My hypertensive patient needs hemodialysis. How dialyzable are common antihypertensives?

Among antihypertensives, most commonly used angiotensin converting enzyme inhibitors (ACE-Is) such as captopril, enalapril, lisinopril, and benazepril are at least partially removed by hemodialysis; ramipril and fosinopril are not appreciably removed.1,2

In contrast, none of the commonly used angiotensin receptor blockers such as losartan, valsartan, and irbesartan are removed by hemodialysis.

Among β-blockers and combined α- and β-blockers, atenolol and metoprolol are removed by hemodialysis while carvedilol, bisoprolol, propranolol and labetalol are not.

Many other antihypertensives such as calcium channel blockers, α-blockers, clonidine, and hydralazine are not appreciably removed by hemodialysis, while isosorbide dinitrate appears to be.

Of interest, a 2015 retrospective cohort study found that initiation of high- dialyzability β-blockers (atenolol, acebutolol, or metoprolol) was associated with a higher risk of death in the following 180 days compared to that of low-dialyzability  β-blockers (bisoprolol or propranolol), suggesting that perhaps we should be more selective in our choice of β-blockers in this patient population.2 In contrast, no significant difference in all-cause mortality was noted among older patients receiving ACE-Is with high vs low dialyzability potential.3

 

References

  1. Inrig JK, Antihypertensive agents in hemodialysis patients: A current perspective. Semin dial 2010;23:290-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061334/pdf/nihms206964.pdf
  2. β-Blocker dialyzability and mortality in older patients receiving hemodialysis. J Am Soc Nephrol 2015;26:987-96. https://www.ncbi.nlm.nih.gov/pubmed/25359874
  3. Weir MA, Fleet JL, Dixon SN, et al. Angiotensin converting enzyme inhibitor dialyzability and outcomes in older patients receiving hemodialysis. Blood Purif 2015;40:232-42.  https://www.ncbi.nlm.nih.gov/pubmed/26382240   

Contributed in part by Andrew Lundquist, MD, PhD, Mass General Hospital, Boston, MA.

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My hypertensive patient needs hemodialysis. How dialyzable are common antihypertensives?

Should my patient with non-valvular atrial fibrillation on hemodialysis be anticoagulated?

Whether patients with end-stage kidney disease (ESKD) and non-valvular atrial fibrillation (AF) benefit from anticoagulation is a matter of controversy. 1,3 Although there may be some suggestion of benefit of warfarin for stroke prevention in this patient population, 2 there is also a higher concern for bleeding. 4-6 An increased risk of stroke among patients with ESKD and AF on warfarin has also been reported. 7

A 2018 Kidney Disease:Improving Global Outcomes (KDIGO) Controversies Conference concluded that there is “insufficient high-quality evidence” to recommend anticoagulation for prevention of stroke in patients with ESKD and atrial fibrillation. 8

However, the 2014 American College of Cardiology (ACC)/American Heart Association (AHA)/ Heart Rhythm (HRS) guideline states that it is reasonable to consider warfarin therapy in patients with ESKD and non-valvular AF with CHA2DS2 -VASc score of 2 or greater (Class IIa recommendation, level of evidence B).8 Of interest, the FDA recently approved the use of a direct oral anticoagulant (DOAC), apixaban, in ESKD potentially providing an alternative to the use of warfarin when anticoagulation is considered.10

Perhaps the decision to anticoagulate patients with ESKD for atrial fibrillation is best made on a case-by-case basis taking into account a variety of factors, including the risk of thromboembolic event, the risk of bleeding complications as well as patient preference.

