SEARCH · PubMed Health

Results for “FANCONI SYNDROME”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed2001

Late-onset downregulation of NaPi-2 in experimental Fanconi syndrome.

The pathogenesis of renal phosphate (Pi) leak in Fanconi syndrome is unknown. Disorders of apical membrane transporters, leaky apical membrane, depleted cellular Pi and ATP, and impaired sodium (Na) pumps have been proposed as underlying defects. The present study examined the role of type II Na-Pi cotransport system (NaPi-2) in experimental Fanconi syndrome in rats. Following a single injection of maleic acid (MA), 75 mg/kg body weight i.p., rats were sacrificed after 90 min, 4 h, and 24 h. Renal cortical expression of NaPi-2 mRNA was determined by Northern blotting, and brush border membrane (BBM) NaPi-2 protein by Western blotting. Increased urinary excretion of phosphate was demonstrated as soon as 90 min after MA injection, and was sustained at 4 and 24 h, NaPi-2 mRNA expression and NaPi-2 protein were not decreased after 90 min. NaPi-2 mRNA decreased after 4 h, while NaPi-2 protein decreased only at 24 h. Hence, the immediate phosphaturia in experimental Fanconi syndrome may be independent of NaPi-2 downregulation, possibly resulting from energy depletion or membrane dysfunction. The decrease in NaPi-2 mRNA expression and the subsequent NaPi-2 protein decrease may account for the second-phase phosphaturia.

Animals↗

PubMed1985

Vitamin D metabolites and osteomalacia in the human Fanconi syndrome.

Experimental evidence suggests that renal 1 alpha-hydroxylase activity is impaired in Fanconi syndrome. We have evaluated plasma vitamin D metabolites in five patients with Fanconi syndrome, three of whom had metabolic bone disease; plasma 1,25(OH)2D3 was low in the three patients with bone disease, and normal in the two patients without a bone mineralisation defect. The data supports the hypothesis that renal 1 alpha-hydroxylase activity may be impaired in human Fanconi syndrome, and that altered vitamin D metabolism may contribute to the pathogenesis of metabolic bone disease in Fanconi syndrome.

Aged↗

PubMed1995

Insights into the biochemical mechanism of maleic acid-induced Fanconi syndrome.

Maleic acid administration is known to produce the Fanconi syndrome, although the biochemical mechanism is incompletely understood. In this study the effect of a single injection of maleic acid (50 mg/kg body wt, i.v.) on the rat renal ATPases was examined. Maleic acid rapidly caused bicarbonaturia, natriuresis, and kaliuresis. When nephron segments were microdissected, there was an 81 +/- 2% reduction in proximal convoluted tubule (PCT) Na-K-ATPase activity (P < 0.005) and a 48 +/- 4% reduction in PCT H-ATPase activity (P < 0.01). Enzyme activity (Na-K-ATPase, H-ATPase, H-K-ATPase) in the medullary thick ascending limb of Henle's loop and distal nephron segments was normal. In vitro, maleic acid (1 and 10 mM) inhibited Na-K-ATPase in PCT, but it had no effect on H-ATPase in PCT. Prior phosphate infusion to maleic acid-treated rats attenuated urinary bicarbonate wastage by 50% (P < 0.05); activity of proximal tubule Na-K-ATPase and H-ATPase activities were partially protected as compared to the animals given maleic acid alone (P < 0.05). Renal cortical ATP levels were not altered at the concentration of maleic acid used in this study (that is, 50 mg/kg body wt), but higher doses of maleic acid (that is, 500 and 1000 mg/kg body wt) caused ATP levels to fall. Maleic acid did not affect cortical medullary total phosphate concentration, however, P32 turnover (1 and 24 hr) was altered by prior phosphate infusion. A protective effect of prior phosphate loading on the membrane bound Pi pool (insoluble) was seen while the cytosolic Pi pool (soluble) was not different from control. Thus, maleic acid-induced "Fanconi" syndrome likely results from both direct inhibition of proximal tubule Na-K-ATPase activity and membrane-bound phosphorus depletion. The former mechanism would reduce activity of the sodium-dependent transporters (that is, Na/H antiporter), while the latter would inhibit the electrogenic proton pump (H-ATPase). The combination of reduced proximal tubule Na-H exchange and H-ATPase activities would markedly inhibit bicarbonate reabsorption and result in the metabolic acidosis universally seen in the Fanconi syndrome.

Adenosine Triphosphate↗

PubMed1986

[Fatal form of pericardo-myocarditis in Wissler-Fanconi syndrome].

