Drug-induced Fanconi Syndrome Research Articles

Drug-Induced Fanconi Syndrome with Hyperphosphatemia

Drug-Induced Fanconi Syndrome with Hyperphosphatemia

Drug-Induced Fanconi Syndrome Presenting as Chronic Constipation: A Well-Known but Forgotten Entity

Drug-Induced Fanconi Syndrome Presenting as Chronic Constipation: A Well-Known but Forgotten Entity

Drug-induced Fanconi syndrome in patients with kidney allograft transplantation

BackgroundPatients after kidney transplantation need to take long-term immunosuppressive and other drugs. Some of these drug side effects are easily confused with the symptoms of Fanconi syndrome, resulting in misdiagnosis and missed diagnosis, and causing serious consequences to patients. Therefore, improving awareness, early diagnosis and treatment of Fanconi syndrome after kidney transplantation is critical.MethodsThis retrospective study analyzed 1728 cases of allogeneic kidney transplant patients admitted to the Second Xiangya Hospital of Central South University from July 2016 to January 2021. Two patients with Fanconi syndrome secondary to drugs, adefovir dipivoxil (ADV) and tacrolimus, were screened. We summarized the diagnostic process, clinical data, and prognosis.ResultsThe onset of Fanconi syndrome secondary to ADV after renal transplantation was insidious, and the condition developed after long-term medication (>10 years). It mainly manifested as bone pain, osteomalacia, and scoliosis in the late stage and was accompanied by obvious proximal renal tubular damage (severe hypophosphatemia, hypokalemia, hypocalcemia, hypouricemia, glycosuria, protein urine, acidosis, etc.) and renal function damage (increased creatinine and azotemia). The pathological findings included mitochondrial swelling and deformity in renal tubular epithelial cells. The above symptoms and signs were relieved after drug withdrawal, but the scoliosis was difficult to rectify. Fanconi syndrome secondary to tacrolimus has a single manifestation, increased creatinine, which can be easily confused with tacrolimus nephrotoxicity. However, it is often ineffective to reduce the dose of tacrolomus, and proximal renal failure can be found in the later stage of disease development. There was no abnormality in the bone metabolism index and imageological examination findings. The creatinine level decreased rapidly, the proximal renal tubule function returned to normal, and no severe electrolyte imbalance or urinary component loss occurred when the immunosuppression was changed from tacrolimus to cyclosporine A.ConclusionsFor the first time, drug-induced Fanconi syndrome after kidney transplantation was reported. These results confirmed that the long-term use of ADV or tacrolimus after kidney transplantation may have serious consequences, some of which are irreversible. Greater understanding of Fanconi syndrome after kidney transplantation is necessary in order to avoid incorrect and missed diagnosis.

Case report of Fanconi syndrome in Wilms tumor

Fanconi syndrome is a group of clinical manifestations including aminoaciduria, proteinuria, glycosuria, hypophosphatemia, and metabolic acidosis. It may occur after exposure to certain drugs. The most common causes are antiepileptic, antiviral, antibiotic, and antineoplastic drugs.1 The two most common causes in the antineoplastic regimen are cisplatin and ifosfamide. Ifosfamide, a derivative of cyclophosphamide, has been used to treat pediatric solid tumors.2 Its high efficacy in numerous studies has led to its long-term administration for pediatric malignancies, including Wilms tumor. Along with other treatment modalities, ifosfamide considerably improved the survival rate (90%) of Wilms tumor while only a few cases resulted in Fanconi syndrome.1,3,4
 Here we illustrate a case of presumed drug induced Fanconi syndrome in a Wilms tumor patient who previously achieved remission for 10 months.

Long-term adefovir therapy may induce Fanconi syndrome: A report of four cases.

