Medullary Sponge Kidney Research Articles

Renal Autotransplantation and Modified Pyelovesicostomy for Intractable Metabolic Stone Disease

Some patients with intractable metabolic stone disease experience narcotic dependence, which cannot be managed with standard treatments. We offered these patients renal autotransplantation with a modified pyelovesicostomy as an alternative solution. Renal autotransplantation with pyelovesicostomy was performed for 15 kidneys in 12 patients (3 bilateral, 2 solitary), 9 female and 3 male, with a mean age of 33.8 years (range 16 to 55). The etiology of metabolic stone disease was calcium oxalate (40%), cystinuria (33%), type 1 renal tubular acidosis (14%), calcium oxalate/urate (7%) and medullary sponge kidney (7%). Patients reported that lifetime stone events ranged from 10 to more than 70, that underwent an average of 3 to 4 surgical interventions per year in the previous 2 years and that they were dependent on daily oral narcotics for stone related pain. All 15 kidneys were successfully autotransplanted with a mean followup of 41.8 months (range 3 to 74). We used a modified pyelovesicostomy with ureteral strip in 13 and standard Boari tube in 2 cases. All patients continued to pass small stone debris per urethra with minimal symptoms. Of 12 patients 11 (92%) were weaned off daily narcotics. There have been 17 stone episodes in 4 patients (3 cystinuria) for which medical intervention and pain medication was required. The number of urological procedures/patients before (155/12 [12.9]) and after (8/12 [0.66]) autotransplantation was dramatically reduced (paired t test p = 0.0001). The preoperative mean estimated glomerular filtration rate was 77.2 cc/minute, and 73.5, 71.9, 79.2 cc/minute at 12, 36 and 60 months, respectively. Renal autotransplantation and pyelovesicostomy offer patients with intractable metabolic stone disease the opportunity to improve quality of life and to decrease daily narcotic use.

E02 Inheritance of the medullary sponge kidney: A systematic analysis of a large cohort

E02 Inheritance of the medullary sponge kidney: A systematic analysis of a large cohort

Clinical characteristics of potential kidney donors with asymptomatic kidney stones

Patients with symptomatic kidney stones are characterized by older age, male gender, white race, hypertension, obesity, metabolic syndrome and chronic kidney disease. Whether these characteristics differ in patients with asymptomatic kidney stones is unknown. All potential kidney donors who underwent protocol computed tomography angiograms/urograms (2000-08) at the Mayo Clinic were identified. Renal abnormalities, including kidney stones, were assessed radiographically. Comorbidities, including past symptomatic kidney stones, were abstracted from the medical record. Characteristics of persons with and without radiographic stones were compared. Stone burden among persons with and without past symptomatic stones was compared. Among 1957 potential kidney donors, 3% had past symptomatic stones and 11% had radiographic stones (10% had only asymptomatic radiographic stones). Asymptomatic stone formers were more likely to be of white race, have low urine volumes and have radiographic findings of renal parenchymal thinning, focal renal scarring, medullary sponge kidney and polycystic kidney disease. Asymptomatic stone formers were not characterized by older age, male gender, hypertension, obesity, metabolic syndrome, abnormal kidney function, hyperuricemia, hypercalcemia or hypophosphatemia. Among persons with radiographic stones, those with past symptomatic stones had a slightly higher number of stones (mean 2.7 versus 2.4; P = 0.04), but a much greater diameter for the largest stone (mean 4.8 versus 1.6 mm; P < 0.001). Asymptomatic kidney stone formers have different demographic characteristics and many lack the comorbidities that have been described in persons with symptomatic kidney stones. These findings suggest that different pathophysiologic mechanisms could be involved in asymptomatic stone formation versus symptomatic stone passage.

