Renal histology of Fanconi syndrome associated with adefovir dipivoxil: A case report.

A sporadic occurrence of Fanconi syndrome associated with adefovir dipivoxil (ADV) has been reported, particularly when confirmed by renal biopsy. This study presents the case of a 53-year-old man who had been taking ADV 10 mg daily for 10 years to treat chronic hepatitis B (CHB) and subsequently developed Fanconi syndrome. The clinical manifestations included hypophosphatemic osteomalacia, glucosuria, renal tubular acidosis, low-molecular-weight proteinuria, and renal insufficiency. Renal biopsy revealed significant injury to proximal tubular epithelial cells, including vacuolar degeneration and regeneration of tubular epithelial cells. The ultrastructural pathology indicated severe morphological abnormalities of mitochondria, such as densely packed and enlarged mitochondria, with loss, blunting, and disordered arrangement of cristae. Following discontinuation of ADV and supplementation with oral phosphate, hypophosphatemia, glucosuria, and proteinuria were resolved. These findings support the previous hypothesis that ADV-induced nephrotoxicity may involve mitochondrial injury.

Fanconi syndrome, diabetes insipidus, and acute kidney injury due to tenofovir disoproxil fumarate: A case report.

BACKGROUND: Tenofovir disoproxil fumarate is widely used in Botswana as part of the first-line antiretroviral regimen in the 'Treat All' strategy implemented in 2016 by the Ministry of Health. Its use has been associated with several uncommon adverse renal effects, though rarely all in conjunction or without the combined use of protease inhibitors. CASE PRESENTATION: A 49-year-old woman living with HIV whose viral load is suppressed on tenofovir disoproxil fumarate, lamivudine, and dolutegravir presented with 1 day of generalized weakness and myalgia causing an inability to ambulate. This was associated with nausea and vomiting and profound fatigue. She was found to have an acute kidney injury, non-anion-gap metabolic acidosis, hypernatremia, hypokalemia, and hypophosphatemia. Urinalysis revealed pyuria with white blood cell casts, glucosuria, and proteinuria. The diagnosis was made of tenofovir-induced nephrotoxicity. The tenofovir was discontinued, and the patient was initiated on intravenous fluids and electrolyte and bicarbonate supplementation with improvement in her symptoms and laboratory values. CONCLUSIONS: This report suggests the possibility of severe tenofovir-induced nephrotoxicity with combined acute kidney injury, Fanconi syndrome, and nephrogenic diabetes insipidus in the absence of other provoking factors such as use with protease inhibitors or advanced HIV disease, chronic kidney disease, and age. With its wide use in Botswana and other countries, health-care providers should have a high index of suspicion for tenofovir-induced nephrotoxicity for HIV patients on tenofovir with deranged renal function tests and electrolytes.

Fanconi Syndrome Associated with Long-term Treatment with Zoledronate.

Intravenous bisphosphonate therapy is used to prevent fractures in the management of bone metastasis. However, it may induce renal damage. We herein report an 81-year-old woman with Fanconi syndrome and osteomalacia who had been diagnosed with metastatic breast cancer and received treatment with zolendronate for over 5 years. Her bone markers normalized after switching zolendronate to denosmab and starting vitamin D and mineral supplementation. This case shows that chronic renal damage induced by zolendronate can cause osteomalacia. In patients with intravenous zolendronate therapy, close monitoring of renal and bone markers is needed, even under long-term therapy.

Beneficial effects of starting oral cysteamine treatment in the first 2 months of life on glomerular and tubular kidney function in infantile nephropathic cystinosis.

