A Case of Fanconi's Syndrome due to Chinese Herb Nephropathy

Glycosuria—glucose reabsorption in the proximal tubule is carried out by two different pairs of apical Na+-dependent (SGLT1 and -2) and basolateral Na+-independent (GLUT1 and -2) glucose transporters. Abnormalities in renal glucose transport can be seen in association with other defects of proximal tubular transport. Familial renal glycosuria is a rare autosomal recessive condition caused by mutations in the SGLT2-encoding gene, SLC5A2. Phosphate-handling disorders—the plasma concentration of inorganic phosphate depends on the balance between intestinal absorption, renal excretion, and the internal contribution from bone. Changes of serum phosphate levels can be caused by numerous inherited and acquired conditions. Disorders associated with increased urinary phosphate excretion and low serum phosphate levels produce symptoms that mainly affect the bones: rickets in children and osteomalacia in adults. Magnesium-handling disorders—normal plasma magnesium concentration is achieved by variation of urinary magnesium excretion in response to altered uptake by the intestine. The main site of magnesium absorption is the small bowel, via paracellular simple diffusion at high intraluminal concentrations, and via active transcellular uptake through the magnesium channel TRPM6 at low concentrations. Regulation and fine-tuning of serum magnesium concentration occurs primarily in the kidney. Genetic disorders of magnesium handling include Gitelman’s syndrome. Aminoaciduria and renal Fanconi’s syndrome—most amino acids (except for tryptophan, which is protein bound) are freely filtered by the glomerulus, after which 95 to 99.9% are reabsorbed in the proximal tubules by apical Na+-dependent cotransporters and Na+-independent cotransporters. Aminoaciduria is defined as urinary excretion of more than 5% of the filtered load of an amino acid. Renal Fanconi’s syndrome is characterized by a generalized defect of both Na+-coupled and receptor-mediated proximal tubular transport.

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Ifosfamide, Fanconi's syndrome, and rickets.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.8.1495 ◽

1991 ◽

Vol 9 (8) ◽

pp. 1495-1499 ◽

Cited By ~ 101

Author(s):

C B Pratt ◽

W H Meyer ◽

J J Jenkins ◽

L Avery ◽

C P McKay ◽

...

Keyword(s):

Total Dose ◽

Side Effect ◽

Fanconi’S Syndrome ◽

Fanconi's Syndrome

Three of 218 children treated with ifosfamide plus the uroprotectant mesna, in single- or combination-agent protocols, have developed Fanconi's renal syndrome, all of whom were in a subgroup of 86 children who had also received cisplatin or carboplatin therapy. Patients receiving ifosfamide who have received prior cisplatin (or carboplatin) are at significantly higher risk of developing Fanconi's syndrome than are those who have received no prior nephrotoxic therapy (P = .04). The role of prior nephrotoxic therapy, including cisplatin and its derivatives, and the total dose of ifosfamide should be considered in the assessment of this rare but serious and apparently irreversible side effect.

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The Incidence of Leukemia in Families of Patients with Hypoplasia of the Marrow

Blood ◽

10.1182/blood.v14.9.1008.1008 ◽

1959 ◽

Vol 14 (9) ◽

pp. 1008-1014 ◽

Cited By ~ 98

Author(s):

SERGIO GARRIGA ◽

WILLIAM H. CROSBY

Keyword(s):

Bone Marrow ◽

Special Interest ◽

Mesenchymal Origin ◽

Fanconi’S Syndrome ◽

High Incidence ◽

Fanconi's Syndrome

Abstract The authors have reviewed the published cases of Fanconi’s syndrome of hypoplasia of the bone marrow. They have tabulated the features of the syndrome, pointing out that atrophy of the spleen is a common fault and may reflect a generalized dystrophy of the tissues of mesenchymal origin. Of special interest is the demonstration of a high incidence of leukemia in the families of patients with hereditary hypoplasia of the bone marrow.

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Constitutional Anemia (Fanconi’s Syndrome) and Leukemia in Two Brothers

Blood ◽

10.1182/blood.v10.8.788.788 ◽

1955 ◽

Vol 10 (8) ◽

pp. 788-801 ◽

Cited By ~ 37

Author(s):

R. H. COWDELL ◽

P. J. R. PHIZACKERLEY ◽

D. A. PYKE

Keyword(s):

Bone Marrow ◽

Acute Leukemia ◽

Short Stature ◽

Left Kidney ◽

The Other ◽

Congenital Defects ◽

Fanconi’S Syndrome ◽

Bone Marrow Hypoplasia ◽

Fanconi's Syndrome ◽

Hypoplastic Anemia

Abstract Two brothers physically very alike became ill in their third decade, one with severe bone marrow hypoplasia and the other with acute leukemia. Both died and the autopsy findings are described. The two shared certain congenital defects, notably short stature with small heads, cutaneous pigmentation, pituitary and genital hypoplasia, and deformity of the thumbs. The brother with hypoplastic anemia also had aortic hypoplasia and his left kidney was absent. No previous report has been discovered of the association of Fanconi’s syndrome (of bone marrow hypoplasia with congenital defects) and leukemia with similar congenital defects in brothers. In two reports of leukemia affecting cousins of patients with Fanconi's syndrome, the leukemic cousins were without congenital defects.

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Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.1.159 ◽

1994 ◽

Vol 12 (1) ◽

pp. 159-165 ◽

Cited By ~ 89

Author(s):

R Rossi ◽

A Gödde ◽

A Kleinebrand ◽

M Riepenhausen ◽

J Boos ◽

...

Keyword(s):

Risk Factors ◽

Renal Function ◽

Unilateral Nephrectomy ◽

Tubular Dysfunction ◽

Schwartz Formula ◽

Cytostatic Treatment ◽

Fanconi’S Syndrome ◽

Fractional Excretion Of Sodium ◽

Proximal Tubular ◽

Fanconi's Syndrome

PURPOSE This study was performed to identify risk factors of ifosfamide-induced renal damage. PATIENTS AND METHODS Renal function was assessed in 120 patients at a minimum of 3 months after completion of chemotherapy including ifosfamide. The cumulative ifosfamide dose ranged from 2 to 95 g/m2 (median, 30 g/m2). Ten patients had undergone unilateral nephrectomy; combination cytostatic treatment included cisplatin in 51 and methotrexate in 57. Sixty-eight patients had received gentamicin treatment. The glomerular filtration rate was estimated using the Schwartz formula. Proximal tubular function was assessed by the percent reabsorptions of glucose and 16 amino acids, the fractional excretion of sodium, and the fractional reabsorption of phosphate. In addition, the serum bicarbonate level was measured. RESULTS Proximal tubular dysfunction--with a predominance of renal amino acid (66.3%) and phosphate loss (38.3%)--was much more frequent than both glomerular impairment and acidosis. Seven patients were identified as having renal Fanconi's syndrome, and generalized tubulopathy was noted in another 15 patients. Ifosfamide-induced nephrotoxicity was dose-dependent, with a weak linear inverse correlation between cumulative ifosfamide dose and fractional phosphate reabsorption. Unilateral nephrectomy proved to be the single most important risk factor (odds ratio for the development of renal Fanconi's syndrome, 11.4), but cisplatin also significantly enhanced ifosfamide-mediated nephrotoxicity. Methotrexate, gentamicin, and patient age at primary diagnosis had no influence on renal function. CONCLUSION Ifosfamide chemotherapy should probably be restricted in patients after unilateral nephrectomy.

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