The Wissler-Fanconi syndrome is an inflammatory disease of unknown origin, similar to Still's disease, a systemic form of juvenile arthritis. The long-term evolution is marked by recurrent febrile exacerbations, sometimes complicated by pericardo-myocarditis which usually resolves without sequellae. The authors report a case with chronic pericardo-myocarditis progressing over a 7 year period to refractory congestive cardiac failure.

Adult↗

PubMed2004

Fanconi syndrome caused by antiepileptic therapy with valproic Acid.

PURPOSE: Valproic acid (VPA) is commonly used as an antiepileptic drug (AED). Regular screening for renal side effects is uncommon. Fanconi syndrome, a generalized dysfunction of renal proximal tubular cells, occurs with some inborn errors of metabolism. In addition, it can be acquired by exposure to several toxic substances. We report a case of Fanconi syndrome after long-term therapy with VPA. METHODS: An 8-year-old severely disabled and developmentally retarded boy with epilepsy was treated with VPA over a period of 7 years. He was hospitalized after a status epilepticus with laboratory findings suggesting a Fanconi syndrome. A PubMed-based worldwide review of the literature revealed that Fanconi syndrome is a rare side effect in children during long-term VPA treatment. We analyzed all 10 previously published cases by comparing age, underlying diseases, medication, and outcome. RESULTS: Examination revealed metabolic acidosis suggestive of renal tubular malfunction. Based on typical clinical and laboratory findings, an acquired Fanconi syndrome was diagnosed. This was treated with large doses of sodium bicarbonate. After discontinuation of VPA, renal function completely normalized within 2 months. CONCLUSIONS: Fanconi syndrome appears to be a rare but severe consequence of long-term VPA therapy. Therefore patients treated with VPA should be checked regularly for the possible development of VPA-induced Fanconi syndrome.

Anticonvulsants↗

PubMed1995

Increased renal parenchymal echogenicity in ifosfamide-induced renal Fanconi syndrome.

Three children who presented with a Fanconi syndrome induced by the chemotherapeutic drug ifosfamide were found to have renal abnormalities on sonogram examinations. Renal echographic changes consisted in hyperechogenicity of the parenchyma with good corticomedullar differentiation. After discontinuation of the chemotherapy, the serum and urine metabolic abnormalities due to proximal tubulopathy were completely or greatly improved. Imaging studies at that time showed a complete resolution of the renal hyperechogenicity. We suggest that in patients exposed to ifosfamide, renal sonogram may be of value to monitor the tubular toxicity of this drug. In these patients, urine and serum monitoring as well as prospective echographic follow-up kidney abnormalities may lead to earlier detection of ifosfamide-induced Fanconi syndrome as well as earlier detection of disease reversibility.

Child↗

PubMedDate not supplied

Idiopathic Fanconi syndrome with progressive renal failure: a case report and discussion.

Fanconi syndrome is a complex of renal tubular dysfunctions defined by glycosuria without diabetes, aminoaciduria, phosphaturia, and renal tubular acidosis. It is often associated with hypokalemia, hypophosphatemia, and rickets or osteomalacia. Although it is usually found in the setting of other well-established non-renal diseases, Fanconi syndrome may present without identifiable etiology or association. Very infrequently a patient with idiopathic Fanconi syndrome will progress to chronic renal failure. This case report details the course of such a patient over the 20 years since his diagnosis and discusses the syndrome's genetic background, clinical features, putative pathophysiology, and therapeutic options, including transplantation.

Adult↗

PubMed2000

Genetic and physical mapping of the locus for autosomal dominant renal Fanconi syndrome, on chromosome 15q15.3.

Autosomal dominant renal Fanconi syndrome is a genetic model for the study of proximal renal tubular transport pathology. We were able to map the locus for this disease to human chromosome 15q15.3 by genotyping a central Wisconsin pedigree with 10 affected individuals. After a whole-genome scan with highly polymorphic simple sequence repeat markers, a maximum LOD score of 3.01 was calculated for marker D15S659 on chromosome 15q15.3. Linkage and haplotype analysis for an additional 24 markers flanking D15S659 narrowed the interval to approximately 3 cM, with the two highest single-point LOD scores observed being 4.44 and 4.68 (for D15S182 and D15S537, respectively). Subsequently, a complete bacterial artificial chromosome contig was constructed, from the High Throughput Genomic Sequence Database, for the region bounded by D15S182 and D15S143. The identification of the gene and gene product altered in autosomal dominant renal Fanconi syndrome will allow the study of the physiology of proximal renal tubular transport.

Chromosome Mapping↗

PubMed1975

Fanconi syndrome in adults. A manifestation of a latent form of myeloma.