References

1. Genovesi S, Vincenti A, Rossi E, et al. Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients. Am J Kidney Dis 2008;51:255-62. https://www.ncbi.nlm.nih.gov/pubmed/18215703

2. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012;367:625-35. https://www.ncbi.nlm.nih.gov/pubmed/22894575

3. Shah M, Avgil TM, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation2014;129:1196-203. https://www.ncbi.nlm.nih.gov/pubmed/24452752

4. Elliott MJ, Zimmerman D, Holden RM. Warfarin anticoagulation in hemodialysis patients: a systematic review of bleeding rates. Am J Kidney Dis 2007;50:433-40. https://www.ncbi.nlm.nih.gov/pubmed/17720522

5. Holden RM, Harman GJ, Wang M, Holland D, Day AG. Major bleeding in hemodialysis patients. Clin J Am Soc Nephrol 2008;3:105-10. https://www.ncbi.nlm.nih.gov/pubmed/18003768

6. Wizemann V, Tong L, Satayathum S, et al. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int 2010;77:1098-106. https://www.ncbi.nlm.nih.gov/pubmed/20054291

7. Chan KE, Lazarus JM, Thadhani R, Hakim RM. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol2009;20:2223-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754104/

8. Turakhia MP, Blankestijn PJ, Carrero J, et al. Chronic kidney disease and arrythias: conclusions from a Kidney Disease:Improving Global Outcomes (KDIGO) Controversies Conference. Eur Heart J, ehy060. Published 07 March 2018. https://www.ncbi.nlm.nih.gov/pubmed/29522134

9. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation 2014;130:2071-104. http://circ.ahajournals.org/content/130/23/2071 

10. Moll S. Use of direct oral anticoagulants in patients on hemodialysis. Diffusion, October 11, 2017. http://www.hematology.org/Thehematologist/Diffusion/7794.aspx 

Contributed by Brad Lander, MD, Mass General Hospital, Boston, MA.

Should my patient with non-valvular atrial fibrillation on hemodialysis be anticoagulated?

Can my patient with renal insufficiency safely undergo gadolinium-based contrast MRI?

It may be possible for patients with renal insufficiency, including those with end-stage kidney disease (ESKD), to undergo MRI using potentially safer preparations of gadolinium-based contrast agents (GBCAs) with “very low, if any” risk of the feared nephrogenic systemic sclerosis (NSF). 1

In contrast to the so called “linear” chelates of gadolinium (eg, gadodiamide, gadopentetate), “cyclic” GBCA’s (eg, gadoteridol) have not been clearly associated with NSF. 2 A Veterans Administration study involving gadoteridol identified no cases of NSF among the 141 patients on hemodialysis following 198 exposures. 2 In fact, the 2017 American College of Radiology (ACR) Manual on Contrast Media reports the risk of NSF with cyclic chelates as “very low, if any”. 1 Even when a cyclic GBCA is used in patients with ESKD, however, hemodialysis is recommended as soon as possible after MRI. 3

GBCAs are chelates with 2 major components: gadolinium and either a linear or cyclic ligand. Cyclic ligands bind to gadolinium more avidly, resulting in lower probability of circulating renally-cleared free gadolinium which when deposited in tissue is thought to potentially trigger NSF.2

Although NSF is characterized by progressive fibrosis of skin and soft tissue, it may involve multiple organs with an estimated 30% mortality rate. 4

 Bonus Pearl: Did you know NSF is really a new disease, with no evidence of its existence before 1997?

References

  1. “Nephrogenic Systemic Fibrosis”. In ACR Manual on Contrast Media; Version 10.3; May 31, 2017. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf
  2. Reilly RF. Risk for nephrogenic systemic fibrosis with gadoteridol (ProHance) in patients who are on long-term hemodialysis. Clin J Am Soc Nephrol 2008;3:747-51. https://www.ncbi.nlm.nih.gov/pubmed/18287249
  3. Wang Y, Alkasab TK, Nari O, et al. Incidence of nephrogenic systemic fibrosis after adoption of restrictive gadolinium-based contrast agent guidelines. Radiology 2011;260:105-111.  https://www.ncbi.nlm.nih.gov/pubmed/21586680
  4. Schlaudecker JD, Bernheisel CR. Gadolinium-associated nephrogenic systemic fibrosis. Am Fam Physician 2009;80:711-14. https://www.aafp.org/afp/2009/1001/p711.pdf

 

Contributed by Richard Newcomb, MD, Mass General Hospital, Boston, MA.

