Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
Advanced search 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 532 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 

Table of Contents   
Year : 2016  |  Volume : 27  |  Issue : 4  |  Page : 808-811
Fanconi syndrome induced by tenofovir: A case report

1 Department of Nephrology, Hemodialysis and Transplantation, Ibn Rochd University Hospital, Casablanca, Morocco
2 Department of Infectious Diseases, Ibn Rochd University Hospital, Casablanca, Morocco

Click here for correspondence address and email

Date of Web Publication5-Jul-2016


Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor discovered in the USA in 2001. It is currently the treatment of choice for patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus. Its antiretroviral efficacy and good tolerance are responsible for the higher frequency of prescriptions compared with other nucleoside analogs. However, it can induce acute renal toxicity causing impairment of the proximal tubular function of the kidney. This is highly dependent on factors such as associated co-prescription didanosine or a protease inhibitor "boosted" with ritonavir, preexisting renal insufficiency, low body weight, or presence of associated diabetes. In contrast, long-term renal toxicity remains highly debated. Some studies describe a decrease in estimated glomerular filtration rate during prolonged treatment with TDF. Others reported renal safety even during prolonged use. The differences between patients enrolled in the different studies, the measured parameters and their interpretation could explain these discrepancies. We describe a case of a patient infected with HIV, who presented with Fanconi syndrome with acute renal failure six months after starting antiretroviral treatment including tenofovir.

How to cite this article:
Lify B, Dabo G, Nascimento O, Iraqui S, Elkhayat S, Zamd M, Medkouri G, Benghanem M, Ramdani B, Sodqi M M, Marih L, Chakib A, El FilaliMarhoum K. Fanconi syndrome induced by tenofovir: A case report. Saudi J Kidney Dis Transpl 2016;27:808-11

How to cite this URL:
Lify B, Dabo G, Nascimento O, Iraqui S, Elkhayat S, Zamd M, Medkouri G, Benghanem M, Ramdani B, Sodqi M M, Marih L, Chakib A, El FilaliMarhoum K. Fanconi syndrome induced by tenofovir: A case report. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Aug 7];27:808-11. Available from: https://www.sjkdt.org/text.asp?2016/27/4/808/185269

   Introduction Top

Fanconi syndrome is a metabolic defect in the renal transport, characterized by the inability of the renal tubule to reabsorb water, phosphate, potassium, glucose, amino acids, and other substances. It results from a dysfunction of the proximal tubular cells of the kidney. [1],[2],[3] We report a case of Fanconi syndrome associated with the use of tenofovir to attract the attention of clinicians to the need for close monitoring of renal patients infected with human immunodeficiency virus (HIV) and treated with highly active antiretroviral therapy (HAART) including tenofovir.

   Case Report Top

Mr. H. AS, aged 31 on follow-up in the Infectious Diseases Hospital Ibn Rushd Casablanca for HIV1 infection since 2009, when the patient presented with candidiasis of gastrointestinal tract and HIV encephalitis. The initial CD4 lymphocyte count was 104 cells/mm 3 and viral load 140.462 copies/mL (6.15 log10). The tests for tuberculosis were negative. The fundus was normal and the tests for HBsAg, anti-HCV, and syphilis serology (TPHA, VDRL) antibody were negative. Serodiagnosis of toxoplasmosis was positive (IgG:133 IU/mL, absence of IgM). The blood count, liver function tests, and renal function tests (creatinine = 7 mg/L) were normal. Antiretroviral treatment with tenofovir/emtricitabine/ efavirenz was started in August 2009 with a good immuno-virological response. The results in the 3 rd month of antiretroviral treatment performed at the hospital the day showed a number of CD4 T lymphocytes to 432 cells/ mm 3 and an undetectable viral load (<40 copies/mL). Tests were normal for renal function (creatinine = 10 mg/L), as well as calcium and phosphate. The dipstick showed only traces of protein. In the 6 th month of antiretroviral treatment, the number of CD4 lymphocytes was 478 cells/mm 3 and undetectable viral load (<50 copies/mL). Monitoring of renal function showed a creatinine of 16.4 mg/L with a glomerular filtration rate (GFR) at 49 mL/min. The phosphate levels were normal. Fasting glucose was 0.85 g/L. The dipstick again showed only traces of protein. At nine months of antiretroviral therapy, the patient presented to the outpatient clinic. Clinical examination revealed that he was afebrile at 37°C, blood pressure 100/50 mm Hg, weight 43 kg, height 173 cm, and a body mass index of 14.4. Polyuria polydipsia syndrome was present and had mild dehydration without edema of the lower limbs. The rest of the physical examination was unremarkable. The dipstick showed glucose ++++ and proteins ++. This time the investigations showed renal insufficiency: plasma creatinine 67.8 mg/L and GFR 10 mL/min, blood urea 1.74 g/L (NV: 0.13-0.43), hypokalemia with serum potassium of 3.30 mEq/L (NV: 3.5-5), normal serum sodium 140 mmol/ L (NV: 135-145). The patient was admitted to hospital. Twenty-four hours urine output was 4 L. The rest of the laboratory tests showed normal chloride 105 mmol/L (NV: 98-107), normal phosphate 43.60 mg/L (NV: 27-45), and hypocalcemia 78.8 mg/L (NV: 86-107). Blood glucose was normal at 0.94 g/L.