From a review of 17 cases of Fanconi syndrome with Bence Jones proteinuria and myeloma or amyloidosis, including three new cases reported here in detail, there emerges a well defined set of characteristics. In most cases, the diagnosis of Fanconi syndrome preceded the development of myeloma or amyloidosis. Myeloma preceding the development of Fanconi syndrome has not been reported. All the patients had Bence Jones proteinuria, but in some it could be detected only by electrophoresis or immunoelectrophoresis, In the seven cases in which the Bence Jones protein was typed, it was of kappa type. There were no serum protein monoclonal abnormalities. In the bone marrow and renal samples of half of the patients, crystalline cytoplasmic inclusion bodies were present in lymphoplasmacytic elements and renal tubular cells. It is proposed that patients with Fanconi syndrome and Bence Jones proteinuria have a distinct type of plasma cell disorder or variant of the monoclonal gammopathies, characterized by a slow progression of the tumor and by an early phase dominated by the metabolic complications of the renal proximal tubular dysfunction. Adult patients with Fanconi syndrome should be carefully investigated for the presence of Bence Jones protein and a plasmacytic dyscrasia should be excluded.

Aged↗

PubMed2006

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.

Anti-Bacterial Agents↗

PubMed1989

Two case studies from a family with primary Fanconi syndrome.

We report two cases from a family with primary Fanconi syndrome. A 39-year-old white woman with a history of frequent bone fractures developed hypophosphatemia, hypouricemia, hypokalemia, metabolic acidosis, and renal glycosuria. Her 15-year-old son had renal glycosuria without metabolic acidosis. Both had mildly to moderately impaired renal function. Determination of amino acids in 24-hour urine specimens confirmed the generalized nature of aminoaciduria. Acid-loading, bicarbonate-loading, and phosphate-loading tests revealed that the mother had proximal (type II) renal tubular acidosis and excessive renal loss of phosphate for her level of renal function. These tests for the son were normal or within normal limits of his renal function. Known causes of Fanconi syndrome, such as cystinosis and Wilson's disease, were excluded by slit-lamp eye examination and leukocyte cystine level determination. One unexpected finding in the son was the preseNce of nephrocalcinosis on x-rays; a percutaneous needle biopsy of the kidney showed tubular atrophy, interstitial fibrosis, and calcium oxalate crystal deposits. The two cases presented here represent a familial variety of the primary Fanconi syndrome, a rare entity with a limited number of cases reported in the literature.

Adolescent↗

PubMed1996

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.

Animals↗

PubMed1996

Membranous nephropathy, interstitial nephritis, and Fanconi syndrome-- glomerular antigen.

We characterized the glomerular antigen of membranous nephropathy (MN) in a child with the triad of MN, proximal renal tubular basement membrane autoantibody (TBMAb)-associated interstitial nephritis (ITN), and Fanconi syndrome. Granular staining was demonstrated for human gp600 in the vicinity of immune deposits of MN along glomerular capillary loops, using a monospecific polyclonal antibody to human gp600 by indirect immunofluorescence. However, no staining was observed in the MN deposits for receptor-associated protein. Membranous nephropathy preceded the development of TBMAbs, ITN, and Fanconi syndrome by 1 year, showing that the MN lesion does not result from the initial immunological injury to the tubulointerstitium, as postulated earlier. We confirmed the reactivity of TBMAbs with the recently described rabbit 58-kilodalton (kDa) tubular basement membrane antigen (TBMAg). However, this is the first report to show reactivity of these antibodies with the human 58-kDa protein. Also, we found that TBMAg is comprised of a single protein band of 58 kDa, unlike the previously described combination of two protein band (58 kDa and 175 kDa). In this patient, following prednisone treatment, the TBMAbs became undetectable, and the nephrotic syndrome and Fanconi syndrome resolved, thus suggesting a causal role of TBMAbs in the pathogenesis of Fanconi syndrome. We postulate that in this rare disorder, renal lesions result from an autoimmune response to the 58-kDa TBMAg and possibly to gp600, and that the predisposition to autoimmunity is genetically linked to the HLA B7 serotype.

Anti-Inflammatory Agents↗

PubMed2000

The characteristic pattern of aminoaciduria in patients with aristolochic acid-induced Fanconi syndrome: could iminoaciduria be the hallmark of this syndrome?

BACKGROUND: In Japan the patients with Chinese herbs nephropathy (CHN), aristolochic acids-(AAs) associated renal failure, often present Fanconi syndrome. The aim of this study was to investigate the pattern of aminoaciduria in patients with AAs-induced Fanconi syndrome and to clarify whether it is different from other Fanconi syndromes reported in the literature. SUBJECTS AND METHODS: The subjects consisted of 4 patients with Fanconi syndrome due to AAs. We studied biochemical data and urinary excretion of amino acids in the 4 patients. Amino acids in their urine were analyzed by high performance liquid chromatography (HPLC). RESULTS: Three out of 4 patients showed in common very increased excretion ofproline, hydroxyproline and citruline. Last patient showed the very increased levels of proline and valine. Regarding glycine, which is considered to belong to the same group as imino acid and to be shared with high-affinity transport system ofproline, there was not very increased excretion. CONCLUSION: These findings suggest that AAs would predominantly affect the low-affinity transport system of proline in the brushborder membrane of proximal tubules because the low-affinity system is considered not to be shared with glycine transport.

