Scott G. Hubosky, MD
BASICS
DESCRIPTION
• Medullary cystic kidney disease (MCKD) is a rare congenital, cystic disease of the kidneys which results in progressive renal deterioration and to eventual end-stage renal disease (ESRD)
• Symptoms develop insidiously and diagnosis is not common until renal insufficiency is detected and initiates evaluation (1)[C]
EPIDEMIOLOGY
Incidence
Less than 1: 100,000
Prevalence
N/A
RISK FACTORS
Positive family history
Genetics
• Mode of inheritance is autosomal dominant (2)[C]
– Medullary cystic kidney disease-1 (MCKD1)
Mutation in MCKD1 gene localized to chromosome 1q21
– MCKD2
Mutation in MCKD2 gene localized to chromosome 16p12
PATHOPHYSIOLOGY
• Unlike other renal cystic diseases such as autosomal dominant polycystic kidney disease (ADPKD), there is no clear correlation between genetic mutation and identifiable protein product responsible for the MCKD phenotype (3)[C]
ASSOCIATED CONDITIONS
• Hyperuricemia and gouty arthritis are associated with MCKD2
• In contrast to juvenile nephronophthisis, MCKD does not have many extrarenal manifestations
GENERAL PREVENTION
N/A
DIAGNOSIS
HISTORY
• Polyuria
– Usually the 1st clinical manifestation
– Occurs due to reduced urinary concentrating ability of the kidney
• Polydipsia
• Family history of ESRD, or renal cysts
PHYSICAL EXAM
Hypertension may be noted with disease progression
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis
– Proteinuria and hematuria are usually absent
• CBC
– Anemia present in advanced cases due to lack of erythropoietin
• Serum electrolytes
– Elevated creatinine
– Hyperkalemia or metabolic acidosis in later stages due to renal insufficiency
Imaging
• Renal ultrasound
– Kidneys may be atrophic depending on stage of disease
– Cysts may be visible at the corticomedullary junction in later disease but are usually not detectable in early stages
– Increased parenchymal echogenicity from tubulointerstitial fibrosis
• CT scan
– Can detect cysts at the corticomedullary junction better than ultrasound
– Need for IV contrast is suboptimal in patients with ESRD
Diagnostic Procedures/Surgery
Percutaneous renal biopsy confirms the diagnosis
Pathologic Findings
• Gross findings
– Initially before disease progression, the kidneys are of normal size
– Cortical atrophy with progression
– Cysts develop at the corticomedullary junction and range in size from 1 to 10 mm.
– With disease advancement the kidneys become very small and demonstrate a granular exterior surface
• Microscopic findings
– Interstitial nephritis
– Dilated, atrophic tubules
– Inflammatory cell infiltrates
DIFFERENTIAL DIAGNOSIS
• Juvenile nephronophthisis
– Clinically and anatomically similar to MCKD
– Autosomal recessive inheritance
– ESRD usually manifests as early as age 13 yr
– Extrarenal manifestations are common
Retinal disorders (retinitis pigmentosa)
Hepatic fibrosis
Bardet–Biedl syndrome (obesity, retinitis pigmentosa, mental retardation, polydactyly)
• Polycystic kidney disease
– Autosomal recessive polycystic kidney disease (infantile form)
– Autosomal dominant polycystic kidney disease (adult form)
• Multicystic dysplastic kidney
• Benign multilocular cyst (cystic nephroma)
• Medullary sponge kidney
TREATMENT
GENERAL MEASURES
• Same as for any patient with renal insufficiency
– Control hypertension if present
– Monitor fluid balance/daily weights
– Monitor serum electrolytes
MEDICATION
First Line
• None for primary treatment
• Antihypertensive regimens sometimes necessary
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Dialysis when ESRD develops
• Renal transplant
– Allograft is not affected by MCKD after transplantation
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• MCKD1 patients manifest with ESRD at median age of 62 yr
• MCKD2 patients manifest with ESRD at median age of 32 yr
COMPLICATIONS
Similar to any patient with renal insufficiency or ESRD
FOLLOW-UP
Patient Monitoring
Close nephrology follow-up is essential
Patient Resources
• National Kidney Foundation
– www.kidney.org/patients
REFERENCES
1. Scolari F, Ghiggeri GM. Nephronophthisis-medullary cystic kidney disease: From bedside to bench and back again. Saudi J Kidney Dis Transplant. 2003;14:316–327.
2. Hildebrandt F, Omram H. New Insights: Nephronophthisis-medullary cystic kidney disease. Pediatr Nephrol. 2001;16:168–176.
3. Kim CM, Glassberg KI. Molecular mechanisms of renal development. Cur Urol Rep. 2003;4:164–170.
ADDITIONAL READING
Hildebrandt F, Otto E. Molecular genetics of nephronophthisis and medullary cystic kidney disease. J Am Soc Nephrol. 2000;11:1753–1761.
See Also (Topic, Algorithm, Media)
• Nephronophthisis (Juvenile, Infantile, and Adolescent)
• Renal Cysts (Intrarenal, Peripelvic, and Parapelvic)
• Renal Mass
CODES
ICD9
• 585.6 End stage renal disease
• 753.16 Medullary cystic kidney
• 788.42 Polyuria
ICD10
• N18.6 End stage renal disease
• Q61.5 Medullary cystic kidney
• R35.8 Other polyuria
CLINICAL/SURGICAL PEARLS
• MCKD has an insidious disease onset.
• Symptoms usually not present until patient has renal insufficiency documented on serum testing.
• Polyuria is commonly the 1st clinical manifestation.