Annals of African Medicine
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Year : 2023  |  Volume : 22  |  Issue : 1  |  Page : 128-130  

Tenofovir as a cause of acquired fanconi's syndrome

Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India

Date of Submission20-Sep-2021
Date of Decision16-Mar-2022
Date of Acceptance22-Aug-2022
Date of Web Publication24-Jan-2023

Correspondence Address:
Monisha Simon
#80/2 Sunny Brooks, 10th Street, Sarjapur Main Road (Next to Wipro Corporate Office), Bengaluru - 560 035, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aam.aam_198_21

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Fanconi's syndrome is a disorder that results in generalized involvement of the proximal tubule of the kidney. It is characterized by variable degrees of phosphate, glucose, and amino acid wasting in the urine and a hyperchloremic normal anion gap metabolic acidosis – secondary to defective hydrogen ion excretion and bicarbonate ion absorption. There are hereditary variants such as cystinosis (most common), hereditary fructose intolerance, galactosemia, tyrosinemia, Dents disease, and acquired variants of Fanconi's syndrome. Toxins, drug-induced diseases, and systemic diseases (multiple myeloma, Sjogren's syndrome) are the most common acquired causes of Fanconi's syndrome. The case report describes a middle-aged female patient, a known case of human immunodeficiency virus (HIV)-positive status who developed tenofovir disoproxil fumarate-induced Fanconi's syndrome, an increasingly recognized cause of acquired Fanconi's syndrome in HIV-positive patients.

   Abstract in French 

Le syndrome de Fanconi est un trouble qui entraîne une atteinte généralisée du tubule proximal du rein. Elle se caractérise par des degrés variables de perte de phosphate, de glucose, d'acide urique, d'acides aminés et de bicarbonate dans l'urine avec un trou anionique normal, une acidose métabolique hyperchlorémique. Il existe des variantes héréditaires (comme la cystinose, la tyrosinémie) et des variantes acquises du syndrome de Fanconi. Les toxines, les maladies induites par les médicaments et les maladies systémiques (myélome multiple, syndrome de Sjögren) étant la cause acquise la plus fréquente du syndrome de Fanconi.
Mots-clés: Le rapport de cas décrit une patiente d'âge moyen, un cas connu de séropositivité au VIH (virus de l'immunodéficience humaine) qui a développé le syndrome de Fanconi induit par le ténofovir, une cause de plus en plus reconnue de syndrome de Fanconi acquis chez les patients séropositifs

Keywords: Fanconi's syndrome, proximal renal tubular acidosis, tenofovir disoproxil fumarate

How to cite this article:
Simon M, Meah A. Tenofovir as a cause of acquired fanconi's syndrome. Ann Afr Med 2023;22:128-30

How to cite this URL:
Simon M, Meah A. Tenofovir as a cause of acquired fanconi's syndrome. Ann Afr Med [serial online] 2023 [cited 2023 Feb 1];22:128-30. Available from:

   Introduction Top

Fanconi's syndrome is a disorder which affects the proximal tubule of the kidney, causing defective absorbtion of bicarbonates and excretion of hydrogen ions [Figure 1]. Tenofovir disoproxil fumarate (TDF) was the first nucleotide reverse transcriptase inhibitor approved for the management of HIV.[1] Tenofovir was found to have a good safety profile during the first 5 years of administration. The most common adverse reactions noted were diarrhea, nausea, vomiting, and anorexia.[2] Cases of lactic acidosis and hepatic steatosis have been reported especially when used alongside nucleoside analogs.[3] It is excreted in the kidney via filtration and active secretion. Nephrotoxicity is an increasingly recognized adverse effect of TDF with an incidence ranging from 1% to 6%. Studies showed that TDF was associated with a higher risk of acute kidney injury-risk difference 0.7%.[4] Tenofovir alafenamide has been shown to have relatively lesser adverse effects on glomerular and tubular injury and bone mineral density.[5]
Figure 1: Cellular mechanisms of proximal tubule

