Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Centro de Estudos em Paramiloidose Antônio Rodrigues de Mello, Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Divisão de Nefrologia, Rio de Janeiro, RJ, Brazil.
J Bras Nefrol. 2024 Oct-Dec;46(4):e20240016. doi: 10.1590/2175-8239-JBN-2024-0016en.
Hereditary transthyretin amyloidosis (ATTRv) is a severe autosomal dominant systemic disease. It affects the peripheral and autonomic nervous systems, heart, kidneys, and eyes. Amyloid deposition has been demonstrated in the glomerular and tubulointerstitial compartments of the kidney. Therefore, urinary acidification disorders such as renal tubular acidosis (RTA) may be early manifestations of renal involvement in this population.
To evaluate the prevalence of RTA in individuals with ATTRv.
We included symptomatic and asymptomatic individuals with TTR mutation, older than 18 years, GFR >45 mL/min/1.73m2, without systemic metabolic acidosis. Urinary acidification protocol was performed with furosemide and fludrocortisone after 12 h of water deprivation (water deprivation test - WDT) and measurements of urine ammonium ( UNH 4 + ) and titratable acidity (UTA). Proximal RTA (pRTA) was diagnosed when FEHCO3>10%. Incomplete form distal RTA (dRTA) was diagnosed if UpH>5.3.
We selected 49 individuals with a mean age of 40 (35.5-56.5) years, 63% of which were female, 84% were Caucasian, and mean GFR was 85.5 ± 20.5 mL/min/1.73m2. 94% had the genetic variant Val50Met and 57% were symptomatic. The prevalence of pRTA was 2% and of dRTA was 16.3%. In the subgroup with dRTA, there was no significant increase in excretion of UNH 4 + and UTA. We observed a good correlation between UpH by potentiometry and UpH dipstick. A UpH<5.5 on the dipstick had 100% sensitivity and negative predictive value to exclude dRTA.
A high prevalence of RTA was found in individuals with TTR mutations. The UpH dipstick after WDT had good accuracy for screening for dRTA. Further studies are needed to evaluate the impact of early diagnosis and treatment of RTA in this population.
遗传性转甲状腺素蛋白淀粉样变性（ATTRv）是一种严重的常染色体显性系统性疾病。它会影响外周和自主神经系统、心脏、肾脏和眼睛。已经在肾脏的肾小球和肾小管间质腔室中证明了淀粉样物质的沉积。因此，在该人群中，肾脏受累的早期表现可能是肾脏酸化功能障碍，如肾小管酸中毒（RTA）。
评估 ATTRv 个体中 RTA 的患病率。
我们纳入了年龄大于 18 岁、肾小球滤过率（GFR）>45 mL/min/1.73m2、无全身代谢性酸中毒的 TTR 突变的有症状和无症状个体。在 12 小时禁水后进行呋塞米和氟氢可的松尿液酸化试验（WDT），并测量尿铵（UNH4+）和可滴定酸度（UTA）。如果 FEHCO3>10%，则诊断为近端 RTA（pRTA）。如果 UpH>5.3，则诊断为不完全远端 RTA（dRTA）。
我们选择了 49 名平均年龄为 40 岁（35.5-56.5 岁）的个体，其中 63%为女性，84%为白种人，平均 GFR 为 85.5±20.5 mL/min/1.73m2。94%的个体存在 Val50Met 基因突变，57%的个体有症状。pRTA 的患病率为 2%，dRTA 的患病率为 16.3%。在 dRTA 亚组中，UNH4+和 UTA 的排泄量没有显著增加。我们观察到通过电位滴定法测定的 UpH 与尿比色法测定的 UpH 之间存在良好的相关性。尿比色法测定的 UpH<5.5 对排除 dRTA 具有 100%的敏感性和阴性预测值。
在 TTR 突变个体中发现了高患病率的 RTA。WDT 后尿比色法对筛查 dRTA 具有良好的准确性。需要进一步研究以评估在该人群中早期诊断和治疗 RTA 的影响。
