Imaging of kidney cysts and cystic kidney diseases in children: an international working group consensus statement

Kidney cysts can manifest as focal disease (simple and complex kidney cysts), affect a whole kidney (eg, multicystic dysplastic kidney or cystic dysplasia), or manifest as bilateral cystic disease (eg, autosomal recessive polycystic kidney disease [ARPKD] or autosomal dominant polycystic kidney disease [ADPKD]). In children, as opposed to adults, a larger proportion of kidney cysts are due to genetic diseases (eg, HNF1B nephropathy, various ciliopathies, and tuberous sclerosis complex), and fewer patients have simple cysts or acquired cystic kidney disease. The purpose of this consensus statement is to provide clinical guidance on standardization of imaging tests to evaluate kidney cysts in children. A committee of international experts in pediatric nephrology, pediatric radiology, pediatric US, and adult nephrology prepared systematic literature reviews and formulated recommendations at a consensus meeting. The final statement was endorsed by the European Society of Pediatric Radiology, the European Federation of Societies for Ultrasound in Medicine and Biology, the European Society of Pediatric Nephrology, and reviewed by the European Reference Network for Rare Kidney Diseases. Main recommendations are as follows: US is the method of choice when assessing pediatric kidney cysts, with selected indications for MRI and contrast-enhanced US. CT should be avoided whenever possible because of ionizing radiation. Renal US yields essential diagnostic information in many cases. In patients with ARPKD or other ciliopathies, abdominal US is needed for diagnosis and screening of portal hypertension. US is usually sufficient for follow-up kidney imaging, but MRI can be valuable for clinical trials in patients with ADPKD or in older children with tuberous sclerosis complex to evaluate both kidney cysts and angiomyolipomas

Radioactivity control strategy for the JUNO detector

602siopenJUNO is a massive liquid scintillator detector with a primary scientific goal of determining the neutrino mass ordering by studying the oscillated anti-neutrino flux coming from two nuclear power plants at 53 km distance. The expected signal anti-neutrino interaction rate is only 60 counts per day (cpd), therefore a careful control of the background sources due to radioactivity is critical. In particular, natural radioactivity present in all materials and in the environment represents a serious issue that could impair the sensitivity of the experiment if appropriate countermeasures were not foreseen. In this paper we discuss the background reduction strategies undertaken by the JUNO collaboration to reduce at minimum the impact of natural radioactivity. We describe our efforts for an