Re: The Impact of Potassium Citrate Therapy in the Natural Course of Medullary Sponge Kidney with Associated Nephrolithiasis. Assimos Dean G The Journal of urology 10.1097/01.JU.0000585776.57180.54
    Breaking the ice: urine proteomics of medullary sponge kidney disease. Chutipongtanate Somchai Kidney international Urinary proteomics is a promising tool for biomarker investigation, particularly in complex kidney diseases. Fabris and colleagues report that urinary laminin subunit alpha-2 is a potential diagnostic marker of medullary sponge kidney (MSK) disease by using a label-free quantitative proteomics platform and a clinically compatible enzyme-linked immunosorbent assay. The neglected issue of stone pathogenesis was also evidenced. This commentary discusses several considerations in biomarker validation, and how urinary proteomics breaks new ground in MSK research. 10.1016/j.kint.2016.10.032
    The Clinical Efficacy and Safety of Ureteroscopic Laser Papillotomy to Treat Intraductal Papillary Calculi Associated With Medullary Sponge Kidney. Xu Gang,Wen Jiaming,Wang Bohan,Li Zhongyi,Du Chuanjun Urology OBJECTIVE:To evaluate the safety, efficacy, and durability of ureteroscopic laser papillotomy for the treatment of radiographically visible intraductal papillary calculi and/or free collecting system calculi associated with medullary sponge kidney (MSK). METHODS:The medical records of 25 MSK patients who underwent ureteroscopic laser papillotomy were reviewed at our institution from 2010 to 2013. The follow-up was made in our outpatient department. Pain was assessed using a standard verbal analog pain scale. Patients' pain score, plain abdominal radiograph, ultrasound examination, and urine analysis were routinely performed for each follow-up. We evaluated the procedure-related complications and mean-estimated glomerular filtration rate. RESULTS:Ureteroscopic laser papillotomy was performed a total of 37 times in 25 patients, including 12 bilateral procedures and 13 unilateral procedures. Significantly less pain was reported after 32 procedures. The mean operative time for unilateral procedure was 38.5 ± 8.2 minutes. The main complications after surgery included urinary infection (2 patients). No serious bleeding was presented in all the patients. The maximum follow-up time was 28.5 months. There was no significant change in the mean-estimated glomerular filtration rate before and after the procedure and at the end of follow-up. Twenty-three patients remained asymptomatic, whereas 2 patients had urinary tract infection (pyelonephritis) during follow-up. CONCLUSION:In MSK patients with repeated recurrences of symptomatic stones, ureteroscopic laser papillotomy could be a safe and effective treatment option for radiographically visible intraductal papillary calculi. 10.1016/j.urology.2015.06.037
    The impact of potassium citrate therapy in the natural course of Medullary Sponge Kidney with associated nephrolithiasis. Cicerello Elisa,Ciaccia Matteo,Cova Giandavide,Mangano Mario Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica OBJECTIVES:The present study was carried out to evaluate the effectiveness of medical therapy with potassium citrate in preventing calculosis complicating Medullary Sponge Kidney (MSK) without renal acidification defects. MATERIALS AND METHODS:In a open, uncontrolled, retrospective analysis, 49 MSK patients with nephrolithiasis without renal tubular acidosis, underwent a complete metabolic evaluation and received potassium citrate therapy 4-6 g/day. The course of stone disease before and after citrate therapy was determined in each patient from a combination of clinical history, past records, radiographs and kidney ultrasound. The rate of new stone formation/pt/yr, of endourological and extracorporeal procedures, of urinary tract infection (UTI) and number of hospitalization before and after medical treatment were calculated. RESULTS:Metabolic anomalies (hypercalciuria, hypocitraturia, hyperuricuria and hyperoxaluria) were present in 83% of the patients. Follow-up before and after alkali citrate therapy was comparable (4.7+/-1.4 and 4.9+/-1.7 years respectively). Medical treatment significantly reduced rates of stone formation from 2.0+/-1.0 to 0.2+/-0.5 pt/yr, ureteroscopy (URS) from 0.9+/0.8 to 0.4+/-0.5 pt/yr, extratracoporeal lithotripsy (ESWL) from 1.1+/-0.8 to 0.4+/-0.6 pt/yr, urinary tract infections (UTIs) from 0.8+/-1.2 to 0.3+/-0.5 pt/yr and hospitalization from 1.1+/-0.6 to 0.2+/-0.3 pt/yr, p < 0.001. This effect was observed also in MSK patients without metabolic anomalies. In 35 patients the asymptomatic disappearance of calcium stones was also observed. CONCLUSIONS:Our study documents the effectiveness of potassium citrate therapy in preventing neprolithiasis in MSK patients also in the absence of distal tubular acidosis. It suggests that in MSK patients alkali citrate may promote calcium stone dissolution by oral administration. 10.4081/aiua.2019.2.102
