Proteomic-based research strategy identified laminin subunit alpha 2 as a potential urinary-specific biomarker for the medullary sponge kidney disease.

Medullary sponge kidney (MSK) disease, a rare kidney malformation featuring recurrent renal stones and nephrocalcinosis, continues to be diagnosed using expensive and time-consuming clinical/instrumental tests (mainly urography). Currently, no molecular diagnostic biomarkers are available. To identify such we employed a proteomic-based research strategy utilizing urine from 22 patients with MSK and 22 patients affected by idiopathic calcium nephrolithiasis (ICN) as controls. Notably, two patients with ICN presented cysts. In the discovery phase, the urine of 11 MSK and 10 controls, were randomly selected, processed, and analyzed by mass spectrometry. Subsequently, several statistical algorithms were undertaken to select the most discriminative proteins between the two study groups. ELISA, performed on the entire patients' cohort, was used to validate the proteomic results. After an initial statistical analysis, 249 and 396 proteins were identified exclusive for ICN and MSK, respectively. A Volcano plot and ROC analysis, performed to restrict the number of MSK-associated proteins, indicated that 328 and 44 proteins, respectively, were specific for MSK. Interestingly, 119 proteins were found to differentiate patients with cysts (all patients with MSK and the two ICN with renal cysts) from ICN without cysts. Eventually, 16 proteins were found to be common to three statistical methods with laminin subunit alpha 2 (LAMA-2) reaching the higher rank by a Support Vector Machine, a binary classification/prediction scheme. ELISA for LAMA-2 validated proteomic results. Thus, using high-throughput technology, our study identified a candidate MSK biomarker possibly employable in future for the early diagnosis of this disease.

Medullary sponge kidney.

PURPOSE OF REVIEW: After it was first described in 1939, medullary sponge kidney (MSK) received relatively little attention. This was because it was believed to have a low prevalence and because it was considered a benign condition. Studies in recent years have been changing these convictions however, hence the present review. RECENT FINDINGS: Insight has been obtained on the genetic basis of this disease, supporting the hypothesis that MSK is due to a disruption at the 'ureteric bud-metanephric mesenchyme' interface. This explains why so many tubular defects coexist in this disease, and particularly a distal tubular acidification defect of which the highly prevalent metabolic bone disease is one very important consequence. In addition to the typical clinical phenotype of recurrent stone disease, other clinical profiles have now been recognized, that is, an indolent, almost asymptomatic MSK, and a rare form characterized by intractable, excruciating pain. SUMMARY: Findings suggest the need for a more comprehensive clinical characterization of MSK patients. The genetic grounds for the condition warrant further investigation, and reliable methods are needed to diagnose MSK.

Amyloid A amyloidosis on medullary sponge kidney in a 28-year-old male with gout: A case report and literature review.

Amyloidosis is a large group of diseases that occur through misfolding of extracellular proteins that accumulate in tissues and organs. Gout is the most common inflammatory arthritis worldwide and starts with the crystallization of uric acid within the joints and soft tissues. Although gouty arthritis is accompanied by inflammation, AA amyloidosis is rarely seen in patients with gout. Here we present a case of AA amyloidosis on the medullary sponge kidney in a 28-year-old man with gout. Our case had been diagnosed with gout 3 years previously, and his older brother was also diagnosed with early-onset gout. As a result of the hyperuricemic nephropathy clinic and familial history, a whole gene sequence analysis was performed on the HPRT1 gene and UMOD gene, but no pathogenic changes were detected. Renal ultrasound revealed a bilateral medullary sponge kidney and amyloidosis was detected in the renal needle biopsy performed for the etiology of proteinuria. In our literature review, we found 16 cases in which gout was accompanied by AA amyloidosis. We present a 17th case and compare it with the other 16 cases.

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.

Coexistence of medullary sponge kidney and renal AA amyloidosis in a patient with nephrotic range proteinuria.

We report a patient with medullary sponge kidney (MSK) who presented with hematuria and nephrotic-range proteinuria. Renal biopsy revealed a diagnosis of renal AA amyloidosis. No secondary factors contributing to renal amyloidosis were demonstrated. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and renal AA amyloidosis.

Urinary proteome in inherited nephrolithiasis.

In the last decades, proteomics has been largely applied to the Nephrology field, with the double aim to (1) elucidate the biological processes underlying renal diseases; (2) identify disease-specific biomarkers, predictor factors of therapeutic efficacy and prognostic factors of disease progression. Kidney stone disease, and in particular, inherited nephrolithiasis (INL) are not an exception. Given the multifactorial origin of these disorders, the combination of genomics and proteomics studies may complement each other, with the final objective to give a global and comprehensive mechanistic view. In this review, we summarize the results of recent proteomic studies which have expanded our knowledge about INL, focusing the attention on monogenic forms of nephrolithiasis (cystinuria, Dent's disease, Bartter syndrome, distal renal tubular acidosis and primary hyperoxaluria), on polygenic hypercalciuria and on medullary sponge kidney disease.