optimized experimental design, a careful material screening and accurate detector production handling, and a constant control of the expected results through a meticulous Monte Carlo simulation program. We show that all these actions should allow us to keep the background count rate safely below the target value of 10 Hz (i.e. ∼1 cpd accidental background) in the default fiducial volume, above an energy threshold of 0.7 MeV. [Figure not available: see fulltext.]openAbusleme A.; Adam T.; Ahmad S.; Ahmed R.; Aiello S.; Akram M.; An F.; An Q.; Andronico G.; Anfimov N.; Antonelli V.; Antoshkina T.; Asavapibhop B.; de Andre J.P.A.M.; Auguste D.; Babic A.; Baldini W.; Barresi A.; Basilico D.; Baussan E.; Bellato M.; Bergnoli A.; Birkenfeld T.; Blin S.; Blum D.; Blyth S.; Bolshakova A.; Bongrand M.; Bordereau C.; Breton D.; Brigatti A.; Brugnera R.; Bruno R.; Budano A.; Buscemi M.; Busto J.; Butorov I.; Cabrera A.; Cai H.; Cai X.; Cai Y.; Cai Z.; Cammi A.; Campeny A.; Cao C.; Cao G.; Cao J.; Caruso R.; Cerna C.; Chang J.; Chang Y.; Chen P.; Chen P.-A.; Chen S.; Chen X.; Chen Y.-W.; Chen Y.; Chen Y.; Chen Z.; Cheng J.; Cheng Y.; Chetverikov A.; Chiesa D.; Chimenti P.; Chukanov A.; Claverie G.; Clementi C.; Clerbaux B.; Conforti Di Lorenzo S.; Corti D.; Cremonesi O.; Dal Corso F.; Dalager O.; De La Taille C.; Deng J.; Deng Z.; Deng Z.; Depnering W.; Diaz M.; Ding X.; Ding Y.; Dirgantara B.; Dmitrievsky S.; Dohnal T.; Dolzhikov D.; Donchenko G.; Dong J.; Doroshkevich E.; Dracos M.; Druillole F.; Du S.; Dusini S.; Dvorak M.; Enqvist T.; Enzmann H.; Fabbri A.; Fajt L.; Fan D.; Fan L.; Fang J.; Fang W.; Fargetta M.; Fedoseev D.; Fekete V.; Feng L.-C.; Feng Q.; Ford R.; Formozov A.; Fournier A.; Gan H.; Gao F.; Garfagnini A.; Giammarchi M.; Giaz A.; Giudice N.; Gonchar M.; Gong G.; Gong H.; Gornushkin Y.; Gottel A.; Grassi M.; Grewing C.; Gromov V.; Gu M.; Gu X.; Gu Y.; Guan M.; Guardone N.; Gul M.; Guo C.; Guo J.; Guo W.; Guo X.; Guo Y.; Hackspacher P.; Hagner C.; Han R.; Han Y.; Hassan M.S.; He M.; He W.; Heinz T.; Hellmuth P.; Heng Y.; Herrera R.; Hor Y.K.; Hou S.; Hsiung Y.; Hu B.-Z.; Hu H.; Hu J.; Hu J.; Hu S.; Hu T.; Hu Z.; Huang C.; Huang G.; Huang H.; Huang W.; Huang X.; Huang X.; Huang Y.; Hui J.; Huo L.; Huo W.; Huss C.; Hussain S.; Ioannisian A.; Isocrate R.; Jelmini B.; Jen K.-L.; Jeria I.; Ji X.; Ji X.; Jia H.; Jia J.; Jian S.; Jiang D.; Jiang X.; Jin R.; Jing X.; Jollet C.; Joutsenvaara J.; Jungthawan S.; Kalousis L.; Kampmann P.; Kang L.; Karaparambil R.; Kazarian N.; Khan W.; Khosonthongkee K.; Korablev D.; Kouzakov K.; Krasnoperov A.; Kruth A.; Kutovskiy N.; Kuusiniemi P.; Lachenmaier T.; Landini C.; Leblanc S.; Lebrin V.; Lefevre F.; Lei R.; Leitner R.; Leung J.; Li D.; Li F.; Li F.; Li H.; Li H.; Li J.; Li M.; Li M.; Li N.; Li N.; Li Q.; Li R.; Li S.; Li T.; Li W.; Li W.; Li X.; Li X.; Li X.; Li Y.; Li Y.; Li Z.; Li Z.; Li Z.; Liang H.; Liang H.; Liao J.; Liebau D.; Limphirat A.; Limpijumnong S.; Lin G.