    Chronic pain in medullary sponge kidney: a rare and never described clinical presentation. Gambaro G,Goldfarb D S,Baccaro R,Hirsch J,Topilow N,D'Alonzo S,Gambassi G,Ferraro P M Journal of nephrology Medullary sponge kidney (MSK) is a cause of nephrocalcinosis, associated with hematuria, renal colic, pyelonephritis. There are rare and atypical MSK cases characterized by chronic severe pain (CP), whose features are unknown, in particular the relationship with the stone disease activity. This study analyzes a cohort of MSK-CP patients belonging to three North-America self-support Facebook groups. Patients had to self-administer an on-line questionnaire (on intensity, progression and MSK-associated conditions, stone-related disease, pain features, drug use), the Brief Pain Inventory, the Fatigue Severity Score, and Wisconsin Quality of Life (WQL) in stone formers questionnaires. Ninety-two patients with a diagnosis of MSK joined our survey. Stone rate was very high (3.1 stones per patient-year, < 15% of patients had ≤ 1 stone per year). Most patients had repeated hospitalizations for stones symptoms (p < 0.001) or pain (p < 0.005). 71% of participants referred a daily pain that interfered strongly with everyday life and quality of life (WQL mean value 29.4). 69% used pain medications daily (70% opioids). In most cases, pain was associated with stone passage, while 15% referred a sine materia pain. We showed how MSK-CP symptoms affect very negatively on the quality of life of these patients. They also have a definite risk of progressing to end-stage kidney disease. Generally, CP seems to be associated with an exceptionally high lithogenic activity, suggesting that a better and earlier metabolic treatment for stone prevention should be the first approach in these patients before mini-invasive treatments to prevent pain. 10.1007/s40620-018-0480-8
    Biopsy proven medullary sponge kidney: clinical findings, histopathology, and role of osteogenesis in stone and plaque formation. Evan Andrew P,Worcester Elaine M,Williams James C,Sommer Andre J,Lingeman James E,Phillips Carrie L,Coe Fredric L Anatomical record (Hoboken, N.J. : 2007) Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall's) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall's plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation. 10.1002/ar.23105
    Proteomic Analysis of Urinary Microvesicles and Exosomes in Medullary Sponge Kidney Disease and Autosomal Dominant Polycystic Kidney Disease. Bruschi Maurizio,Granata Simona,Santucci Laura,Candiano Giovanni,Fabris Antonia,Antonucci Nadia,Petretto Andrea,Bartolucci Martina,Del Zotto Genny,Antonini Francesca,Ghiggeri Gian Marco,Lupo Antonio,Gambaro Giovanni,Zaza Gianluigi Clinical journal of the American Society of Nephrology : CJASN BACKGROUND AND OBJECTIVES:Microvesicles and exosomes are involved in the pathogenesis of autosomal dominant polycystic kidney disease. However, it is unclear whether they also contribute to medullary sponge kidney, a sporadic kidney malformation featuring cysts, nephrocalcinosis, and recurrent kidney stones. We addressed this knowledge gap by comparative proteomic analysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:The protein content of microvesicles and exosomes isolated from the urine of 15 patients with medullary sponge kidney and 15 patients with autosomal dominant polycystic kidney disease was determined by mass spectrometry followed by weighted gene coexpression network analysis, support vector machine learning, and partial least squares discriminant analysis to compare the profiles and select the most discriminative proteins. The proteomic data were verified by ELISA. RESULTS:A total of 2950 proteins were isolated from microvesicles and exosomes, including 1579 (54%) identified in all samples but only 178 (6%) and 88 (3%) specific for medullary sponge kidney microvesicles and exosomes, and 183 (6%) and 98 (3%) specific for autosomal dominant polycystic kidney disease microvesicles and exosomes, respectively. The weighted gene coexpression network analysis revealed ten modules comprising proteins with similar expression profiles. Support vector machine learning and partial least squares discriminant analysis identified 34 proteins that were highly discriminative between the diseases. Among these, CD133 was upregulated in exosomes from autosomal dominant polycystic kidney disease and validated by ELISA. CONCLUSIONS:Our data indicate a different proteomic profile of urinary microvesicles and exosomes in patients with medullary sponge kidney compared with patients with autosomal dominant polycystic kidney disease. The urine proteomic profile of patients with autosomal dominant polycystic kidney disease was enriched of proteins involved in cell proliferation and matrix remodeling. Instead, proteins identified in patients with medullary sponge kidney were associated with parenchymal calcium deposition/nephrolithiasis and systemic metabolic derangements associated with stones formation and bone mineralization defects. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_04_24_CJASNPodcast_19_06_.mp3. 10.2215/CJN.12191018
