Correspondence

Polycystic Kidney Disease

N Engl J Med 2004; 350:2622June 17, 2004

Article

To the Editor:

According to Table 1 in Wilson's review of polycystic kidney disease (Jan. 8 issue),1 the MCKD2 gene has not been identified when, in fact, it has, and a genetic test is currently available. MCKD2 involves the mutation of a common urinary protein (Tamm–Horsfall protein), the function of which is unknown.2 This disease appears to be an example of an endoplasmic-reticulum storage disease.

Anthony J. Bleyer, M.D.
Wake Forest University School of Medicine, Winston-Salem, NC 27157
ableyer@wfubmc.edu

Thomas C. Hart, D.D.S., Ph.D.
National Institute of Dental and Craniofacial Research, Bethesda, MD 20892

2 References

1. 1

   Wilson PD. Polycystic kidney disease. N Engl J Med 2004;350:151-164
   Full Text | Web of Science | Medline

2. 2

   Hart TC, Gorry MC, Hart PS, et al. Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J Med Genet 2002;39:882-892
   CrossRef | Web of Science | Medline

Author/Editor Response

Drs. Bleyer and Hart correctly note that since the compilation of my review, the MCKD2 gene has been identified as UMOD, which encodes the 640-amino-acid protein, uromodulin (Tamm–Horsfall), a glycosyl-phosphatidyl inositol (GPI)-linked abundant membrane protein of unknown function that is synthesized by the thick, ascending limb and excreted into the urine. Mutations are thought to interfere with the quaternary structure of the protein and to lead to intracellular trafficking defects. Also reflecting the rapid pace of identification of genes associated with human disease in this post–human-genome era, an additional juvenile nephronophthisis gene, NPHP4 on chromosome 1p36, has been identified as encoding the 4.5-kb and 8-kb transcripts,1 and NPHP3 has been shown to encode the 6.5-kb and 8-kb transcripts.2

Additional important results include the modulation of cystic development in rodent models with the use of inhibitors of the arginine vasopressin V2 receptor, which have promising potential for autosomal recessive polycystic kidney disease and medullary cystic diseases.3,4 As in all studies of animal models, however, caution must prevail until the effects are tested in human cells and until the long-term effects are evaluated to rule out side effects such as diabetes insipidus.

Patricia D. Wilson, Ph.D.
Mount Sinai School of Medicine, New York, NY 10029
pat.wilson@mssm.edu

4 References

1. 1

   Mollet G, Salomon R, Gribuval O, et al. The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. Nat Genet 2002;32:300-305[Erratum, Nat Genet 2002;32:459.]
   CrossRef | Web of Science | Medline

2. 2

   Olbrich H, Fliegauf M, Hoefele J, et al. Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis. Nat Genet 2003;34:455-459
   CrossRef | Web of Science | Medline

3. 3

   Gattone VH II, Wang X, Harris PC, Torres VE. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med 2003;9:1323-1326
   CrossRef | Web of Science | Medline

4. 4

   Torres VE, Wang X, Qian Q, Somlo S, Harris PC, Gattone VH II. Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med 2004;10:363-364
   CrossRef | Web of Science | Medline