Nephropathic cystinosis is a rare lysosomal storage disease whose basic defect, impaired transport of cystine out of lysosomes, results in intracellular cystine storage. Affected individuals exhibit renal Fanconi Syndrome in infancy, end-stage kidney disease at approximately 10 years of age, and many other systemic complications. Oral cysteamine therapy mitigates the detrimental effects on glomerular function and prevents most of the late complications of the disease but has not shown benefit with respect to the early tubular damage of cystinosis. This is because cystinosis is generally diagnosed in the second year of life, after the damage to kidney tubular function has already occurred. We longitudinally evaluated 6 infants diagnosed and treated with cysteamine from before 2 months of age. The 4 infants with good compliance with cysteamine and consistently low leucocyte cystine levels maintained normal eGFR values, exhibited only minor degrees of renal Fanconi Syndrome, and maintained normal serum levels of potassium, bicarbonate, phosphate, and calcium without electrolyte or mineral supplementation through 2, 4, 10 and 16 years of age. Thus, renal Fanconi syndrome can be attenuated by early administration of cysteamine and renew the call for molecular-based newborn screening for cystinosis.

C-Terminal Fibroblast Growth Factor-23 Levels in Non-Nutritional Hypophosphatemic Rickets.

Fibroblast growth factor-23 (FGF23) is central to phosphate homeostasis. The author examined if blood levels of FGF23 allow discrimination of classic hypophosphatemic rickets from other causes of non-nutritional rickets with hypophosphatemia. Forty-two children (median age: 102 mo) with non-nutritional rickets and hypophosphatemia were clinically classified as having distal renal tubular acidosis (RTA, n = 12), Fanconi syndrome (n = 8), classic hypophosphatemic rickets (n = 11), vitamin D dependent rickets (n = 7) and Dent disease (n = 4). Median blood FGF23 (measured by C-terminal ELISA) concentrations were similar in all groups (P = 0.24). These levels did not correlate with phosphate, tubular maximum for phosphate, calcium, 25-hydroxyvitamin D, creatinine, and parathormone levels. Patients with distal RTA showed variable degree of proximal tubular dysfunction that resolved following alkali supplements. Blood FGF23 levels did not satisfactorily differentiate classic hypophosphatemic rickets from other causes of hypophosphatemic rickets.

Acquired Fanconi syndrome secondary to light chain deposition disease associated with monoclonal gammopathy of renal significance: A case report.

RATIONALE: Renal Fanconi syndrome (FS) is a rare complication of monoclonal gammopathy. It is characterized by the impairment of renal proximal tubular function leading to normoglycemic glycosuria, aminoaciduria, hypophosphatemia, hypouricemia and proximal renal tubular acidosis. Renal impairment in monoclonal gammopathy, without fulfilling the criteria of multiple myeloma, is categorized as monoclonal gammopathy of renal significance (MGRS). PATIENT CONCERNS: A 54-year-old male presented with progressively aggravated bone pain and limitation of activity was admitted to our department. A proximal renal tubular damage was suggested by hypophosphatemia, compensated metabolic acidosis, renal glycosuria, aminoaciduria, and hypouricemia. M-protein of IgA kappa was detected by immunofixation electrophoresis. Mildly increased plasma cells were found in bone marrow cytomorphologic examination. Renal biopsy revealed diffuse linear monoclonal IgA-kappa light chain deposits along tubular basement membranes (TBMs), while lambda was negative. Electron microscopy showed granular electron-dense deposits along the outer aspect of TBMs. DIAGNOSES: The patient was diagnosed as FS induced osteomalacia secondary to monoclonal gammopathy of renal significance (MGRS) (IgA-κ type) and LCDD. INTERVENTIONS: He was treated with bortezomib, supplementation by phosphate, alkali agents, and active vitamin D. He responded well to the treatment symptomatically. OUTCOMES: We reported a rare case of adult acquired FS with hypophosphatemic osteomalacia secondary to LCDD associated with MGRS and the patient was successfully treated with bortezomib. LESSONS: Although few cases of LCDD with isolated symptoms of tubulointerstitial nephropathy, rather than glomerular symptoms have been reported. It still needs to be recognized as a differential diagnosis in monoclonal gammopathy.

