Medullary Sponge Kidney (MSK) is defined as a particular renal condition characterized by the presence of diffuse and bilateral medullary cysts as a consequences of abnormalities present in the terminal collecting ducts.
The main clinical signs of MSK include the presence of blood in the urine and the formation of stone in the kidneys. These main ones are usually combined with other signs which underline some infection underway, frequently associated with intense pain and burning felt while urinating. The pain is caused by the stones produced in the kidney and is felt in the area around the lower back and abdomen. Stones are generally expelled through urine, but if their size is large enough they might cause serious blocks in the urine flow from the bladder.
These basic problems are often followed by the loss of the capacity of the kidneys to filter the waste products into the urine itself, which has to be seen as a consequence of the dilatation of the collecting tubules, or other typical renal complications such as tubular acidosis, kidney failure, urinary tract infection, urolithiasis/ureteric calculi, and haematuria (the presence of blood in the urea).
It should be remembered that a great number of affected individuals remain asymptomatic and show no clinical sign at all for many years.
Physical examination can reveal the first signs which indicate the diagnosis of MSK. These include costovertebral angle tenderness and ipsilateral groin, which usually underline the presence of nephrolithiasis, and fever, tachycardia, and hypotension, suggestive of obstructing stones into the kidneys and the kidney ducts. If patients show some of these signs, or all of them combined, they are strongly advised to send them to a specialist.
MSK is often diagnosed when patients are analyzed for another reason altogether, such as renal stone, infections, or colic, as an incidental finding during radiological investigations. If the physician suspects MSK, he/she can employ intravenous urography to further confirm the diagnosis.
This test is frequently employed in the cases of recurrent stone formations. Stone formation can be combined with the presence of dilated collecting tubules which in turn can be associated or not with nephrolithiasis. It has to be noted that the contrast pools in the dilated tubules inside the tips of the papilla cause the formation of particular patters characterized by the typical appearance of "papillary blush" or "paintbrush". MSK might involve both kidneys, or just one, but can also frequently be limited in one single papilla.
Plain abdominal x-ray
Plain abdominal x-ray is less specific and sensitive than IVU, but has the advantage of being cheaper and faster, requiring a much lower level of radiation and being very useful when patients suffer from non-specific abdominal pain. Calyces, pelvis, or ureter can be easily detected and usually indicate stone formation . Nephrocalcinosis can be present in 1 or more several papillae.
Ultrasound too, as plain x-ray, can be used in case of non-specific abdominal pain. It has the disadvantage of being less specific and sensitive than IVU, but much more sensitive than plain x-ray.
Non-contrast CT is ideal to detect stone formation, but cannot confirm the diagnosis of MSK, which still requires the use of other methodologies.
The following tests can further confirm the presence of nephrolithiasis, UTI, and pyelonephritis:
WBC count and urine culture can underline the presence of infection underway. Furthermore, stone-risk profiles can provide the physicians with a general clinical overview of the patients, which include metabolic risk factors for calcium stones like hyperoxaluria, hypercalciuria, hypocitraturia, or high pH levels in the urine. The analysis of stone composition should not be neglected, as it can provide precious information to organize a long-term preventive plan.
Since many patients remain asymptomatic for many years and because of the benign nature of MSK itself, there is no specific treatment to suggest to effectively treat this disorder. When patients show clinical signs, particular attention should be given in treating UTI, removing the stone, and trying to prevent recurrence of infections and stone formation. Hematuria usually appears as a consequence of UTI or renal stones, and the underlying cause should be further investigated to avoid additional severe complications.
If UTI occurs, physicians are advised to treat patients with antibiotics. Quinolones is the generally prescribed drug, while trimethoprim and sulfamethoxazole are particularly indicated when complicated UTI occurs. The classical duration of the antibiotic treatment is generally 14 days.
With nephrolithiasis (renal stones)
The identification of risk factors through 24-hour stone risk profiles, combined with appropriate diet modifications and drug administrations, can help prevent recurrent stone formation. Some clinical data seem to suggest that potassium citrate increases the level of urine citrate and decreases that of hypercalciuria in patients associated with high metabolic stone risk factors, even though the underlying molecular mechanism has not been clarified yet .
Patients are advised to keep fluid intake high by increasing it to more than 2 liters per day, so that urine output can be increased and the risk of developing renal stones and hypercalciuria can be reduced. In the cases of infected stones, treatment requires a longer course of antibiotics for removing the renal stones.
MSK is a benign disorder with no serious morbidity and mortality, even though renal insufficiency is a very frequent clinical consequence which occurs in up to 10% of the patients. Other possible clinical consequences include recurrent nephrolithiasis, with a significant associated morbidity, and renal failure after repeated pyelonephritis or urinary tract obstruction.
A significant morbidity is observed as a consequence of renal stone formation and recurrent UTI in around 10% of the cases. Kidneys are rarely completely obstructed, and since the stones are frequently very small in size and pass through the kidneys and their tubules spontaneously, usually there is no need of clinical interventions.
It is frequent to observe the appearance of chronic pain which is associated with the presence of no infection, stone, and obstruction, and in these cases patients are simply treated straight away with a regiment of painkillers. Today, patients with MSK and under high risk of developing further consequences are identified with a recently developed grading system that uses the findings obtained from intravenous urography .
