TAVR and Chronic Kidney Disease: An Emerging Odd Couple

Transcatheter aortic valve replacement (TAVR) appears to stabilize or improve renal function in most patients with severe aortic stenosis and chronic kidney disease (CKD), according to new data from the PARTNER trials.

The improvement in renal function was most evident in patients with advanced CKD stage 3B or 4.

“Less than 1% of stage 4 patients actually got worse or ended up on dialysis and we thought that was really impactful and, in fact, about 50% of those patients actually moved up to stage 3B or stage 2, in some instances,” Robert J. Cubeddu, MD, Heart and Vascular Institute, Cleveland Clinic Florida, Weston, Florida, the study’s lead author, told theheart.org | Medscape Cardiology.

Baseline and post-operative renal function are known risk factors for mortality after TAVR, and the procedure itself carries a risk for acute kidney injury. Recent studies, however, have reported that 61% of CKD patients had improved renal function after surgical valve replacement and that only 24% of inoperable and high-risk patients in PARTNER IA and IB had worsening estimated glomerular filtration rate (eGFR) post-TAVR.

Cubeddu and colleagues cast the net wider, evaluating 5190 patients of inoperable, high, and intermediate risk with severe symptomatic aortic stenosis (AS) in the PARTNER 1, 2, and 2 S3 trials. The trials excluded patients on dialysis or who were peridialysis (creatinine >3.0 mg/dL).

Most patients were male (55%), their mean age was 84 years, and 2901 had an eGFR measurement within 7 days post-TAVR.

At baseline, CKD was stage 1 in 9.4% of patients, stage 2 in 37%, stage 3A in 27%, stage 3B in 21%, and stage 4 in 5.8%.

The prevalence of CKD stage 2 or greater reached 91%, Cubeddu noted.

“I don’t think as clinicians we have formally tied these two entities together as correlates of disease and cross-organ crosstalk,” he said. “Sometimes we just take it into account; we feel well, the GFR is 55 but they’re also 82 years old and we just attribute it to their hypertension, their age. But I think that high prevalence alone really says a lot and the fact that some of these patients get better is highly indicative and supportive that there’s an intrinsic mechanistic relationship here.”

CKD stage was improved or unchanged in 89% of patients within 7 days of TAVR, and only 2% of patients (70/3546) required temporary dialysis.

Specifically, CKD stage was stable or improved in 77% of patients in stage 1, 90% in stage 2, 89% in stage 3A, 94% in stage 3B, and 99% in stage 4; and worsened in 23%, 10%, 11%, 6.2%, and 0.82%, respectively.

Higher preoperative eGFR and transfemoral access were strong predictors of postoperative renal function. Contrast volume did not pan out as a predictor of worsening kidney function, likely because volume decreased over time and was inversely correlated with baseline eGFR, Cubeddu suggested.

Similar to other studies, lower post-TAVR eGFR was associated with higher 1-year mortality, the authors reported in the Journal of the American College of Cardiology.

“The findings of Cubeddu et al may change the prevailing approach to patients with severe symptomatic AS and CKD,” Benjamin Galper, MD, MPH, from the Mid-Atlantic Permanente Medical Group, McLean, Virginia, and colleagues write in an accompanying editorial. “Previously, both CKD patients and their physicians may have been reluctant to pursue TAVR, fearing worsening post-procedure renal function.”

Though the data provide guidance and reassurance, Cubeddu and colleagues also propose that in patients with asymptomatic severe AS the presence of impaired renal function may represent a marker of disease severity and early end-organ damage.

“I remember writing that and I thought, this is really the message,” Cubeddu remarked. “The highlight of this paper is that we sit on patients with aortic stenosis and their creatinine a year ago was 1.0 but now it’s 1.3. Well a lot of people think that doesn’t mean that much: ‘give them a little fluid,’ but that’s a 30% increase in worsening renal function,” he said. “It’s very subtle and we just kind of dismiss it. But I think it’s the kidneys telling us, hey, I’m hypoperfused, there’s venous congestion, your adrenals are probably a little bit more squeezed because they’ve got to generate a higher stroke volume to overcome the aortic stenosis and your perfusion pressure and gradients across the kidneys are compromised to the extent that you should now start seeing a bump in renal function, a bump in creatinine or a drop in eGFR.”

That said, variables such as perfusion pressure, gradients, cytokines, and urine or sodium concentrations were never measured in the secondary analysis, Cubeddu noted. “So it’s kind of speculative but certainly very provocative and it would explain the results of our findings.”

Based on the results, however, Galper and colleagues say it’s reasonable to recommend TAVR with judicious contrast use as part of a strategy to stabilize and improve kidney function in patients with progressive CKD and severe AS who are otherwise good TAVR candidates.

“Given the interplay between worsening AS and kidney function in cardiorenal syndrome, the progression of CKD may actually be the first ‘symptom’ of severe AS and an indication that a patient with CKD may benefit from TAVR, even before subjective symptoms are present,” they write.

Future research such as the EARLY TAVR trial, evaluating TAVR with the Edwards SAPIEN 3 / SAPIEN 3 Ultra heart valves versus clinical surveillance, may help determine the role of early TAVR in otherwise asymptomatic patients, including some with cardiorenal syndrome, Galper said.

The PARTNER trial was funded by Edwards Lifesciences. This study was supported in part by the Drs Sidney and Becca Fleischer Heart and Vascular Education Chair and The Delos M. Cosgrove, MD, Chair for Heart Disease Research. Cubeddu has received fees for educational speaker and proctor-related activities through Edwards Lifesciences and Abbott Vascular. Coauthor conflicts of interest are listed in the paper. Galper and coeditorialist Andrew Goldsweig reported no relevant financial relationships. Coeditorialist Deepak Bhatt reported numerous relationships with industry, including serving on the advisory board for Medscape Cardiology.

J Am Coll Cardiol. 2020;76:1410-21 and 1422-24. Abstract, Editorial

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