Dent's disease

Guy H. Neild1, Rajesh V. Thakker2, Robert J. Unwin1 and Oliver M. Wrong1

1 Department of Nephrology, UCL Hospitals Trust, Middlesex Hospital, London W1T 3AA and 2 Nuffield Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford OX3 7LJ, UK

Correspondence and offprint requests to: Professor Guy H. Neild, Middlesex Hospital, Mortimer Street, London W1T 3AA, UK. Email: g.neild{at}ucl.ac.uk

Keywords: Dent's disease; CLCN5 gene; nephrocalcinosis; renal cysts

Case

A 42-year-old engineer developed right renal colic, and a plain radiograph showed bilateral nephrocalcinosis with calculi filling the upper part of the right ureter (Figure 1). Renal glycosuria and proteinuria had been found at an employment examination at the age of 16, and he had since passed numerous renal stones. Plasma creatinine was 236 µmol/l (2.67 mg/dl), Ca2+ 2.5, K+ 2.9, HCO3 25, PO4 0.89 mmol/l; urine contained large amounts of low-molecular-weight protein, 1 plus glucose and 22 mmol of calcium (880 mg)/24 h. The diagnosis of Dent's disease was confirmed by DNA sequence analysis of the CLCN5 gene on the X-chromosome, which showed a donor splice site mutation that would result in a deletion of residues 132–172 of the gene product [1].



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Fig. 1. X-ray showing nephrocalcinosis with calculi filling the upper part of the right ureter.

 
His right ureter was cleared of calculi by laser dissolution. Renal function thereafter slowly deteriorated. He commenced haemodialysis aged 51 and 3 years later had a successful cadaver renal transplant. Because of recurrent attacks of infection in his native kidneys, these were removed a year later. Figure 2 shows his excised left kidney. Both kidneys were slightly reduced in length with dense pericapsular adhesions and multiple small renal cysts throughout both cortex and medulla; histology, which is described elsewhere [2], showed severe tubular epithelial cell degeneration and atrophy, with calcium deposition in tubular lumens and interstitium, many hyalinized glomeruli and others with a thickened capsule. His subsequent course has been complicated by hypertension and ischaemic heart disease, requiring coronary angioplasty at the age of 56, but currently at aged 60, he is well.



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Fig. 2. Left kidney showing multiple small renal cysts throughout both cortex and medulla.

 
Multiple small cysts throughout the renal substance, as in this patient, are common in Dent's disease [3], but are not specific for this disease as they are found in other conditions associated with nephrocalcinosis [4]. The combination of nephrocalcinosis, hypercalciuria, low-molecular-weight proteinuria, hypokalaemia and progressive renal failure in a male patient were the features suggesting Dent's disease, which was confirmed by the finding of the CLCN5 gene mutation on the X-chromosome.

Conflict of interest statement. None declared.

References

  1. Lloyd SE, Pearce SHS, Fisher SE et al. A common molecular basis for three inherited kidney stone diseases. Nature, 1996; 379: 445–449[CrossRef][ISI][Medline]
  2. Moulin P, Igarashi T, Ven Der Smissen P et al. Altered polarity and expression of H+-ATPase without ultrastructural change in kidneys of Dent's disease patients. Kidney Internat 2003; 63: 1285–1295[CrossRef][ISI][Medline]
  3. Wrong OM, Norden AGW, Feest TG. Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance. Q J Med, 1994; 87: 473–493[ISI]
  4. Wrong, O. Nephrocalcinosis. In: Davidson AM, Cameron JS, Grünfeld J-P et al. (eds), Oxford Textbook of Clinical Nephrology, 3rd edn. Oxford University Press, 2005, pp. 1257–1279




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