Nephrocalcinosis: re-defined in the era of endourology

Nephrocalcinosis generally refers to the presence of calcium salts within renal tissue, but this term is also used radiologically in diagnostic imaging in disease states that also produce renal stones, so that it is not always clear whether it is tissue calcifications or urinary calculi that give rise to the characteristic appearance of the kidney on x-ray or computed tomography (CT). Recent advances in endoscopic imaging now allow the visual distinction between stones and papillary nephrocalcinosis, and intrarenal endoscopy can also verify the complete removal of urinary stones, so that subsequent radiographic appearance can be confidently attributed to nephrocalcinosis. This report shows exemplary cases of primary hyperparathyroidism, type I distal renal tubular acidosis, medullary sponge kidney, and common calcium oxalate stone formation. In the first three cases--all being conditions commonly associated with nephrocalcinosis--it is shown that the majority of calcifications seen by radiograph may actually be stones. In common calcium oxalate stones formers, it is shown that Randall's plaque can appear as a small calculus on CT scan, even when calyces are known to be completely clear of stones. In the current era with the use of non-contrast CT for the diagnosis of nephrolithiasis, the finding of calcifications in close association with the renal papillae is common. Distinguishing nephrolithiasis from nephrocalcinosis requires direct visual inspection of the papillae and so the diagnosis of nephrocalcinosis is essentially an endoscopic, not radiologic, diagnosis.

Adult Renal Cystic Disease: A Genetic, Biological, and Developmental Primer

Renal cystic diseases in adults are a heterogeneous group of disorders characterized by the presence of multiple cysts in the kidneys. These diseases may be categorized as hereditary, acquired, or developmental on the basis of their pathogenesis. Hereditary conditions include autosomal dominant polycystic kidney disease, medullary cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis. Acquired conditions include cystic kidney disease, which develops in patients with end-stage renal disease. Developmental cystic diseases of the adult kidney include localized renal cystic disease, multicystic dysplastic kidney, and medullary sponge kidney. In recent years, many molecular and cellular mechanisms involved in the pathogenesis of renal cystic diseases have been identified. Hereditary renal cystic diseases are characterized by genetic mutations that lead to defects in the structure and function of the primary cilia of renal tubular epithelial cells, abnormal proliferation of tubular epithelium, and increased fluid secretion, all of which ultimately result in the development of renal cysts. A better understanding of these pathophysiologic mechanisms is now providing the basis for the development of more targeted therapeutic drugs for some of these disorders. Cross-sectional imaging provides useful information for diagnosis, surveillance, prognostication, and evaluation of treatment response in renal cystic diseases.

Medullary sponge kidney: causes and treatments

Medullary sponge kidney is a little known and little understood disease. A patient with a medullary sponge kidney may undergo decades of suffering in the form of infections and pain before any diagnosis is even made. When a diagnosis is made, it is more than likely to be an incidental finding from a test for another problem. However, on diagnosis there are a number of options available to treat this condition. These include non-invasive treatments such as drug therapy, diet or extracorporeal shock wave lithotripsy, to invasive therapies such as percutaneous nephrolithotomy, ureteroscopy and more advanced surgery. The aim of this article is to highlight this little known condition, outline the effects, and discuss the treatment options available to patients.

Long-Term Treatment with Potassium Citrate and Renal Stones in Medullary Sponge Kidney

Medullary sponge kidney (MSK) is a renal malformation typically associated with nephrocalcinosis and recurrent calcium stones. Incomplete distal renal tubular acidosis, hypocitraturia, and hypercalciuria are common. For stone prevention, patients with MSK generally receive the standard "stone clinic" recommendations and often receive potassium citrate (KC). However, the effect on stone recurrence of citrate treatment in these patients has never been studied. The issue was retrospectively analyzed on an outpatient basis in 97 patients with a radiologic diagnosis of MSK: 65 had at least one stone risk factor (SRF; hypercalciuria, hypocitraturia, hyperuricosuria, hyperoxaluria) and received KC [29 +/- 8 (SD) mEq/d]; 10 patients with SRF and 22 without received only general stone clinic suggestions. Follow-up was 78 +/- 13, 72 +/- 15, and 83 +/- 14 months, respectively. The 24-hour urinary excretion of calcium, oxalate, uric acid, citrate, and morning urine pH were investigated at baseline and at the end of follow-up. Parallel to a significant rise in urinary citrate and decreased urinary calcium (all P < 0.001), KC led to a dramatic reduction in the stone event rate (from 0.58 to 0.10 stones/yr per patient). The existence of a group of patients with MSK, those without SRF, with a very low stone rate and no SRF was recognized. Treatment with KC is effective in preventing renal stones in the typical patient with MSK. It seems that two clinical phenotypes among patients showing typical MSK features during radiologic study exist.

