Knee Replacement: Kidney Injury Common With Antibiotic Spacers

A large study has revealed that acute kidney injury (AKI) is a relatively common occurrence in patients treated for periprosthetic joint infections after total knee arthroplasty (TKA) with antibiotic-loaded bone-cement (ALBC) spacers.

More than one in 10 such patients developed AKI and 2% went on to develop chronic kidney disease, according to a team of Mayo Clinic researchers.

“We found that 14% of people with healthy kidneys and nearly 50% of those with a history of chronic kidney disease will have acute kidney injury with the procedures required to treat periprosthetic joint infections of the knee,” Matthew P. Abdel, MD, told Medscape Medical News. “So the sheer number of people impacted is notable.”

In addition,” said Abdel, “it appears that a several factors that affect perioperative blood supply to the kidneys also increased the risk of AKI.” Abdel is the Andrew A. and Mary S. Sugg Professor of Orthopedic Surgery and Chair of the Division of Orthopedic Surgery Research at the Mayo Clinic in Rochester, Minnesota.

As Abdel explained, the most common method for managing periprosthetic joint infections after TKA is two-stage exchange arthroplasty using high-dose ALBC spacers plus intravenous or oral antibiotics. Yet despite the popularity of the approach, there is concern that high doses of local antibiotics may be systemically absorbed, thereby increasing the risk for nephrotoxicity, particularly when combined with systemic antibiotics and surgery.

Nevertheless, little is known about the incidence and outcome of AKI among these individuals, or about risk factors for the development of the injury. What’s more, although there have been other reports of nephrotoxicity in these patients, there is scant evidence regarding the long-term outcomes of renal injury in this setting.

Given these issues, the researchers reviewed the institution’s total joint registry for all two-stage exchange arthroplasties performed from 2000 to 2017 that had been treated with an ALBC spacer after resection arthroplasty for a chronic periprosthetic joint infection following TKA. In total, they identified 424 patients (53% men; mean age, 67 years; mean BMI, 33 kg/m2) treated with 455 spacers. Fifteen percent of the patients had pre-existing chronic kidney disease.

Spacers contained a mean of 8 g vancomycin and 9 g of an aminoglycoside, which were kept in situ for a mean of 11 weeks. Eighty-six spacers also had amphotericin B (mean, 412 mg). At the same time, all patients received systemic antibiotics for a mean of 6 weeks.

For purposes of the investigation, AKI was defined as a creatinine level at least 1.5 times greater than baseline or an increase of at least 0.3 mg/dL in any 48-hour period. Patients were followed for a mean of 6 years (range, 2 – 17 years).

As Abdel reported, 54 AKIs occurred in 52 of the 359 patients who did not have pre-existing chronic kidney disease (14%). By comparison, 32 AKIs were observed in 29 of the 65 patients who did have pre-existing chronic kidney disease (45%; odds ratio [OR], 5.0; P = .0001). Nevertheless, no patient required acute dialysis.

Interestingly, the investigation also showed that when the vancomycin or aminoglycoside concentration exceeded 3.6 g/batch of cement, the risk for AKI increased significantly (OR, 1.9 and 1.8, respectively; P = .02 for both).

Among patients without pre-existing chronic kidney disease, the causes of acute renal blood flow impairment were shown to be independent predictors of AKI. This included hypertension (b = 0.17; P = .002), perioperative hypovolemia (b = 0.28; P = .0001), and acute atrial fibrillation (b = 0.13; P = .009).

At the trial’s final follow-up, eight of the individuals who had an AKI had progressed to chronic kidney disease. Four of these patients received dialysis.

Given the high risk for AKI after TKA among patients with pre-existing chronic kidney disease, the investigators emphasized the importance of screening to identify patients with possible decreases in kidney function before two-stage exchange arthroplasty.

“These surgeries need to be performed given patient debility and risk for septicemia and death in some,” Abdel explained. “But as a result of the study, we are now much more in tune with our patients’ preoperative kidney function, as well as the kidney function in the perioperative period.”

And, continued Abdel, “we’re also much more aware of their perioperative fluid status, and make sure we keep the kidneys hydrated, with appropriate blood supply…. Finally, the study highlights the need to optimize these patients preoperatively and perioperatively to protect their kidneys. That includes avoiding nephrotoxic agents, certain anti-inflammatory medications, and potentially renally adjusting antibiotic dosing.”

Commenting on the findings for Medscape Medical News, Bryan D. Springer, MD, Fellowship Director at the OrthoCarolina Hip and Knee Center, Charlotte, North Carolina, said the challenge in treating patients with periprosthetic joint infection is in delivering a high enough concentration of antibiotic to the site without creating systemic problems. “While local delivery allows for high concentration of antibiotic delivery, there is clearly systemic absorption and when combined with systemic administration of antibiotics, patients are at risk for kidney injury.”

Springer said that one of the most helpful aspects of this study is that it identifies patients at higher risk for development of AKI. “This study emphasizes that all patients undergoing two-stage exchange for periprosthetic joint infection need to be closely monitored in the postoperative period for AKI, and that those at high risk for AKI perhaps need to have adjustments made to the antibiotic utilized in the cement and systemically should avoid all other nephrotoxic drugs and need to be monitored for hypovolemia.”

Abdel disclosed a financial relationship with Stryker, unrelated to the current research. Springer has disclosed no relevant financial relationships.

J Bone Joint Surg Am. Published online March 29, 2021. Abstract

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