Fanconi syndrome is a rare disease characterized by dysfunction of the proximal renal tubules as a result of various pathogenic events. Drug-induced Fanconi syndrome may be neglected or misdiagnosed, which increases the level of suffering. The aim of the present study was to conduct an investigation into the effects of adefovir (ADV)-induced Fanconi syndrome. Four typical cases of Fanconi syndrome caused by long-term ADV therapy (2-9 years) were diagnosed at our hospital. A complete medical and therapy history was collected from all four patients prior to a physical examination. Laboratory and diagnostic examinations were also conducted. Following this, the patients were diagnosed and a treatment regimen was decided upon. Outcomes of the treatment regimen were observed. Common manifestations of all the four patients were: Renal tubular reabsorption dysfunction; imbalanced electrolyte acid-base ratio; elevated cystatin C levels; severe hypophosphatemia and diffused systemic pain; osteoporosis; and difficultly walking. When ADV was replaced with supportive treatment, all the four patients exhibited symptom relief. These findings indicate that long-term ADV therapy may induce Fanconi syndrome. For patients with a history of such therapy, the possibility of Fanconi syndrome should be assessed and monitored closely for indicators, including altered glomerular and renal tubular function. Once diagnosed, the agent should be immediately discontinued and prompt symptomatic treatment should be administered.

Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: a case series.

BackgroundFumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced Fanconi syndrome.MethodsDescriptive case series with two cases of Fanconi syndrome associated with FAE treatment diagnosed at two Dutch university nephrology departments, three cases reported at the Dutch and German national pharmacovigilance databases and six previously reported cases.ResultsAll 11 cases involved female patients with psoriasis. The median age at the time of onset was 38 years [interquartile range (IQR) 37–46]. Patients received long-term FAEs treatment with a median treatment duration of 60 months (IQR 28–111). Laboratory tests were typically significant for low serum levels of phosphate and uric acid, while urinalysis showed glycosuria and proteinuria. Eight (73%) patients had developed a hypophosphataemic osteomalacia and three (27%) had pathological bone fractures. All patients discontinued FAEs, while four (36%) patients were treated with supplementation of phosphate and/or vitamin D. Five (45%) patients had persisting symptoms despite FAEs discontinuation.ConclusionsFAEs treatment can cause drug-induced Fanconi syndrome, but the association has been reported infrequently. Female patients with psoriasis treated long term with FAEs seem to be particularly at risk. Physicians treating patients with FAEs should be vigilant and monitor for the potential occurrence of Fanconi syndrome. Measurement of the urinary albumin:total protein ratio is a suggested screening tool for tubular proteinuria in Fanconi syndrome.

Hypophosphatemic Osteomalacia Due to Drug-induced Fanconi's Syndrome Associated with Adefovir Dipivoxil Treatment for Hepatitis B

We herein present the case of a 58-year-old Japanese man with Fanconi's syndrome with a 13-month history of bone pain in his ribs, hips, knees and ankles. He had been receiving low-dose adefovir dipivoxil (ADV) for the treatment of lamivudine-resistant chronic hepatitis B virus infection for eight years and subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. Magnetic resonance imaging showed multiple insufficiency fractures in the ribs, ileum, tibia and calcaneus. Whole-body bone scintigraphy demonstrated increased uptake in those areas. Following dose reduction of ADV and the administration of treatment with calcitriol and phosphates, the patient's serum phosphate level increased and his clinical symptoms improved. Physicians prescribing ADV should carefully monitor the renal function and serum phosphate level.

Detection of maleate-induced Fanconi syndrome by decreasing accumulation of125I-3-iodo-a-methyl-L-tyrosine in the proximal tubule segment-1 region of renal cortex in mice: A trial of separate evaluation of reabsorption

