An experimental renal acidification defect in patients with hereditary fructose intolerance

Rc, Morris

doi:10.1172/jci105856

Cited by 70 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…), the administration of fructose induced an impairment in renal bicarbonate reabsorption typical of that observed in adult patients with hereditary fructose intolerance studied at normal or supernormal plasma bicarbonate concentrations (1,2). Within 30 min of the initiating dose of fructose, the fractional (urinary) excretion of filtered bicarbonate (clearance of bicarbonate/clearance of inulin) increased from zero to >15% and remained at the high values for as long as blood fructose was maintained at 10-16 mg/100 ml and the plasma bicarbonate concentration was maintained at 22 mmol/liter or higher (Fig.…”

Section: Resultsmentioning

confidence: 88%

“…In patients with hereditary fructose intolerance and intact parathyroid function, the experimental dysfunction of the proximal renal tubule occurs minutes after fructose is initiated and persists at a predictable degree of severity throughout sustained blood fructose concentrations of 15 mg/100 ml and lower (2). But in the patient with hereditary fructose intolerance and hypoparathyroidism, a strikingly attenuated experimental renal dysfunction attended sustained blood fructose concentrations of 20 mg/100 ml until PTH was initiated, whereupon there occurred almost immediately a dysfunction of the severity anticipated with intact parathyroid function.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3]. These and other physiologic, metabolic, and enzymatic findings provide compelling evidence that the experimental renal dysfunction is caused by a fructose-induced, dose-dependent abnormality of renal cortical metabolism unique to patients with hereditary fructose intolerance and mediated by their genetic deficiency of renal aldolase B (3)(4)(5).…”

mentioning

confidence: 91%

“…In patients with hereditary fructose intolerance the experimental administration of fructose induces a complex dysfunction of the proximal renal tubule like that of clinical Fanconi's syndrome: impaired reabsorption of phosphate, amino acid, glucose, and uric acid (1,2) and an acidification defect characterized by a greater than 15% reduction of tubular reabsorption of bicarbonate (THCO3-) at normal plasma bicarbonate concentrations (type II, "proximal" renal tubular acidosis, refs. [1][2][3].…”

mentioning

confidence: 99%

See 3 more Smart Citations

Modulation of Experimental Renal Dysfunction of Hereditary Fructose Intolerance by Circulating Parathyroid Hormone

McSherry

Sebastián

1971

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

In a woman with hereditary fructose intolerance and intact parathyroid function, the experimental administration of fructose at different dosage schedules invariably induced the dose-dependent, complex dysfunction of the proximal renal tubule now recognized as characteristic. But in a woman with hereditary fructose intolerance and hypoparathyroidism given similar amounts of fructose, the experimental dysfunction was strikingly attenuated or nondemonstrable unless or until fructose and parathyroid hormone were administered in sustained combination. Thereupon, a renal dysfunction of characteristic type and severity occurred invariably and almost immediately. Thus, the concentration of circulating parathyroid hormone can modulate the functional expression of the experimental renal disorder. This effect of parathyroid hormone, which appears to involve more than simple physiologic summation, may have important clinical implications.In patients with hereditary fructose intolerance the experimental administration of fructose induces a complex dysfunction of the proximal renal tubule like that of clinical Fanconi's syndrome: impaired reabsorption of phosphate, amino acid, glucose, and uric acid (1, 2) and an acidification defect characterized by a greater than 15% reduction of tubular reabsorption of bicarbonate (THCO3-) at normal plasma bicarbonate concentrations (type II, "proximal" renal tubular acidosis, refs. 1-3). These and other physiologic, metabolic, and enzymatic findings provide compelling evidence that the experimental renal dysfunction is caused by a fructose-induced, dose-dependent abnormality of renal cortical metabolism unique to patients with hereditary fructose intolerance and mediated by their genetic deficiency of renal aldolase B (3-5). Apart from exogenous fructose, nongenetic requirements for the experimental renal dysfunction have not been systematically investigated. Other than the blood concentration of fructose, determinants of the severity of the dysfunction have not been identified. In clinical Fanconi's syndrome caused by the genetically transmitted disease cystinosis, increased concentrations of circulating parathyroid hormone (PTH) appear to amplify the acidification defect (6). In clinical vitamin D deficiency, secondary hyperparathyroidism appears to be a requirement for the occurrence of renal aminoaciduria (7, 8) and "proximal" renal tubular acidosis (6). We now report evidence that the experimental renal dysfunction of hereditary fructose intolerance is modulated by the concentration of circulating PTH. At lower blood fructose concentrations, occurrence of the renal dysfunction appears to require circulating PTH. METHODSThe effect of intravenous administration of fructose on renal bicarbonate reabsorption and other renal tubular functions was determined in eight studies of two unrelated women with previously diagnosed (1) hereditary fructose intolerance: D.M., age 43, who had hypoparathyroidism, and E.A., age 38, who did not. Neither patient had clinical or laboratory evidenc...

