Table 2.

Main differential diagnosis between medullary sponge kidney and other cystic kidney diseases

Diseases	Bilateral/Unilateral	Kidney size	Ultrasound appearance of kidneys and cysts	Hereditary/acquired	Genetics	Clinical findings
Autosomal dominant polycystic kidney disease (ADPKD) [15, 18, 24, 25]	Bilateral	Increased	Presence of multiple, variably sized, cortical and medullary cysts, that increase in number and size with time	Hereditary (autosomal dominant)	PKD1, PKD2, GANAB	Chronic kidney disease typically occurs in adulthood; cysts could be found in other organs (eg: liver, pancreas, seminal vesicles); possible presence of intracranial aneurysms
Medullary cystic kidney disease (MCKD)/ Autosomal dominant tubulointerstitial kidney disease (ADTKD) [16, 18, 26]	Bilateral	Small to normal size kidneys	Multiple cysts in the medulla and at the cortico-medullary junction with cortical sparing	Herditary (autosomal dominant)	MCKD1 (now MUC1), MCKD2	Chronic renal failure manifesting in adulthood; no associated syndrome
Nephronophtisis (NPH) [15, 16, 21, 24]	Bilateral	Moderately enlarged (infantile NPH); small to normal size (juvenile and adolescent/adult NPH)	Small, hyperechoic kidneys with loss of cortico-medullary differentiation; progressive cystic disease with numerous small discrete cysts in the medulla and cortico-medullary junction	Hereditary (autosomal recessive)	More than ten mutations identified until now (eg; NPHP 1 e NPHP4)	Polyuria and polydipsia because of renal concentration defect; growth retardation; chronic anemia resistant to therapy; chronic renal failure with end-stage renal disease developing in infancy or at a median age of 13 years (juvenile NPH) or 19 (adolescent/adult NPH). Presence of associated syndromes
Multicystic dysplastic kidney [15, 17, 18]	Unilateral	Small kidney that disappear in adulthood	Kidney replaced by noncommunicating cysts with a central region of soft tissue; absence or severe atrophy of ipsilateral ureter, renal collecting system and renal vasculature	Acquired	None	Often detected in utero or infancy; possible association with contralateral vescico-ureteral reflux (5–43% of cases)
Acquired cystic kidney disease [17, 18]	Bilateral	Small	Atrophic hyperechoic kidneys with cysts (at least three in each kidney) varying in size and complexity	Acquired	None	Presence of end-stage renal disease, the incidence increases with the length of time on dialysis; cysts could be complicated (hemorrhage, nephrolithiasis); possible development of renal malignancy
Medullary sponge kidney (MSK) [1, 2, 15, 18, 23]	Generally bilateral, mild cases can be diagnosed as unilateral by ultrasound	Normal (size is more linked to the presence or absence of chronic kidney disease)	Hypoechoic medullary areas with hyperechoic spots and microcystic dilatation of papillary zone; multiple calcifications (linear, small stones or calcified intracystic sediment) in each papilla. In some cases nephrocalcinosis could be described	Hereditary in a half of cases (autosomal dominant)	Mutations of GDNF (12% of cases). Genetics under investigation	Typically observed in renal stone formers; possible presentation as pielonephritis; michroematuria and episods of machroematuria associated with nephrolithiasis. Possible presence of hyperparatiroidism. Association with tubular defect (eg: distal renal tubular acidosis, hypocitraturia defective urinary concentration, an altered Tm (transport maximum) for glucose, phosphate and para-aminohippuric acid, low molecular weight proteinuria).