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   Case Report Top

A 53-year-old female, a known case of HIV for the past 6 years, was admitted with complaints of generalized weakness, multiple episodes of loose stools, and vomiting for the past 3 days. She had no known comorbidities and she denied a history of alcohol intake or glue sniffing. On admission, she was alert, conscious, and oriented. On examination, her vitals were stable. Systemic examination revealed soft, nontender abdomen, no hepatosplenomegaly, and no palpable mass. Central nervous system examination revealed no focal neurological deficit. Respiratory and cardiovascular examination was unremarkable. She had developed generalized tonic–clinic seizures soon after admission. Laboratory reports revealed a serum sodium level of 103 mEq/L. Prompt correction was initiated with 3% hypertonic saline. In view of hypotension, she was started on vasopressor support. Serum cortisol levels were sent and were found to be low. She was started on hydrocortisone, suspecting adrenal insufficiency. A full workup for generalised tonic clonic seizures (GTCS) and altered sensorium was performed including cerebrospinal fluid routine analysis and India ink to rule out cryptococcal infection and toxoplasma IgG. Magnetic resonance (MR) imaging brain and MR spectroscopy was done which were within normal limits. A diagnosis of metabolic encephalopathy secondary to hyponatremia was made.

She was on antiretroviral treatment comprising lamivudine + efavirenz (300 mg/600 mg), all of which were low. Urine showed mild proteinuria (protein-creatinine ratio - 0.18). Urine spot potassium values were −25 mEq/L. Arterial blood gas (ABG) showed hyperchloremic normal anion gap metabolic acidosis, and hence, a diagnosis of TDF-induced proximal Renal Tubular Acidosis (RTA) (Fanconi's syndrome) was made. Hydrocortisone 50 mg intravenous was given every 6 h. The patient's blood pressure improved after the initiation of steroids. Over 10 days, steroids were tapered and stopped. Adrenocorticotropic hormone (ACTH) stimulation test was done, magnesium (1.57 mg/dl), other reports were as follows: serum potassium - 2.94 mEq/L, phosphorus - 1.88 mg/dl, and uric acid - 2.5 mg/dl, serum cortisol after 60 min - 15.42 μg/dl. A diagnosis of subclinical Addison's disease was made. She was started on stress dosing of steroids for the same.

Tenofovir was stopped and started on abacavir following a negative HLA-B*5701 test. She improved and dyselectrolytemia was corrected.

Ten days after discharge, she presented with symptoms of urinary tract infection and hypotension (systolic blood pressure - 80 mmHg). Culture reports suggested growth of Escherichia coli sensitive to cefoperazone sulbactam. She was started on injection cefoperazone sulbactam and hydrocortisone infusion at a rate of 10 mg/h. She responded well to treatment and improved clinically.

She has been on regular follow-up postdischarge for 1 year now.

   Discussion Top

In the 1930s, deToni, Debre, and Fanconi independently described Fanconi's syndrome in young children with hypophosphatemic rickets and glycosuria.[6] At present, Fanconi's syndrome is a well-defined syndrome described as a global proximal tubule dysfunction, leading to urinary excretion of amino acid, glucose, phosphate, bicarbonate, and uric acid, leading to acidosis, dehydration, and electrolyte derangement.[7]

The probable pathogenesis includes sieve-like, leaky brush borders of the cells in the basolateral membrane of the proximal tubule and abnormal Na+-K+-ATPase pump.[8]

Proximal renal tubular impairment can have varied presentations, such as proximal muscle weakness and constipation due to hypokalaemia, osteomalacia in adults, and rickets and failure to thrive in children due to phosphorus loss.[9],[10] Antibiotics such as tetracycline, cisplatin, and antiepileptics such as valproic acid and heavy metal exposure (cadmium, mercury, and lead) are a few well-known causes of drug-induced proximal RTA.[11]

Failure to identify exogenous toxins and drug-induced Fanconi's syndrome can cause extensive and potentially irreversible damage to the proximal convoluted tubule. Such patients require strict electrolyte and ABG monitoring and prompt correction of dyselectrolytemia and metabolic derangement. In addition, Vitamin D levels and calcium levels must be monitored.[12]

In the above case presented, TDF was found to be the likely cause of Fanconi's syndrome. With the discontinuation of tenofovir, her metabolic parameters improved.