Can my patient with renal insufficiency safely undergo gadolinium-based contrast MRI?

Is measurement of amylase and lipase useful in patients with renal insufficiency suspected of pancreatitis?

Depends on how high the serum levels are! Although the clearance of both amylase and lipase appears to be impaired in patients with significant renal insufficiency (eg,  creatinine clearance <50ml/min), serum levels greater than 2-4 times the upper limits of normal for these enzymes are still considered suggestive of pancreatitis in these patients1-3.

Interestingly, in hemodialysis patients, elevation of lipase may also be due to the lipolytic effect of heparin during this procedure.  That’s why obtaining serum lipase levels before, not after,  hemodialysis has been recommended4

Also fascinating is that most of the elevation of serum amylase in patients with significant renal insufficiency appears to be related to the elevation of salivary, not pancreatic, isoenzyme of amylase4.

Final fun fact: Did you know that at one time the diagnosis of pancreatitis was based on the activity of serum on starch (for amylase) and olive oil (for lipase)? 5

References

  1. Levitt MD, Rapoport M, Cooperband SR. The renal clearance of amylase in renal insufficiency, acute pancreatitis, and macroamylasemia. Ann Intern Med 1969;71:920-25. http://annals.org/aim/article/683643/renal-clearance-amylase-renal-insufficiency-acute-pancreatitis-macroamylasemia
  2. Collen MJ, Ansher AF, Chapman AB, et al. Serum amylase in patients with renal insufficiency and renal failure. Am J Gastroenterol 1990;85:1377-80. https://www.ncbi.nlm.nih.gov/pubmed/1699413
  3. Royce VL, Jensen DM, Corwin HL. Pancreatic enzymes in chronic renal failure. Arch Intern Med 1987;147:537-39. https://www.ncbi.nlm.nih.gov/pubmed/2435254
  4. Vaziri ND, Change D, Malekpour A, et al. Pancreatic enzymes in patients with end-stage renal disease maintained on hemodialysis. Am J Gastroenterol 1988;83:410-12. https://www.ncbi.nlm.nih.gov/pubmed/2450453
  5. Editorial. Pancreatic enzymes. N Engl J Med 1963;268:901-2. http://www.nejm.org/doi/pdf/10.1056/NEJM196304182681613
Is measurement of amylase and lipase useful in patients with renal insufficiency suspected of pancreatitis?

My patient with a thrombosed hemodialysis access is found to have an asymptomatic segmental pulmonary embolism following a vascular access declotting procedure. Does he need systemic anticoagulation?

There is no firm evidence either for or against the use of systemic anticoagulants (ACs) in patients with asymptomatic pulmonary embolism (PE) following hemodialysis vascular access declotting (HVAD).  

However, despite the common occurrence of asymptomatic PE following HVAD procedures (~40%), symptomatic PE—at times fatal—has also been reported in these patients1,2.

In the absence of hard data and any contraindications, anticoagulation can be justified in our patient for the following reasons:

  • Asymptomatic segmental PE is commonly treated as symptomatic PE irrespective of setting2,3
  • Hemodialysis patients are often considered hypercoagulable due to a variety of factors eg, platelet activation due to extracorporeal circulation, anti-cardiolipin antibody, lupus anticoagulant, decreased protein C or S activity, and/or reduced anti-thrombin III activity4-7
  • Overall, chronic dialysis patients have higher incidence of PE compared to the general population8
  • There is no evidence that asymptomatic PE following HVAD has a more benign course compared to that in other settings
  • Untreated PE may be associated with repeated latent thrombosis or progression of thrombosis in the pulmonary artery5

 