show abstract

Section: Resultsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

mentioning

confidence: 99%

See 2 more Smart Citations

Modulation of Experimental Renal Dysfunction of Hereditary Fructose Intolerance by Circulating Parathyroid Hormone

McSherry

Sebastián

1971

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Inherited forms occur in a number of genetic disorders such as, hereditary, tyrosinemia, hepatorenal, cystinosis, Lowe syndrome, galactosemia, fructose intolerance glycogen storage disease type 1 and Wilson's disease [71][72][73][74][75][76]. It can also be acquired through heavy metal exposure, multiple myeloma, and immunologic disorders [77,78].…”

Section: Tenofovir Renal Toxicity: Evaluation Of Case Reportsmentioning

confidence: 99%

Tenofovir Renal Toxicity: Evaluation of Cohorts and Clinical Studies—Part 2

Adikwu¹,

Ijeoma²,

Edikpo³

et al. 2014

View full text Add to dashboard Cite

Tenofovir is a nucleotide reverse transcriptase inhibitor used as part of antiretroviral regimens. It is well tolerated with relative toxicological effects but recent reports have linked it with renal toxicity which is of clinical concern. This study reviews literary work on tenofovir renal toxicity with more light on case reports. Tenofovir renal toxicity manifests as Fanconi's syndrome, nephrogenic diabetes insipidus and acute renal failure. Fanconi's syndrome is characterised by acidosis, protenuria, albuminuria, aminoaciduria, hyperchloremic, metabolic acidosis, hypouricemia, hypophosphatemia and glycosuria. The presence of urine osmolality, polydipsia and polyuria could give credence totenofovir induced nephrogenic diabetes insipidus. In some cases of tenofovir renal toxicity, renal biopsy revealed sclerosed glomeruli with ischemic injury including portal collapse of capillary loops. Histopathological changes in glumeruli include mild mesangial proliferation, increased mesangial matrix and thickened capillary loops. Moderate degenerative tubular changes, loss of tubular mass, interstitial scarring and scattered cellular infiltrates. Pharmacodynamic and pharmacokinetic interactions may occur with the co administration of tenofovir with non steroidal anti-inflammatory drugs, aminoglycosides and some protease inhibitors which may potentiate renal toxicity. Tenofovir renal toxicity is associated with some risk factors including genetic polymorphism as supported by dichotomy in renal toxicity among different race and the association between ABCC2 gene and tenofovir kidney tubular dysfunction. The pharmacology of tenofovir renal toxicity is unclear but it is attributed to the interaction between tenofovir and theorganic anion transporters (hOAT1, and to a lesser extent, OAT3) favoring intracellular accumulation in renal proximal tubule cells. This may lead to ultrastructural mitochondrial abnormalities and decreased mtDNA levels which could stimulate reactive oxygen species production, depletion of antioxidants and antioxidant enzymes. These processes can stimulate the destruction of biomolecules such as DNA, proteins, and lipids, thus causing the deregulation of redox-sensitive metabolic pathways, signaling pathways, and cell death. Despite tenofovir renal toxicity it has achieved notable therapeutic success nevertheless patients on tenofovir containing regimens should be monitored for renal function parameters. Co administration with potential nephrotoxic drugs should be avoided except when benefit outweighs risk.

show abstract

Hereditary Fructose Intolerance in Childhood

Odièvre¹

1978

Am J Dis Child

129

View full text Add to dashboard Cite

The early manifestations of hereditary fructose intolerance are described in a series of 55 patients. Management of this metabolic disorder depends on the severity of liver impairment. When the patients are given a fructose-free diet, the improvement is a dramatic but liver enlargement and fatty vacuolization of liver cells often persist. These hepatic findings were also observed in the five homozygous infants who were given a fructose-free diet from birth; this outcome may support the hypothesis that minimal amounts of fructose are esential for human beings.

show abstract

An experimental renal acidification defect in patients with hereditary fructose intolerance

Cited by 70 publications

References 23 publications

Modulation of Experimental Renal Dysfunction of Hereditary Fructose Intolerance by Circulating Parathyroid Hormone

Modulation of Experimental Renal Dysfunction of Hereditary Fructose Intolerance by Circulating Parathyroid Hormone

Tenofovir Renal Toxicity: Evaluation of Cohorts and Clinical Studies—Part 2

Hereditary Fructose Intolerance in Childhood

Contact Info

Product

Resources

About