A case study of Amiodarone-induced nephropathy

Amiodarone is well known for a myriad of side effects, some severe and life-threatening, including pulmonary toxicity, hepatotoxicity, and thyrotoxicity. One of the organs which could be affected by Amiodarone is Kidney,


Amiodarone is well known for a myriad of side effects, some severe and life-threatening, including pulmonary toxicity, hepatotoxicity, and thyrotoxicity. One of the organs which could be affected by Amiodarone is Kidney, which, fortunately, is not a common occurrence. Searching literature does not return much information regarding the renal side effects of amiodarone. There have been few case studies in this regard, as I have listed in references. In one study by R. Luciani et al., renal impairment has been attributed to severe hypothyroidism, caused by amiodarone and not a direct effect of amiodarone [5]. In another report by Pintavorn et al., amiodarone-induced phospholipidosis has been shown in the biopsy samples, but this patient has also received many other medications during hospitalization, many of them known to be nephrotoxic [2]. In the case I am presenting, the patient started with a normal renal function and did not receive any other nephrotoxic medications. Her TSH did rise, but T4 remained normal.

Case Presentation

An 80-year old female was referred for cardiac review after noticing an “irregular” pulse on a physical exam. Her only complaint was slight fatigue; otherwise, she was feeling well, with good exercise tolerance. She was independent for all daily activities, driving and played tennis once a week. Her past medical history was only remarkable for hypertension and gout, and her father died of a stroke at 59. She was non-smoker with no diabetes. Her BP was 110/60 mmHg, and pulse was 115 bpm, in Atrial Fibrillation. Her physical exam was otherwise unremarkable. She was on Telmisartan HCTZ 80/12.5, Crestor 5 mg/d, Amlodipine 5 mg/d, and Atenolol 50 mg BID. Her renal function was normal.

During the first visit, she was started on Rivaroxaban 20 mg daily and her Atenolol was switched to Sotalol, 40 mg BID, which was increased to a maximum of 120 mg BID withing three weeks, with no success. 

Initial ECG
Atrial Fibrillation - Click to enlarge
ECG on Sotalol - Click to enlarge

Echocardiogram: Here are few initial echocardiogram loops showing impaired global left ventricular function with mild to moderate mitral regurgitation, while in Atrial Fibrillation.

At this time, Sotalol was ceased, and she was started on Amiodarone; 400 mg TDS for three days, 400 mg BID for five days, then 200 mg/d. Two weeks later, she was in sinus rhythm and was feeling “more energetic.”  


Sinus Rhythm on Amiodarone

Nearly one month after initiation of Amiodarone, her Creatinine and TSH started rising (115 mmol/L and 7.9 mIu/L respectively), while T4 remained stable. Two months later, her Creatinine was 245 mmol/L (2.77 mg/dl), and TSH rose to a maximum of 13. At this time, Most of her medications, including Rivaroxaban and Amiodarone, were ceased, and she was only on Atenolol 50 mg daily and Amlodipine 5 mg daily. She remained in Sinus rhythm and was totally asymptomatic. She refused admission to the hospital since the beginning of her presentation. Lab results along the plots, are attached below.

click to enlarge
click to enlarge

One month later, after cessation of Amiodarone, she remained in Sinus rhythm, and Creatinine was improving. She was asymptomatic all along. Her BP was stable at 130/70 mmHg and heart rate at 55 bpm. When eGFR reached 37, she was restarted on Rivaroxaban, 15 mg daily. Her renal function continued to improve, LV function normalized, and mitral regurgitation reduced significantly.

Sinus Rhythm on Atenolol

Echocardiogramin Sinus Rhythm: Here are few echocardiogram loops showing improved left ventricular function with near complete resolution of mitral regurgitation.


Extensive research has been done regarding the pathophysiology of Amiodarone-induced toxicity, and it seems that Drug-induced Phospholipidosis (DIP), plays a big role. This is basically, excessive accumulation of phospholipids in lysosomes of various tissue types. 

DIP was first reported in 1948 when Nelson and Fitzhugh observed the induction of foamy macrophages in rats treated with chloroquine. Pulmonary and Hepatic Phospholipidosis has been well-recognized and documented side effects of Amiodarone. On the other hand, Renal Phospholipidosis is less recognized, especially in the drug-induced form. 

Some other drugs that are known to cause DIP include Gentamycin, Chloroquine, and Hydroxychloroquine, as well as Perhexiline. These are cationic amphiphilic substances, which cause an acquired form of Lysosomal Storage Disease mostly by deactivating various types of lysosomal phospholipases. Having said that, the exact mechanism for DIP is not well-known, limiting the use of some highly effective drugs, such as Amiodarone. 

If there was a way to assess the individual susceptibility to DIP prior to the use of such drugs, many side effects would be avoided, and many would benefit from the effects. Whether our patient has a genetic susceptibility to DIP is not quite known. 

Awareness should be raised regarding the potential renal side effects of Amiodarone and the need to monitor renal function regularly after subscription.


1. Shayman JA, Abe A. Drug induced phospholipidosis: an acquired lysosomal storage disorder. Biochim Biophys Acta. 2013;1831(3):602–611. doi:10.1016/j.bbalip.2012.08.013

2. Pintavorn P, Cook WJ. Progressive renal insufficiency associated with amiodarone-induced phospholipidosis. Kidney Int. 2008;74(10):1354–1357. doi:10.1038/ki.2008.229

3. Fitzhugh OG, Nelson AA, Holland OL. The chronic oral toxicity of chloroquine. The Journal of pharmacology and experimental therapeutics. 1948; 93:147–152. [PubMed: 18865197

4. Reasor MJ, Kacew S. Drug-induced phospholipidosis: are there functional consequences? Exp Biol Med 2001; 226: 825–830.

5. Luciani R, Falcone C, Principe F, Punzo G, Menè P. Acute renal failure due to amiodarone-induced hypothyroidism. Clin Nephrol. 2009;72(1):79–80. doi:10.5414/cnp72079

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