Sjögren's Syndrome Associated with Fanconi's Syndrome and Osteomalacia.

BACKGROUND Sjögren's syndrome is a chronic inflammatory autoimmune disease, which is also known as sicca syndrome, due to the symptoms of dry eyes and dry mouth, and is associated with other connective tissue diseases and autoimmune diseases. Sjögren's syndrome can also be associated with renal involvement. Fanconi's syndrome is associated with impaired reabsorption in the proximal renal tubule associated with tubulointerstitial nephritis and is associated with renal tubular acidosis and hypophosphatemia. Osteomalacia is a rare association with Sjögren's syndrome, which may result from renal disease. CASE REPORT We report the case of a 34-year-old woman who presented with xerostomia, xerophthalmia, bone fractures, and osteomuscular pain. A Schirmer test showed reduced tear production, and a biopsy of a minor salivary gland of the lip, with high titers of antinuclear antibodies (ANA), and positive anti-SSA/Ro and anti-SSB/La antibodies confirmed the diagnosis of Sjögren's syndrome. Serum and urinary laboratories tests and clinical manifestations confirmed Fanconi's syndrome associated with osteomalacia. The patient was treated with potassium supplements, 25-hydroxyvitamin D (25(OH)D), hydroxychloroquine, mycophenolate mofetil, and prednisone, with a favorable response. CONCLUSIONS This case is of a rare association between Sjögren's syndrome, Fanconi's syndrome, and osteomalacia. Even though these are rare clinical associations, early detection can improve the quality of life and prevent further complications.

Glycosuria and hyperglycemia in the neonatal period as the first clinical sign of Fanconi-Bickel syndrome.

Fanconi-Bickel syndrome is a rare inherited disease characterized by the combination of hepatorenal glycogen accumulation, proximal renal tubular dysfunction and impaired utilization of glucose and galactose. The first symptoms of the disorder are recognized in late infancy as clinical characteristics appear. Therapeutic approach is mainly conservative with supplements of calcium, phosphate and vitamin D and small frequent feedings to avoid hypoglycemia. We report 1 clinical case of very early diagnosis, a 19 days old baby girl, in which the first clinical sign of the disease was the detection of glycosuria and vomits. Serum alkaline phosphatase levels were very high without rickets. The patient presented postprandial hyperglycemia and fasting hypoglycemia. A complete 24-hour glucose profile was obtained using a continuous glucose monitoring system in real time, which was fundamental not only for the diagnosis but also for the prevention of hypoglycemia. She received frequent small meals, galactose-free milk diet, and oral intakes of calcium, phosphorum, bicarbonate and vitamin D supplements with good evolution and normal height and weight gain.

[A Case of Tenofovir-associated Fanconi Syndrome in Patient with Chronic Hepatitis B].

Tenofovir disoproxil fumarate (TDF) is one of the most widely used treatment options for human immunodeficiency virus (HIV) and HBV infections. Despite its efficacy and safety, some cases of nephrotoxicity have been reported in the treatment of HIV patients. Even more recently, very few cases of Fanconi syndrome associated with tenofovir therapy in HBV monoinfection have been reported. Herein, we report a case of a 47-year-old male with an HBV monoinfection, who developed Fanconi syndrome and a secondary osteomalacia with multiple bone pain. After TDF withdrawal and supplementation of calcitriol, his renal function was reverted. Although the overall risk of TDF-associated nephrotoxicity is very low, both glomerular and tubular function should be monitored in patients undergoing TDF treatment.

Sodium valproate-induced Fanconi type proximal renal tubular acidosis.

