eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Medullary Cystic Disease

Prasad Devarajan, MD, Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Nephrology Laboratories, Chief Executive Officer of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Updated: Dec 15, 2008

Introduction

Background

Medullary cystic kidney disease (MCKD) and nephronophthisis (NPH) refer to 2 inherited diseases with similar renal morphology characterized by bilateral small corticomedullary cysts in kidneys of normal or reduced size and tubulointerstitial sclerosis leading to end-stage renal disease (ESRD). These disorders have traditionally been considered as parts of a complex (the nephronophthisis complex) because they share many of the clinical and histopathological features. The major differences are in the modes of inheritance, the age of onset of ESRD, and the extrarenal manifestations. In this article, the 2 diseases are discussed as a single clinicopathologic entity of nephronophthisis–medullary cystic kidney disease to reflect current recommendations for the classification of renal cystic diseases. 

Nephronophthisis was first described by Smith et al in 1945, and then by Fanconi et al in 1951, as a familial disorder leading to progressive renal damage and death in late childhood. Nephronophthisis has an autosomal recessive inheritance pattern. Positional cloning and candidate gene approaches have led to the identification of 9 causative genes, all of which appear to encode for proteins expressed in the primary cilia of renal epithelial cells; hence, these disorders are now referred to as ciliopathies.^1,2 Nephronophthisis presents in childhood or adolescence with progressive renal insufficiency and is frequently associated with extrarenal organ involvement such as retinitis pigmentosa, hepatic fibrosis, skeletal defects, and cerebellar aplasia. Three clinical variants have been described, based on the age of onset of ESRD.

• The juvenile form is the most common, in which ESRD usually occurs in the second decade of life (mean age, 13 y). It is characterized by the presence of small medullary cysts, extensive tubular atrophy, thickened tubular basement membranes, and prominent interstitial fibrosis. Recent advances in molecular genetics have identified mutations in 7 distinct genes (designated as NPHP1, NPHP4, NPHP5, NPHP6, NPHP7, NPHP8, and NPHP9) that are associated with defects in distinct proteins that lead to heterogeneity in clinical manifestations. 
• The adolescent form is characterized by ESRD developing around age 20 years. It is associated with defects in the NPHP3 gene but with histologic features similar to the juvenile form. The genotype-phenotype correlations are not always clear-cut, and some patients with an NPHP3 mutation can progress to ESRD before age 10 years.
• The infantile form is characterized by progression to ESRD before age 2 years. It is associated with defects in the NPHP2 gene. Histopathology reveals cystic dilatations of the collecting ducts, but the typical tubular basement changes seen in juvenile nephronophthisis are usually absent. In contrast with the other 2 forms, these children usually demonstrate severe hypertension and moderately enlarged kidneys on ultrasonography.

Medullary cystic kidney disease is inherited in an autosomal dominant pattern and usually presents with adult-onset renal failure and no extrarenal involvement. The following 2 clinical variants have been described:

• Type 1 has a median onset of ESRD at age 62 years and is caused by defects in the MCKD1 gene. The function of the protein product is unknown.
• Type 2 has an earlier onset of ESRD (mean age, 32 y) and is the result of defects in the MCKD2 gene that encodes the uromodulin/Tamm-Horsfall mucoprotein.

Pathophysiology

Advances in molecular genetics have led to the identification of the gene defects underlying several forms of nephronophthisis–medullary cystic kidney disease. Characterization of the encoded proteins is revealing novel pathogenetic mechanisms. Many have been shown to localize to primary cilia, which are highly conserved structures that sense and process various extracellular signals. An important role of normal cilia in renal tubular cells is mechanosensation, whereby flow-mediated bending of primary cilia elicits signal transduction pathways that regulate the cell cycle, cell proliferation, and cell death. Defects in these cellular functions may contribute to cystogenesis. Because cilia are present in almost all cells and tissues, ciliary dysfunction may also account for the extrarenal manifestations encountered in some forms of nephronophthisis. 

• Nephronophthisis type 1 is characterized by mutations in the NPHP1 gene, which encodes the protein nephrocystin-1. Nephrocystin-1 interacts with the products of other NPHP genes as well as components of cell-cell and cell-matrix signaling. Nephrocystin-1 and its interacting partners are localized to the cell-cell junction (adherens junction) and cell-matrix interface (focal adhesion), suggesting important roles in maintaining the integrity of the tubular epithelium. Thus, cystogenesis in nephronophthisis type 1 may result from defects in tubular cell-cell and cell-substratum contacts. Nephrocystin-1 and other NPHP gene products are also prominently localized to the primary cilia in the apical (luminal) membranes of renal tubular epithelial cells.
• In nephronophthisis type 2, the mutated gene NPHP2/INVS encodes for inversin, which interacts with nephrocystin-1 and b-tubulin and localizes to primary cilia in renal tubular cells. B-tubulin constitutes the microtubule axoneme of primary cilia. Hence, defects in these interactions may impair ciliary function and thereby contribute to cyst development.

