Among 158 distinct variants, 80 (50.6%) were previously unreported, confirming broad allelic heterogeneity. Eleven patients showed more than one variant. Segregation analysis indicated biallelic disease in five patients, digenic in one, de novo variant with unknown phase in two. Furthermore, our NGS protocol allowed the identification of two patients with somatic mosaicism, which was undetectable with Sanger sequencing. Among patients without PKD1/PKD2 variants, we identified three with possible alternative diagnosis: a patient with biallelic mutations in PKHD1, confirming the overlap between recessive and dominant PKD, and two patients with variants in ALG8 and PRKCSH, respectively. Genotype-phenotype correlations showed that patients with PKD1 variants predicted to truncate (T) the protein experienced end-stage renal disease 9 years earlier than patients with PKD1 non-truncating (NT) mutations and >13 years earlier than patients with PKD2 mutations. ADPKD-PKD1 T cases showed a disease onset significantly earlier than ADPKD-PKD1 NT and ADPK-PKD2, as well as a significant earlier diagnosis. These data emphasize the need to combine clinical information with genetic data to achieve useful prognostic predictions.

Background Adult polycystic kidney disease (ADPKD) still represents a major cause of renal failure and intracranial aneurisms (IA) have a higher prevalence in ADPKD than in the general population. Current guidelines suggest performing brain MRI only in the subjects with a positive familiar history of IAs or subarachnoid hemorrhage (SAH). This is a retrospective case-control analysis to evaluate the usefulness of a MR screening program in ADPKD patients. Methods We retrospectively analyzed all ADPKD patients followed in our outpatient clinic between 2016 and 2019 who underwent a brain MRI screening. We evaluated the presence of IAs and others brain abnormalities and compared our results with a non-ADPKD population (n = 300). We performed univariate and multivariate regression analysis to evaluate if general and demographic features, laboratory findings, clinical parameters and genetic test results correlated with IAs or other brain abnormalities presence. Results Among the patients evaluated 17 out of 156 (13.6%) ADPKD patients had IAs, compared to 16 out of 300 (5.3%) non-ADPKD controls (p < 0.005). Considering ADPKD patients presenting IAs, 12 (70.6%) had no family history for IAs or SAH. Genetic analysis was available for 97 patients: in the sub-population with IAs, 13 (76.5%) presented a PKD1 mutation and none a PKD2 mutation. We found that arachnoid cysts (AC) (p < 0.001) and arterial anatomical variants (p < 0.04) were significantly more frequent in ADPKD patients. Conclusion In our population ADPKD patients showed a higher prevalence of IAs, AC and arterial variants compared to non-ADPKD. Most of the IAs were found in patients presenting a PKD1 mutation. We found a significant number of alterations even in those patients without a family history of IAs or SAH. The practice of submitting only patients with familial IAs or kidney transplantation candidates to MRI scan should be re-evaluated.

Pancake kidney is a very rare congenital anomaly involving complete fusion of medial renal parenchyma. The interface is devoid of any intervening septum. As described, the kidneys form a single lobulated mass in pelvic location. However, dual collecting systems are retained, and the shortened, anteriorly seated ureters enter the bladder normally. This condition is usually discovered incidentally but may confer a heightened susceptibility to recurrent urinary tract infections or stone formation, given the likelihood of anomalous collecting system rotation and the potential for ureteral stasis or obstruction. Excretory urography, the customary method of detection, has been replaced by ultrasonography, CT, MRI, and radionucleotide scanning. Herein, we present a male patient with a pelvic pancake kidney, never symptomatic. A conservative approach of regular follow up visits and laboratory testing was elected, thus avoiding any unnecessary investigations or extensive surgery.

Honeycombing is a dynamic process in which the overall trend is represented by a dimensional increase in cystic pattern; however, single cysts may have a different evolution (enlargement, reduction or complications). This behaviour could be explained by the variety of the pathogenetic processes underlying honeycombing, with cysts that may present abnormal communication with the airway, including the development of a check-valve mechanism.

Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is a multisystemic disease characterized by the progressive development of bilateral renal cysts, resulting in enlargement of the kidney volume due to cystic formations, hypertension, haematuria, and loss of renal function. Recent advances in genomics have contributed to have a better understanding of the pathogenesis of the disease suggesting new treatment strategies to inhibit or delay cysts formation and expansion.Since 2015, the European Medicines Agency approved Vaptans as therapy to slow the growth of kidney volume and the decline in kidney function in patients defined rapid progressors. In 2016 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups on Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ ERBP) published a position statement for definition of rapid progression. These recommendations included two algorithms to assess indications for initiation of ADPKD treatment. They selected three criteria based on: 1) the relationship between TKV(total kidney volume) and the decline in renal function according CRISP study, using Mayo Clinic Score 2) eGFR slope with an average ≥2.5 mL/min/1.73 m2/ yearly loss of renal function over a period of 5 yearsor 3) the link between genetic mutation and clinical information study using Propkd score.A 5 –years follow-up is not always available to achieve the criteria for rapid progressor, therefore the use of scores in clinical practice is widespread.In this scenario both scores (MAYO and PRO-PKD) are able to define rapid progressor patients and it is possible to use them alternatively as reported in literature. The aim of this study is to evaluate the prognostic scores in a real life experience. Method All ADPKD patients in follow-up in our Nephrology Unit from January 2017 to July 2019 were included in the study. Descriptive statistics were used to summarize demographic and clinical characteristics. Therefore we classified them for TKV, genetic mutation, renal function, Mayo score and Propkd score. Rapid progression was defined as 1C-D-E Mayo and high risk PRO PKD while non rapid progressors was 1A-1B mayo and low and intermediate PRO-PKD. Kappa statistic was used to determinate the concordance between Mayo and PROPKD score. Change in renal function within patients with the same class of score where analysed using Paired Wilcoxon signed rank sum test. Results We examined75 patients, 78% between 18-50 years, equally distributed for sex. The results shown thatdisease was more frequent familiar (88 %) witha percentage of mutations of PKD1 versus PKD2 mutation (90,7%/9,3%). 31patients (41%) had a GFR between 45-89 ml/min, 52patients (69%) achieved the criteria for nephromegaly according guideline (TKV &gt; 750CC). Respectively 76% (57pt) and 21%(16pt) were defined as rapid progressors for Mayo score ad Propkd score. The slope of GFR was worse in patients defined rapid progressor in spite of non rapidprogressor according MAYO score (-2,8 ml/min vs 0,3 ml/min) as for propkd classification (-3 vs - 1,75ml/min). Only for 15 patients the results were concordant for this two scores,43 patients identified as rapid progressor for Mayo score were non rapid progressor for Propkd score, in the same way 2 patients classified for Propkd were not rapid progressor for Mayo score. K of Coen of 0,07. Conclusion High risk patients present a significant decline in renal function in the first year with both score systems, confirming results of previous studies. Currently the scores used to define rapid progressors select patients differently. Concordance between scores il low (K of Cohen 0,076). The Propkd score is more selective compared to Mayo score. NeverthelessProPKD allows to identify some rapid progressor patients excluded from the use of the Mayo score only. The combined use of scoring may however increases the ability to identify progressive patients.