NAPLEX / Renal disease / fluids & electrolytes

Answer A.
1g of calcium chloride (10mL) = 13.6mEq of elemental calcium
1g of calcium gluconate (10mL) = 4.65mEq of elemental calcium
Reference:
CALCIUM CHLORIDE - Intravenous (IV) Dilution. Globalrphcom. 2016. Available at: http://www.globalrph.com/calcium_dilution.htm . Accessed September 30, 2016.

Answer B. Calcium salts and phosphates are inherently incompatible and will precipitate, thus one should not infusing sodium phosphate and calcium chloride together in the same intravenous line.
Reference:
Clinical Pharmacology. Retrieved December 10, 2016, from http://www.clinicalpharmacology-ip.com/Forms/Reports/ivreport.aspx

Answer A. Corrected Calcium Formula: Serum calcium + 0.8 (4- serum Albumin) 6.0 + 0.8 (4-2.3) = 7.36
Reference:
EBM Consult : Calcium Correction for Hypoalbuminemia Medical Calculator. Ebmconsultcom. 2016. Available at: http://www.ebmconsult.com/app/medical-calculators/calcium-correction-albumin-calculator Accessed September 30, 2016.

40% of atenolol is renally excreted, thus a patient’s renal function effects dosing of this beta-blocker. Individuals with a CrCl of 10 – 30 mL/min should not take more than 50 mg daily. Individuals with a CrCl of <10 mL/min should not take more than 25 mg daily.
Reference:
Tenormin (atenolol) [prescribing information]. Morristown, NJ: Almatica Pharma LLC; January 2021.

Procainamide is excreted in the urine with approximately 50% excreted as the active metabolite N-acetyl procainamide (NAPA), which has approximately 70% of the antiarrhythmic properties of procainamide. NAPA has a longer half-life than procainamide and can accumulate in patients with kidney disease.
Meperidine is hydrolyzed in the liver to both an inactive metabolite, and to an active metabolite, normeperidine. Normeperidine has stronger CNS effects compared to its parent drug and can induce toxicity in patients if not closely monitored. Normeperidine accumulation can occur with prolonged or high doses of meperidine, in patients with altered kidney function, or in patients with increased hepatic metabolism (CYP3A4 substrate). Morphine is metabolized into several inactive metabolites, and an active metabolite morphine-6-glucuronide (M6G) via hepatic conjugation before excretion in the urine. M6G has a higher affinity for u-receptors and contributes to a stronger analgesic effect than its parent drug. M6G can accumulate in patients with altered kidney function and these patients should be monitored for over-sedation closely.
Lithium is excreted in the kidneys primarily as unchanged drug.
Reference:
1. Funck-Brentano C, Light RT, Lineberry MD, et al. Pharmacokinetic and pharmacodynamic interaction of N-acetyl procainamide and procainamide in humans. J Cardiovasc Pharmacol. 1989 Sep;14(3):364-73. doi: 10.1097/00005344-198909000-00003.
2. Simopoulos TT, Smith HS, Peeters-Asdourian C, Stevens DS. Use of meperidine in patient-controlled analgesia and the development of a normeperidine toxic reaction. Arch Surg. 2002 Jan;137(1):84-8. doi: 10.1001/archsurg.137.1.84.
3. Klimas R, Mikus G. Morphine-6-glucuronide is responsible for the analgesic effect after morphine administration: a quantitative review of morphine, morphine-6-glucuronide, and morphine-3-glucuronide. Br J Anaesth. 2014 Dec;113(6):935-44. doi: 10.1093/bja/aeu186.
4. Lithobid (lithium carbonate) [prescribing information]. Baudette, MN: ANI Pharmaceuticals, Inc; January 2020

While all 4 drugs have narrow therapeutic indexes and require therapeutic drug monitoring, carbamazepine is largely excreted as unchanged drug in the urine and thus does not require renal dose adjustments.
Reference:
Tegretol and Tegretol-XR (carbamazepine) [prescribing information]. East Hanover, NJ: Pharmaceuticals Co.; March 2020.

