Polycystic kidney disease (PKD) is a common hereditary kidney disease. Although PKD occurrence is associated with certain gene mutations, its onset regulatory mechanisms are still not well understood. Here, we first report that the key enzyme geranylgeranyl diphosphate synthase (GGPPS) is specifically expressed in renal tubular epithelial cells of mouse kidneys. We aimed to explore the role of GGPPS in PKD. In this study, we established a Ggppsfl/fl:Cdh16cre mouse model and compared its phenotype with that of wild-type mice. A Ggpps-downregulation HK2 cell model was also used to further determine the role of GGPPS. We found that GGPPS was specifically expressed in renal tubular epithelial cells of mouse kidneys. Its expression also increased with age. Low GGPPS expression was observed in human ADPKD tissues. In the Ggppsfl/fl:Cdh16cre mouse model, Ggpps deletion in renal tubular epithelial cells induced the occurrence and development of renal tubule cystic dilation and caused the death of mice after birth due to abnormal renal function. Enhanced proliferation of cyst-lining epithelial cells was also observed after the knockout of Ggpps. These processes were related to the increased rate of Rheb on membrane/cytoplasm and hyperactivation of mTORC1 signaling. In conclusion, the deficiency of GGPPS in kidney tubules induced the formation of renal cysts. It may play a critical role in PKD pathophysiology. A novel therapeutic strategy could be designed according to this work.

Non-tumorous kidney diseases include a variety of conditions affecting both the structure and function of the kidneys, thereby causing a range of health-related problems. Positron emission tomography/computed tomography (PET/CT) has emerged as a potential diagnostic tool, offering a multifaceted approach to evaluating non-tumorous kidney diseases. Its clinical significance extends beyond its conventional role in cancer imaging, enabling a comprehensive assessment of renal structure and function. This review explores the diverse applications of PET/CT imaging in the evaluation of non-cancerous kidney diseases. It examines PET/CT\'s role in assessing acute kidney injuries, including acute pyelonephritis and other forms of nephritis, as well as chronic conditions such as immune complex-mediated glomerulonephritis and chronic kidney disease. Additionally, the review delves into PET/CT\'s utility in evaluating complications in renal transplant recipients, identifying renal histiocytosis and detecting renal amyloidosis. The current review aims to promote further research and technological advancements to popularize PET/CT\'s clinical utility in diagnosing and treating non-tumorous kidney diseases.

Xanthogranulomatous pyelonephritis (XGP) is an extremely rare, chronic granulomatous inflammatory condition thought to arise secondary to a combination of obstruction, recurrent bacterial infection and an incomplete immune response although the etiology of XGP is more complex. We would like to report a case of XGP occurring in a patient with polycystic kidney disease (PCKD), which has not been previously documented in etiology. A 29-year-old woman presented to our hospital with right upper quadrant pain for 5 days. She had experienced a low-grade fever, generalized weakness, and myalgia throughout her body for 2 weeks. She had no history of renal stones or recurrent UTIs. Contrast-enhanced CT revealed a well-enhancing large septated cystic mass in the right kidney and numerous cysts in the liver and both kidneys. Open right radical nephrectomy was performed due to the suspicion of renal cell carcinoma, as there was no response to antibiotics over 7 days. Gross specimen demonstrated architectural distortion due to xanthomatous nodules and a dilated pelvico-calyceal system filled with pus and blood. Microscopic examination revealed infiltration of neutrophils and lipid-laden macrophages. The patient is currently being followed up in the outpatient clinic without recurrence of XGP. This is the first reported case of XGP in a patient with underlying PCKD. Physicians should consider PCKD as a potential underlying cause of XGP.

UNASSIGNED: The aim of this study was to determine the long-term effect of increasing water intake in patients with autosomal dominant polycystic kidney disease (ADPKD) on longitudinal changes in health-related quality of life (HRQoL) in the setting of a clinical trial.
UNASSIGNED: Self-completed HRQoL (using the KDQoL-SF, v.1.3 questionnaire) was assessed annually in participants of a 3-year randomized controlled clinical trial (n = 187), allocated (1:1) either to increase water intake to reduce urine osmolality to ≤270 mosmol/kg (implemented by dietetic coaching, self-monitoring tools, text messaging) or continue usual water intake.
UNASSIGNED: Overall, 96% and 81.8% of participants (n = 187) completed the questionnaire at the baseline and final study visits, respectively. At baseline, the physical component summary score (PCS) and mental component summary score (MCS) were similar in the two groups (P > 0.05) and the five dimensions with the lowest scores in both groups were: energy and fatigue; general and overall health; sleep; emotional well-being; and pain. Within each group, there were no longitudinal changes over time. At the final visit, the PCS was higher in the increased water intake group (51.3 ± 7.6, mean ± standard deviation) compared to the usual water intake group 48.8 ± 9.3; P = 0.037) whereas the MCS was numerically similar. The improvement in the PCS was due to higher sub-scale values for physical functioning and pain (both P < 0.05). By multivariate analysis, only baseline PCS and height-corrected total kidney volume were associated with the final PCS (P < 0.05).
UNASSIGNED: HRQoL scores remained stable over a 3 year period, and were not adversely affected by the intervention to increase water intake. Future studies should evaluate the clinical significance of the higher PCS in the increased water intake group.