The products of the other genes mutated in nephronophthisis are currently under investigation, but emerging unifying features include their localization to primary cilia and their interactions with each other.

Frequency

United States

The incidence of juvenile nephronophthisis is 9 cases per 8.3 million population. Nephronophthisis is the most common genetic cause of ESRD in the first 2 decades of life, accounting for 5-15% of cases of ESRD. Medullary cystic kidney disease is rare and has been primarily reported in the United States.

International

The incidence of nephronophthisis is higher in Europe, where it accounts for 15-25% of cases of childhood ESRD.

Mortality/Morbidity

ESRD develops in all patients, although the rate of progression is faster in the recessive form of the disease than in the dominant form. Mortality is related to the complications of renal failure.

Race

No racial predilection is noted.

Sex

Both sexes are equally affected.

Age

Nephronophthisis occurs during childhood and progresses to renal failure before the age 20 years. The median age of onset of ESRD is 13 years in juvenile nephronophthisis, 1-3 years in infantile nephronophthisis, and 19 years in adolescent nephronophthisis. If ESRD has not developed by age 25 years, the diagnosis of recessive nephronophthisis is unlikely, and autosomal dominant medullary cystic kidney disease should be considered. ESRD typically develops when patients with medullary cystic kidney disease are aged 25-50 years. Median onset of ESRD is age 62 years for medullary cystic kidney disease type 1 and age 32 years for medullary cystic kidney disease type 2. 

Clinical

History

A family history of consanguinity, early death, or renal disease is present in 67% of patients with nephronophthisis (NPH).

• In juvenile nephronophthisis (the most common form), the first symptoms usually develop around age 5 years and consist of polyuria and polydipsia. These symptoms are related to a reduced urinary concentrating capacity and loss of sodium conservation and occur early in the course of the disease, well before a reduction in glomerular filtration rate. Typically, the urine osmolarity is less than 400 mosm/kg in the first morning sample.
• Children exhibit decreased growth velocity, initially related to chronic dehydration and subsequently confounded by renal insufficiency.
• Features that distinguish nephronophthisis from medullary cystic kidney disease (MCKD) include the following:
  • The inheritance pattern is autosomal recessive.
  • The median age of onset of end-stage renal disease (ESRD) is 13 years in juvenile nephronophthisis, 1-3 years in infantile nephronophthisis, and 19 years in adolescent nephronophthisis.
• Extrarenal associations of nephronophthisis include the following:
  • Cogan syndrome - Oculomotor apraxia
  • Senior-Loken syndrome - Retinitis pigmentosa
  • Mainzer-Saldino syndrome - Liver fibrosis, bone dysplasia
  • Joubert syndrome - Coloboma or retinal degeneration, nystagmus, ptosis, aplasia of cerebellar vermis with ataxia and psychomotor retardation, polydactyly, and neonatal tachypnea or dyspnea
  • Sensenbrenner syndrome - Cranioectodermal dysplasia and electroretinal abnormalities
• Distinguishing features of medullary cystic kidney disease include the following:
  • The inheritance pattern is autosomal dominant.
  • The median onset of ESRD for medullary cystic disease type 1 is age 62 years and for medullary cystic kidney disease type 2 is age 32 years.
  • Extrarenal associations are restricted to hyperuricemia and gout.
• The following conditions have renal histologic features similar to those of nephronophthisis:
  • Jeune syndrome or asphyxiating thoracic dysplasia - Small thorax, short limbs, and hypoplastic Iliac wings
  • Ellis-van Creveld syndrome - Chondroectodermal dysplasia
  • PHYNS syndrome - Retinitis pigmentosa, hypopituitarism, nephronophthisis, and skeletal dysplasia
  • Laurence-Moon-Bardet-Biedl syndrome - Retinitis pigmentosa, obesity, polydactyly, and mental retardation

Physical

The clinical findings are related to tubular injury that leads to a reduction in urinary concentrating capacity, renal sodium loss, and insidious but inevitable progression to renal failure. The tubular defects precede the decline in renal function and may be present in asymptomatic siblings with the disease.