Creatinine is a waste product generated from muscle metabolism that is filtered in the kidneys and disposed of in the urine. When kidney function is disrupted, serum creatinine increases. BUN measures urea nitrogen in the blood and can help determine hydration status in an individual. When the kidneys are working properly, urea nitrogen is excreted, and when they are not, BUN increases. Serum ammonia is a lab test used to identify hepatic encephalopathy and serum lactic acid is a lab test that is used when diagnosis sepsis or septic shock.
Reference:
Lyman JL. Blood urea nitrogen and creatinine. Emerg Med Clin North Am. 1986 May;4(2):223-33.

The Cockcoft-Gault Equation is [(140 – age) x IBW] x 0.85 if female/ (80 x SCr). BUN is not needed to calculate GFR in this equation; however it can be useful to determine hydration status in a patient with altered kidney function.
Reference:
Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013 Jun 4;158(11):825-30. doi: 10.7326/0003-4819-158-11-201306040-00007.

As serum creatinine rises, patients renal function decreases, as the kidneys are not working properly to clear creatinine. Creatinine is a waste byproduct of muscle breakdown, therefore, patients with reduced muscle mass will not be able to product enough creatinine. This can lead to lower serum creatinine’s, falsely indicating adequate renal function. A 24-hour urine collection is the most accurate assessment of renal function because it evaluates how the kidneys are functioning over a full day.
Reference:
1. Lyman JL. Blood urea nitrogen and creatinine. Emerg Med Clin North Am. 1986 May;4(2):223-33.
2. Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013 Jun 4;158(11):825-30. doi: 10.7326/0003-4819-158-11-201306040-00007.

Intrinsic AKF: Acute kidney injury that occurs because of a process within the kidneys. Examples include acute tubular necrosis from either a nephrotoxic medication or from prolonged hypotension, or glomerulonephritis (acute inflammation in the glomeruli). Post-renal ARF: Acute kidney injury that occurs due to decreased urine output. Causes include prostate hypertrophy, renal stones, or certain cancers. Pre-renal ARF: Acute kidney injury that occurs due to decreased kidney perfusion. Causes include decreased intravascular volume or decreased arterial pressure due to sepsis.
Reference:
1. Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013 May;61(5):649-72. doi: 10.1053/j.ajkd.2013.02.349.
2. Rahman M, Shad F, Smith MC. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician. 2012 Oct 1;86(7):631-9.

Explanation: Intrinsic AKF: Acute kidney injury that occurs because of a process within the kidneys. Examples include acute tubular necrosis from either a nephrotoxic medication or from prolonged hypotension, or glomerulonephritis (acute inflammation in the glomeruli). Post-renal ARF: Acute kidney injury that occurs due to decreased urine output. Causes include prostate hypertrophy, renal stones, or certain cancers. Pre-renal ARF: Acute kidney injury that occurs due to decreased kidney perfusion. Causes include decreased intravascular volume or decreased arterial pressure due to sepsis.
Reference:
1. Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013 May;61(5):649-72. doi: 10.1053/j.ajkd.2013.02.349.
2. Rahman M, Shad F, Smith MC. Acute kidney injury: a guide to diagnosis and management. Am Fam Physician. 2012 Oct 1;86(7):631-9.

Low-dose dopamine (<5 mcg/kg/min) was hypothesized to increase renal blood flow and UOP in intrinsic AKI; however, this is controversial and has not been established to be true. Fluid resuscitation (if indicated) is recommended to restore perfusion to the kidneys, avoiding nephrotoxic medications, and loop diuretics are all recommended by the KDIGO guidelines to help manage AKI.
Reference:
1. Lauschke A, Teichgräber UK, Frei U, Eckardt KU. 'Low-dose' dopamine worsens renal perfusion in patients with acute renal failure. Kidney Int. 2006 May;69(9):1669-74. doi: 10.1038/sj.ki.5000310.
2. Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013 May;61(5):649-72. doi: 10.1053/j.ajkd.2013.02.349.

Normal saline is the drug of choice according to the KDIGO guidelines and Muller et al study to prevent contrast-induced nephropathy. It is recommended according to literature to start fluids 1 hour before contrast dye administration and continue fluids for approximately 3 – 6 hours after.
Reference:
Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013 May;61(5):649-72. doi: 10.1053/j.ajkd.2013.02.349.

