Acquired cystic disease associated renal cell carcinomas (ACD-RCC) are rare and their molecular and histopathological characteristics are still being explored. We therefore investigated the clinicopathologic and molecular characteristics of 31 tumors. The patients were predominantly male (n = 30), with tumors mainly left-sided (n = 17), unifocal (n = 19), and unilateral (n = 29) and a mean tumor size of 25 mm (range, 3-65 mm). Microscopically, several histologic patterns were present, including pure classic sieve-like (n = 4), and varied proportions of mixed classic sieve-like with papillary (n = 23), tubulocystic (n = 9), compact tubular (n = 4) and solid (n = 1) patterns. Calcium-oxalate crystals were seen in all tumors. Molecular analysis of 9 tumors using next generation sequencing showed alterations in SMARCB1 in 3 tumors (1 with frameshift deletion and 2 with copy number loss in chromosome 22 involving SMARCB1 region), however, INI1 stain was retained in all. Nonrecurrent genetic alterations in SETD2, NF1, NOTCH4, BRCA2 and CANT1 genes were also seen. Additionally, MTOR p.Pro351Ser was identified in one tumor. Copy number analysis showed gains in chromosome 16 (n = 5), 17 (n = 2) and 8 (n = 2) as well as loss in chromosome 22 (n = 2). In summary, ACD-RCC is a recognized subtype of kidney tumors, with several histological architectural patterns. Our molecular data identifies genetic alterations in chromatin modifying genes (SMARCB1 and SETD2), which may suggest a role of such genes in ACD-RCC development.

BACKGROUND: Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes.
METHODS: The aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment.
RESULTS: A total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264_267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation.
CONCLUSIONS: Whole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations.

BACKGROUND: Although simple renal cyst (SRC) is a kind of structural alterations of kidney with age, the relationship between SRC and renal function is still obscure. We investigated the relationship between SRC and renal function in Chinese population.
METHODS: The medical records of 41,842 individuals who underwent physical examinations at the Health Check-up Center at our institution in 2018 were reviewed. According to whether with SRC, they were divided into no-SRC and SRC groups. SRCs were classified into subgroups based on number (< 2 vs. ≥ 2) and size (< 2 cm vs. ≥ 2 cm). Logistic regression was used to examine the relationship between SRC and estimated glomerular filtration rate (eGFR).
RESULTS: Multinomial logistic regression analysis showed that the adjusted odds ratio (OR) for eGFR slight decline in subjects with SRC was 1.26(95% confidence interval (95% CI):1.17-1.35, p < 0.001), and the OR for eGFR severe decline was 1.35(95% CI: 1.16-1.56, p < 0.001) compared with no-SRC. The adjusted OR of SRC number ≥ 2 and ≥ 2 cm on the risk of eGFR severe decline was the highest (OR:1.68, 95% CI:1.25-2.23, p < 0.01) of four SRC subgroups.
CONCLUSIONS: SRC is related to eGFR decline, especially when the person with one more SRCs and the size of SRC is more than 2 cm. SRC could be a warning sign for clinicians to judge the decline of renal function.

UNASSIGNED: Acquired Cystic Kidney Disease (ACKD) is a known complication in patients on maintenance hemodialysis, and it is associated with a high risk of malignant transformation. There is a paucity of data on ACKD in sub-Saharan Africa. Objectives: To determine the prevalence and factors associated with acquired cystic kidney disease in patients on maintenance hemodialysis.
UNASSIGNED: patients on maintenance hemodialysis were screened for ACKD. Patients with hereditary cystic kidney disease were excluded. Renal ultrasounds were performed by two radiologists. ACKD was defined as 3 or more bilateral renal cysts in a small or normal size kidney. Associated factors were determined using logistic regression. A p-value <0.05 was significant.
UNASSIGNED: a total of 158 participants were enrolled and 61.4% (97) were male. Their mean (SD) age was 45.8 (14.9) years. The median dialysis vintage was 33.5 [10.7-63.2] months. The mean (SD) length of the kidneys was 85.1 (17.5) mm on the left and 81.2 (17.1) mm on the right. The prevalence of ACKD was 31.6% (n=50). Septated cysts (4), calcification of the wall of the cysts (2), irregular thick calcified wall (1), septated cysts with calcification (1) and hemorrhagic cyst (1) cysts were also observed. Dialysis vintage > 36 months (OR 7.1, 95% CI: 3.3 - 15.5) and male sex (OR 2.6, 95% CI: 1.2-5.6) were independently associated with ACKD.
UNASSIGNED: the prevalence of ACKD is high in a population of Cameroonians on maintenance. This result calls for the implementation of strategies to screen for the condition and its complications.