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.

Medullary sponge kidney and Caroli's disease in a patient with stricture urethra: look for the hidden in presence of the apparent.

Caroli's disease is a rare congenital disorder with incidence rate of approximately 1 in 1 000 000 population. Renal anomalies which may be associated with Caroli's disease include medullary sponge kidney (MSK), cortical cysts, adult recessive polycystic kidney disease and rarely autosomal dominant polycystic kidney disease. Exact incidence of MSK in patients of Caroli's disease is not known. There are only a handful of reported cases of this association in literature. We hereby report a case of Caroli's disease with MSK with nephrocalcinosis. He presented to primary health centre with symptoms of urethral stricture due to lichen sclerosus et atrophicus and was managed with repeated co-axial dilatation but was never evaluated for underlying chronic renal insufficiency due to MSK. The thorough clinical examination and proper evaluation is important in patient of urethral stricture with underlying chronic renal insufficiency to avoid delayed diagnosis, management and related complications.

A case of medullary sponge kidney (Cacchi-Ricci disease) mimicking a renal mass.

Medullary sponge kidney (MSK) is an uncommon benign congenital disorder, generally asymptomatic. In symptomatic patients the diagnosis is usually made by excretory urography performed in the most frequent complications such as renal stones, urinary tract infections and haematuria. Excretory urography can be very characteristic, showing cystic collections of ectatic collecting ducts like "bunches of grapes" or "bouquet of flowers". When haematuria represents the only symptom, and radiographic findings are not characteristic of MSK, the differential diagnosis with a renal tumor can be very difficult. We report a case of MSK that underwent nephrectomy since clinical and radiological features mimicked a renal tumor.

Medullary sponge kidney.

Medullary sponge kidney is a benign asymptomatic developmental anomaly of the kidney mostly seen in adult females. Presentation in childhood is uncommon. Urinary tract infection, nephrolithiasis, hematuria and hypercalciuria are the common complications. We report a eleven-year-old female child who presented with recurrent urinary tract infection and nephrolithiasis and was found to have bilateral medullary sponge kidney.

[Clinical picture of 11 patients with sponge kidney]. / Klinický obraz 11 nemocných s houbovitými ledvinami.

The authors review clinical data assembled in 11 patients with sponge kidneys followed up for prolonged periods. The disease is manifested by colics, haematuria and symptoms of bacterial inflammation of the urinary pathways. The basis of the diagnosis is excretory urography with typical changes in the renal pyramids: cystic dilatation of the collecting tubules, calcifications and concrements. The main functional disorder is a decline of the concentrating capacity of the kidneys. In some patients renal tubular acidosis of the distal type can be proved.

[Medullary sponge kidney. Description of a pediatric case]. / Il rene a spugna midollare. Descrizione di un caso pediatrico.

The case of a 11 year old boy with medullary sponge Kidney and nephrolithiasis discovered because of abdominal pain is described. Functional tubular impairment (concentrating defect, distal tubular acidosis) was present. No hypercalciuria nor hyperparathyroidism was detected. The diagnosis of medullary sponge Kidney was confirmed histopathologically. The pediatric cases described in the literature are characterized by a higher incidence of concentrating defect and acidosis, while the adults subjects often show hypercalciuria and or hyperparathyroidism. The careful study of tubular functions in the pediatric cases appears to be very useful to understand which are primary tubular disturbances and which are only secondary.

[Papillary drusen associated with bird shot retinochoroidopathy and the Cacchi-Ricci syndrome]. / Drusen papilar asociat cu retinocoroidopatie birdshot si sindrom Cacchi-Ricci.

The paper presents the observations on a case of drusen of the optic nerve head associated with bird shot retinochoroidopathy and Cacchi-Ricci syndrome on a 45-years-old patient. The drusen of the optic nerve head and the birdshot syndrome are diseases of unknown etiology, with low frequency of appearance. They are often seen in individuals with perfectly normal vision (diagnostically these lesions have to be found on occasionally ophthalmoscopic examinations). Therapeutically, there is no restorative treatment. This association of drusen of the optic nerve head, bird shot retinochoroidopathy and Cacchi-Ricci syndrome hasn't been mentioned in the medical literature.

[A woman with urinary tract infections and flank pain]. / Een vrouw met urineweginfecties en flankpijn.

A 52-year-old woman presented with recurrent urinary tract infections and flank pain. Both an abdominal CT-scan and a plain abdominal X-ray showed bilateral nephrocalcinosis and a kidney stone in the left ureter. These findings are suggestive of medullary sponge kidneys.