• Nephronophthisis and medullary cystic kidney disease share several clinical features.
  • In most patients, the signs associated with decreased urinary concentration capacity are present by age 5 years.
  • The signs include polyuria, polydipsia, enuresis, and dehydration.
  • Common findings include a failure to thrive and weakness.
  • Anorexia, nausea, pruritus, bone pain, and neurologic symptoms herald ESRD.
  • Because of salt wasting, hypertension is rare, except in the infantile form of nephronophthisis.
• Pallor is another characteristic finding.
  • In contrast to other renal diseases in which the degree of anemia depends on the stage of renal insufficiency, in nephronophthisis, the severity of the anemia exceeds the degree of renal insufficiency.
  • Anemia may occur before renal insufficiency develops.
  • This normocytic and normochromic anemia is more severe than that of other chronic renal diseases and does not result from iron deficiency or hemolysis.
• Studies have shown that, in patients with nephronophthisis, the serum erythropoietin (EPO) concentration is lower than that of patients with other progressive renal diseases.
  • EPO is a glycoprotein hormone that controls the differentiation of erythroid progenitor cells in the bone marrow and the production of erythrocytes.
  • After birth, EPO is produced mainly in the kidneys, specifically in the peritubular fibroblasts.
  • In patients with nephronophthisis, the synthesis of EPO is decreased.

Causes

All of the disease variants of the nephronophthisis–medullary cystic kidney disease complex are caused by defects in different genes at distinct chromosomal loci.

Molecular Genetic Features of the Nephronophthisis–Medullary Cystic Kidney Disease Complex

*Co-localizes with familial juvenile hyperuricemic nephropathy

Differential Diagnoses

Other Problems to Be Considered

Simple renal cysts
Tuberous sclerosis

Workup

Laboratory Studies

• Urinalysis may be helpful in patients with nephronophthisis (NPH)–medullary cystic kidney disease (MCKD) complex.
  • A low specific gravity in the first morning voiding sample, which should be concentrated, is a characteristic feature of this disease. The concentrating ability rarely exceeds 800 mOsm/kg of water.
  • Hematuria, proteinuria, and bacteriuria are uncommon.
  • Proteinuria, if present, is mild and of tubular origin.
  • Significant proteinuria develops late in the course of the disease, reflecting secondary glomerular sclerosis.
• Metabolic acidosis, elevated serum BUN and creatinine concentrations, hypocalcemia, and hyperphosphatemia are indicators of renal failure.
• The CBC count frequently reveals profound normocytic normochromic anemia.
  • Approximately one third of patients develop anemia before renal insufficiency occurs.
  • Low erythropoietin (EPO) levels have been found in patients with nephronophthisis.
• Liver function tests are used to detect congenital hepatic fibrosis.

Imaging Studies

• Contrast-enhanced thin-section CT scanning is the modality of choice.³
  • The kidneys are imaged with 1-mm to 2-mm-thick sections.
  • Multiple cysts are typically seen in the medulla and corticomedullary region.
  • The cysts range from smaller than 0.5 mm to 2 cm in diameter.
• Renal ultrasonography may be helpful in assessing nephronophthisis–medullary cystic kidney disease.
  • The kidneys are of normal or moderately reduced size, with a smooth outline.
  • Typically, corticomedullary differentiation is lost, and echogenicity is increased.
  • Cysts may or may not be present at the corticomedullary border.
  • These findings are distinct from those of autosomal dominant or autosomal recessive polycystic kidney disease (PKD), in which the kidneys are enlarged and the cysts are uniformly distributed throughout the entire kidney.
  • Patients with end-stage renal disease (ESRD) have multiple small and large cysts that can be seen in the corticomedullary area.
  • No cysts are located in organs other than the kidney.
  • The absence of cysts on the sonogram does not exclude the diagnosis of nephronophthisis–medullary cystic kidney disease.
• Hepatic ultrasonography is used to detect congenital hepatic fibrosis.
• Skeletal radiography is used to identify dysplastic lesions.