We present a case series of three patients with sodium valproate-induced Fanconi's syndrome, with ages ranging from 5 years to 12 years. The most important diagnostic features of this syndrome include hypophosphataemia, glycosuria and proteinuria, which are also noted in our series. Furthermore, also added is that clinical fractures representing an underlying osteopaenia may provide an opportunity for early intervention as it raises the suspicion of Fanconi's syndrome. Previous case reports suggest there is a subpopulation of individuals who are at risk of developing this condition. These individuals share similar characteristics, including being non-ambulatory, developmentally delayed and/or tube fed. Withdrawing sodium valproate therapy is the ultimate treatment for valproate-induced Fanconi's syndrome and from previous case series, normalised renal function occurs in approximately 6 months. Often, supplement support is also required for deranged electrolyte balance.

Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation of a Gitelman syndrome.

BACKGROUND: Gitelman syndrome is an autosomal recessive tubulopathy characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. The majority of patients do not present with symptoms until late childhood or adulthood, and the symptoms are generally mild. We report here the first case of Gitelman syndrome presenting with the biological features of Fanconi syndrome and an early polyuria since the neonatal period. We discuss in this article the atypical electrolytes losses found in our patient, as well as the possible mechanisms of severe polyuria. CASE PRESENTATION: A 6-year-old Caucasian girl was admitted via the Emergency department for vomiting, and initial laboratory investigations found hyponatremia, hypokalemia, metabolic acidosis with normal anion gap, hypophosphatemia, and hypouricemia. Urinalysis revealed Na, K, Ph and uric acid losses. Thus, the initial biological profile was in favor of a proximal tubular defect. However, etiological investigations were inconclusive and the patient was discharged with potassium chloride and phosphorus supplementation. Three weeks later, further laboratory analysis indicated persistent hypokalemia, a metabolic alkalosis, hypomagnesemia, and hypocalciuria. We therefore sequenced the SLC12A3 gene and found a compound heterozygosity for 2 known missense mutations. CONCLUSIONS: Gitelman syndrome can have varying and sometimes atypical presentations, and should be suspected in case of hypokalemic tubular disorders that do not belong to any obvious syndromic entity. In this case, the proximal tubular dysfunction could be secondary to the severe hypokalemia. This report emphasizes the need for clinicians to repeat laboratory tests in undiagnosed tubular disorders, especially not during decompensation episodes.

Severe renal tubulopathy in a newborn due to BCS1L gene mutation: effects of different treatment modalities on the clinical course.

Very early onset Toni-Debré-Fanconi Syndrome, a disorder of proximal renal tubules of the kidney which results in the increased urinary excretion of glucose, amino acids, uric acid, phosphate and bicarbonate, could be the manifestation of various inborn errors. Defects of oxidative phosphorylation are a heterogeneous group of disorders with various clinical presentations. Recently, patients with early liver failure, renal tubulopathy and encephalopathy due to the mutations in the BCS1L gene coding for a structural protein in mitochondrial complex III have been described. Ten-day-old female newborn was referred to our clinic because of intractable acidosis. Physical examination revealed severe hypotonia, and hepatomegaly. The laboratory examinations revealed lactic acidosis, increased blood alanine, alanine aminotransferase and aspartate aminotransferase levels, generalized aminoaciduria and glucosuria. The tubular reabsorption of phosphate was reduced. Because of multisystem involvement, mitochondrial disease was suspected and the mutational analysis of the BCS1L gene revealed homozygous P99L mutation. As the patient was unresponsive to bicarbonate replacement, oral dichloroacetate and peritoneal dialysis, continuous high dose intravenous sodium bicarbonate therapy with a dose up to 1.25 mEq/kg/h was started. The patient got on well until the age of 9 months when she died of sepsis. It was stressed that high dose intravenous continuous sodium bicarbonate therapy could be an alternative treatment option in patients with severe acidosis and renal tubulopathy resistant to dichloroacetate and peritoneal dialysis. Patients with BCS1L mutations should be considered in the differential diagnosis of severe tubulopathy in the newborn period.

Hypophosphataemic osteomalacia in patients on adefovir dipivoxil.