Identification of GDNF Gene Sequence Variations in Patients with Medullary Sponge Kidney Disease

Medullary sponge kidney (MSK) is a rare nephropathy characterized by cystic anomalies of precalyceal ducts, nephrocalcinosis, renal stones, and tubule dysfunctions. Its association with various malformations and cases of familial aggregation supports the conviction that genetic factors are involved, but no genetic studies have been conducted to date. It is hypothesized that MSK is due to a disruption at the "ureteric bud/metanephric blastema" interface caused by critical developmental genes functioning abnormally. Fifty-five apparently sporadic MSK patients were analyzed by direct DNA sequencing of all exons and exon-intron boundaries of glial cell-derived neurotrophic factor (GDNF) gene and rearranged during transfection (RET) gene, which have a leading role in renal development. Two novel variants were found in heterozygosity in the MSK case population: GDNF{ENST00000344622}:c.-45G>C and c.-27+18G>A in a putative binding domain for paired-box 2 transcription factor. As a whole, eight patients showed these variations: four patients carried the c.[-45G>C; -27+18G>A] complex allele, and the others had the c.-27+18G>A alone. A case-control study revealed that these two alleles were significantly associated with MSK. Five of the eight cases were found to be familial, and the allele variants cosegregated with the disease in a seemingly dominant pattern of inheritance. Patients revealed no mutations in the RET gene. This is the first report identifying GDNF gene sequence variations in patients with MSK and suggesting a role for this gene in the pathogenesis of some cases of the disease.

Renal agenesis in a child with ipsilateral hemihypertrophy

Hemihypertrophy is a clinical condition defined as an asymmetric enlargement of one side of the body. Inguinal hernias, renal cysts, cryptorchidism, ectasias of collecting tubes, medullary sponge kidney and horse-shoe kidney are examples of abnormalities associated with hemihypertrophy that have been described in the literature. We report here a 17.2-year-old patient with a left hemihypertrophy and renal agenesis with contralateral right compensatory renal hypertrophy together with normal renal function and blood pressure in the absence of proteinuria. He also presented with faint macular hyperpigmented skin lesions on his left upper arm, forehead and abdomen. To the best of our knowledge, this is the first report of renal agenesis and hemihypertrophy in the same patient. Hemihypertrophy can be seen as a component of Klippel-Trenaunay-Weber syndrome. The other components of this syndrome are varicose veins, skin naevus and arteriovenous malformations. Although renal agenesis, hemihypertrophy and hyperpigmented macular skin lesions (skin naevuses) may be incidental findings, together they may form a variant of Klippel-Trenaunay-Weber syndrome, as in our case.

Alterações anatômicas em pacientes com nefrolitíase

Nephrolithiasis is a multifactorial disease related to genetic disorders and environmental factors. Kidney stones are more common in adults and are associated with several metabolic and anatomical disorders. The major anatomical abnormalities, such as obstruction of the ureteropelvic junction, horseshoe kidney, complete or incomplete duplicated ureter, bifid pelvis, and medullary sponge kidney, are known to be responsible for stone formation. The objective of this study is to evaluate anatomical alterations in patients with nephrolithiasis in our region. Retrospective study on 1,378 patients with evidence of recent formation of kidney stones. Laboratory investigation and chemical analysis were performed when stones were available. Renal imaging techniques comprised at least renal ultrasound and excretory urography. Of the 1,378 patients with nephrolithiasis cared for, only 367 (26.5%) (mean age, 36.8 ± 4.3 years) underwent anatomical investigation, of whom 198 (54.5%) were females. At least one anatomical alteration was found in 132 (36%) patients, the most common being renal cyst, completely or incompletely duplicated ureter, and obstruction of the ureteropelvic junction. Anatomical alterations were found in 36% of the investigated patients. Renal cyst, ureteral duplication, and obstruction of the ureteropelvic junction were the most frequently found anatomical alterations in the group.

