Medullary sponge kidney
- David S Goldfarb, MD, FACP, FASN
David S Goldfarb, MD, FACP, FASN
- Professor of Medicine and Physiology
- New York University School of Medicine
Medullary sponge kidney is a congenital disorder characterized by malformation of the terminal collecting ducts in the pericalyceal region of the renal pyramids [1-3]. This collecting duct dilatation, or ectasia, is associated with the formation of both small (microscopic) and large medullary cysts that are often diffuse but do not involve the cortex.
Medullary sponge kidney (originally called Lenarduzzi-Cacchi-Ricci disease) is usually asymptomatic. The diagnosis is commonly made as an incidental finding during an imaging test performed for a different indication. Although considered benign, the associated complications of medullary sponge kidney (eg, nephrolithiasis and urinary tract infections) may rarely lead to chronic kidney disease and even renal failure .
ETIOLOGY AND PATHOPHYSIOLOGY
The changes seen in medullary sponge kidney are thought to reflect a developmental abnormality, though the underlying defect is not fully understood. The association of medullary sponge kidney with malformations affecting the kidney such as hemihypertrophy and Beckwith-Wiedemann syndrome has led to speculation that the disorder results from a disruption of the interface between the ureteral-bud and the metanephric blastema during embryonic development .
Evidence for genetic transmission of medullary sponge kidney is limited. Some patients with medullary sponge kidney have mutations in the gene for glial cell-derived neurotrophic factor (GDNF), a protein that is pivotal in renal development . One study suggested that mutations in GDNF may lead to osteogenic differentiation in renal papillary cells, resulting in medullary sponge kidney . In this study, a patient heterozygous for a GDNF mutation and medullary sponge kidney underwent nephrectomy for a different clinical indication; cells from the papilla of the resected kidney were cultured and, after several months, developed mineralization. The investigators subsequently showed that similar mineralization occurred in an immortalized human kidney cell line when the GDNF gene was knocked down.
Although occasional families with medullary sponge kidney appear to show autosomal dominant inheritance [1,3], a positive family history is often absent. Despite this, family clustering of medullary sponge kidney may be common. In a study of 50 patients with documented medullary sponge kidney, 27 had affected family members identified with imaging (either contrast-enhanced computerized tomography or ultrasound) or, among deceased family members, a suggestive clinical history [8,9]. The responsible genotypes for this clustering are uncertain and were not due to mutations in GDNF.
- Hildebrandt F, Sayer JA, Jungers P, et al. Nephronophthisis-medullary cystic and medullary sponge kidney disease. In: Diseases of the Kidney & Urinary Tract, 8th ed, Schrier RW (Ed), Lippinicott Williams & Wilkins, Philadelphia 2007. p.478.
- MORRIS RC, YAMAUCHI H, PALUBINSKAS AJ, HOWENSTINE J. MEDULLARY SPONGE KIDNEY. Am J Med 1965; 38:883.
- Goldman SH, Walker SR, Merigan TC Jr, et al. Hereditary occurrence of cystic disease of the renal medulla. N Engl J Med 1966; 274:984.
- Jungers P, Joly D, Barbey F, et al. ESRD caused by nephrolithiasis: prevalence, mechanisms, and prevention. Am J Kidney Dis 2004; 44:799.
- Gambaro G, Feltrin GP, Lupo A, et al. Medullary sponge kidney (Lenarduzzi-Cacchi-Ricci disease): a Padua Medical School discovery in the 1930s. Kidney Int 2006; 69:663.
- Torregrossa R, Anglani F, Fabris A, et al. Identification of GDNF gene sequence variations in patients with medullary sponge kidney disease. Clin J Am Soc Nephrol 2010; 5:1205.
- Mezzabotta F, Cristofaro R, Ceol M, et al. Spontaneous calcification process in primary renal cells from a medullary sponge kidney patient harbouring a GDNF mutation. J Cell Mol Med 2015; 19:889.
- Fabris A, Lupo A, Ferraro PM, et al. Familial clustering of medullary sponge kidney is autosomal dominant with reduced penetrance and variable expressivity. Kidney Int 2013; 83:272.
- Goldfarb DS. Evidence for inheritance of medullary sponge kidney. Kidney Int 2013; 83:193.
- Parks JH, Coe FL, Strauss AL. Calcium nephrolithiasis and medullary sponge kidney in women. N Engl J Med 1982; 306:1088.
- Yagisawa T, Kobayashi C, Hayashi T, et al. Contributory metabolic factors in the development of nephrolithiasis in patients with medullary sponge kidney. Am J Kidney Dis 2001; 37:1140.