Twenty-four hours proteinuria was found to be raised at 0.53 g (NV <0.25) and high urine glucose (2.63 g/L). The uric acid level in the blood was low at 33 mg/L (NV: 35-72). The urine culture was sterile. The blood count showed a normochromic macrocytic anemia to 6.8 g/dL (NV: 14-116). CRP was 1.4 mg/L (NV <6) and bicarbonate was 12 mmol/L. Parathyroid hormone and Vitamin D levels were not done. Radiographs of the pelvis and spine showed diffuse bone demineralization. Renal ultrasound revealed normal sized kidneys with normal urinary tract. The diagnosis of acute renal failure with Fanconi syndrome secondary to tenofovir was made. Therapeutic management was to stop antiretroviral therapy and manage electrolyte imbalance. The patient was transfused with two units of red blood cells. One month after discontinuation of antiretroviral drugs, there was marked improvement evidenced by a gradual normalization of diuresis (<2100 mL/day) and renal function (creatinine 18 mg/L with a GFR 44 mL/min) along with normalization of other of biochemical parameters. Two months later, renal function was normal and a new antiretroviral regimen excluding tenofovir and didanosine was started. The patient is now in good general condition and renal function in within normal limits. A renal biopsy was not done. This clinical picture of interstitial nephritis can be considered secondary to the HAART drugs.

   Discussion Top

Our case illustrates the first case of Fanconi syndrome that occurred in Infectious Diseases Hospital Ibn Rushd Casablanca in a patient infected with HIV-1 and treated with a triple regimen including tenofovir. The overall incidence of renal toxicity including Fanconi syndrome due to tenofovir remains quite rare. Data from the European literature indicate a frequency of <5% of kidney damage during antiretroviral treatment including tenofovir disoproxil fumarate (TDF). [4] In Africa, the Fanconi syndrome induced by antiretroviral therapy, including the TDF is not described. [1] Fanconi syndrome is not the exclusive prerogative of antiretroviral treatment, even less for tenofovir alone. [5] However, it is increasingly described with antiretrovirals metabolized in the kidney. The pathogenic mechanisms are poorly understood. Several studies suggest that the accumulation of tenofovir in proximal tubules because of its affinity for the organic anion transporter hOAT1 and hOAT3 to a lesser degree is one of the key mechanisms. [6] The clinical manifestations of Fanconi syndrome are polymorphic since they are the result of various metabolic disorders. The circumstances of discovery can be varied: a polyuria polydipsia syndrome, digestive disturbances, and general fatigue such as symptoms, cachexia, myalgia, and polyarthralgia. However, the discovery may be fortuitous during routine laboratory tests showing the signs of kidney failure as in our patient. [1] The diagnosis is suggested primarily on biochemical data. Some parameters are constant, identified as specific markers of proximal tubular damage and therefore Fanconi syndrome, namely normoglycemic glycosuria, tubular proteinuria, hypo-phosphatemia, phosphaturia, metabolic acidosis, hyperaminoaciduria, hypouricemia, and hypokalemia. [7] In our patient, the combination of clinical data: the polyuria polydipsia syndrome and low muscle mass with a body mass index of 14.4 and biochemistry: the normoglycemic glycosuria, renal failure, hypokalemia, hypocalcemia, and hypouricemia led to the diagnosis of Fanconi syndrome. Radiological evidence was diffuse bone demineralization of the bones of the pelvis and spine. [8] The findings described in our patient are consistent with the majority of cases described in the literature. In the analysis of literature, Fanconi syndrome occurs on an average of 10 months after the introduction of TDF, ranging from 1 to 24 months interval. [1] The exposure time for our patient is nine months. In our case, the diagnosis was made late because the patient was being seen only every three months for consultation because he lives far away.