Other Tests

• Ophthalmoscopy and electroretinography are used to determine the presence or tapetoretinal degeneration.
• Molecular genetic analysis is the only diagnostic procedure with which the diagnosis of nephronophthisis can be confirmed with certainty. Details are available at Renal Genes.
  • Before genetic counseling is given, a thorough pedigree analysis should be performed to distinguish recessive (early-onset) disease from dominant (late-onset) disease, and extrarenal involvement should be excluded.
  • Blood may be obtained from a patient with clinical and renal ultrasonographic findings suggestive of nephronophthisis–medullary cystic kidney disease complex or from an affected parent. DNA is extracted from this blood and amplified by using the polymerase chain reaction (PCR) to detect the homozygous deletion in the NPH1 gene.
  • Approximately 66% of children with nephronophthisis type 1 have this large homozygous deletion.
  • However, because of the additional loci for nephronophthisis, the disease cannot be excluded if mutations in the NPH1 gene are not detected.
  • If a homozygous deletion is not found, a heterozygous deletion can be detected by performing fluorescence in situ hybridization (FISH) and/or by performing direct sequencing of all 20 nephronophthisis type 1 exons to seek a corresponding heterozygous point mutation.

Histologic Findings

• On renal biopsy findings, the characteristic histologic triad is identical in the findings in childhood and adult forms of nephronophthisis. First, tubular basement membrane disintegration with irregular thickening is present with membrane attenuation. In later stages, biopsy findings include distal tubular atrophy and cystic formation predominantly at the corticomedullary junction. Second, the interstitium shows round cell infiltration and fibrosis. Third, periglomerular fibrosis is observed. These histologic changes are characteristic but not pathognomonic for the disease complex. Nephronophthisis type 3 should be considered if the histologic features are consistent with nephronophthisis in the absence of molecular defects in nephronophthisis type 1.
• Early histologic findings reveal peritubular lymphohistiocytic infiltrations. As renal failure progresses, diffuse tubulointerstitial fibrosis occurs, with tubular atrophy and dilatation. Light microscopy and electron microscopy reveal periglomerular and peritubular basement membrane thickening and splitting.
• The renal architecture is characterized by a uniformly thinned cortex and a segmental distribution of variably sized cysts in the medulla and corticomedullary junction. Cysts can be barely visible to several centimeters in size, and they vary in number from fewer than 5 to more than 50 in a segmental distribution. The cysts do not communicate with nephrons. The presence of cysts is not a diagnostic requirement because it is a late finding, and cysts may not be detected at biopsy.

Treatment

Medical Care

• In all variants of nephronophthisis (NPH)–medullary cystic kidney disease (MCKD), end-stage renal disease (ESRD) insidiously ensues within characteristic age ranges, and no specific therapy is available. Management is symptomatic and directed at preventing and treating complications of progressive renal insufficiency, such as the correction of electrolyte, acid-base, and water-balance disturbances.
• Anemia may be treated with erythropoietin.
• Growth retardation is responsive to recombinant growth hormone.
• All patients eventually require renal replacement therapy including peritoneal dialysis or hemodialysis or preemptive kidney transplantation.

Surgical Care

• Access for hemodialysis or peritoneal dialysis should be secured before ESRD develops.
• Kidney transplantation is the treatment of choice for patients who have nephronophthisis–medullary cystic kidney disease and ESRD.
  • ESRD does not recur in the transplanted kidney.
  • Living, related donors should be thoroughly screened for the disease prior to the transplantation procedures.

Consultations

• All children with polyuria, polydipsia, or a failure to thrive must be evaluated by a pediatric nephrologist. Children found to have nephronophthisis–medullary cystic kidney disease should be referred for an ophthalmologic examination and closely followed up by the nephrologist.
• Offer genetic counseling to the family.
  • A carefully constructed pedigree may help in distinguishing between the recessive and dominant forms of the disease.
  • Because of the genetic locus heterogeneity among diseases in the nephronophthisis–medullary cystic kidney disease complex, prenatal diagnosis can be performed only by means of direct genetic testing. This testing requires a setting in which a specific deletion or mutation of the NPH1 gene has already been characterized in an affected sibling. The urinary concentrating ability of asymptomatic siblings should be tested at yearly intervals.

Diet

• In children with nephronophthisis, their nutrition should be appropriate for their age.
• Adequate hydration is important to replace urinary water losses and sodium loss in patients with salt-wasting.
• As renal insufficiency progresses, foods high in phosphorus and potassium should be limited.

Activity

• Activities may be pursued as tolerated.
• Strenuous exercise and prolonged heat exposure should be avoided because children with NPH-MCKD are prone to dehydration.

Medication

Pharmacotherapy in patients with nephronophthisis (NPH)–medullary cystic kidney disease (MCKD) is symptomatic and directed at preventing and treating complications of progressive renal insufficiency.