When considering dosing drugs in patients on hemodialysis, volume of distribution should be considered. Drugs with higher volumes of distribution are less likely to be dialyzed. Drugs with larger molecular weights are unable to pass through the dialytic membrane to be dialyzed compared to drugs with smaller molecular weight. Drugs that are water soluble are more likely to be dialyzed because dialysis solution is aqueous. Drugs that are highly protein bound will have less free drug available to be dialyzed. Elimination rate constant of drugs does not effect hemodialysis.
Reference:
Keller F, Wilms H, Schultze G, Offerman G, Molzahn M. Effect of plasma protein binding, volume of distribution and molecular weight on the fraction of drugs eliminated by hemodialysis. Clin Nephrol. 1983 Apr;19(4):201-5

Sodium Polystyrene Sulfonate (Kayexalate), is a potassium binder that exchanges K+ ions for Na+ ions. Regular insulin and albuterol stimulate intracellular K+ uptake and sodium bicarbonate increases serum pH all in an effort to redistribute potassium intracellularly.
Reference:
1. Mistry M, Shea A, Giguère P, Nguyen ML. Evaluation of Sodium Polystyrene Sulfonate Dosing Strategies in the Inpatient Management of Hyperkalemia. Ann Pharmacother. 2016 Jun;50(6):455-62. doi: 10.1177/1060028016641427.
2. Kim HJ, Han SW. Therapeutic approach to hyperkalemia. Nephron. 2002;92 Suppl 1:33-40. doi: 10.1159/000065375.

These are all examples of phosphate binders. Calcium containing phosphate binders include calcium carbonate and calcium acetate. Non-calcium containing phosphate binders include aluminum hydroxide and sevelamer HCl. While all are equally effective in lowering phosphate, calcium-containing phosphate binders are not recommended as often, due to the risk of hypercalcemia. Additionally, Aluminum hydroxide is also not recommended as often due to the risk of aluminum toxicity.
Reference:
1. Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013 Jun 4;158(11):825-30. doi: 10.7326/0003-4819-158-11-201306040-00007.
2. Emmett M. A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. Kidney Int Suppl. 2004 Sep;(90):S25-32. doi: 10.1111/j.1523-1755.2004.09005.x.

The key treatment goals of CKD include early detection, to slow progression of the disease, to manage complications of CKD including bone and mineral disorders and anemia, and to control hypertension, which helps slow progression. Controlling hyperlipidemia is still an important health goal; however, not a direct treatment goal for CKD. Reference: Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013 Jun 4;158(11):825-30. doi: 10.7326/0003-4819-158-11-201306040-00007.

As CKD progresses, patients experience a variety of complications. Kidney production of erythropoietin decreases which leads to anemia, additionally, phosphate excretion is diminished which leads to hyperphosphatemia. Hyperphosphatemia disrupts several feedback loops leading to increased parathyroid hormone otherwise known as secondary hyperparathyroidism. Additionally, as CKD progresses, patients may experience peripheral neuropathy due to several factors. Possible causes of peripheral neuropathy include hyperkalemia, and increased uremia as well as concurrent progression of diabetes mellitus. Hypotension is not a complication of CKD, rather hypertension is. Reference: 1. Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013 Jun 4;158(11):825-30. doi: 10.7326/0003-4819-158-11-201306040-00007.
2. Arnold R, Issar T, Krishnan AV, Pussell BA. Neurological complications in chronic kidney disease. JRSM Cardiovasc Dis. 2016 Nov 3;5:2048004016677687. doi: 10.1177/2048004016677687.

While all of these factors contribute to anemia in CKD, erythropoietin deficiency is the primary cause. As CKD progresses, the kidneys produce less erythropoietin (EPO), a hormone that contributes to red blood cell production. With less red blood cell production, CKD patients experience anemia. Reference: Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013 Jun 4;158(11):825-30. doi: 10.7326/0003-4819-158-11-201306040-00007.