References

  1. Calderon K, Jhaveri KD, Mossey R. Pulmonary embolism following thrombolysis of dialysis access: Is anticoagulation really necessary? Semin Dial 2010:23:522-25. https://www.ncbi.nlm.nih.gov/pubmed/21039878
  2. Sadjadi SA, Sharif-Hassanabadi M. Fatal pulmonary embolism after hemodialysis vascular access declotting. Am J Case Rep 2014;15:172-75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004792/pdf/amjcaserep-15-172.pdf
  3. Chiu V, O’Connell C. Management of the incidental pulmonary embolism. AJR 2017;208:485-88. http://www.ajronline.org/doi/pdf/10.2214/AJR.16.17201
  4. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: Chest guideline and expert panel report. CHEST 2016;149:315-52. http://journal.chestnet.org/article/S0012-3692(15)00335-9/fulltext
  5. Yamasaki K, Haruyama N, Taniguchi M, et al. Subacute pulmonary embolism in a hemodialysis patient, successfully treated with surgical thrombectomy. CEN Case Rep 2016;5:74-77 https://link.springer.com/article/10.1007/s13730-015-0195-9
  6. Nampoory MR, Das KC, Johny KV, et al. Hypercoagulability, a serious problem in patients with ESRD on maintenance hemodialysis, and its correction after kidney transplantation. Am J Kidney Dis 2003;42:797-805. https://www.ncbi.nlm.nih.gov/pubmed/14520631
  7. O’Shea SI, Lawson JH, Reddan D, et al. Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis. J Vasc Surg 2003;38: 541-48. http://www.jvascsurg.org/article/S0741-5214(03)00321-5/pdf
  8. Tveit DP, Hypolite IO, Hshieh P, et al. Chronic dialysis patients have high risk for pulmonary embolism. Am J Kidney Dis 2002;39:1011-17. https://www.ncbi.nlm.nih.gov/pubmed/11979344
My patient with a thrombosed hemodialysis access is found to have an asymptomatic segmental pulmonary embolism following a vascular access declotting procedure. Does he need systemic anticoagulation?

Should I order serum procalcitonin on my patient with suspected infection?

Two things to ask before you order procalcitonin (PCT): 1. Will it impact patient management?; and 2. If so, will the result be available in a timely manner ie, within hours not days?

Whatever the result, PCT should always be interpreted in the context of the patient’s illness and other objective data. Not surprisingly then, as a “screening” test, PCT may be more useful in patients with low pre-test likelihood of having bacterial infection, not dissimilar to the use of D-dimer in patients with low pre-test probability of pulmonary embolism1.  

Several potential clinical uses of this biomarker have emerged in recent years,  including:1,2

  • Helping decide when to initiate antibiotics in patients with upper acute respiratory tract infections and bronchitis. A normal or low PCT supports viral infection.
  • Helping decide when to discontinue antibiotics (ie, when PCT normalizes) in community-acquired or ventilator-associated pneumonia.
  • Helping monitor patient progress with an expected drop in PCT of about 50% per day (half-life ~ 24 hrs) with effective therapy.

Few caveats…

  • PCT may be unremarkable in about a third of patients with bacteremia (especially due to less virulent bacteria, including many gram-positives)3.  
  • PCT levels are lowered by high-flux membrane hemodialysis, so check a baseline level before, not after, hemodialysis4.
  • Lastly, despite its higher specificity for bacterial infections compared to other biomarkers such as C-reactive protein, PCT may be elevated in a variety of non-infectious conditions, including pancreatitis, burns, pulmonary edema or aspiration, mesenteric infarction (ischemic bowel), cardiogenic shock, and hypotension during surgery2.

 

References:

  1. Schuetz P, Muller B, Chirst-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections (review). Evid-Based Child Health (A Cochrane Review Journal) 2013;8:4;1297-137. http://onlinelibrary.wiley.com/doi/10.1002/ebch.1927/pdf
  2. Gilbert GN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol 2010;48:2325-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897488/pdf/0655-10.pdf
  3. Yan ST, Sun LC, Jia HB. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med 2017;35:779-83. https://www.ncbi.nlm.nih.gov/m/pubmed/27979420/#fft
  4. Grace E, Turner RM. Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy. Clin Infect Dis 2014;59:1761-7. https://www.ncbi.nlm.nih.gov/pubmed/25228701
Should I order serum procalcitonin on my patient with suspected infection?