Erythropoietin

This is a glycoprotein normally produced in the kidneys that is responsible for the stimulation of red blood cell production. Anemia occurs because of deficient erythropoietin production during renal failure.

Epoetin alfa (Epogen, Procrit)

Indicated for the treatment of anemia associated with chronic renal failure. Stimulates division and differentiation of committed erythroid progenitor cells; induces release of reticulocytes from bone marrow into bloodstream.

Dosing

Adult

50-100 U/kg 3 times/wk initially; reduce dose by 25 U/kg when hematocrit approaches 36% or increases >4 points in any 2-wk period; increase dose if hematocrit does not increase by 5-6 points after 8 wk of therapy or if hematocrit is below suggested target range

Pediatric

Administer as in adults

Interactions

May increase heparin requirements

Contraindications

Documented hypersensitivity; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in porphyria, hypertension, history of seizures; decrease dose if hematocrit increases by >4 U in any 2-wk period

Follow-up

Transfer

• Transfer to a pediatric dialysis unit is required when the child with nephronophthisis (NPH)–medullary cystic kidney disease (MCKD) develops end-stage renal disease (ESRD).

Complications

• Complications are those of progressive renal failure.

Prognosis

• ESRD develops in all patients.
• The disease does not recur in transplanted kidneys.

Patient Education

• As ESRD develops, appropriate nutritional and medical education should be made available.

Miscellaneous

Medicolegal Pitfalls

• Failure to recognize nephronophthisis (NPH)–medullary cystic kidney disease (MCKD) in a child with polyuria, anemia, growth retardation, and normal kidney function

References

1. Badano JL, Mitsuma N, Beales PL, Katsanis N. The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet. 2006;7:125-148. [Medline].

2. Fliegauf M, Benzing T, Omran H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol. Nov 2007;8(11):880-893. [Medline].

3. Elzouki AY, al-Suhaibani H, Mirza K. Thin-section computed tomography scans detect medullary cysts in patients believed to have juvenile nephronophthisis. Am J Kidney Dis. Feb 1996;27(2):216-9. [Medline].

4. Dixon-Salazar T, Silhavy JL, Marsh SE, et al. Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria. Am J Hum Genet. Dec 2004;75(6):979-87. [Medline]. [Full Text].

5. Eley L, Gabrielides C, Adams M, et al. Jouberin localizes to collecting ducts and interacts with nephrocystin-1. Kidney Int. Nov 2008;74(9):1139-1149. [Medline].

6. Heninger E, Otto E, Imm A. Improved strategy for molecular genetic diagnostics in juvenile nephronophthisis. American Journal of Kidney Disease. 2001;37:1131-9. [Medline].

7. Hildebrandt F, Omram H. New insights: nephronophthisis-medullary cystic kidney disease. Pediatric Nephrology. 2001;16:168-76. [Medline].

8. Hildebrandt F, Otto E. Molecular genetics of nephronophthisis and medullary cystic kidney disease. J Am Soc Nephrol. Sep 2000;11(9):1753-61. [Medline].

9. Hildebrandt F, Rensing C, Betz R. Establishing an algorithm for molecular genetic diagnostics in 127 families with juvenile nephronophthisis. Kidney International. 2001;59:434-45. [Medline].

10. Hildebrandt F, Zhou W. Nephronophthisis-associated ciliopathies. J Am Soc Nephrol. Jun 2007;18(6):1855-71. [Medline].

11. Hoefele J, Sudbrak R, Reinhardt R, et al. Mutational analysis of the NPHP4 gene in 250 patients with nephronophthisis. Hum Mutat. Apr 2005;25(4):411. [Medline].

12. Komatsuda A, Wakui H. Nephronophthisis: diagnostic difficulties and recent advances in molecular genetic diagnostics. Clin Exp Nephrol. Dec 2005;9(4):340-2. [Medline].

13. Marshall WF, Nonaka S. Cilia: tuning in to the cell's antenna. Curr Biol. Aug 2006;16(15):R604-R614. [Medline].

14. Marshall WF. The cell biological basis of ciliary disease. J Cell Biol. Jan 2008;180(1):17-21. [Medline].

15. Mollet G, Salomon R, Gribouval O, et al. The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. Nat Genet. Oct 2002;32(2):300-5. [Medline].

16. Nurnberger J, Kribben A, Opazo Saez A, et al. The Invs gene encodes a microtubule-associated protein. J Am Soc Nephrol. Jul 2004;15(7):1700-10. [Medline]. [Full Text].

