The bedridden osteomalacic patient with Fanconi syndrome in pre-terminal renal failure

(Section Editor: K. Kühn)

Martin Zeier and Eberhard Ritz

Department of Medicine, Ruperto-Carola-University of Heidelberg, Heidelberg, Germany

Keywords: Fanconi-syndrome; nephrocalcinosis; osteomalacia; renal failure

Introduction

Phosphate retention is a major factor in aggravating and perpetuating secondary hyperparathyroidism of patients with advanced renal failure. This effect is mediated by indirect [i.e. phosphate-induced suppression of 1,25 (OH)2 D3] and direct mechanisms (i.e. stimulation of the parathyroids by phosphate). These patients often suffer from symptomatic osteomalacia, induced by hypophosphataemia, calling for the administration of phosphate.

Advanced renal failure poses a therapeutic dilemma in the uraemic patient with tubular disorders which is illustrated by the following case.

Case

The female patient born in 1948, was first seen in the department of paediatrics at the age of 12 years. She was diagnosed with glucosuria at 3 years of age and at the age of 9 years, she first complained about pain in the femoral and tibial bones. At the age of 12, leg deformities were noted which necessitated long-term immobilization. Minor trauma caused a poorly healing fracture of the right leg at 13 years of age. Thereafter she could walk only with a cane.

When seen at the age 14 years, she was markedly stunted (growth deficit 25 cm), and she had clinical and radiological signs of severe rickets and diminished mineral density of the skeleton was noted. In addition hypocalcaemia, hypophosphataemia, elevated alkaline phosphatase, reduced tubular bicarbonate absorption and hyperchloraemic acidosis were observed. Clinical examination yielded no evidence of muscle weakness or systemic diseases associated with Fanconi syndrome.

Administration of very high doses of 5 mg cholecalciferol (i.e. 200 000 U, every other day) caused symptomatic improvement of hypocalcaemia and hypophosphataemia, and the lowering of alkaline phosphatase. A total dose of 120 mg (i.e. 2.4x106 U) was given. Subsequently, she was continued on 10 mg of vitamin D (400 000 U) per day and calcium supplements.

She was admitted again at the age of 14 years, and the dose of vitamin D was reduced to 2000 U cholecalciferol per day because nephrocalcinosis was noted by X-ray. Inulin clearance was 78 ml/min at a serum creatinine of 1.1 mg/dl. She had constant hypocalcaemia of 2.9–3.3 mmol/l. The serum phosphate concentration ranged from 1.6 to 1.9 mg/dl.

As shown in Table 1Go, a subsequent progressive decrease of endogenous creatinine clearance was noted. When she was first seen in the adult renal unit at 44 years of age, she complained of diffuse skeletal pain, particularly in the right lower leg. Orthopaedic examination showed loosening of the marrow spike. In the 4 years preceding admission she had several surgical interventions for internal fixation of both femoral and tibial bones. These interventions were complicated by new fractures of the bone or broken marrow spikes. Serum chemistry showed an elevated serum creatinine of 2.2 mg/dl, low uric acid of 2.6 mg/dl, hypophosphataemia of 0.5 mmol/l and elevated serum alkaline phosphatase of 339 U/l. Endogenous creatinine clearance was 34 ml/min and proteinuria was in the range of 1.5 g in 24 h. Ultrasonography showed that both kidneys were shrunken (<8 cm) and there was evidence of nephrocalcinosis.


View this table:
[in this window]
[in a new window]
 
Table 1. Development of renal insufficiency during the past 23 years (endogenous creatinine clearance ml/min)

 
At the age of 45 years the patient was almost bedridden because of skeletal pain, particularly of the lower extremities. Pain was aggravated when she started to walk. Because of a fracture of the internal fixation of the left tibial bone, re-operation was necessary. During the procedure a bone biopsy was obtained. Bone histology revealed microcallus formation, fibrotic tissue reaction adjacent to the marrow spike and osteomalacia. There were no microscopic signs of hyperparathyroidism or aluminium deposits.

This situation raised the issue of how to treat the skeletal problems? Phosphate was felt to be dangerous because of the risk of hyperparathyroidism, especially when in another case hyperparathyroidism was noted despite hypophosphataemia. On the other hand she suffered from symptomatic osteomalacia induced by hypophosphataemia. Clearly the administration of phosphate was a therapeutic gamble. With informed consent in 1996 the patient was put on an oral phosphate supplement (phosphate supplement 136 mg Na-hydrogen phosphate in 1000 ml water, pH 5.9). She tolerated the treatment well, specifically without tetanic episodes. At the start of treatment she experienced mild abdominal discomfort. Within months the patient improved and was able to walk without any help. Currently she is completely free of pain.

Teaching point

Although phosphorous retention is a major cause of secondary hyperparathyroidism and ostitis fibrosa in patients with pre-terminal renal failure, the rare patient with tubular phosphate loss can paradoxically be cured by administration of phosphate.



View larger version (98K):
[in this window]
[in a new window]
 
Fig. 1. (a and b) Growth retardation of the patient with Fanconi-syndrome.

 



View larger version (125K):
[in this window]
[in a new window]
 
Fig. 2. Dislocation of the marrow spike (tibial bone) in the patient with Fanconi syndrome.

 


View this table:
[in this window]
[in a new window]
 
Table 2. Evolution of clinical findings, parathyroid hormone and alkaline phosphatase

 

Notes

Supported by an educational grant from

Fresenius Medical Care

Correspondence and offprint requests to: Martin Zeier, Department Medicine/Nephrology, University of Heidelberg, Bergheimerstr. 56a, D-69115 Heidelberg, Germany. Back

Suggested readings

  1. Manz F, Schärer K. Long-term management of inherited renal tubular disorders. Klin Wochenschr1982; 60: 1115–1125[ISI][Medline]
  2. Aparicio M, Combe C, Lafage MH, De Precigout V, Potaux L, Bouchet JL. In advanced renal failure, dietary phosphorous restriction reverses hyperparathyroidism independent of changes in the levels of calcitriol. Nephron1993; 63: 122–123[ISI][Medline]
  3. Kramar R, Haffner D, Wühl E, Mehls O. Role of phosphate for the development of renal hyperparathyroidism: lessons from a hypophosphataemic patient with nephropathic cystinosis. Nephrol Dial Transplant1995; 10: 2343–2345[ISI][Medline]




This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Zeier, M.
Articles by Ritz, E.
PubMed
PubMed Citation
Articles by Zeier, M.
Articles by Ritz, E.