Is Renal Infarction Linked to Cardiac Amyloidosis?

Veronica Hackethal, MD

June 04, 2019

Renal infarction in cardiac amyloidosis may not be as rare as previously thought, especially in patients with acute kidney injury (AKI), according to a French study recently published in the Mayo Clinic Proceedings.

The work is the first detailed investigation of renal infarction in patients with cardiac amyloidosis. Amyloidosis refers to a group of disorders in which amyloid, a misfolded protein, forms fibers that accumulate in various organs and disrupts organ functioning.

"The prevalence of renal infarction and the risk factors for this condition have never before been assessed in this patient population," senior author Vincent Audard, MD, PhD, said in a press release.  

Audard is affiliated with the Université Paris Est Créteil, France.

He and his colleagues note their study therefore suggests that renal infarction, which is generally considered a rare event, is likely more widespread in patients with heart failure than previously thought.

"Overall, these data suggest that renal infarction should probably be added to the spectrum of renal manifestations related to systemic amyloidosis in cases of heart involvement," Audard notes.

"We recommend that a diagnosis of renal infarction should be systematically considered in patients with unexplained AKI in the context of cardiac amyloidosis," he adds.

In a linked editorial, however, Nelson Leung, MD, of the Mayo Clinic, Rochester, Minnesota, writes that the 20-25% prevalence rate of renal infarction is "unexpected," and he questions the results.

"These findings are intriguing, as I have yet to diagnose a case of renal infarction, despite having seen hundreds of patients with amyloidosis," he says. In particular, he queries the method used to screen for renal infarction.

Investigating Amyloidosis, With and Without Cardiac Involvement

The organs involved in systemic amyloidosis depend, in part, on the type of amyloid and innate property of the individual proteins, which remains incompletely understood.

One of the most common types of amyloidosis is nonmutated, wild-type transthyretin (TTR) amyloidosis, which predominantly affects the heart.

Other common types include acquired systemic immunoglobulin light chain (AL) amyloidosis (which can affect all organs but usually spares the brain) and hereditary forms caused by genetic mutations that code for abnormal proteins (mutant TTR amyloidosis, which usually affects the heart, nerves, and eyes).

Cardiac involvement and progressive renal impairment are common in systemic amyloidosis. Patients often develop cardiac arrhythmias, especially atrial fibrillation and/or nephrotic syndrome, both of which can increase the risk for blood clots. These clots, in turn, could play a role in renal infarction.

Prognosis of the patient is predominately determined by the presence of heart involvement. Those with severe heart involvement, classified as stage IIIB heart failure, have the shortest survival, at a median of 6 months. The cause of death in patients with cardiac amyloidosis is usually sudden cardiac death, so strategies to address this have involved the use of implantable cardioverter defibrillators (ICDs).

To investigate the prevalence of and risk factors for renal infarction in patients with cardiac amyloidosis, first author Julien Dang, MD, of Assistance Publique des Hôpitaux de Paris, France, and colleagues, conducted an observational study that included 87 patients with confirmed cardiac amyloidosis and 16 with amyloidosis but without cardiac involvement.

Patients were seen in the Amyloidosis Referral Center of Henri-Mondor Hospital, Créteil, France, between October 2015 through February 2018.

Among participants with cardiac involvement who were screened for renal infarction using technetium-99m-labeled dimercaptosuccinic acid renal scintigraphy (99mTc_DMSA), 24 had AL amyloidosis; 24 had mutated-TTR amyloidosis, one of the hereditary forms; and 39 had wild-type TTR amyloidosis.

Almost Half of Those With Amyloidosis and AKI Had a Renal Infarction

Results showed relatively high rates of renal infarction: 20.7% (18 of 87) among those with amyloidosis with cardiac involvement and 25% (4 of 16) among those without cardiac involvement.

Those with cardiac involvement had similar rates of renal infarction regardless of the type of amyloidosis.

And those with cardiac involvement and AKI were significantly more likely to have renal infarction — experience by almost half — compared to those with cardiac involvement without AKI (47.1% [8/17] vs 14.5% [10/69]; P = .003).

There was also an association between AKI on the day of the DMSA and a positive DMSA scan. Two patients died and two patients required renal replacement therapy within a month of a positive DMSA scan.

But analyses that excluded heart transplant patients suggested no difference in survival between those with and without renal infarction (P = .64).

However, after censoring for death and heart transplant, kidney survival was significantly lower in those with renal infarction compared to those without (P < .001).

The study cannot determine the cause of renal infarction in patients with cardiac amyloidosis, only that the two conditions may be associated, say the authors. 

They mention several possible explanations, such as kidney damage caused by amyloid deposits, renal failure due to low cardiac output, or blood clots caused by cardiac arrhythmias. Further research is needed to investigate underlying mechanisms and determine optimal treatment, they conclude.

"Regardless of the type of amyloidosis, a diagnosis of renal infarction should be considered in patients with unexplained AKI," they stress.

"Further studies are now required to evaluate the potential value and optimal type of curative anticoagulation therapy and to identify the mechanisms underlying renal infarction in patients with cardiac amyloidosis," they conclude.

Study Should Stimulate More Research

In his editorial, Leung explains that CT and MRI are the gold standards for diagnosing renal infarction.

But many patients with amyloidosis cannot undergo CT because the contrast could exacerbate underlying renal disease. Likewise, these patients often have heart devices, such as ICDs, and are therefore not candidates for MRI.

In the current study, the French researchers screened for renal infarction using 99mTc_DMSA, which they validated in a kidney transplant patient.

However, this method may not accurately detect renal infarction in patients with amyloidosis, Leung argues.

He also notes that thromboembolism to the kidney is "exceedingly rare" and that the study provides no evidence to support thromboembolism, as neither intestinal ischemia, limb ischemia, nor loin pain occurred in patients with abnormal scans.

It's possible that the abnormal DMSA scans may represent vascular deposits of amyloid and regions of renal ischemia, rather than renal infarcts, he suggests.

"This would explain the higher rate of stage I and II AKI on the day of the scan as well as the gradual loss of kidney function over the course of the study, whereas the patients with negative scans exhibited stable renal function," he said.

Nevertheless, he concludes that the study has value as a stimulus for further research.

"These intriguing and novel findings call attention, in general, to the presence and spectrum of renal involvement [in amyloidosis] beyond that which is conventionally considered and, in particular, to the occurrence of regional renal ischemia."

The authors and editorialist have reported no relevant financial relationships.

Mayo Clin Proc. 2019;94:936-938, 961-975.

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