BACKGROUND: The kidneys are the genitourinary organs most susceptible to trauma. One case is high-grade kidney trauma that can lead to kidney failure, such as Polycystic Kidney Disease (PKD). Here, we report a case of high-grade kidney trauma on PKD.
METHODS: A 28-year-old man was involved in a traffic accident and was diagnosed with a left kidney rupture. There was minimal free fluid in the abdominal cavum and left pleural effusion. The results of USG in the left kidney showed a rupture in the posterior part of the cortex-medulla reaching the calyx, accompanied by a left posterior peri-renal hematoma and a PKD in the right kidney. In the CT scan examination, the hematoma extended to the lower left retroperitoneum and peripancreatic. The size of the left kidney was enlarged. In the right kidney, PKD was accompanied by an enlargement of the kidney size, but no rupture was obtained. Patient had been diagnosed with high-grade kidney trauma (AAST Grade IV). The patient was given conservative therapy. He was alive and discharged from the hospital.
UNASSIGNED: Non-operative management (NOM) is the standard in kidney trauma management, with good outcomes in preventing morbidity and mortality. The trend toward this procedure results in a decrease in the number of unnecessary nephrectomies and a potential improvement in the quality of patient inhalation. Ultrasound and CT scan examinations are important markers.
CONCLUSIONS: The management of high-grade kidney trauma on PKD can be carried out conservatively and show good patient outcomes.

Autosomal dominant polycystic kidney disease (ADPKD) affects 1 in 1000 adults. Most cases result from causative PKD1 or PKD2 variants. HNF1B, GANAB and ALG9 variants are also associated with ADPKD. Recent evidence indicates that monoallelic loss-of-function (LoF) IFT140 variants are a cause for non-syndromic ADPKD. We describe 368 patients with IFT140 LoF variants and a spectrum of phenotypic findings that support the association of IFT140 with PKD. We reviewed patients with an unknown cause for their cystic disease and those with heterozygous LoF IFT140 variants classified as pathogenic or likely pathogenic from a cohort that received genetic testing using a panel of 385 renal disease-associated genes. IFT140 LoF variants were significantly enriched in patients with cystic disease when compared with those without cystic disease. A cystic phenotype was reported in 223 of the 368 (60.6%) individuals harboring an IFT140 LoF variant, 98% of which had no other identified cause for their cystic disease. Of 122 unique LoF IFT140 variants identified, 56 (46%) were frameshift, 38 (31%) nonsense, 22 (18%) splice site and 6 (5%) exon-level deletions. Only six IFT140 individuals were reported with end-stage kidney disease, consistent with observed milder clinical presentations in IFT140-related PKD. This study offers further evidence for the involvement of LoF IFT140 variants in PKD, particularly when no additional molecular etiology has been identified.

UNASSIGNED: Intracranial aneurysms (IA) are a common complication of autosomal dominant polycystic kidney disease (ADPKD). Screening protocols that exist for IA in ADPKD patients are an important component of disease monitoring to enable appropriate preventative measures and precautions to avoid IA rupture with its associated morbidly and mortality.
UNASSIGNED: The aims of this review are to analyse the different types of screening protocols that exist by referencing the lead time between IA diagnosis and rupture in ADPKD patients, the purpose and importance of screening, the types of imaging modalities used, and patient outcomes. We will also consider cost-effectiveness and its relation in establishing a screening protocol as this is an important factor.
UNASSIGNED: A literature search was conducted in April 2022 using PubMed, BMJ electronic databases, Dynamed, NICE guidelines and Cochrane databases for articles published between 1990 and 2022 with special interest in IA, ADPKD and screening protocols. The only exclusion criteria were patients who were diagnosed with ADPKD <30 years of age.
UNASSIGNED: Our findings suggest that if a patient with ADPKD presents with either a positive family history of IA and/or cerebrovascular events and/or is above 40 years of age, then they should have a magnetic resonance angiography (MRA) scan every 5 years to monitor IA formation and growth with annual follow-ups. This may contribute to decreased patient morbidity and mortality in ADPKD-positive patients.
UNASSIGNED: While there is some evidence proving that screening protocols decrease the morbidity and mortality of ADPKD patients, none have been recommended. The screening protocol suggested in this review should be used as a guideline for future studies that will try and establish a national or international guidelines that can be used by nephrologists and neurosurgeons worldwide.