Liver and kidney disease in ciliopathies

Hepatorenal fibrocystic diseases (HRFCDs) are among the most common inherited human disorders. The discovery that proteins defective in the autosomal dominant and recessive polycystic kidney diseases (ADPKD and ARPKD) localize to the primary cilia and the recognition of the role these organelles play in the pathogenesis of HRFCDs led to the term "ciliopathies." While ADPKD and ARPKD are the most common ciliopathies associated with both liver and kidney disease, variable degrees of renal and/or hepatic involvement occur in many other ciliopathies, including Joubert, Bardet-Biedl, Meckel-Gruber, and oral-facial-digital syndromes. The ductal plate malformation (DPM), a developmental abnormality of the portobiliary system, is the basis of the liver disease in ciliopathies that manifest congenital hepatic fibrosis (CHF), Caroli syndrome (CS), and polycystic liver disease (PLD). Hepatocellular function remains relatively preserved in ciliopathy-associated liver diseases. The major morbidity associated with CHF is portal hypertension (PH), often leading to esophageal varices and hypersplenism. In addition, CD predisposes to recurrent cholangitis. PLD is not typically associated with PH, but may result in complications due to mass effects. The kidney pathology in ciliopathies ranges from non-functional cystic dysplastic kidneys to an isolated urinary concentration defect; the disorders contributing to this pathology, in addition to ADPKD and ARPKD, include nephronophithisis (NPHP), glomerulocystic kidney disease and medullary sponge kidneys. Decreased urinary concentration ability, resulting in polyuria and polydypsia, is the first and most common renal symptom in ciliopathies. While the majority of ADPKD, ARPKD, and NPHP patients require renal transplantation, the frequency and rate of progression to renal failure varies considerably in other ciliopathies. This review focuses on the kidney and liver disease found in the different ciliopathies.

Bone Disease in Medullary Sponge Kidney and Effect of Potassium Citrate Treatment

In medullary sponge kidney (MSK)-a common malformative renal condition in patients with calcium nephrolithiasis-hypercalciuria, incomplete distal renal tubular acidosis, and hypocitraturia are common. Clinical conditions with concomitant hypercalciuria and/or incomplete distal renal tubular acidosis are almost invariably associated with bone disease, making osteopathy highly likely in MSK, too. Patients with MSK have never been investigated for osteopathy; neither has the potential effect of potassium citrate administration (CA) on their urinary metabolic risk factors and on bone mineralization. These issues were retrospectively analyzed in 75 patients with MSK and primary stone risk factor (PSRF; hypercalciuria, hypocitraturia, hyperuricosuria, and/or hyperoxaluria) on an outpatient basis; 65 received CA (2.9 +/- 0.8 g/d), whereas 10 received only general "stone clinic" suggestions. The 24-h urinary excretion of calcium, phosphate, oxalate, uric acid, and citrate; morning urine pH; serum biochemistry; and bone mineral density were investigated at baseline and at the end of follow-up (78 +/- 13 and 72 +/- 15 mo in groups A and B, respectively). CA led to a significant rise in urinary pH and citrate and decreased urinary calcium and phosphate (all P < 0.001). Patients with MSK and PSRF had reduced bone density. Bone density improved significantly in the group that was treated with oral CA. Bone disease is very frequent in patients with MSK and concomitant PSRF. Long-term CA improves bone density. The concurrent effects of treatment on PSRF suggest that the subtle acidosis plays a pivotal role in bone disease and hypercalciuria in patients with MSK.

Recurrent pyelonephritis as a sign of ‘sponge kidney’

Intravenous urography is the gold standard for the diagnosis of medullary sponge kidney. Computed tomography and ultrasonography have limited ability to clearly show tubular ectasia.

