View as “PDF version”
Patient Safety Tip
of the Week
February 4, 2020
Drugs and Chronic
Kidney Disease
Medication use is an
important aspect of management of CKD (chronic kidney disease). There are at
least 5 important issues:
·
medications
that should be avoided because they may worsen CKD
·
medications
that should be avoided because they may worsen complications of CKD
·
medications
that need dosage adjustment in the presence of CKD
·
medications
that should be used because they may prevent CKD progression
·
other
agents that may need avoidance or dose reduction in patients with CKD (eg. contrast agents)
In the last couple months there have been several studies pertinent to these issues. First, there was an excellent recent review of the management of CKD by Chen et al. in JAMA (Chen 2019). Then there was a study (Tuttle 2019) showing, in patients at risk for CKD, low rates of prescribing potentially beneficial medications (eg. ACE inhibitors or ARB’s) but common use of potentially nephrotoxic agents (eg, NSAID’s and PPI’s). Yet another study (Lefebvre 2020) found that potentially nephrotoxic medications are prescribed at high rates to children with CKD. And, then, an expert panel published in the Annals of Pharmacotherapy (Taji 2020) a consensus-based pragmatic list of medications used in primary care that require dosage adjustment or avoidance in people with CKD.
The Tuttle study (Tuttle 2019) mined detailed patient-level EHR data from more than 600,000 adults and over 12,000 children with CKD in the CURE-CKD registry. 33.7% of adults with CKD received potentially nephrotoxic agents nonsteroidal anti-inflammatory drugs (NSAID’s) or proton pump inhibitors (PPI’s), compared to renoprotective drugs like renin-angiotensin system inhibitors, which were prescribed to only 20.6%. Although nearly two-thirds of the adults with CKD had diabetes, hypertension, or prediabetes, rates of laboratory testing for albuminuria or proteinuria and of prescribing ACE inhibitors or ARBs were low. Given the most common cause of death in CKD is cardiovascular disease, the low use of cardiovascular preventive agents, such as statins and aspirin, is also concerning. The Tuttle study did not report prescription rates for other potentially nephrotoxic drugs.
Though the CURE-CKD data registry included children, the Tuttle study reported primarily on adults with CKD. On the other hand, Lefebvre and colleagues (Lefebvre 2020) looked at use of potentially nephrotoxic medications in patients aged <18 years in a large research database of patients in primary care practices in the UK, matching patients with CKD to those without CKD. The overall rate of nephrotoxic medication prescriptions was 71 prescriptions per 100 person-years in patients with CKD and eight prescriptions per 100 person-years in patients without CKD (adjusted rate ratio, 4.1). One would actually have expected the CKD group would have lower rates of nephrotoxic medication prescriptions, so the findings were particularly bothersome.
One of the most
important things in management of CKD is to avoid potential nephrotoxins.
NSAID’s (non-steroidal anti-inflammatory drugs) are probably the biggest
offender that are commonly used. The Chen review (Chen 2019)
notes “Routine administration of
NSAID’s in CKD is not recommended, especially among individuals who are taking
ACE-I or ARB therapy.”
The Chen review also
discussed common medications that require dose reductions in the presence of
CKD, including most antibiotics, direct oral anticoagulants, gabapentin and
pregabalin, oral hypoglycemic agents, insulin, chemotherapeutic agents, and
opiates, among others. Most of these categories also made the Taji (Taji
2020) consensus-based final
list of 24 medications routinely used in the primary care setting that should
be avoided or dose adjusted based on a patient’s eGFR:
·
antibiotics
(ciprofloxacin, co-trimoxazole, levofloxacin, nitrofurantoin)
·
anticoagulants
(apixaban, dabigatran, edoxaban, rivaroxaban)
·
anticonvulsants
(gabapentin, pregabalin
·
antivirals
(acyclovir, valacyclovir)
·
antidiabetic
agents (canagliflozin, dapagliflozin, empagliflozin, glyburide, metformin),
·
other
medications (baclofen, digoxin, colchicine, lithium, spironolactone, fibrates,
duloxetine)
The Taji study also produced a list of 12 medications that
could be considered for dose adjustment or avoidance, including:
·
solifenacin
·
tolterodine
·
famciclovir
·
oseltamivir
·
gliclazide
·
saxagliptin
·
sitagliptin
·
bisphosphonates
·
escitalopram
·
metoclopramide
·
rosuvastatin,
·
venlafaxine
The Taji
lists do not include over-the-counter medications or commonly used herbal or
alternative medication remedies. The Chen review notes, in
particular, those herbal remedies containing aristolochic acid or
anthraquinones have been associated with a variety of adverse renal effects.
Not included in the
list compiled by Taji et al. (Taji
2020) are drugs that should be avoided because they may aggravate
some complications of CKD. For example, the Chen review notes that phosphate-based bowel preparations (both oral
and enema formulations), which are readily available over-the-counter,
can lead to acute phosphate nephropathy.
The Chen review also
clarified some issues about the use of PPI’s (proton pump inhibitors) in
patients with CKD. Though it concludes that uniform discontinuation of proton
pump inhibitors in CKD is not necessary, it does suggest that indications for
use of PPI’s should be addressed at each primary care visit. (Of course, in our
many columns on polypharmacy and deprescribing, we’ve frequently discussed that
PPI’s are often inadvertently continued without clear-cut indications in all
patients, not just those with CKD.)