-L.; Lin S.; Lin T.; Ling J.; Lippi I.; Liu F.; Liu H.; Liu H.; Liu H.; Liu H.; Liu H.; Liu J.; Liu J.; Liu M.; Liu Q.; Liu Q.; Liu R.; Liu S.; Liu S.; Liu S.; Liu X.; Liu X.; Liu Y.; Liu Y.; Lokhov A.; Lombardi P.; Lombardo C.; Loo K.; Lu C.; Lu H.; Lu J.; Lu J.; Lu S.; Lu X.; Lubsandorzhiev B.; Lubsandorzhiev S.; Ludhova L.; Luo F.; Luo G.; Luo P.; Luo S.; Luo W.; Lyashuk V.; Ma B.; Ma Q.; Ma S.; Ma X.; Ma X.; Maalmi J.; Malyshkin Y.; Mantovani F.; Manzali F.; Mao X.; Mao Y.; Mari S.M.; Marini F.; Marium S.; Martellini C.; Martin-Chassard G.; Martini A.; Mayer M.; Mayilyan D.; Mednieks I.; Meng Y.; Meregaglia A.; Meroni E.; Meyhofer D.; Mezzetto M.; Miller J.; Miramonti L.; Montini P.; Montuschi M.; Muller A.; Nastasi M.; Naumov D.V.; Naumova E.; Navas-Nicolas D.; Nemchenok I.; Nguyen Thi M.T.; Ning F.; Ning Z.; Nunokawa H.; Oberauer L.; Ochoa-Ricoux J.P.; Olshevskiy A.; Orestano D.; Ortica F.; Othegraven R.; Pan H.-R.; Paoloni A.; Parmeggiano S.; Pei Y.; Pelliccia N.; Peng A.; Peng H.; Perrot F.; Petitjean P.-A.; Petrucci F.; Pilarczyk O.; Pineres Rico L.F.; Popov A.; Poussot P.; Pratumwan W.; Previtali E.; Qi F.; Qi M.; Qian S.; Qian X.; Qian Z.; Qiao H.; Qin Z.; Qiu S.; Rajput M.U.; Ranucci G.; Raper N.; Re A.; Rebber H.; Rebii A.; Ren B.; Ren J.; Ricci B.; Robens M.; Roche M.; Rodphai N.; Romani A.; Roskovec B.; Roth C.; Ruan X.; Ruan X.; Rujirawat S.; Rybnikov A.; Sadovsky A.; Saggese P.; Sanfilippo S.; Sangka A.; Sanguansak N.; Sawangwit U.; Sawatzki J.; Sawy F.; Schever M.; Schwab C.; Schweizer K.; Selyunin A.; Serafini A.; Settanta G.; Settimo M.; Shao Z.; Sharov V.; Shaydurova A.; Shi J.; Shi Y.; Shutov V.; Sidorenkov A.; Simkovic F.; Sirignano C.; Siripak J.; Sisti M.; Slupecki M.; Smirnov M.; Smirnov O.; Sogo-Bezerra T.; Sokolov S.; Songwadhana J.; Soonthornthum B.; Sotnikov A.; Sramek O.; Sreethawong W.; Stahl A.; Stanco L.; Stankevich K.; Stefanik D.; Steiger H.; Steinmann J.; Sterr T.; Stock M.R.; Strati V.; Studenikin A.; Sun S.; Sun X.; Sun Y.; Sun Y.; Suwonjandee N.; Szelezniak M.; Tang J.; Tang Q.; Tang Q.; Tang X.; Tietzsch A.; Tkachev I.; Tmej T.; Treskov K.; Triossi A.; Troni G.; Trzaska W.; Tuve C.; Ushakov N.; van den Boom J.; van Waasen S.; Vanroyen G.; Vassilopoulos N.; Vedin V.; Verde G.; Vialkov M.; Viaud B.; Vollbrecht M.C.; Volpe C.; Vorobel V.; Voronin D.; Votano L.; Walker P.; Wang C.; Wang C.-H.; Wang E.; Wang G.; Wang J.; Wang J.; Wang K.; Wang L.; Wang M.; Wang M.; Wang M.; Wang R.; Wang S.; Wang W.; Wang W.; Wang W.; Wang X.; Wang X.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Z.; Wang Z.; Wang Z.; Wang Z.; Waqas M.; Watcharangkool A.; Wei L.; Wei W.; Wei W.; Wei Y.; Wen L.; Wiebusch C.; Wong S.C.