Medullary sponge kidney presenting in a neonate with distal renal tubular acidosis and failure to thrive: a case report

IntroductionMedullary sponge kidney is a congenital anomaly characterized by diffuse ectasy of the collecting tubules of one or both kidneys. It is usually diagnosed in the second or third decade of life.Case presentationDistal renal tubular acidosis is commonly observed in patients with medullary sponge kidney. We describe here a 50-day-old Egyptian Caucasian girl with medullary sponge kidney who had features of distal renal tubular acidosis, (persistent alkaline urine, hypercalciuria, hypocitraturia) and failure to thrive. Renal ultrasound revealed left renal increased medullary echogenicity and bilateral nephrocalcinosis.ConclusionEarly gene(s) expression of medullary sponge kidney disease might be responsible for persistent metabolic acidosis during the neonatal period.

Relationships Between Carbonation Rate of Carbapatite and Morphologic Characteristics of Calcium Phosphate Stones and Etiology

To examine the significance of the carbonation rate (CR) in carbonated apatite (carbapatite [CA]) stones and its relationships with the morphologic characteristics of CA and etiology. CA stones without struvite can result from metabolic disorders or urinary tract infection, but the latter etiology is still debated. Infection stones caused by urea-splitting bacteria are made of CA admixed with struvite and exhibit a high CO(3)(2-)/PO(4)(3-) ratio (CR). However, little is known as to the significance of the CR of CA in the absence of struvite in idiopathic calcium phosphate stones. We studied 39 urinary calculi mainly composed of CA without struvite. Of the 39 patients, 13 had a past or present history of urinary tract infection, 24 had hypercalciuria, and 2 had medullary sponge kidney. The stones were examined by Fourier transform infrared spectroscopy and scanning electron microscopy. The presence of amorphous carbonated calcium phosphate or whitlockite was also considered. The CR of CA was 14% +/- 9%. On scanning electron microscopy, the CA particles appeared as spherules of 4.5 +/- 3.0 mum in diameter and were significantly larger in females than in males. In 16 cases, scanning electron microscopy showed bacterial imprints. In these calculi, the CR was significantly greater (22% +/- 7%) than in those without a visible bacterial imprint (8% +/- 5%, P < .0001). Amorphous carbonated calcium phosphate was found in 15 of 16 stones (93.8%) with imprints and in none of the 23 stones without imprints (P < .0001). A close relationship was observed between the presence of bacterial imprints, indicative of past or current urinary tract infection, and both the presence of amorphous carbonated calcium phosphate (or whitlockite) and a high CR of CA.

Medullary sponge kidney associated with primary distal renal tubular acidosis and mutations of the H+-ATPase genes

Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilation of precalyceal collecting tubules. Although its pathogenesis is unknown, the association with various congenital diseases suggests that it could be a developmental disorder. In addition to the typical clinical features of nephrocalcinosis and urolithiasis, patients with MSK show tubular function defects of acidification and concentration. These are considered to be secondary to morphological changes of collecting tubules. Primary distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H(+) ions in the intercalated cells of the collecting duct required for final excretion of fixed acids. Both autosomal dominant and autosomal recessive forms have been described, the latter is also associated with sensorineural hearing loss. We report two patients presenting with dRTA, late sensorineural hearing loss and MSK, in whom molecular investigations demonstrated the presence of mutations of the H(+) proton pump ATP6V1B1 and ATP6V0A4 genes. These observations, including a previous description of a similar case in the literature, indicate that MSK could be a consequence of the proton pump defect, thus can potentially provide new insights into the pathogenesis of MSK.

Impact of Long-Term Potassium Citrate Therapy on Urinary Profiles and Recurrent Stone Formation

Potassium citrate therapy has become one of the cornerstones of medical stone management. We elucidated the long-term effects of potassium citrate on urinary metabolic profiles and its impact on stone formation rates. We performed a retrospective cohort study in patients treated at the Comprehensive Kidney Stone Center at our institution between 2000 and 2006. Patients with pre-therapy and post-therapy 24-hour urinary profiles available who remained on potassium citrate for at least 6 months were included in the analysis. Of the 1,480 patients with 24-hour urinary profiles 503 met study inclusion criteria. Mean therapy duration was 41 months (range 6 to 168). Overall a significant and durable change in urinary metabolic profiles was noted as soon as 6 months after the onset of therapy. These changes included increased urinary pH (5.90 to 6.46, p <0.0001) and increased urinary citrate (470 to 700 mg a day, p <0.0001). The stone formation rate also significantly decreased after the initiation of potassium citrate from 1.89 to 0.46 stones per year (p <0.0001). There was a 68% remission rate and a 93% decrease in the stone formation rate. Potassium citrate provides a significant alkali and citraturic response during short-term and long-term therapy with the change in urinary metabolic profiles sustained as long as 14 years of treatment. Moreover, long-term potassium citrate significantly decreases the stone formation rate, confirming its usefulness in patients with recurrent nephrolithiasis.

