Many UK Children With Kidney Disease May Be Prescribed Nephrotoxic Drugs

By Marilynn Larkin

December 18, 2019

NEW YORK (Reuters Health) - Primary care practices in the UK seem to be prescribing nephrotoxic drugs to many children with chronic kidney disease (CKD), a retrospective analysis reveals.

"CKD is rare in children," Dr. Michael Zappitelli of the Toronto Hospital for Sick Children told Reuters Health by email. "However, children have many years ahead of them; therefore, anything which can slow the progression of CKD and delay its complications, need for dialysis or kidney transplant, or avoid episodes of acute kidney dysfunction, has the potential to greatly benefit these patients and reduce healthcare costs."

Avoiding nephrotoxic medication is one way to minimize CKD worsening/progression, he said. "Of note, non-nephrotoxic drug alternatives are often available."

The study included data from children registered at UK general practices from 1997 to 2017. Those with a clinical code indicating an incident diagnosis of CKD were matched 1:4 to children without CKD. Children were followed for a mean of 3.3 years.

The prevalence of the following potentially nephrotoxic medication prescriptions was calculated:

- Category A: aminoglycosides, antivirals, nonsteroidal antiinflammatory drugs, salicylates, proton pump inhibitors, immunomodulators.

- Category B: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

As reported in the Clinical Journal of the American Society of Nephrology, from among more than 1.5 million eligible patients, 1,018 incident CKD and 4,072 non-CKD matches (mean age, 9.8 years; 52% male) were included.

Overall, 26% of children with and 15% of those without CKD were prescribed one or more potentially nephrotoxic drugs during follow-up. The overall rate of category A nephrotoxic medication prescriptions was 71 prescriptions per 100 person-years in children with CKD and eight per 100 person-years in those without (adjusted rate ratio, 4.1).

When category B drugs were considered, the rate was 278 prescriptions per 100 person-years in children with CKD and 44 per 100 person-years in patients without CKD (aRR, 4.0).

Dr. Zappitelli said, "On a clinical level, nephrology specialists need to communicate to primary care physicians the risk associated with prescribing nephrotoxic medications; in turn, patients with CKD also need to become aware of the risk."

"Similarly," he noted, "pharmacists would ideally be highly attuned to understanding and/or checking which drugs may cause kidney damage, inform patients and communicate with physicians to find alternatives."

"Achieving this will require knowledge dissemination," he said. "As a start, nephrology specialists and pharmacists working in centers caring for patients with CKD can begin systematically including nephrotoxic medication avoidance as a recommendation to PCPs in their medical communications and consider institutional 'best practice' guidelines on prescription of nephrotoxic medication."

"On a national or provincial level, it could be feasible to work with pharmacy societies to determine the best way to institute simple strategies to evaluate risk when dispensing medication," he suggested. "One example would be a simple question such as 'Have you ever had kidney problems before?' which could prompt evaluation for a suitable alternative drug."

Dr. Stuart Goldstein of Cincinnati Children's Hospital in Ohio, author of a related editorial, commented by email that CCHMC has a program to educate patients with CKD and those who have had an episode of acute kidney injury and their families about medications to avoid. Patients or family members are instructed to call the hospital if they are prescribed any new medications.

"I am currently working with the American Society of Nephrology on their AKI!NOW initiative ( to educate patients who survive an acute kidney injury episode on the issue of nephrotoxic medications," he told Reuters Health. "The National Kidney Foundation and American Society of Pediatric Nephrology also have many patient-centered educational materials on this topic."

SOURCE: and Clinical Journal of the American Society of Nephrology, online December 12, 2019.