Fanconi syndrome results from generalised renal tubular toxicity and, owing to phosphate wasting can cause hypophosphataemic osteomalacia. Large clinical trials advocated the safety of adefovir dipivoxil at a daily dose of 10 mg, the standard dose given to patients with hepatitis B. We diagnosed Fanconi syndrome in conjunction with severe osteomalacia in 2 hepatitis B-positive patients on standard-dose adefovir therapy. The first patient was a 40-year-old male with a 5 month history of bone pain involving his knees, ankles, and ribs. He had been receiving adefovir dipivoxil for 27 months before the development of hypophosphataemia, urinary phosphate wasting, and aminoaciduria. These abnormalities resolved within weeks of discontinuation of adefovir dipivoxil and supplementation with elemental phosphate, calcium carbonate, and cholecalciferol. The second patient was a 53-year-old female with a 6 month history of lethargy, cachexia, and generalized bone pain. She had been receiving adefovir for 64 months before the development of these symptoms. She had hypophosphataemia, hypocalcaemia, metabolic acidosis, and severe vitamin D deficiency, but initially no urinary phosphate wasting. Four months of high-dose cholecalciferol supplementation unmasked her Fanconi syndrome including significant urinary phosphate wasting. The patient improved within weeks of discontinuation of adefovir and supplementation with elemental phosphate, calcium carbonate, and calcitriol. Despite large clinical trials advocating the safety of adefovir dipivoxil at 10-mg daily, long-term use of this agent may be nephrotoxic and in rare cases, cause Fanconi syndrome and severe hypophosphataemic osteomalacia. Clinicians prescribing this drug should be aware of this potential complication.

Fanconi syndrome in lymphoma patients: report of the first case series.

BACKGROUND: Fanconi syndrome (FS) is a generalized transport defect in the proximal renal tubule leading to renal losses of phosphate, calcium, uric acid, bicarbonates as well as glucose, amino acids and other organic compounds. It is caused by inherited or acquired disorders including low mass or high mass multiple myeloma. OBJECTIVES: To report the first case series of patients with lymphoma and FS. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Patients with lymphoma and FS were identified in the nephrology department of two teaching hospitals in Paris, France and Ghent, Belgium. FS was defined by the presence of at least three out of the four following criteria: hypophosphataemia, metabolic acidosis, normoglycaemic glucosuria and hypokalaemia. Patients files were reviewed and relevant data were collected. RESULTS: Eight patients with lymphoma and FS were identified. In six patients, the lymphoma was of the acute T cell leukaemia/lymphoma (ATLL) type, related to human T cell lymphotropic virus 1 (HTLV1) infection. In all patients, FS was severe requiring supplementation. A kidney biopsy performed in a patient with post-transplantation primary renal lymphoma disclosed intense proximal tubule infiltration by lymphomatous cells. In one patient with ATLL, FS features regressed following the successful treatment of lymphoma. CONCLUSION: Patients with lymphoma require careful monitoring for features of FS; lymphoma should also be added to the spectrum of disorders associated to FS. Prospective studies are needed to ascertain the implication of HTLV1 in the genesis of FS.

Aristolochic acid nephropathy due to herbal drug intake manifested differently as Fanconi's syndrome and end-stage renal failure--a 7-year follow-up.

Aristolochic acid (AA) may reduce glomerular or proximal tubular function, or both. We report a married couple taking AA-containing herbal drugs. The man developed Fanconi's syndrome (FS) whereas his wife reached end-stage renal failure (ESRF). He was a 36-year-old alcoholic cirrhotic patient who had taken the Chinese herbal drugs for 6 years, presenting with muscle weakness and laboratory findings of FS; the renal pathological findings were compatible with the diagnosis of aristolochic acid nephropathy (AAN). His 38-year-old wife, who took a lower cumulative amount of the same herbal drug for a shorter duration, developed advanced renal failure and severe anemia with pathological findings of extensive tubular atrophy, interstitial fibrosis but spared glomeruli. AA-I was detected in one of the herbal drugs. The wife has been on hemodialysis for 7 years, but the husband is still at the stage of slowly progressive chronic renal failure and persistent FS. None of their 5 children ever took the herbal drug, and none had renal problems during follow-up. It is important to trace the history of herbal drug intake in all the family members because of the possibility of sharing of drugs within a family. In addition to the effect of cumulative doses of AAs and the potentially higher susceptibility of females to AAN, the roles of liver cirrhosis and related vasodilators in the protection of the renal interstitium from fibrosis are questions that warrant further study.

