low-osmolar (780 – 800 mOsm/kg) High-osmolar (>1000 mOsm/kg) Incidence  3rd leading cause of AKI (in-patient) (~50%)  High in-hospital mortality (~34%) © 2024 Prof. Nguyen 74 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 ATN: CA-AKI Pathogenesis Direct tubular toxicity due to reactive oxygen species Renal ischemia due to intrarenal hemodynamic alterations Presentations Initial osmotic diuresis, followed by tubular proteinuria Scr rises & peaks ~2 – 5 days ~50% develop oliguria & require dialysis © 2024 Prof. Nguyen 75 ATN: CA-AKI Risk Factors CKD DM Volume depletion Age >75 yrs Anemia Conditions ↓ BF to the kidney (e.g., CHF) Hypotension Other nephrotoxins Large dose of contrast © 2024 Prof. Nguyen 76 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 CA-AKI: Preventions Hydration PO or IV NS 1 mL/kg/hr x 12 hrs pre- & post-procedures  Drug of choice ± NaHCO3 (D5W + 150 mEq NaHCO3 @ 3 mL/kg/hr, 1 hr pre-, follow by 1 mL/kg/hr x6 hrs post-procedure Maintain UO >150 mL/hr Monitor: VS, UO, Electrolytes, fluid overload © 2024 Prof. Nguyen 77 CA-AKI: Preventions Use alternative imaging study Stop nephrotoxic agents Use low-osmolar or iso-osmolar contrasts Other strategies: N-acetylcysteine Antioxidant & vasodilatory 600 mg or 1200 mg po q12h x4 doses (2 pre- & 2 post-) SE: N/V, unpleasant taste, smell Many conflicting reports © 2024 Prof. Nguyen 78 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 CA-AKI: Preventions (fyi) Other strategies: Ascorbic acid Theophylline Fenoldopam Agonist for D1-like dopamine receptors Rapid acting vasodilator Use: severe HTN, malignant HTN Avoid, trial showed no benefit but ↑ HTN Dialysis Others… © 2024 Prof. Nguyen 79 ATN (fyi) Cisplatin & Carboplatin  Direct tubular toxin Amphotericin B  Direct proximal & distal tubular toxicity  Arterial vasoconstriction © 2024 Prof. Nguyen 80 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Hemodynamically Mediated KF ↓ intraglomerular pressure through the vasoconstriction of afferent arterioles or the vasodilation of efferent arterioles ACEIs Pathogenesis  Vasodilation of the efferent arteriole  ↓ in glomerular hydrostatic pressure & a resultant ↓ in GFR © 2024 Prof. Nguyen 81 Hemodynamically Mediated KF ACEIs Presentation Predictable dose-related ↓ in GFR Scr is usually expected to rises ~30% Usually occurs within 2 – 5 days & stabilizes in 2 - 3 wks Usually reversible (d/c) ↑ >30% may be detrimental © 2024 Prof. Nguyen 82 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Hemodynamically Mediated KF Risk Factors  Bilateral renal artery stenosis, ↓ effective kidney BF (CHF, cirrhosis), CKD, volume depletion Prevention  Initiate low doses, short acting, gradually titrate upward  Switch to long-acting prn  Initially, monitor KF, Scr (daily if in-pt, wkly if out-pt)  Avoid diuretics if possible during initiation (fyi) © 2024 Prof. Nguyen 83 Hemodynamically Mediated KF NSAIDs Incidence ~500,000 to 2.5 million Pathogenesis  ↓ prostaglandins, resulting in afferent vasoconstriction & ↓ glomerular BF Presentation  Can occur within days  Low urine volume, Na  ↑ BUN, Scr, K, edema & weight (fyi) © 2024 Prof. Nguyen 84 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Hemodynamically Mediated KF Risk Factors  CKD, systemic lupus erythrematous, CHF, hepatic disease, diuretic therapy, atherosclerotic disease, advanced age Prevention  Avoid NSAIDs  If NSAIDs-induced AKI is suspected  D/C drug  Supportive care  Recovery is usually rapid (fyi) © 2024 Prof. Nguyen 85 Active Learning AE is a 75 yo female with PMH of heart disease, HTN, DM, & had a cardiac catheterization done. AE received radiocontrast dye & subsequently had elevated BUN & Scr. Her baseline BUN was 30 and now 45 mg/dL, Scr was 2 and now 3 mg/dL. Meds: furosemide, ASA, metoprolol xl, enalapril, docusate, ibuprofen © 2024 Prof. Nguyen 86 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Active Learning Other labs: FeNa 2.2 Questions: 1) List risk factors for AKI 2) What type of AKI does she have? 3) Describe preventive measures to help prevent CIN © 2024 Prof. Nguyen 87 CHRONIC KIDNEY DISEASE (CKD) © 2024 Prof. Nguyen 88 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 CKD An irreversible ↓ in the number of functioning nephrons resulting in progressive & permanent deterioration of KF Kidney damage or ↓ in GFR 3 months CKD is classified based on cause, GFR category, & albuminuria category (CGA) Kidney Inter. Suppl. 2013;3:1-150; Kidney Inter. 2020 98S1-S115. © 2024 Prof. Nguyen 90 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 CKD & CKD Classifications Chronic kidney disease Chronic kidney failure Chronic renal insufficiency Chronic Kidney Disease Chronic renal failure (CKD) End stage renal disease End stage kidney disease Stages of CKD Estimate Glomerular Filtration Rate (mL/min) 1 ≥90* 2 60 – 89 3a 45 – 59 3 30 – 59** 3b 30 – 44 4 15 – 29 5 Future may include serum Cystatin C Renal ultrasound © 2024 Prof. Nguyen 94 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Progression of CKD Renin-angiotensin-aldosterone systems Free radicals production MBD vascular calcification HTN Inflammation © 2024 Prof. Nguyen 95 Slow Down Progression of CKD ACEI, ARB, Aldosterone antagonist or combination ↓ proteinuria (30 mg/24 hr or non-DM w/urine albumin >300 mg/24 hr  Monitor: Scr, K; if Scr ↑ >30%  hold or d/c  2nd line: Non-DHP CCB (eg, diltiazem, verapamil), Others  Misc.: ESKD/HD – Hydralazine, minoxidil, clonidine, CCB, BB HD – restrict wt gain to 1-2 kg/HD sessions © 2024 Prof. Nguyen 107 Electrolytes Balance Sodium (Na) Kidneys can not excrete Fluid overload, HTN, CHF Restrict to no added salt diet (80 – 120 mEq/day) Potassium (K) Watch K loads; maintain low K diet Avoid drugs (ACEI, ARB, K-sparing, salt substitutes) Low K bath used in dialysis © 2024 Prof. Nguyen 108 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 Mineral and Bone Disorders ↓ GFR ↓ Phosphate excretion (Phosphorous retention) ↓ Ca ↓ calcitriol ↑ PTH ↑ Ca resorption from bone Osteitis fibrosa © 2024 Prof. Nguyen 109 MBD: Goals Control serum Ca P Ca x P products Suppress iPTH Restore normal skeletal development Prevent complications CVD, CAD, vascular calcifications © 2024 Prof. Nguyen 110 © 2024 Prof. Nguyen All rights reserved. PHM 411 MOST 1 Fall 2024 MBD PARAMETERS: NKF-KDOQI Guidelines ParameterCKD CKD CKD stage 3 stage 4 stage 5 cCa (mg/dL) Normal Normal 8.4 – 9.5 Phosphorus 2.7 – 4.6 2.1 – 4.6 3.5 – 5.5 (mg/dL) iPTH 35 – 70 70 – 110 150 – 300 Ca x P