Adult↗

PubMed2005

[Inventory of Fanconi syndrome in Basenji dogs in The Netherlands].

The Fanconi syndrome is a familial disease in the Basenji. Its typical clinical signs are glycosuria and euglycaemia. In the United States, 10% of the Basenji population shows signs of glycosuria. The purpose of this study was to investigate the presence of glycosuria in the Basenji population in The Netherlands. Results showed few dogs to have glycosuria. Furthermore, a hereditary background to Fanconi syndrome in Basenji dogs could not be demonstrated.

Animals↗

PubMed1995

Ifosfamide-induced Fanconi syndrome.

OBJECTIVE: To report a case of possible ifosfamide-induced Fanconi syndrome in and adult with cancer. CASE SUMMARY: A 20-year old man was treated for an osteosarcoma with a chemotherapy regimen that included ifosfamide, methotrexate, and doxorubicin. Three months after completing therapy he developed polyuria, polydypsia, and bilateral ankle pain. Laboratory findings showed decreased serum concentrations of phosphorus, uric acid, calcium potassium, and bicarbonate; elevated blood urea nitrogen and creatinine; and increased urinary excretion of phosphorus, potassium, calcium, citrate, and protein. The patient was diagnosed with Fanconi syndrome and osteomalacia. Treatment with oral supplements of potassium, sodium, citric acid, calcium, and calcitriol corrected the electrolyte abnormalities. DISCUSSION: The adverse effect most frequently associated with ifosfamide is hemorrhagic cystitis. The incidence of hemorrhagic cystitis is decreased with the concomitant administration of the uroprotective agent mesna. The development of Fanconi syndrome after ifosfamide therapy has been described previously, although it occurs more frequently in children than adults. the mechanism by which ifosfamide causes renal tubular damage is not well understood, but it appears to involve metabolites of the drug. CONCLUSIONS: The development of renal tubular defects and renal failure should be considered in patients receiving ifosfamide. Although this complication appears more frequently in children, adults also can be affected. Renal function should be monitored closely to detect the appearance of this adverse effect. Renal tubular dysfunction can, as this case illustrates, develop months after completing chemotherapy.

Adult↗

PubMedDate not supplied

[Intracytoplasmic crystals and Fanconi syndrome in a patient with IgA kappa myeloma].

A 45 year old man with IgA-Kappa myeloma had adult Fanconi Syndrome. Examination of renal biopsy revealed lesions in proximal tubules without glomerular lesions and without intratubular casts. By electron microscopy cytoplasmic crystalline inclusions were observed in renal proximal tubular epithelium. Increased plasma cells (28%) in bone marrow aspiration also contained crystalline inclusions. The treatment of myeloma produced partial remission of proliferative disease and Fanconi syndrome. We discuss the pathogenesis of Fanconi syndrome induced by light chains as well as the composition of crystalline deposits and the effects of treatment on Fanconi Syndrome.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1980

Hyperreninemia, lysozymuria, and erythrocytosis in Fanconi syndrome with medullary cystic kidney.

Adult onset Fanconi syndrome with medullary cystic kidney was diagnosed in a 30-year-old male with muscular weakness, hypokalemia, normal BP, hyperreninemia, and secondary aldosteronism. He also had non-specific aminoaciduria, lysozymuria, and beta 2-microglobulinuria. Urinary concentrating and acidifying capacity was impaired, and both sodium and potassium were lost into the urine. I.v. pyelography revealed medullary cystic kidney. Renal biopsy showed juxtaglomerular hyperplasia, heavy subintimal deposits and C3 and IgG in preglomerular arteriolar walls, and degenerative changes in the tubules, including loss of brush border and "macula densa-like" lesions. Polycythemia with elevated serum erythropoietin levels, and raised blood ACTH values with features of cortisolism were also present. Indomethacin therapy decreased plasma renin activity (PRA), plasma aldosterone, and urinary loss of potassium and sodium, while serum potassium approached normal levels. Metoprolol, a beta-adrenergic blocking agent, caused similar effects. Insensitivity to the pressor effect of angiotensin II was reversed by indomethacin treatment. Somatostatin infusion lowered PRA and aldosterone without affecting BP. Several biochemical aberrations of this patient resemble Bartter's syndrome, including the effect of indomethacin.

Adult↗