17. O'Toole JF, Otto EA, Hoefele J, Helou J, Hildebrandt F. Mutational analysis in 119 families with nephronophthisis. Pediatr Nephrol. March 2007;22(3):366-370. [Medline].

18. 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. Aug 2003;34(4):455-9. [Medline].

19. Omran H, Sasmaz G, Haffner K, et al. Identification of a gene locus for Senior-Loken syndrome in the region of the nephronophthisis type 3 gene. J Am Soc Nephrol. Jan 2002;13(1):75-9. [Medline]. [Full Text].

20. Otto EA, Helou J, Allen SJ, et al. Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencing. Hum Mutat. Mar 2008;29(3):418-426. [Medline].

21. Otto EA, Loeys B, Khanna H, et al. Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin. Nat Genet. Mar 2005;37(3):282-8. [Medline].

22. Otto EA, Schermer B, Obara T, et al. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet. Aug 2003;34(4):413-20. [Medline].

23. Parisi MA, Doherty D, Eckert ML, et al. AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome. J Med Genet. Apr 2006;43(4):334-9. [Medline].

24. Pazour GJ. Intraflagellar transport and cilia-dependent renal disease: the ciliary hypothesis of polycystic kidney disease. J Am Soc Nephrol. Oct 2004;15(10):2528-36. [Medline]. [Full Text].

25. Salomon R, Saunier S, Niaudet P. Nephronophthisis. Pediatr Nephrol. July 8, 2008;[Medline].

26. Saunier S, Salomon R, Antignac C. Nephronophthisis. Curr Opin Genet Dev. Jun 2005;15(3):324-31. [Medline].

27. Schafer T, Putz M, Lienkamp S, et al. Genetic and physical interaction between the NPHP5 and NPHP6 gene products. Hum Mol Genet. Dec 2008;17(23):3655-62. [Medline].

28. Simons M, Gloy J, Ganner A, et al. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet. May 2005;37(5):537-43. [Medline].

29. Utsch B, Sayer JA, Attanasio M, et al. Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome. Pediatr Nephrol. Jan 2006;21(1):32-5. [Medline].

30. von Schnakenburg C, Fliegauf M, Omran H. Nephrocystin and ciliary defects not only in the kidney?. Pediatr Nephrol. June 2007;22(6):765-769. [Medline].

Keywords

medullary cystic disease, nephronophthisis, NPH, juvenile nephronophthisis, NPH1, infantile nephronophthisis, NPH2, adolescent nephronophthisis, NPH3, medullary cystic kidney disease, MCKD, MCKD1, MCKD2, juvenile nephronophthisis–medullary cystic kidney disease complex, juvenile nephronophthisis–medullary cystic kidney disease, nephronophthisis–medullary cystic kidney disease complex, nephronophthisis–medullary cystic kidney disease, nephronophthisis–medullary cystic disease, NPH-MCKD, ciliopathies, end-stage renal disease, ESRD, renal insufficiency, polyuria, polydipsia, Cogan syndrome, Senior-Loken syndrome, Mainzer-Saldino syndrome, Joubert syndrome, Sensenbrenner syndrome, hyperuricemia, gout, Jeune syndrome, asphyxiating thoracic dysplasia, obesity, Ellis-van Creveld syndrome, PHYNS syndrome, Laurence-Moon-Bardet-Biedl syndrome, renal failure

Contributor Information and Disclosures

Author

Prasad Devarajan, MD, Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Nephrology Laboratories, Chief Executive Officer of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine
Prasad Devarajan, MD is a member of the following medical societies: American Heart Association, American Society of Nephrology, American Society of Pediatric Nephrology, National Kidney Foundation, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Deogracias Pena, MD, Medical Director of Dialysis, Department of Pediatrics, Cook Children's Medical Center; Clinical Associate Professor, Texas Tech University School of Medicine
Deogracias Pena, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and American Society of Pediatric Nephrology
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Frederick J Kaskel, MD, PhD, Director of the Division and Training Program in Pediatric Nephrology, Vice Chair, Department of Pediatrics, Montefiore Medical Center and Albert Einstein School of Medicine
Frederick J Kaskel, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation, Eastern Society for Pediatric Research, Federation of American Societies for Experimental Biology, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Renal Physicians Association, Sigma Xi, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Howard Trachtman, MD, Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine
Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology
Disclosure: Amgen Grant/research funds None; Abbott Honoraria Speaking and teaching; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Marcia Del Rio, MD, to the development and writing of this article.

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