The Chen review
notes that gadolinium-based contrast agents are contraindicated in individuals
with acute kidney injury, eGFR less than 30 mL/min/1.73 m2, or end-stage kidney
disease, given the risk of nephrogenic systemic fibrosis (NSF). It goes on to
note that newer macrocyclic chelate formulations (eg,
gadoteridol, gadobutrol, or gadoterate)
are much less likely to cause nephrogenic systemic fibrosis, but that the best
prevention may still be to avoid gadolinium altogether. They recommend that, if
administration of gadolinium is deemed essential, the patient must be counseled
on the potential risk of nephrogenic systemic fibrosis and a nephrologist may
be consulted for consideration of postexposure hemodialysis.
Other contrast dyes,
such as those used in CT scanning and angiography, may rarely be associated
with Contrast Induced Nephropathy (CIN). About 2 percent of people receiving
dyes can develop CIN (NKF 2019). However, the risk for CIN can increase for people with diabetes, a
history of heart and blood diseases, and chronic kidney disease (CKD). The risk
of CIN in people with advanced CKD (GFR below 30 mL/min/1.73m2) increases to 30
to 40 percent. And the risk of CIN in people with both CKD and diabetes is 20
to 50 percent.
Clearly, caution
must be used when using such contrast agents in patients with CKD. The most
important consideration is whether contrast is absolutely
necessary for the study. If it is necessary, steps should be taken to
minimize the risk of CIN, such as ensuring adequate hydration, using the least
amount of contrast necessary, and avoiding repeat contrast administration too
soon.
It’s also important
to monitor the patient for CIN or NSF after studies utilizing each type of
contrast agent, respectively.
Similarly, your CPOE and e-Prescribing systems and radiology information systems (RIS) should have decision support tools that automatically check the eGFR when any study is ordered using contrast or gadolinium contrast and issue alerts as appropriate.
Update: After we posted this column, Wooden and
colleagues (Woolen
2020) published a systematic review
and meta-analysis on the incidence of the risk of nephrogenic systemic fibrosis
in patients with stage 4 or 5 chronic kidney disease receiving a group II
gadolinium-based contrast agent. Agents in the American College of Radiology
classification group II GBCA are: gadobenate dimeglumine, gadobutrol, gadoterate meglumine, and gadoteridol. They found that the
risk of NSF from group II GBCA administration in stage 4 or 5 CKD is likely
less than 0.07%. They suggest that the potential diagnostic harms of
withholding group II GBCA for indicated examinations may outweigh the risk of
NSF in this population.
The accompanying
editorial (Maripuri
2020) concurs that the
strength of the evidence favors a more permissive approach to using group II
GBCAs in patients with CKD, especially when contrast-enhanced MRI is the superior
imaging modality. It points out a disconnect between the more conservative
approach still maintained by the FDA and the more permissive guidelines from
the ACR. It notes a probable similar disconnect between nephrologists and
radiologists, with the former concerned that the lack of cases may be driven by
avoidance of GBCAs in high-risk patients and the latter more convinced by the
biochemical case for safety of newer GBCAs.
Some of our prior columns on dialysis, CKD, and ESRD:
March 26, 2007 “Alarms Should Point to the Problem”
February 2009 “Unintended Consequences of eGFR Reporting”
May 2009 “Erythropoiesis-Stimulating Agents and
Mortality”
September 20, 2011 “When Practice Changes the Evidence: The CKD
Story”
September 2013 “Is Nephrologist Caseload Related to Dialysis Mortality?”
September 2014 “New Tubing Connections”
June 23, 2015 “Again! Mistaking Antiseptic Solution for
Radiographic Contrast”
November 1, 2016 “CMS Emergency Preparedness Rule”
April 25, 2017 “Dialysis and Alarm Fatigue”
July 16, 2019 “Avoiding PICC’s in CKD”
December 10, 2019 “Dialysis Line Dislodgements”
References:
Chen TK, Knicely DH, Grams ME. Chronic Kidney Disease Diagnosis and Management: A Review. JAMA 2019; 322(13): 1294-1304
https://jamanetwork.com/journals/jama/article-abstract/2752067
Tuttle KR, Alicic RZ, Duru OK, et al. Clinical Characteristics of and Risk Factors for Chronic Kidney Disease Among Adults and Children: An Analysis of the CURE-CKD Registry. JAMA Netw Open 2019; 2(12): e1918169
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2757881
Lefebvre CE, Filion KB, Reynier P, et al. Primary Care Prescriptions of Potentially -Nephrotoxic Medications in Children with CKD. CJASN 2020; 15(1): 61-68
https://cjasn.asnjournals.org/content/15/1/61
Taji L, Battistella M, Grill AK, et al. Medications Used Routinely in Primary Care to be Dose-Adjusted or Avoided in People With Chronic Kidney Disease: Results of a Modified Delphi Study. Annals of Pharmacotherapy 2020; First Published January 2, 2020
https://journals.sagepub.com/doi/abs/10.1177/1060028019897371?journalCode=aopd
NKF (National Kidney Foundation). Contrast
Dye and the Kidneys. NKF 2019; Accessed January 28, 2020
https://www.kidney.org/atoz/content/Contrast-Dye-and-Kidneys
Woolen SA, Shankar
PR, Gagnier JJ, MacEachern MP, Singer L, Davenport
MS. Risk of Nephrogenic Systemic Fibrosis in Patients With
Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based
Contrast Agent: A Systematic Review and Meta-analysis. JAMA Intern Med.
2020;180(2):223–230
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2757311
Maripuri S, Johansen KL. Risk of Gadolinium-Based
Contrast Agents in Chronic Kidney Disease—Is Zero Good Enough? JAMA Intern Med.
2020;180(2):230–232
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2757307
Print “PDF version”
|
|
http://www.patientsafetysolutions.com/