BACKGROUND: Screening for primary aldosteronism is based on measuring aldosterone-to-renin ratio. Non-suppressed renin may cause false negative screening results, and such patients may miss focused, potentially curable treatment. We investigated the association between renal cysts and non-suppressed plasma renin.
METHODS: Altogether, 114 consecutive patients with confirmed primary aldosteronism undergoing adrenal vein sampling were prospectively recruited between October 7, 2020 and December 30, 2021. During the procedure, plasma samples for renin analyses were collected from the right and left renal veins and the inferior vena cava. Renal cysts were identified using contrast-enhanced computed tomography.
RESULTS: Renal cysts were found in 58.2% of the 114 patients. Neither screening nor renal vein renin concentrations were significantly different in patients with and without cysts, or when the kidneys with and without cysts were evaluated. However, cysts were significantly more prevalent in the \"high-normal renin\" group (cut point 23.0 mU/L) than in the \"low to low-normal renin\" group (90.9%, n = 11 vs. 56.0%, n = 102, P = .027, respectively). All patients ≤50 years of age in the \"high-normal renin\" group had renal cysts. Strong correlations were found between renin concentrations in the right and left renal veins (r = .984), and between renin concentration and renin activity in the inferior vena cava (r = .817).
CONCLUSIONS: Renal cysts are found in the majority of patients with primary aldosteronism, and they may interfere with diagnostics, especially in patients aged 50 years or less. In patients with non-suppressed renin due to renal cysts, aldosterone-to-renin ratio below the diagnostic threshold does not always exclude the diagnosis of primary aldosteronism.

The term congenital ocular motor apraxia (COMA), coined by Cogan in 1952, designates the incapacity to initiate voluntary eye movements performing rapid gaze shift, so called saccades. While regarded as a nosological entity by some authors, there is growing evidence that COMA designates merely a neurological symptom with etiologic heterogeneity. In 2016, we reported an observational study in a cohort of 21 patients diagnosed as having COMA. Thorough re-evaluation of the neuroimaging features of these 21 subjects revealed a previously not recognized molar tooth sign (MTS) in 11 of them, thus leading to a diagnostic reassignment as Joubert syndrome (JBTS). Specific MRI features in two further individuals indicated a Poretti-Boltshauser syndrome (PTBHS) and a tubulinopathy. In eight patients, a more precise diagnosis was not achieved. We pursued this cohort aiming at clarification of the definite genetic basis of COMA in each patient.
Using a candidate gene approach, molecular genetic panels or exome sequencing, we detected causative molecular genetic variants in 17 of 21 patients with COMA. In nine of those 11 subjects diagnosed with JBTS due to newly recognized MTS on neuroimaging, we found pathogenic mutations in five different genes known to be associated with JBTS, including KIAA0586, NPHP1, CC2D2A, MKS1, and TMEM67. In two individuals without MTS on MRI, pathogenic variants were detected in NPHP1 and KIAA0586, arriving at a diagnosis of JBTS type 4 and 23, respectively. Three patients carried heterozygous truncating variants in SUFU, representing the first description of a newly identified forme fruste of JBTS. The clinical diagnoses of PTBHS and tubulinopathy were confirmed by detection of causative variants in LAMA1 and TUBA1A, respectively. In one patient with normal MRI, biallelic pathogenic variants in ATM indicated variant ataxia telangiectasia. Exome sequencing failed to reveal causative genetic variants in the remaining four subjects, two of them with clear MTS on MRI.
Our findings indicate marked etiologic heterogeneity in COMA with detection of causative mutations in 81% (17/21) in our cohort and nine different genes being affected, mostly genes associated with JBTS. We provide a diagnostic algorithm for COMA.