Flexible ureterorenoscopy and laser lithotripsy in children

Background:Flexible ureterorenoscopy (FUR) and laser lithotripsy (LL) are techniques used in the management of upper urinary tract disorders. These techniques, so far established in adults, are now being used in children as well. We report our experience with 26 cases of pediatric upper urinary tract disorders treated using these techniques.Methods:In the period from 1997 to 2006, FUR was performed in 26 children (14 males and 12 females) in the age group of three months to 15 years with a mean age of 8.2 years. Twenty five were stented prior to undergoing FUR and 24 presented with suspected upper tract stones (17 pelvicalyceal and seven midureteric). Two cases showed JJ stent migration post-pyeloplasty.Results:Eight cases involved diagnostic procedures. Six excluded the presence of renal calculi, one had focal medullary sponge kidney, and one had calcified papillae. There were 15 cases of therapeutic FUR. Of these, 12 had LL with only one had incomplete stone fragmentation which subsequently passed spontaneously. Other therapeutic procedures included removal of migrated JJ stents and FUR with the basket removal of a midureteric calculus. Three cases failed ureterorenoscopy due to technical difficulties. The overall success rate was 88.5% for FUR.Conclusion:FUR and LL are valuable minimally invasive techniques for the examination and treatment of pediatric upper urinary tract conditions. Preoperative stenting improves passage of the ureteroscope and with progressive miniaturization of instruments, the lower weight limit will decrease.

Jouberin localizes to collecting ducts and interacts with nephrocystin-1

Joubert syndrome and related disorders are autosomal recessive multisystem diseases characterized by cerebellar vermis aplasia/hypoplasia, retinal degeneration and cystic kidney disease. There are five known genes; mutations of which give rise to a spectrum of renal cystic diseases the most common of which is nephronophthisis, a disorder characterized by early loss of urinary concentrating ability, renal fibrosis, corticomedullary cyst formation and renal failure. Many of the proteins encoded by these genes interact with one another and are located at adherens junctions or the primary cilia and or basal bodies. Here we characterize Jouberin, a multi-domain protein encoded by the AHI1 gene. Immunohistochemistry with a novel antibody showed that endogenous Jouberin is expressed in brain, kidney and HEK293 cells. In the kidney, Jouberin co-localized with aquaporin-2 in the collecting ducts. We show that Jouberin interacts with nephrocystin-1 as determined by yeast-2-hybrid system and this was confirmed by exogenous and endogenous co-immunoprecipitation in HEK293 cells. Jouberin is expressed at cell-cell junctions, primary cilia and basal body of mIMCD3 cells while a Jouberin-GFP construct localized to centrosomes in subconfluent and dividing MDCK cells. Our results suggest that Jouberin is a protein whose expression pattern supports both the adherens junction and the ciliary hypotheses for abnormalities leading to nephronophthisis.

Medullary Sponge Kidney and Urinary Calculi: Aeromedical Concerns

Medullary sponge kidney (MSK) is a benign disorder associated with a lifetime risk of renal stones in 60% of patients. Patients frequently have episodic painless hematuria, but are often otherwise asymptomatic unless renal calculi or infections complicate the disease. Nephrolithiasis is a relative, but frequently enforced, contraindication to space or other high-performance flight. Two case reports of asymptomatic NASA flight crew with MSK and three cases of United States Air Force (USAF) military aviators diagnosed with MSK are reviewed. All cases resulted in waiver and return to flight status after treatment and a vigorous followup and prophylaxis protocol. MSK in aviation and spaceflight necessitates case-by-case evaluation and treatment to rule out other potential confounding factors that might also contribute to stone formation and in order to requalify the aviator for flight duties.