The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines (2000) recommended that the selected Hb targets should generally be maintained in the range of 11.0 to 12.0 g/dL in patients with CKD, whether or not they were receiving dialysis. The goal hgb for CKD patients Hgb <10 are not recommended for any patients and hgb >12 may increase risk of cardiovascular events in patients with CKD on HD. Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
Reference:
Zhou Jing, Yuan Wei-jie, Zhu Nan, Zhou Yi, and Wang Ling Hemoglobin Targets for Chronic Kidney Disease Patients with Anemia: A Systematic Review and Meta-analysis. PLoS One. 2012; 7(8): e43655. Published online 2012 Aug 30. doi: 10.1371/journal.pone.0043655
PROCRIT (Epoetin alfa) FOR INJECTION [prescribing information]. Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 ; Accessed March 2022.

Patients with stage 5 CKD are preferably treated with IV iron. Iron sucrose has less anaphylactic risk compared to ferric gluconate and iron dextran. Additionally, the goal for iron replacement therapy is a total of 1 gram, so by providing iron sucrose at 200 mg IV for 5 doses = 1 gram total. Reference: Kliger AS, Foley RN, Goldfarb DS, Goldstein SL, Johansen K, Singh A, Szczech L. KDOQI US commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD. Am J Kidney Dis. 2013 Nov;62(5):849-59. doi: 10.1053/j.ajkd.2013.06.008.

Ferric gluconate and iron dextran are both IV iron preparations that require a test dose before infusion due to the possibility of severe adverse reactions such as anaphylaxis. Ferrous sulfate is an oral iron preparation. Iron sucrose does not require a test dose. Reference: 1. Ferrlecit (sodium ferric gluconate complex in sucrose) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; July 2021.
2. INFeD (iron dextran complex) [prescribing information]. Madison, NJ: Allergan USA Inc; September 2021.
3. Venofer (iron sucrose) [prescribing information]. Shirley, NY: American Regent Inc; October 2020.

Factors that contribute to renal osteodystrophy include hyperphosphatemia, as this is the first factor that disrupts PTH feedback loop, also contributing to decreased production of 1,25 dihydroxyvitamin D3. Reduced Vitamin D3 leads to hypocalcemia. The entire feedback loop is mediated by PTH, which is increased as CKD progresses. Reference: Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.

Aluminum hydroxide is a phosphate binder that is typically avoided per recommendation by the KDIGO guidelines, except for short-term therapy. Aluminum hydroxide places patients at risk for aluminum toxicity (aluminum levels >20 mcg/L). Chronic toxicity can lead to bone and muscle pain, osteomalacia, and dementia. Other phosphate binders like sevelamer HCl are now recommended instead. Reference: 1. Alfrey AC. Aluminum toxicity in patients with chronic renal failure. Ther Drug Monit. 1993 Dec;15(6):593-7. doi: 10.1097/00007691-199312000-00025.
2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009 Aug;(113):S1-130. doi: 10.1038/ki.2009.188.

Calcium-containing phosphate binders are not recommended in patients with hypercalcemia due to the risk of further increasing calcium levels. Reference: Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.

Vitamin D (calcitriol) deficiency stimulates PTH synthesis. High levels of PTH are associated with bone and mineral disorders and increased levels of morbidity and mortality in CKD patients. Vitamin D derivatives help suppress PTH and restore a normal bone/mineral feedback loop. Reference: Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.

Patients with severe CKD and secondary hyperparathyroidism may require a vitamin D analog such as paricalcitol, doxercalciferol, or calcitriol to help suppress PTH levels. Cinacalcet is a calcimimetic also used to lower PTH and ergocalciferol is a provitamin that can be used for vitamin D deficiency. Reference: Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.

Calcitriol is the active form of vitamin D and when it binds to vitamin D receptors it decreases PTH synthesis by increasing renal tubular reabsorption of calcium and increased intestinal calcium absorption. This can lead to a high risk of hypercalcemia. Reference: Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.

Cinacalcet is a calcimimetic used to lower PTH synthesis. A common side effect of this medication is hypocalcemia. Patients on Cinacalcet should have calcium levels monitored closely. Reference: Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.

Cinacalcet is a calcimimetic used to lower PTH synthesis. A common side effect of this medication is hypocalcemia. Patients on Cinacalcet should have calcium levels monitored closely. Reference: Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.

Cinacalcet is a calcimimetic used to lower PTH synthesis. A common side effect of this medication is hypocalcemia, and severe hypocalcemia can lead to seizures. Thus patients with seizure disorders on cinacalcet should be monitored closely. Reference: Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001.