-F.; Wonsak B.; Wu D.; Wu F.; Wu Q.; Wu Z.; Wurm M.; Wurtz J.; Wysotzki C.; Xi Y.; Xia D.; Xie X.; Xie Y.; Xie Z.; Xing Z.; Xu B.; Xu C.; Xu D.; Xu F.; Xu H.; Xu J.; Xu J.; Xu M.; Xu Y.; Xu Y.; Yan B.; Yan T.; Yan W.; Yan X.; Yan Y.; Yang A.; Yang C.; Yang C.; Yang H.; Yang J.; Yang L.; Yang X.; Yang Y.; Yang Y.; Yao H.; Yasin Z.; Ye J.; Ye M.; Ye Z.; Yegin U.; Yermia F.; Yi P.; Yin N.; Yin X.; You Z.; Yu B.; Yu C.; Yu C.; Yu H.; Yu M.; Yu X.; Yu Z.; Yu Z.; Yuan C.; Yuan Y.; Yuan Z.; Yuan Z.; Yue B.; Zafar N.; Zambanini A.; Zavadskyi V.; Zeng S.; Zeng T.; Zeng Y.; Zhan L.; Zhang A.; Zhang F.; Zhang G.; Zhang H.; Zhang H.; Zhang J.; Zhang J.; Zhang J.; Zhang J.; Zhang J.; Zhang P.; Zhang Q.; Zhang S.; Zhang S.; Zhang T.; Zhang X.; Zhang X.; Zhang X.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Z.; Zhang Z.; Zhao F.; Zhao J.; Zhao R.; Zhao S.; Zhao T.; Zheng D.; Zheng H.; Zheng M.; Zheng Y.; Zhong W.; Zhou J.; Zhou L.; Zhou N.; Zhou S.; Zhou T.; Zhou X.; Zhu J.; Zhu K.; Zhu K.; Zhu Z.; Zhuang B.; Zhuang H.; Zong L.; Zou J.Abusleme, A.; Adam, T.; Ahmad, S.; Ahmed, R.; Aiello, S.; Akram, M.; An, F.; An, Q.; Andronico, G.; Anfimov, N.; Antonelli, V.; Antoshkina, T.; Asavapibhop, B.; de Andre, J. P. A. M.; Auguste, D.; Babic, A.; Baldini, W.; Barresi, A.; Basilico, D.; Baussan, E.; Bellato, M.; Bergnoli, A.; Birkenfeld, T.; Blin, S.; Blum, D.; Blyth, S.; Bolshakova, A.; Bongrand, M.; Bordereau, C.; Breton, D.; Brigatti, A.; Brugnera, R.; Bruno, R.; Budano, A.; Buscemi, M.; Busto, J.; Butorov, I.; Cabrera, A.; Cai, H.; Cai, X.; Cai, Y.; Cai, Z.; Cammi, A.; Campeny, A.; Cao, C.; Cao, G.; Cao, J.; Caruso, R.; Cerna, C.; Chang, J.; Chang, Y.; Chen, P.; Chen, P. -A.; Chen, S.; Chen, X.; Chen, Y. -W.; Chen, Y.; Chen, Y.; Chen, Z.; Cheng, J.; Cheng, Y.; Chetverikov, A.; Chiesa, D.; Chimenti, P.; Chukanov, A.; Claverie, G.; Clementi, C.; Clerbaux, B.; Conforti Di Lorenzo, S.; Corti, D.; Cremonesi, O.; Dal Corso, F.; Dalager, O.; De La Taille, C.; Deng, J.; Deng, Z.; Deng, Z.; Depnering, W.; Diaz, M.; Ding, X.; Ding, Y.; Dirgantara, B.; Dmitrievsky, S.; Dohnal, T.; Dolzhikov, D.; Donchenko, G.; Dong, J.; Doroshkevich, E.; Dracos, M.; Druillole, F.; Du, S.; Dusini, S.; Dvorak, M.; Enqvist, T.; Enzmann, H.; Fabbri, A.; Fajt, L.; Fan, D.; Fan, L.; Fang, J.; Fang, W.; Fargetta, M.; Fedoseev, D.; Fekete, V.; Feng, L. -C.; Feng, Q.; Ford, R.; Formozov, A.; Fournier, A.; Gan, H.; Gao, F.; Garfagnini, A.; Giammarchi, M.; Giaz, A.; Giudice, N.; Gonchar, M.; Gong, G.; Gong, H.; Gornushkin, Y.; Gottel, A.; Grassi, M.; Grewing, C.; Gromov, V.; Gu, M.; Gu, X.; Gu, Y.; Guan, M.; Guardone, N.; Gul, M.; Guo, C.; Guo, J.; Guo, W.; Guo, X.; Guo, Y.; Hackspacher, P.; Hagner, C.; Han, R.; Han, Y.; Hassan, M. S.; He, M.; He, W.; Heinz, T.; Hellmuth, P.; Heng, Y.; Herrera, R.; Hor, Y. K.; Hou, S.; Hsiung, Y.; Hu, B. -Z.; Hu, H.; Hu, J.; Hu, J.; Hu, S.; Hu, T.; Hu, Z.; Huang, C.; Huang, G.; Huang, H.; Huang, W.; Huang, X.; Huang, X.; Huang, Y.; Hui, J.; Huo, L.; Huo, W.; Huss, C.; Hussain, S.; Ioannisian, A.; Isocrate, R.; Jelmini, B.; Jen, K. -L.; Jeria, I.; Ji, X.; Ji, X.; Jia, H.; Jia, J.; Jian, S.; Jiang, D.; Jiang, X.; Jin, R.; Jing, X.; Jollet, C.; Joutsenvaara, J.; Jungthawan, S.; Kalousis, L.; Kampmann, P.; Kang, L.; Karaparambil, R.; Kazarian, N.; Khan, W.; Khosonthongkee, K.; Korablev, D.; Kouzakov, K.; Krasnoperov, A.; Kruth, A.; Kutovskiy, N.; Kuusiniemi, P.; Lachenmaier, T.; Landini, C.; Leblanc, S.; Lebrin, V.; Lefevre, F.; Lei, R.; Leitner, R.; Leung, J.; Li, D.; Li, F.; Li, F.; Li, H.; Li, H.; Li, J.; Li, M.; Li, M.; Li, N.; Li, N.; Li, Q.; Li, R.; Li, S.; Li, T.; Li, W.; Li, W.; Li, X.; Li, X.; Li, X.; Li, Y.; Li, Y.; Li, Z.; Li, Z.; Li, Z.; Liang, H.; Liang, H.; Liao, J.; Liebau, D.; Limphirat, A.; Limpijumnong, S.; Lin, G. -L.; Lin, S.; Lin, T.; Ling, J.; Lippi, I.; Liu, F.; Liu, H.; Liu, H.; Liu, H.; Liu, H.; Liu, H.; Liu, J.; Liu, J.; Liu, M.; Liu, Q.; Liu, Q.; Liu, R.; Liu, S.; Liu, S.; Liu, S.; Liu, X.; Liu, X.; Liu, Y.; Liu, Y.; Lokhov, A.; Lombardi, P.; Lombardo, C.; Loo, K.; Lu, C.; Lu, H.; Lu, J.; Lu, J.; Lu, S.; Lu, X.; Lubsandorzhiev, B.; Lubsandorzhiev, S.; Ludhova, L.; Luo, F.; Luo, G.; Luo, P.; Luo, S.; Luo, W.; Lyashuk, V.; Ma, B.; Ma, Q.; Ma, S.; Ma, X.; Ma, X.; Maalmi, J.; Malyshkin, Y.; Mantovani, F.; Manzali, F.; Mao, X.; Mao, Y.; Mari, S. M.; Marini, F.; Marium, S.; Martellini, C.; Martin-Chassard, G.; Martini, A.; Mayer, M.; Mayilyan, D.; Mednieks, I.; Meng, Y.; Meregaglia, A.; Meroni, E.; Meyhofer, D.; Mezzetto, M.; Miller, J.; Miramonti, L.; Montini, P.; Montuschi, M.; Muller, A.; Nastasi, M.; Naumov, D. V.; Naumova, E.; Navas-Nicolas, D.; Nemchenok, I.; Nguyen Thi, M. T.; Ning, F.; Ning, Z.; Nunokawa, H.; Oberauer, L.; Ochoa-Ricoux, J. P.; Olshevskiy, A.; Orestano, D.; Ortica, F.; Othegraven, R.; Pan, H. -R.; Paoloni, A.; Parmeggiano, S.; Pei, Y.; Pelliccia, N.; Peng, A.; Peng, H.; Perrot, F.; Petitjean, P. -A.; Petrucci, F.; Pilarczyk, O.; Pineres Rico, L. F.; Popov, A.; Poussot, P.; Pratumwan, W.; Previtali, E.; Qi, F.; Qi, M.; Qian, S.; Qian, X.; Qian, Z.; Qiao, H.; Qin, Z.; Qiu, S.; Rajput, M. U.; Ranucci, G.; Raper, N.; Re, A.; Rebber, H.; Rebii, A.; Ren, B.; Ren, J.; Ricci, B.; Robens, M.; Roche, M.; Rodphai, N.; Romani, A.; Roskovec, B.; Roth, C.; Ruan, X.; Ruan, X.; Rujirawat, S.; Rybnikov, A.; Sadovsky, A.; Saggese, P.; Sanfilippo, S.; Sangka, A.; Sanguansak, N.; Sawangwit, U.; Sawatzki, J.; Sawy, F.; Schever, M.; Schwab, C.; Schweizer, K.; Selyunin, A.; Serafini, A.; Settanta, G.; Settimo, M.; Shao, Z.; Sharov, V.; Shaydurova, A.; Shi, J.; Shi, Y.; Shutov, V.; Sidorenkov, A.; Simkovic, F.; Sirignano, C.