Excess blood acid from kidney problem common in hATTR: Study
Nearly 20% of adults found to have urinary disorder known as RTA
Nearly every fifth adult with hereditary transthyretin amyloidosis (hATTR), a group of conditions that includes familial amyloid polyneuropathy (FAP), has renal tubular acidosis (RTA) — a problem that occurs when the kidneys fail to remove acids from the blood into the urine.
That’s according to a new study from researchers in Brazil that also found that a simple urine dipstick test may help in diagnosing this urinary disorder, known for short as RTA. Given that measures of overall kidney function were generally within normal ranges in all evaluated patients, RTA “may precede the more classically described renal [kidney] changes,” the team wrote.
“Further studies are needed to evaluate the impact of early diagnosis and treatment of RTA in this population,” the researchers added.
The study, “Renal tubular acidosis in hereditary transthyretin amyloidosis (ATTRv),” was published in the Brazilian Journal of Nephrology.
RTA marked by problem in tiny tubes in kidney
Hereditary transthyretin amyloidosis, also known as ATTRv, is caused by mutations in the TTR gene that result in toxic clumps of abnormal transthyretin protein building up in the body’s tissues and organs, causing damage.
“The clinical presentation is variable, ranging from exclusive neurological involvement [like in FAP] to sporadic cases with strictly [heart-related] manifestations,” called hATTR cardiomyopathy, the researchers wrote. Many patients have both neurological and heart involvement.
Accumulation of toxic transthyretin clumps, or aggregates, also can occur in the kidneys, with about one-third of untreated patients carrying the Val50Met mutation — the most common cause of FAP — experiencing kidney failure.
Toxic aggregates in the kidneys can interfere with how well waste and extra water are removed from the blood.
RTA comprises a problem in the renal (kidney) tubules, the tiny tubes that return needed substances back to the blood. It causes blood acids to build up in the blood, which can disturb many bodily functions. The researchers noted that this condition “could be a valuable tool in early diagnosis of renal involvement in ATTRv.” However, its frequency among patients remains unknown.
To learn more, a team of researchers from the Universidade Federal do Rio de Janeiro evaluated the presence of RTA in 49 adults with ATTRv-causing mutations at a single center in Brazil between March 2019 and February 2020.
The patients’ mean age was 40, 63% were women, and 94% carried the Val50Met mutation. Overall, the patients had been living with this diagnosis for a mean of three years, and more than half (57%) were already experiencing symptoms. Most (87.7%) had preserved kidney function, as assessed with the estimated glomerular filtration rate (eGFR).
In terms of treatment, nine (18.4%) had received a liver transplant, and six (12.2%) were taking tafamidis meglumine, approved in Brazil, under the brand name Vyndaqel, to treat FAP, hATTR cardiomyopathy, and non-hereditary transthyretin-associated cardiomyopathy.
Urine dipstick test found to be highly effective in patients
To test how well their kidneys could acidify the urine, the participants first underwent a water deprivation test in which they did not eat or drink anything for 12 hours to concentrate the urine. Several subsequent tests, including a dipstick to measure urine pH, were used to assess RTA.
The results showed that nine patients (18.37%) had changes in how the kidneys removed acids from the blood: eight (16.33%), of whom two had no symptoms, had distal RTA, and one (2.04%) had proximal RTA. Distal and proximal RTA refer to problems derived from different portions of the renal tubules.
Despite this, in those with distal RTA, there were no significant changes in acid levels in circulation, which could explain the absence of symptoms of RTA.
Also, the urine dipstick test was highly effective at discriminating patients with dRTA. Using a cut-off pH value below 5.5, the test was able to correctly identify all patients who indeed had distal RTA, and effectively rule out those without distal RTA. This suggests that a simple urine dipstick test could help screen for RTA in people with hATTR.
“To our knowledge, this is the first study to demonstrate renal tubular dysfunction in ATTRv patients as assessed by urinary acidification capacity,” the researchers wrote.
Further, the team wrote that “diagnosis of subclinical ATTRv in patients with Val50Met mutation may allow specific treatment not only to avoid the complications of [distal RTA], but also to introduce new agents that stabilize or reduce the production of the mutant [transthyretin].”
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