Fanconi-Bickel syndrome.

We present here the first case of Fanconi-Bickel syndrome, a rare type of glycogen storage disease, from India. A 17-month-old female child presented with severe growth retardation and abdominal distention. Clinical examination revealed a "doll-like" face, massive hepatomegaly, and rickets. Laboratory investigations confirmed severe hypophosphatemic rickets and proximal renal tubular dysfunction. Liver biopsy showed glycogen accumulation in the hepatocytes.

Aminoglycoside-associated Fanconi syndrome.

The objective is to describe a case of probable aminoglycoside-induced Fanconi syndrome and make clinicians aware of the existence of this underrecognized and underdiagnosed complication in patients treated with a prolonged course of high-dose aminoglycosides. A 53-year-old man admitted for recurrent infective exacerbations of chronic bronchiectasis already colonized with Pseudomonas aeruginosa was treated intermittently with intravenous gentamicin (320 to 560 mg/d) for a total of 4 months to a total cumulative dose of 9.4 g. The patient developed profound hypophosphatemia, hypocalcemia, hyperphosphaturia, and aminoaciduria. Electrolyte disturbances persisted until gentamicin therapy was stopped, recurred with rechallenge, and did not correct with calcium and phosphate supplementation. This case shows that prolonged exposure to high-dose aminoglycoside therapy can be associated with Fanconi syndrome, which is a manifestation of proximal tubular dysfunction. There are only a few case reports to date of Fanconi syndrome as a probable complication of high-dose aminoglycoside therapy. The Naranjo Adverse Drug Reaction probability scale score indicated that this was a probable adverse reaction associated with administration of high-dose aminoglycosides. The differential diagnosis of electrolyte disturbances as a manifestation of proximal tubule dysfunction and type 2 renal tubular acidosis is vast; however, Fanconi syndrome needs to be considered in patients treated with high doses of aminoglycosides for longer than 6 days, after more common causes of hypophosphatemia are excluded.

Hypophosphataemic osteomalacia due to de Toni-Debre-Fanconi syndrome in a 19-year old girl.

Osteomalacia associated with adult onset Fanconi syndrome is thought to result from hypophosphataemia due to renal phosphate loss and relative 1,25-dihydroxyvitamin D3 deficiency. In this disorder, the impaired renal phosphate uptake occurs as part of a generalized tubular defect in association with other features such as bicarbonuria, glycosuria and aminoaciduria. Fanconi syndrome is either hereditary--juvenile form--or is associated with various acquired or heritable diseases. In adults, the disease is similar to the juvenile form, but osteomalacia is a prominent feature. We report a sporadic, adult onset, hypophosphataemia in a 19-year old female patient who presented after puberty complaining of bone and joint pain and difficulty in walking following a minor fall. Radiological examination revealed numerous bilateral fractures of the ribs and pelvis while biochemical investigations showed combination of high phosphate clearance, low serum bicarbonate, glycosuria and glycinuria. Known causes of acquired renal tubular dysfunction were ruled out. The patient was diagnosed as having idiopathic Fanconi syndrome and started on vitamin D3 (Alfacalcidol 1 mg/day) and oral phosphorus (Joulie Solution, 1.5 g/day), which led to resolution of symptoms and an increase in serum phosphate (from 0,54 to 0,71 mmol/l) within few months following the initiation of therapy. However, radiological re-examination showed no signs of fracture healing.