; Siripak, J.; Sisti, M.; Slupecki, M.; Smirnov, M.; Smirnov, O.; Sogo-Bezerra, T.; Sokolov, S.; Songwadhana, J.; Soonthornthum, B.; Sotnikov, A.; Sramek, O.; Sreethawong, W.; Stahl, A.; Stanco, L.; Stankevich, K.; Stefanik, D.; Steiger, H.; Steinmann, J.; Sterr, T.; Stock, M. R.; Strati, V.; Studenikin, A.; Sun, S.; Sun, X.; Sun, Y.; Sun, Y.; Suwonjandee, N.; Szelezniak, M.; Tang, J.; Tang, Q.; Tang, Q.; Tang, X.; Tietzsch, A.; Tkachev, I.; Tmej, T.; Treskov, K.; Triossi, A.; Troni, G.; Trzaska, W.; Tuve, C.; Ushakov, N.; van den Boom, J.; van Waasen, S.; Vanroyen, G.; Vassilopoulos, N.; Vedin, V.; Verde, G.; Vialkov, M.; Viaud, B.; Vollbrecht, M. C.; Volpe, C.; Vorobel, V.; Voronin, D.; Votano, L.; Walker, P.; Wang, C.; Wang, C. -H.; Wang, E.; Wang, G.; Wang, J.; Wang, J.; Wang, K.; Wang, L.; Wang, M.; Wang, M.; Wang, M.; Wang, R.; Wang, S.; Wang, W.; Wang, W.; Wang, W.; Wang, X.; Wang, X.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Z.; Wang, Z.; Wang, Z.; Wang, Z.; Waqas, M.; Watcharangkool, A.; Wei, L.; Wei, W.; Wei, W.; Wei, Y.; Wen, L.; Wiebusch, C.; Wong, S. C. -F.; Wonsak, B.; Wu, D.; Wu, F.; Wu, Q.; Wu, Z.; Wurm, M.; Wurtz, J.; Wysotzki, C.; Xi, Y.; Xia, D.; Xie, X.; Xie, Y.; Xie, Z.; Xing, Z.; Xu, B.; Xu, C.; Xu, D.; Xu, F.; Xu, H.; Xu, J.; Xu, J.; Xu, M.; Xu, Y.; Xu, Y.; Yan, B.; Yan, T.; Yan, W.; Yan, X.; Yan, Y.; Yang, A.; Yang, C.; Yang, C.; Yang, H.; Yang, J.; Yang, L.; Yang, X.; Yang, Y.; Yang, Y.; Yao, H.; Yasin, Z.; Ye, J.; Ye, M.; Ye, Z.; Yegin, U.; Yermia, F.; Yi, P.; Yin, N.; Yin, X.; You, Z.; Yu, B.; Yu, C.; Yu, C.; Yu, H.; Yu, M.; Yu, X.; Yu, Z.; Yu, Z.; Yuan, C.; Yuan, Y.; Yuan, Z.; Yuan, Z.; Yue, B.; Zafar, N.; Zambanini, A.; Zavadskyi, V.; Zeng, S.; Zeng, T.; Zeng, Y.; Zhan, L.; Zhang, A.; Zhang, F.; Zhang, G.; Zhang, H.; Zhang, H.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, P.; Zhang, Q.; Zhang, S.; Zhang, S.; Zhang, T.; Zhang, X.; Zhang, X.; Zhang, X.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Z.; Zhang, Z.; Zhao, F.; Zhao, J.; Zhao, R.; Zhao, S.; Zhao, T.; Zheng, D.; Zheng, H.; Zheng, M.; Zheng, Y.; Zhong, W.; Zhou, J.; Zhou, L.; Zhou, N.; Zhou, S.; Zhou, T.; Zhou, X.; Zhu, J.; Zhu, K.; Zhu, K.; Zhu, Z.; Zhuang, B.; Zhuang, H.; Zong, L.; Zou, J

Severe neurological outcomes after very early bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD)

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (� 3 months; VEBNE) and early (4�15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset � 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort. © 2020, The Author(s)

Definition, diagnosis and clinical management of non-obstructive kidney dysplasia: a consensus statement by the ERKNet Working Group on Kidney Malformations