If clinical signs and/or biochemical tests point toward tubulopathy, stopping tenofovir should be done immediately for subsequent reversibility of abnormalities. [9] There is no specific treatment for Fanconi syndrome. Only stopping potentially nephrotoxic drugs including TDF is the main measure reported in the literature. However, the biggest challenge for the clinician is able to offer the patient a nonnephrotoxic molecule as an alternative for TDF. The rest of the care is symptomatic. [1] In our patient, we found a gradual improvement in renal function and other biological parameters within four weeks after discontinuation of TDF and normalization of fluid and electrolyte balance. Fanconi syndrome secondary to TDF has generally good prognosis if we manage to stop the drug and ensure adequate water and electrolyte balance. The renal replacement therapy and renal transplantation may be needed in case of severe renal damage. [10]

   Conclusion Top

Many African countries where the prevalence of HIV infection is very high, TDF is the firstline treatment of choice. TDF may be prescribed to many patients for a long time. According to the best of our knowledge, this is the first case of iatrogenic Fanconi syndrome secondary to tenofovir. This report highlights the need for close monitoring of renal function, calcium and phosphate, proteinuria, and glycosuria in patients treated with antiretroviral drugs, including tenofovir by clinicians, especially in the developing countries. This examination must be performed at least twice a year regardless of the economic conditions of the patient. The importance of training practitioners in monitoring antiretroviral therapy is clear from this case study which will improve the quality of monitoring patients on antiretroviral therapy.

Conflict of interest: None declared.

   References Top

Ondounda M, Tanon A, Ehui E, et al. Two cases of Fanconi's syndrome induced by tenofovir in the Ivory Coast. Med Mal Infect 2011;41:105-7.  Back to cited text no. 1
Rodriguez-Novoa S, Labarga P, Soriano V. Pharmacogenetics of tenofovir treatment. Pharmacogenomics 2009;10:1675-85.  Back to cited text no. 2
Ray AS, Cihlar T, Robinson KL, et al. Mechanism of active renal tubular efflux of tenofovir. Antimicrob Agents Chemother 2006;50:3297-304.  Back to cited text no. 3
Highleyman L. Risk factors for kidney toxicity, in patients taking Tenofovir. Vol. 16. Glasgow: UK-CAB 20; 2007. p. 12-6.  Back to cited text no. 4
Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIVinfected patients: A review of the evidence. Am J Kidney Dis 2011;57:773-80.  Back to cited text no. 5
Kohler JJ, Hosseini SH, Green E, et al. Tenofovir renal proximal tubular toxicity is regulated by OAT1 and MRP4 transporters. Lab Invest 2011;91:852-8.  Back to cited text no. 6
Shepp DH, Curtis S, Rooney JF. Causes and consequences of hypokalemia in patients on tenofovir disoproxil fumarate. AIDS 2007;21:1479-81.  Back to cited text no. 7
Haverkort ME, van der Spek BW, Lips P, et al. Tenofovir-induced Fanconi syndrome and osteomalacia in two HIV-infected patients: Role of intracellular tenofovir diphosphate levels and review of the literature. Scand J Infect Dis 2011;43:821-6.  Back to cited text no. 8
Bentaberry F, Bernard N, Monnier A, Bonnet F, Morlat P. Ostéomalacie dû à un syndrome de Fanconi au cours d'un traitement par ténofovir. Rev Rhum 2006;73:1156.  Back to cited text no. 9
Zimmermann AE, Pizzoferrato T, Bedford J, et al. Les maladies rénales chroniques et aiguës associés au ténofovir: Un cas d'interactions médicamenteuses multiples. Clin Infect Dis 2006;42:283-90.  Back to cited text no. 10

Correspondence Address:
Bouchra Lify
Department of Nephrology, Hemodialysis and Transplantation, Ibn Rochd University Hospital, Casablanca
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.185269

Rights and Permissions


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report

 Article Access Statistics
    PDF Downloaded578    
    Comments [Add]    

Recommend this journal