- O'Neill M, Breslau NA, Pak CY. Metabolic evaluation of nephrolithiasis in patients with medullary sponge kidney. JAMA 1981; 245:1233.
- Higashihara E, Nutahara K, Tago K, et al. Medullary sponge kidney and renal acidification defect. Kidney Int 1984; 25:453.
- Carboni I, Andreucci E, Caruso MR, et al. Medullary sponge kidney associated with primary distal renal tubular acidosis and mutations of the H+-ATPase genes. Nephrol Dial Transplant 2009; 24:2734.
- Baggio B, Priante G, Brunati AM, et al. Specific modulatory effect of arachidonic acid on human red blood cell oxalate transport: clinical implications in calcium oxalate nephrolithiasis. J Am Soc Nephrol 1999; 10 Suppl 14:S381.
- Fabris A, Bernich P, Abaterusso C, et al. Bone disease in medullary sponge kidney and effect of potassium citrate treatment. Clin J Am Soc Nephrol 2009; 4:1974.
- Asplin JR, Donahue S, Kinder J, Coe FL. Urine calcium excretion predicts bone loss in idiopathic hypercalciuria. Kidney Int 2006; 70:1463.
- Maschio G, Tessitore N, D'Angelo A, et al. Medullary sponge kidney and hyperparathyroidism--a puzzling association. Am J Nephrol 1982; 2:77.
- Forster JA, Taylor J, Browning AJ, Biyani CS. A review of the natural progression of medullary sponge kidney and a novel grading system based on intravenous urography findings. Urol Int 2007; 78:264.
- Ginalski JM, Schnyder P, Portmann L, Jaeger P. Medullary sponge kidney on axial computed tomography: comparison with excretory urography. Eur J Radiol 1991; 12:104.
- Maw AM, Megibow AJ, Grasso M, Goldfarb DS. Diagnosis of medullary sponge kidney by computed tomographic urography. Am J Kidney Dis 2007; 50:146.
- Meier P, Farres MT, Mougenot B, et al. Imaging medullary cystic kidney disease with magnetic resonance. Am J Kidney Dis 2003; 42:E5.
- Levine E, Hartman DS, Meilstrup JW, et al. Current concepts and controversies in imaging of renal cystic diseases. Urol Clin North Am 1997; 24:523.
- Katabathina VS, Kota G, Dasyam AK, et al. Adult renal cystic disease: a genetic, biological, and developmental primer. Radiographics 2010; 30:1509.
- Lippert MC. Medullary sponge kidney. In: Adult and Pediatric Urology, 4th ed, Gillenwater JY, Grayhack JT, Howards SS, et al (Eds), Lippincott Williams & Wilkins, Philadelphia 2003. p.863.
- Ohlson L. Normal collecting ducts: visualization at urography. Radiology 1989; 170:33.
- Evan AP, Worcester EM, Williams JC Jr, et al. Biopsy proven medullary sponge kidney: clinical findings, histopathology, and role of osteogenesis in stone and plaque formation. Anat Rec (Hoboken) 2015; 298:865.
- Fabris A, Lupo A, Bernich P, et al. Long-term treatment with potassium citrate and renal stones in medullary sponge kidney. Clin J Am Soc Nephrol 2010; 5:1663.
- Taub DA, Suh RS, Faerber GJ, Wolf JS Jr. Ureteroscopic laser papillotomy to treat papillary calcifications associated with chronic flank pain. Urology 2006; 67:683.
- Gdor Y, Faddegon S, Krambeck AE, et al. Multi-institutional assessment of ureteroscopic laser papillotomy for chronic flank pain associated with papillary calcifications. J Urol 2011; 185:192.
- Xu G, Wen J, Wang B, et al. The Clinical Efficacy and Safety of Ureteroscopic Laser Papillotomy to Treat Intraductal Papillary Calculi Associated With Medullary Sponge Kidney. Urology 2015; 86:472.
- ETIOLOGY AND PATHOPHYSIOLOGY
- CLINICAL MANIFESTATIONS
- Kidney stones and nephrocalcinosis
- Urinary tract infection
- Decreased concentrating ability
- Diminished bone mineral density
- Flank pain in the absence of stones
- IMAGING STUDIES
- Intravenous pyelography
- Computerized tomography (CT)
- Other modalities
- DIFFERENTIAL DIAGNOSIS
- PROGNOSIS AND TREATMENT
- SUMMARY AND RECOMMENDATIONS