The exact etiology of MSK is unknown. However, since a tight link has been found between MSK and the appearance of congenital pathological disorders such as Beckwith-Wiedemann's syndrome, hemi-hypertrophy, and congenital hepatic fibrosis , now experts tend to believe that genetic factors must play a pivotal role in the development of MSK.
According to this view, MSK has to be connected with anomalies in the embryogenesis of kidneys, like the disruption of the ureteric-bud/metanephric-blastema interface, perhaps caused by mutations in specific genes. These sequences include the gene for glial cell-derived neurotrophic factor, which plays a pivotal role in the survival of many types of neurons, and RET oncogene, a most important gene involved in the normal kidney development, parathyroid cell proliferation and development of the liver excretory system .
However, it is not possible to rule out the intervention of other possible factors, as suggested by the correlation with other disorders such as tubular acidosis that seems to cause the decrease of the urine citrate level and an alkaline pH in the urine. These in turn might cause the formation of stones in the kidney, a condition called nephrolithiasis, that occurs before stone formation itself .
Since many patients are asymptomatic and the disorder tend to manifest itself only after the 2nd or 3rd decade of life, the actual prevalence of MSK remains largely unknown. The results of the few studies conducted on this regard remain inconclusive, as the prevalence detected varies greatly from study to study  .
There are no conclusive data to confirm the role of gender as an important epidemiological factor for MSK. On the contrary, age might play an important role, as suggested by the high prevalence found among the elderly, although this could be explained as a consequence of the tendency of MSK to remain undiagnosed for many years. No significant data have been found to indicate the existence of significant epidemiological differences between people of different ethnic and racial groups.
The physiological changes which characterize MSK suggest the existence of some kind of developmental abnormality, although the nature of it has never been fully understood. However, experts believe that the disorder must result from the disruption of the interface between ureteral-bud and the metanephric blastema during embryonic development, as suggested by the connection of MSK wit kidneys malformations such as hemihypertrophy and Beckwith-Wiedemann syndrome.
Still limited are the data suggesting a possible association between MSK and genetic factors. Many studies have underlined the occurrence of key mutations in the glial cell-derived neurotrophic factor, a protein which appears to play a pivotal role in the renal development as well as neuron survival. The available data seem to suggest that the mutations in the glial cell-derived neurotrophic factor gene leads to an osteogenic differentiation in renal papillary cells that finally result in MSK at the end of renal development . Furthermore, it is also possible to observe the presence of an autosomal dominant inheritance among the families with people affected by MSK . It has to be noted that many cases can show no family history, and most of the data on this regard still remain inconclusive.
Physicians are strongly advised to screen patients with MSK using a 24-hour urine collection for the evaluation of stone risk factors such as hypercalciuria, hyperuricosuria, hypocitraturia, or hyperoxaluria . Those patients who, after this test, show any sign of abnormality should be treated with potassium citrate to prevent the formation of renal stone. Physicians are advised to start treatment with an initial dose of potassium citrate of 20 mEq/day and adjust it accordingly. The urinary citrate levels should be kept around 450 mg/day and urinary pH levels below 7.5.
MSP is a benign disorder which occurs when dilatations of the collecting tubules in one or more renal papillae appear. The condition might involve both kidneys, but frequently patients are asymptomatic and MSP remains undiagnosed up until the 2nd or 3rd decade of life  .
The name of the disorder is a little bit misleading, because it seems to suggest the resemblance to a sponge, while the kidneys do not look like sponges at all. For this reason, alternative names have been suggested over the years, like tubular ectasia and cystic dilatation of the collecting ducts, but medullary sponge kidney still remains the main one.
MSK is a congenital disorder which occurs when small cysts appear in the renal tubules or the renal collecting ducts where urine is collected before removal. These cysts might reduce the quantity of urine getting out of the kidney. The disorder might affect one or both kidneys.
The exact cause of MSK is still unknown. The disorder is considered rare and generally appears with no specific family history, especially in women.
MSK is usually benign in nature, and can occur without the appearance of any specific symptom, even though it can cause a series of other related complications such as urinary tract infection or development of renal stones that block of the urine flow. If MSK causes symptoms, these usually appear during adulthood. The main symptoms include severe pain in the side, back, abdomen, and groin, painful and burning urination, the presence of blood in the urine, fever, chills, and nausea. The condition might even lead to renal failure in 10% of the cases.
Many people affected by MSK show no sign at all. Those that do show signs frequently report UTI and development of renal stone associated with the following signs:
Physicians might consider the presence of the history of stone formation and urinary tract infections before deciding to try to confirm MSK with appropriate diagnostic methodologies. Frequently used for the diagnosis of MSK is intravenous urogram, a type of x-ray procedure in which a special dye in injected in the kidney to better visualize it and detect any other problems, particularly the presence of stones and cysts which block urine flow. Ultrasound and computed tomography scan are also frequently used as diagnostic tools.
Physicians might also use laboratory tests to confirm the diagnosis of MSK, like blood and urine tests to analyze the working of the kidneys and detect the presence of infections.
After confirmation through diagnosis, kidneys should be constantly monitored to detect any change in the cysts or the formation of additional renal stones and infections in the urinary tracts. Infections are generally treated with antibiotics, while renal stones might require surgical procedures to be removed. After treatment, patients are advised to increase fluid intake, modify their diet, and get regular check-ups to prevent future episodes of MSK.