Table 3.

Treatment of ATTR amyloidosis: on clinical practice, under investigation and kidney impactful effects

Mechanism	Intervention		Indications (ATTRv and/or ATTRwt)	Kidney Effects/Prognosis
Substitution of the primary source of mutant TTR production	Transplantation	Organ
		Liver	ATTRv The advance of pharmacological therapy made this indication rare	Post–liver transplantation cardiorenal syndrome in long-term survival patients because of progression of ATTR cardiomyopathy Chronic calcineurin inhibitor nephrotoxicity
		Liver and kidney	ATTRv Applied in CKD5 when neurological and heart conditions are favorable and no pharmacological therapy is approved	Complicated urinary tract infections due to neurogenic bladder Progression of cardiac amyloidosis and cardiorenal syndrome
		Liver and heart	ATTRv The advance of pharmacological therapy made this indication rare	Chronic calcineurin inhibitor nephrotoxicity
TTR stabilizers bind to the TTR homotetramers preventing dissociation into monomers	Tafamidis	Meglumine 20 mg	ATTRv Applied to neuropathy	Remission to normoalbuminuria in patients with UACR >300 mg/g and improved CKD staging43
		Meglumine 80 mg or tafamidis 61 mg	ATTRv or wt Approved for cardiomyopathy	The same findings as 20 mg dosage concerning CKD staging45
	Acoramidis	ATTRibute-CM Phase 3 trial 800 mg twice daily	ATTRv or wt cardiomyopathy Evaluation in progress	AKI occurred in 12.4% of patients on the drug versus 10.4% on the placebo (no significant difference in AKI)
	Diflunisal	250 mg twice daily	ATTRv or wt	CKD stage may worsen as it is a nonsteroidal anti-inflammatory drug
TTR silencers bind an degrade TTR mRNA block the synthesis of TTR47	Antisense oligonucleotides	Inotersen 284 mg subcutaneously once weekly	ATTRv In the United States, it will no longer be available; there is a transition plan to next-generation therapy (eplontersen)	Cases associated to AKI, crescentic GN, tubulointerstitial nephritis, low complement levels, PR3-ANCA positivity,54 and segmental and focal glomerulosclerosis48
		Eplontersen 45 mg, subcutaneous, once monthly	ATTRv neuropathy ATTRv or wt cardiomyopathy—evaluation in progress	Proteinuria 8%49
	Small interference RNA	Patisiran 0.3 mg/kg Every 3 wk	ATTRv neuropathy ATTRv or wt cardiomyopathy	Remission of albuminuria37
		Vutrisiran 25 mg every 3 mo	ATTRv neuropathy ATTRv or wt cardiomyopathy50	Absence of de novo kidney features
Permanently reduce or eliminate the production of abnormal TTR by directly targeting and editing the TTR gene in the liver	CRISPR/Cas9 gene editing51	NTLA-2001 Phase 3 trial	ATTRv or wt	Not describeda
Clearance of transthyretin aggregates	IgG1 humanized mouse monoclonal antibody52	Coramitug (PRX004) Phase 2 trial	ATTRv or wt cardiomyopathy	Not describeda
Depletion of ATTR fibrils through antibody-mediated phagocytosis	Recombinant human IgG1 monoclonal antibody53	ALXN2220 Phase 3 trial	ATTRv or wt cardiomyopathy	Not describeda

ATTR, transthyretin amyloidosis; ATTRv, ATTR variant; ATTRwt, ATTR wild-type; CKD5, CKD stage 5; CRISPR/Cas9, clustered regularly interspaced palindromic repeats/Cas9; IgG1, immunoglobulin G subclass 1; TTR, transthyretin; UACR, urine albumin–creatinine ratio.

^aThe trial does not evaluate renal outcome; a trial specifically addressing renal outcomes is not available.