Kidney dysplasia is one of the most frequent causes of chronic kidney failure in children. While dysplasia is a histological diagnosis, the term 'kidney dysplasia' is frequently used in daily clinical life without histopathological confirmation. Clinical parameters of kidney dysplasia have not been clearly defined, leading to imprecise communication amongst healthcare professionals and patients. This lack of consensus hampers precise disease understanding and the development of specific therapies. Based on a structured literature search, we here suggest a common basis for clinical, imaging, genetic, pathological and basic science aspects of non-obstructive kidney dysplasia associated with functional kidney impairment. We propose to accept hallmark sonographic findings as surrogate parameters defining a clinical diagnosis of dysplastic kidneys. We suggest differentiated clinical follow-up plans for children with kidney dysplasia and summarize established monogenic causes for non-obstructive kidney dysplasia. Finally, we point out and discuss research gaps in the field

Maintenance Peritoneal Dialysis in Children With Autosomal Recessive Polycystic Kidney Disease: A Comparative Cohort Study of the International Pediatric Peritoneal Dialysis Network Registry

International Society for Peritoneal Dialysis. Baxter Health Care. Fresenius Medical Care, Germany. Ipsen. Medical Faculty of University of Cologne. Marga and Walter Boll-Foundation. Federal Ministry of Education & Research (BMBF): 01GM1515. European Rare Kidney Disease Reference Network (ERKNet)

mTOR-activating mutations in RRAGD are causative for kidney tubulopathy and cardiomyopathy

BACKGROUND: Over the last decade, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, approximately 20% of all tubulopathy patients lack a genetic diagnosis. METHODS: We performed whole-exome and genome sequencings of a patient cohort with a novel inherited salt-losing tubulopathy, hypomagnesemia, and dilated cardiomyopathy. We also conducted subsequent functional analyses in vitro of identified variants of RRAGD, a gene that encodes a small Rag guanosine triphosphatase (GTPase). RESULTS: In eight children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis, we identified heterozygous missense variants in RRAGD that mostly occurred de novo Six of these patients also had dilated cardiomyopathy and three underwent heart transplantation. We identified a heterozygous variant in RRAGD that segregated with the phenotype in eight members of a large family with similar kidney manifestations. The GTPase RagD encoded by RRAGD plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron included the thick ascending limb and the distal convoluted tubule. The identified RRAGD variants were shown to induce a constitutive activation of mTOR signaling in vitro. CONCLUSIONS: Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function