Subclinical Addison's

She was administered the standard high-dose ACTH test where 250 μg of ACTH was given intramuscularly as bolus. The normal rise in serum cortisol is 18–20 μg/dl 60 min postadministration of ACTH. In our patient, the rise was only 15.42 mg/dl, suggestive of subclinical adrenal insufficiency – warranting stress dosing of steroids. She was hemodynamically stable and steroids were advised during infections/perioperative period.


She is currently on abacavir lamivudine and efavirenz regimen. She's hemodynamically stable.

   Conclusion Top

Tenofovir being the first-line drug for the treatment of HIV in our country, patients initiated on tenofovir therapy have to be closely monitored for electrolyte disturbances to facilitate early recognition and institute prompt treatment of Type 2 renal tubular acidosis. Switching to an alternative antiretroviral treatment would prevent possible irreversible damage to the proximal tubule. HIV, though a known cause of Addison's disease, patients may present with subtle symptoms and signs. It is cardinal to diagnose and treat the patient for steroid insufficiency as it can be fatal if left untreated during episodes of stress such as fever, infections, or surgery.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Fung HB, Stone EA, Piacenti FJ. Tenofovir disoproxil fumarate: A nucleotide reverse transcriptase inhibitor for the treatment of HIV infection. Clin Ther 2002;24:1515-48.  Back to cited text no. 1
Kayaaslan B, Guner R. Adverse effects of oral antiviral therapy in chronic hepatitis B. World J Hepatol 2017;9:227-41.  Back to cited text no. 2
Ying Y, Hu YK, Jin JL, Zhang JM, Zhang WH, Huang YX. Case report: Lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B. BMC Gastroenterol 2018;18:45.  Back to cited text no. 3
Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: Renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis 2010;51:496-505.  Back to cited text no. 4
Gupta SK, Post FA, Arribas JR, Eron JJ Jr., Wohl DA, Clarke AE, et al. Renal safety of tenofovir alafenamide versus tenofovir disoproxil fumarate: A pooled analysis of 26 clinical trials. AIDS 2019;33:1455-65.  Back to cited text no. 5
Foreman JW. Fanconi syndrome. Pediatr Clin North Am 2019;66:159-67.  Back to cited text no. 6
McSherry E. Renal tubular acidosis in childhood. Kidney Int 1981;20:799-809.  Back to cited text no. 7
Pereira PC, Miranda DM, Oliveira EA, Silva AC. Molecular pathophysiology of renal tubular acidosis. Curr Genomics 2009;10:51-9.  Back to cited text no. 8
Sahay M, Sahay R. Renal rickets-practical approach. Indian J Endocrinol Metab 2013;17:S35-44.  Back to cited text no. 9
Agrawa C, Chakraborty PP. Rickets in renal tubular acidosis: A clinical appraisal. J Exp Nephrol 2020;1:17-24.  Back to cited text no. 10
Haque SK, Ariceta G, Batlle D. Proximal renal tubular acidosis: A not so rare disorder of multiple etiologies. Nephrol Dial Transplant 2012;27:4273-87.  Back to cited text no. 11
Karatzas A, Paridis D, Kozyrakis D, Tzortzis V, Samarinas M, Dailiana Z, et al. Fanconi syndrome in the adulthood. The role of early diagnosis and treatment. J Musculoskelet Neuronal Interact 2017;17:303-6.  Back to cited text no. 12


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