    New non-renal congenital disorders associated with medullary sponge kidney (MSK) support the pathogenic role of GDNF and point to the diagnosis of MSK in recurrent stone formers. Ria Paolo,Fabris Antonia,Dalla Gassa Alessandra,Zaza Gianluigi,Lupo Antonio,Gambaro Giovanni Urolithiasis Medullary sponge kidney (MSK) is a congenital renal disorder. Its association with several developmental abnormalities in other organs hints at the likelihood of some shared step(s) in the embryogenesis of the kidney and other organs. It has been suggested that the REarranged during Transfection (RET) proto-oncogene and the Glial cell line-Derived Neurotrophic Factor (GDNF) gene are defective in patients with MSK, and both RET and GDNF are known to have a role in the development of the central nervous system, heart, and craniofacial skeleton. Among a cohort of 143 MSK patients being followed up for nephrolithiasis and chronic kidney disease at our institution, we found six with one or more associated non-renal anomalies: one patient probably has congenital hemihyperplasia and hypertrophic cardiomyopathy with adipose metaplasia and mitral valve prolapse; one has Marfan syndrome; and the other four have novel associations between MSK and nerve and skeleton abnormalities described here for the first time. The discovery of disorders involving the central nervous system, cardiovascular system and craniofacial skeleton in MSK patients supports the hypothesis of a genetic alteration on the RET-GDNF axis having a pivotal role in the pathogenesis of MSK, in a subset of patients at least. MSK seems more and more to be a systemic disease, and the identification of extrarenal developmental defects could be important in arousing the suspicion of MSK in recurrent stone formers. 10.1007/s00240-016-0913-6
    Safety and efficacy of minimally invasive percutaneous nephrolithotomy in the treatment of patients with medullary sponge kidney. Sun Heyang,Zhang Ze,Yuan Jian,Liu Yongda,Lei Ming,Luo Jintai,Wan Shaw P,Zeng Guohua Urolithiasis The purpose of this study was to review the safety and efficacy of the minimally invasive percutaneous nephrolithotomy in the treatment of medullary sponge kidney patients with complex renal calculi. Sixteen medullary sponge kidney patients with complex renal calculi underwent minimally invasive percutaneous nephrolithotomy procedures in our center were entered into this retrospective study. The data analyzed included patients' demographics, stone burden, operative time, operative blood loss, length of hospital stay, complications according to the modified Clavien system, and stone-free rate. All the patients in this study had complex renal stones that included 14 multiple stones and 3 partial staghorn calculi. The mean stone surface area was 779.5 ± 421.1 mm(2). Preoperative urinary tract infection was noted in 5 (31.2 %) patients. Minimally invasive percutaneous nephrolithotomy was successfully completed in 15 renal units in 14 patients. Two patients failed the procedure. The mean operative time was 87.3 ± 32.3 min. Mean hemoglobin drop was 25.3 ± 16.5 g/L. An initial stone-free rate of 60 % was achieved after the procedure, and the final stone-free rate was 86.6 % after auxiliary second look and/or shock-wave lithotripsy. Clavien grade I and II complications occurred in 3 (21.4 %) patients including the one (7.1 %) patient who required transfusion. All the complications were managed conservatively. No major complications occurred. This retrospective analysis confirmed that minimally invasive percutaneous nephrolithotomy was a safe alternative treatment for the medullary sponge kidney patients with complex renal calculi. This procedure provided an acceptable stone-free rate and low incidence of high-grade complications. Stone-free rate further could be further improved with auxiliary procedures. 10.1007/s00240-015-0853-6
    [Effects of percutaneous nephrolithotomy in the treatment of medullary sponge kidney with calculi]. Hong Y,Xu Q Q,Huang X B,Zhu Z J,Ye H Y,Zhang F S,Yang Q Y,An L Z,Xu T Zhonghua wai ke za zhi [Chinese journal of surgery] To evaluate the effects of percutaneous nephrolithotomy (PNL) in the treatment of medullary sponge kidney with calculi. A total of 77 patients (91 renal units) of medullary sponge kidney with calculi (MSK group) and 77 patients (77 renal units) with common kidney stone (control group) received PNL at Department of Urology in Peking University People's Hospital from September 2006 to February 2016 were analyzed retrospectively. The MSK group included 33 males and 44 females with a mean age of (42.1±13.2) years, the mean stone burden was (3.9±1.8) cm. The control group included 36 males and 41 females with a mean age of (45.3±13.0) years, the mean stone burden was (3.6±1.5) cm. The numbers of tracts, the time of operation, the drop of hemoglobin, the change of creatine, the time of hospitalization, the stone free rate and major complications were compared between the two groups. The measurement data and numeration data were compared with test and χ(2) test. There were no significant differences in sex, age, preoperative urinary tract infection, stone type, and stone burden between the two groups (all >0.05). The proportion of bilateral renal calculus in MSK group was higher (18.2% . 0, χ(2)=15.400, =0.000). There were 159 percutaneous channels were established in MSK group while 90 percutaneous channels were established in control group. Compared with the control group, the operation time ((88.1±37.5) minutes . (68.5±30.1) minutes, =3.543, =0.000) and hospitalization time ((15.1±8.3) days . (10.1±3.6) days, =4.816, =0.000) were longer, the creatinine level increased ((101.2±62.6) μmol/L . (71.3±23.6) μmol/L, =3.777, =0.000), the rate of stone free decreased (27.5% . 83.1%, χ(2)=51.840, =0.000) and the rate of complications increased (29.9% . 11.7%, χ(2)=8.114, =0.004) in MSK group. There was no statistically difference in hemoglobin drop ((12.5±13.2) g/L . (13.0±10.9) g/L, =-0.260, =0.795). Using PNL for patients of MSK with calculi has a lower stone free rate and a higher complications. It is an effective method for patients of MSK with large and complex calculi. 10.3760/cma.j.issn.0529-5815.2017.10.005