Fanconi syndrome is a renal dysfunction characterized by various combinations of renal tubular transport dysfunction involving amino acids, glucose, protein and other substances. Most reabsorption of amino acids occurs in proximal renal tubule segment 1 (S1). The present study evaluated the possibility of early detection of drug-induced Fanconi syndrome, based on decreased renal accumulation of 125I-3-iodo-alpha-methyl-L-tyrosine (125I-IMT), an amino acid transport marker, in the S1 region of renal cortex. The present experimental model used maleate (MAL)-induced Fanconi syndrome in mice. Results were compared between 125I-IMT and 3 other clinical renal radiopharmaceuticals: 99mTc-2,3-dimercaptosuccinic acid (99mTc-DMSA); 99mTc-mercaptoacetylglycylglycylglycine (99mTc-MAG3); and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). Male ddY mice (age, 6 weeks; body weight, 25 g) were used to create a Fanconi model of renal dysfunction. A single dose of maleate disodium salt was administered by intraperitoneal injection (6 mmol/kg). Hematoxylin and eosin (HE) staining of the renal cortex, renal autoradiography and measurement of renal radioactivity of labeled compounds were performed at 30, 60, 90 and 120 min after MAL injection. At 5 min after injection of labeled compounds (18.5 kBq for accumulation experiment, 670 kBq for autoradiography), animals were sacrificed by ether overdose and kidneys were removed. For the accumulation experiment, radioactivity was measured using a well-type scintillation counter. For autoradiography, 20-microm sections of frozen kidney were used with Bio-Imaging Analyzer. At 30 min after MAL injection, HE staining showed pyknosis in some proximal tubule cells. At that time, accumulations of 125I-IMT and 99mTc-DMSA in the S1 region were approximately 67% and 55% of control levels (p < 0.005). MAL increased accumulation of 99mTc-DTPA in the S1 region, but had no effect on accumulation of 99mTc-MAG3 in the S 1 region. Decreased accumulation of 123I-IMT in the S1 region appears to represent a useful marker for detection of MAL-induced Fanconi syndrome. In future, we plan to assess the efficacy of using 125I-IMT to monitor renal dysfunction induced by nephrotoxic clinical drugs.

Drug-induced Fanconi's syndrome

Fanconi's syndrome (FS) was first described by Lignac in 1924. Associated with numerous varieties of inherited and acquired conditions, FS is characterized by a generalized transport defect in the proximal tubules, leading to renal losses of glucose, phosphate, calcium, uric acid, amino acids, bicarbonates, and other organic compounds. Cardinal symptoms of the syndrome are hyperaminoaciduria, glucosuria in the face of a normal serum glucose level, and phosphate wasting. Other symptoms may be associated, such as defects in bicarbonate reabsorption; renal acidification; urate reabsorption; urinary concentration; potassium conservation; reabsorption of sodium, calcium, and low-molecular-weight proteins; and secretion of p-aminohippuric acid. Acquired renal tubular defects resulting in FS also have been described in association with many exogenous agents, whether administered or accidentally ingested. This review concentrates on drug-induced FS. Am J Kidney Dis 41:292-309.

Induction of an experimental fanconi syndrome in mice: Its effect on the glomerular filtration function studied by 99mTc-DTPA

An experimental mice model of maleate (MAL)-induced Fanconi syndrome has been used to test 99mTc-DTPA ability to detect hampered glomerular filtration rate (GFR) early in drug-induced Fanconi syndrome. In fact, declining GFR has been reported both in idiopathic and acquired Fanconi syndrome. The above MAL model shows urine biochemistry changes similar to those reported in patients suffering from Fanconi syndrome. Moreover, biodistribution study and whole-body autoradiographies performed after IV injection of 99mTc-DTPA in MAL and control mice show significantly delayed pharmacokinetics of the above radiopharmaceutical in a MAL dose-dependent effect. After administration of a MAL dose of 6 mM/kg BW, the 5-min biodistribution of 99mTc-DTPA, a radiopharmaceutical freely excreted by glomerular filtration, is significantly changed in all organs. In blood of MAL mice, 27.62 ± 2.86% of the injected dose is still circulating compared to 13.67 ± 1.22% of the injected dose in control mice, and only 1.37 ± 0.31% of the injected dose has been excreted in urine of MAL mice compared to 24.66 ± 4.12% of the injected dose in urine of control mice. The obtained results suggest that 99mTc-DTPA may be efficient both in the early detection of abnormal GFR in acquired Fanconi syndrome after application of a nephrotoxic treatment, and in the follow-up of patients in recovery phase after discontinuation of the therapy.