BACKGROUND: To investigate the inter- and intraobserver variability in comparison to an expert gold standard of the new and modified renal cyst Bosniak classification proposed for contrast-enhanced ultrasound findings (CEUS) by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) in 2020.
METHODS: 84 CEUS examinations for the evaluation of renal cysts were evaluated retrospectively by six readers with different levels of ultrasound expertise using the modified Bosniak classification proposed for CEUS. All cases were anonymized, and each case was rated twice in randomized order. The consensus reading of two experts served as the gold standard, to which all other readers were compared. Statistical analysis was performed using Cohen\'s weighted kappa tests, where appropriate.
RESULTS: Intraobserver variability showed substantial to almost perfect agreement (lowest kappa κ=0.74; highest kappa κ=0.94), with expert level observers achieving the best results. Comparison to the gold standard was almost perfect for experts (highest kappa κ=0.95) and lower for beginner and intermediate level readers still achieving mostly substantial agreement (lowest kappa κ=0.59). Confidence of rating was highest for Bosniak classes I and IV and lowest for classes IIF and III.
CONCLUSIONS: Categorization of cystic renal lesions based on the Bosniak classification proposed by the EFSUMB in 2020 showed very good reproducibility. While even less experienced observers achieved mostly substantial agreement, training remains a major factor for better diagnostic performance.
ZIEL: Untersuchung der Inter- und Intraobserver-Variabilität im Vergleich zu einem Experten-Goldstandard der neuen und modifizierten Bosniak-Klassifikation von Nierenzysten, die von der European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) im Jahr 2020 für Befunde im kontrastverstärkten Ultraschall (CEUS) vorgeschlagen wurde.
METHODS: 84 CEUS-Untersuchungen zur Beurteilung von Nierenzysten wurden retrospektiv von 6 Beobachtern mit unterschiedlicher Ultraschallexpertise anhand der für CEUS vorgeschlagenen modifizierten Bosniak-Klassifikation ausgewertet. Alle Fälle wurden anonymisiert, und jeder Fall wurde in randomisierter Reihenfolge 2-mal bewertet. Als Goldstandard diente der Konsens der Auswertung von 2 Experten, mit dem alle anderen Beobachter verglichen wurden. Die statistische Analyse erfolgte, sofern anwendbar, mittels Cohens Kappa.
UNASSIGNED: Die Intraobserver-Variabilität zeigte eine erhebliche bis nahezu perfekte Übereinstimmung (niedrigstes Kappa κ=0,74; höchstes Kappa κ=0,94), wobei die Beobachter auf Expertenebene die besten Ergebnisse erzielten. Der Vergleich mit dem Goldstandard war für Experten nahezu perfekt (höchstes Kappa κ=0,95) und für Anfänger und Fortgeschrittene geringer, wobei dennoch meist eine erhebliche Übereinstimmung erzielt wurde (niedrigstes Kappa κ=0,59). Das Konfidenzniveau war für die Bosniak-Klassen I und IV am höchsten und für die Klassen IIF und III am niedrigsten.
UNASSIGNED: Die Kategorisierung der zystischen Nierenläsionen nach der von der EFSUMB im Jahr 2020 vorgeschlagenen Bosniak-Klassifikation zeigte eine sehr gute Reproduzierbarkeit. Auch wenn selbst weniger erfahrene Beobachter meist eine erhebliche Übereinstimmung erzielten, ist die Ausbildung weiterhin ein wichtiger Faktor für eine bessere diagnostische Leistung.

Joubert syndrome (JS) is an autosomal recessive ciliopathy that mainly affects the morphogenesis of the cerebellum and brain stem. To date, mutations in at least 39 genes have been identified in JS; all these gene-encoding proteins are involved in the biogenesis of the primary cilium and centrioles. Recent studies using the mouse model carrying deleted or mutated JS-related genes exhibited cerebellar hypoplasia with a reduction in neurogenesis; however, investigating specific neuronal behaviors during their development in vivo remains challenging. Here, we describe an in vivo cerebellar electroporation technique that can be used to deliver plasmids carrying GFP and/or shRNAs into the major cerebellar cell type, granule neurons, from their progenitor state to their maturation in a spatiotemporal-specific manner. By combining this method with cerebellar immunostaining and EdU incorporation, these approaches enable the investigation of the cell-autonomous effect of JS-related genes in granule neuron progenitors, including the pathogenesis of ectopic neurons and the defects in neuronal differentiation. This approach provides information toward understanding the multifaceted roles of JS-related genes during cerebellar development in vivo.

We present the case of a young Caucasian patient with renal disease of unclear cause, with a final diagnosis of advanced benign nephroangiosclerosis established by renal biopsy. Due to the possibility of having hypertension in pediatric age (without study or treatment), with the renal biopsy findings, the genetic study showed polymorphisms risk in the APOL1 and MYH9, and also an unexpected diagnosis of a complete deletion of the NPHP1 gene in homozygosis, associated with the development of nephronophthisis. In conclusion, this case illustrates the importance of carrying out a genetic study in youngs patients with renal disease unclear cause, even having a histological diagnosis of nephroangiosclerosis.

Previous studies have found a relationship between hypertension or cardiovascular disease and simple renal cysts (SRCs) in health check-up population, but SRCs incidence is still controversially associated with serum uric acid (SUA) concentration in the nondiabetic participants. In this single-centre nest case-control study, serum uric acid levels were examined in relation to the incidence of SRCs in nondiabetic individuals.
Participants who underwent at least two renal ultrasound examinations with an interval of more than 12 months were enrolled. The results of clinical examinations, laboratory tests and abdominal ultrasound tests were recorded for each participant and analysed in this retrospective observation study.
A total of 144 control and 144 SRC patients were ultimately confirmed and included in further analysis. Hyperuricaemia (OR 2.846, 95% CI 1.519-5.332, p = 0.001) was significantly correlated with SRC formation according to multivariable analysis. In both the male and female groups, SRC patients had significantly higher serum uric acid levels compared with control subjects. In 54 SRC patients with cyst puncture, the serum uric acid concentration was positively correlated with the uric acid concentration in cyst fluid (r = 0.6144, p < 0.0001). The serum uric acid concentration was positively correlated with the maximum cyst diameter in the SRC patients (r = 0.4531, p < 0.0001).
In a nondiabetic population, hyperuricaemia was significantly independently associated with a higher SRCs incidence. In SRC participants with cyst puncture, the SUA level had a significantly positive correlation with the uric acid level in cyst fluid. In SRC patients, the SUA level had a significantly positive correlation with cyst maximum diameter.