State-of-the-art mass spectrometers combined with modern bioinformatics algorithms for peptide-to-spectrum matching (PSM) with robust statistical scoring allow for more variable features (i.e., post-translational modifications) being reliably identified from (tandem-) mass spectrometry data, often without the need for biochemical enrichment. Semi-specific proteome searches, that enforce a theoretical enzymatic digestion to solely the N- or C-terminal end, allow to identify of native protein termini or those arising from endogenous proteolytic activity (also referred to as \"neo-N-termini\" analysis or \"N-terminomics\"). Nevertheless, deriving biological meaning from these search outputs can be challenging in terms of data mining and analysis. Thus, we introduce TermineR, a data analysis approach for the (1) annotation of peptides according to their enzymatic cleavage specificity and known protein processing features, (2) differential abundance and enrichment analysis of N-terminal sequence patterns, and (3) visualization of neo-N-termini location. We illustrate the use of TermineR by applying it to tandem mass tag (TMT)-based proteomics data of a mouse model of polycystic kidney disease, and assess the semi-specific searches for biological interpretation of cleavage events and the variable contribution of proteolytic products to general protein abundance. The TermineR approach and example data are available as an R package at https://github.com/MiguelCos/TermineR.

Kidney cysts in humans are mainly caused by inheritable polycystic kidney disease. Although they are a regular finding in laboratory mice, their occurrence upon dissection has not been systematically investigated, yet. Therefore, the aim of this report was to investigate on prevalence, phenotype and aetiology of spontaneously occurring kidney cysts in mice by retrospectively analysing the laboratory-receipt tables of the in-house laboratory of a central animal facility in North Rhine-Westphalia, Germany, years 2009-2019. A percentage of 0.4% of dissected mice displayed kidney cysts, with more male than female animals affected and average age equal to that of all dissected animals. Preliminary report in half of the cases was distended abdomen, and a few individuals displayed additional pathologic alterations of kidneys, most commonly dilated renal pelvis, or extrarenal comorbidities. Kidney cysts occurred independently of a renal phenotype of the transgenic strain or presence of infectious agents in health monitoring. To conclude, kidney cysts were characterized as harmless for affected mice but, as inheritability is suggested according with the literature, affected animals should be excluded from breeding.

BACKGROUND: Concomitant Wilms tumor (WT) and autosomal dominant polycystic kidney disease (ADPKD) is exceedingly rare, presenting a diagnostic and technical challenge to pediatric surgical oncologists. The simultaneous workup and management of these disease processes are incompletely described.
METHODS: We performed a retrospective analysis of patients treated at our institution with concomitant diagnoses of WT and ADPKD. We also review the literature on the underlying biology and management principles of these conditions.
RESULTS: We present three diverse cases of concomitant unilateral WT and ADPKD who underwent nephrectomy. One patient had preoperative imaging consistent with ADPKD with confirmatory testing postoperatively, one was found to have contralateral renal cysts intraoperatively with confirmatory imaging post nephrectomy, and one was diagnosed in childhood post nephrectomy. All patients are alive at last follow-up, and the patient with longest follow-up has progressed to end-stage kidney failure requiring transplantation and dialysis in adulthood. All patients underwent germline testing and were found to have no cancer predisposition syndrome or pathogenic or likely pathogenic variants for WT.
CONCLUSIONS: Concomitant inheritance of ADPKD and development of WT are extremely rare, and manifestations of ADPKD may not present until late childhood or adulthood. ADPKD is not a known predisposing condition for WT. When ADPKD diagnosis is made by family history, imaging, and/or genetic testing before WT diagnosis and treatment, the need for extensive preoperative characterization of cystic kidney lesions in children and increased risk of post-nephrectomy kidney failure warrant further discussion of surgical approach and perioperative management strategies.