#69 CKD: Prescribing Do’s and Don’ts with @kidney_boy, Joel Topf

November 27, 2017 | By Justin Berk

Flush away your bad prescribing habits in chronic kidney disease with tips from @kidney_boy, Joel Topf, MD Salt Whisperer and Chief of Nephrology at Kashlak Memorial Hospital. Find out which drugs/substances stay on and off Santa’s naughty-list in this fast paced rundown of common nephrotoxins, backed up with a sack full of memorable research studies. Topics include: NSAIDs, proton pump inhibitors, ace inhibitors, trimethoprim-sulfamethoxazole, and contrast-induced nephropathy. Special thanks to Annie Medina, Justin Berk and Kate Grant for writing/producing this show and to physician artist, Kate Grant for her lovely/hilarious artwork (more at paintscientific.com).

Join our mailing list and receive a PDF copy of our show notes every Monday. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com.

Clinical Pearls:

1. Many medications cause serious issues in patients with  chronic kidney disease (CKD).
2. Bactrim (trimethoprim-sulfamethoxazole) was associated with 3 excess cardiac deaths per 1,000 prescriptions presumably due to hyperkalemia (i.e. patients with CKD at risk)
3. Bactrim blocks K+ secretion in renal tubule: blocks ENaC channels in distal nephron causing hyperkalemia (acts like amiloride)
4. Bactrim also competes with creatinine secretion so may cause a benign rise in serum creatinine
5. Patients with CKD depend on prostaglandins for vasodilation of afferent arterioles and renal blood flow. NSAIDs block prostaglandin activity and can cause acute kidney injury. Risk is high in patient taking an NSAID + ACE inhibitor (ACE-I) + diuretic (or if volume depleted)!
6. KDIGO Guidelines recommend avoiding NSAIDS in patients with CKD, but the evidence suggests that risk of NSAID use in CKD patients is pretty low:
7. NSAIDS
   • The Male Physician Study showed no elevation in serum creatinine with consistent NSAID use
   • The PRECISION Trial also showed only ~1% risk of kidney events in CKD patients with daily high-dose NSAIDs
   • We’d avoid in CKD 4. Consider cautious use in CKD 2-3.
8. “Strong” observational data demonstrates a link between proton pump inhibitors and CKD. Mechanism unclear, but theories include recurrent acute interstitial nephritis(AIN)/acute kidney injury (AKI), chronic hypomagnesemia, and interference with the potentially renoprotective alkaline tide phenomenon (Toth-Manikowski, S and Gram M Kidney Int Reports May 2017)
9. With ACE-inhibitors (e.g. lisinopril): Expect a rise in serum creatinine. If the creatinine bump > 30%, stop ACE-I therapy. An increase in creatinine after ACE-I may show greatest risk of mortality (though it unclear what would happen if the patients with bumps were not on ACE-I)
10. Contrast-induced kidney injury (CIN) may be overestimated in literature. The AMACING trial shows that pre-hydration does not reduce kidney injury in those exposed to contrast. True CIN likely much more rare than commonly thought!
11. Metformin is OK to use until estimated GFR is under 30 ml/min
12. ACE-Is demonstrate a significant reduction in progression of chronic kidney disease and reduction in proteinuria per the RENAAL and IDNT trials. Less patients had doubling of serum Cr, and progression to end-stage renal disease (ESRD). Mortality benefit was NOT observed.
13. Spironolactone and non-DHP calcium channel blockers (verapamil, diltiazem) can reduce proteinuria but have not been shown to improve clinical outcomes in CKD (source UpToDate).
14. Canagliflozin and empagliflozin (SGLT2-inhibitors): shown to decrease mortality albuminuria, and loss of renal function among patients type 2 diabetes at high cardiovascular risk in the CANVAS and EMPA-REG studies. View Dr. Topf’s video summary of the studies or read his blogpost on Precious Bodily Fluids

Goal: Listeners will comprehend the potential benefits and harms for common drugs/substances utilized in patients with chronic kidney disease.

Learning objectives:
After listening to this episode listeners will…

1. Avoid the use of trimethoprim-sulfamethoxazole in CKD and recall the risks and proposed mechanisms
2. Reconsider the true risk of using NSAIDs in mild, stable CKD
3. Question whether contrast induced nephropathy is real and/or common
4. Recall the potential renoprotective effects of SGLT2-i
5. Explain the proposed mechanism of nephrotoxicity for commonly utilized medications

Disclosures: Dr Topf lists the following disclosures on his website: “I am on the speakers bureau for Astute Medical. I have an ownership stake in four Davita run dialysis clinics and one vascular access center. Astellas paid for my trip to Australia (Feb ’15) for me to speak at one meeting and three hospitals. Takeda Oncology made a donation to MM4MM the program that is taking me to Mount Everest in 2018.”

Time Stamps

• 00:00 Intro
• 03:00 Which medications should we exercise caution over in CKD?
• 03:31 Bactrim (Trimethoprim+Sulfamethoxazole)
• 07:00 NSAIDS
• 08:29 NSAIDS and the ‘Precision’ Trial NEJM 2016 looking at cardiovascular safety
• 12:50 The Male Physician Study JAMA 2001
• 13:50 Discussion about Nurses Health Study and use of analgesia, and CKD
• 15:15 Acute Interstitial Nephritis, Beta Lactam Antibiotics, and the risk of Acute kidney injury +/- CKD with Proton Pump Inhibitors
• 18:20 Advice for co-prescribing NSAIDS,ACE inhibitors and diuretics
• 20:39 Creatinine levels and ACE/ARB prescribing. How High can you go?
• 24:55 Facebook question from listener: measures to reduce proteinuria in hypertensive patients
• 27:20 Empagliflozin and renal protection in diabetic patients
• 32:00 Contrast Induced Nephropathy, the AMACING trial 2016.
• 38:00 Take Home Points
• 39:57 Outro

Links from the show:

1. Check out Joel Topf’s slide deck and videos from a recent Nephrology Update 2017 talk
2. Bactrim associated with 3 excess cardiac deaths per 1,000 prescriptions
3. The Male Physician Study in JAMA 2001 showed no elevated in Scr with NSAIDs
4. PRECISION Trial  showed that CKD patients with daily high-dose NSAIDs, only ~1% had any kidney events
5. Increase in creatinine after ACE-I may show greatest risk of mortality
6. Contrast-induced kidney injury may be overestimated in literature and by physicians
7. AMACING trial: pre-hydration does not reduce kidney injury in those exposed to contrast
8. RENAAL and IDNT studies show a significant reduction in progression of CKD
9. CANVAS and EMPA-REG studies demonstrated a decrease in renal outcome composites
10. Proton Pump Inhibitors and CKD editorial review https://www.ncbi.nlm.nih.gov/pubmed/28845467