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Background: Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 500–4000 people worldwide. Genetic mutation is a biomarker for predicting renal dysfunction in patients with ADPKD. In this study, we performed a genetic analysis of Japanese patients with ADPKD to investigate the prognostic utility of genetic mutations in predicting renal function outcomes. Methods: Patients clinically diagnosed with ADPKD underwent a panel genetic test for germline mutations in PKD1 and PKD2. This study was conducted with the approval of the Ethics Committee of Juntendo University (no. 2019107). Results: Of 436 patients, 366 (83.9%) had genetic mutations. Notably, patients with PKD1 mutation had a significantly decreased ΔeGFR/year compared to patients with PKD2 mutation, indicating a progression of renal dysfunction (−3.50 vs. −2.04 mL/min/1.73 m2/year, p = 0.066). Furthermore, PKD1 truncated mutations had a significantly decreased ΔeGFR/year compared to PKD1 non-truncated mutations in the population aged over 65 years (−6.56 vs. −2.16 mL/min/1.73 m2/year, p = 0.049). Multivariate analysis showed that PKD1 mutation was a more significant risk factor than PKD2 mutation (odds ratio, 1.81; 95% confidence interval, 1.11–3.16; p = 0.020). Conclusions: The analysis of germline mutations can predict renal prognosis in Japanese patients with ADPKD, and PKD1 mutation is a biomarker of ADPKD. [ABSTRACT FROM AUTHOR]

ADPKD is a genetic disorder with a molecular complexity that remains poorly understood. In this study, we sampled renal cells to construct a comprehensive and spatiotemporally resolved gene expression atlas in whole Pkd1 mutant polycystic mouse kidneys at single-cell resolution. We characterized cell diversity and identified novel collecting duct (CD) cell subtypes in cystic kidneys. We further found that CD cells appear to take different cell fate trajectories, and the first and the most important step might take place around day 14 in Pkd1 homozygous kidneys. After that day, increased numbers of CD cells showed highly proliferative and fibrotic characteristics, as detected in later-stage Pkd1 homozygous kidneys, both of which should contribute to cyst growth and renal fibrosis. With a newly developed modeling algorithm, called CellChat Explorer, we identify cell-to-cell communication networks mediated by the ligand receptor, such as MIF-CD44/CD74, in cystic kidneys, and confirm them via the expression patterns of ligands and receptors in four major cell types, which addresses the key question as to whether and how Pkd1 mutant renal epithelial cells affect their neighboring cells. The allele-specific gene expression profiles show that the secretion of cytokines by Pkd1 mutant epithelial cells may affect the gene expression profiles in recipient cells via epigenetic mechanisms, and vice versa. This study can be used to drive precision therapeutic targeting of ADPKD. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid‐filled cyst development leading to end‐stage renal disease. The rate of disease progression in ADPKD exhibits high inter‐ and intrafamilial variability suggesting involvement of modifier genes and/or environmental factors. Renal hypouricemia (RHUC) is an inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and chronic kidney disease (CKD). However, the two disorders have distinct and well‐delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and RHUC (type 1) in a single individual have been reported. We report a family with two members: an ADPKD 24‐year‐old female which presented bilateral renal cysts in utero and hypouricemia since age 5, and her mother with isolated hypouricemia. Next‐generation sequencing identified two mutations in two genes PKD1 and SLC2A9 in this patient and one isolated SLC2A9 mutation in her mother, showing RHUC type 2, associated to CKD. The coexistence of these two disorders provides evidence of SLC2A9 variant could act as a modifier change, with synergistic actions, that could promote cystogenesis and rapid ADPKD progression. This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. Methods: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1β, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%. Results: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45–5.17] vs. 4.2 [3.45–8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1–27.49] vs. 24.9 [16.23–39.4] pg/mL; p = 0.004) and IL-1β (21.33 [15.8–26.4] vs. 26.78 [18.22–35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09–1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09–9.87]; p = 0.035). Conclusions: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation. [ABSTRACT FROM AUTHOR]

Feline polycystic kidney disease (PKD), an inherited autosomal dominant disease, has been reported to occur mostly in Persian or Persian related cats, and to be associated with a mutation from C to A at position 10063 in exon 29 of the feline PKD1 gene (PKD1 mutation). Many clinical cases have been recognized in Japan, but the mutation rate in cats has not been reported. The objective of this study was to determine epidemiological characteristics and clinical features in cats with the PKD1 mutation. Referring veterinarians sent blood samples of 377 cats for the PKD1 gene evaluation. The blood samples were from 159 cats with renal cysts confirmed by ultrasonography, 60 cats without renal cysts, and 158 cats that did not undergo ultrasonography. In total, 150 cats carried the PKD1 mutation and the signalment, site and number of renal cysts, and results of blood test were evaluated in cats with the PKD1 mutation. The breeds with the highest rate of the PKD1 mutation were Persian (46%), Scottish Fold (54%) and American Shorthair cats (47%). However, mixed breed cats also showed high rates of the PKD1 mutation. Of cats with the mutation, the incidence of high plasma creatinine (=1.6 mg/dl) was greater in cats =3 years old, although a few cats =9 years of age had low plasma creatinine (<1.6 mg/dl). The coincidence of renal and hepatic cysts was 12.6%, with the high prevalence in Persian cats (31%). [ABSTRACT FROM AUTHOR]

Turner syndrome is a chromosomal disorder that involves multiple organ systems and is typically associated with short stature. A multidisciplinary approach with regular screening and surveillance is key to managing this condition's multiple comorbidities. We present a case of a young girl with Turner syndrome and associated short stature on growth hormone treatment who presented with cystic renal disease found to be autosomal dominant kidney disease. We propose reevaluation of renal screening guidelines in this population due to the potential association of growth hormone and cyst proliferation. [ABSTRACT FROM AUTHOR]

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development and progressive enlargement of cysts in the kidneys. The diagnosis of ADPKD is usually determined by criteria of renal ultrasound imaging of the development and number of cysts. However, in atypical cystic disease, for the recognition of ADPKD, DNA-based assays may be required Materials and methods: In the present study PCR amplified fragments of the PKD1 gene (covering exons 15 and 43- 44) from genomic DNA of 134 Lower Silesia patients were analyzed for mutations and polymorphisms. Among them, the clinical significance of different PKD1 mutations was investigated in 81 persons Results: Eight new, previously undescribed, and 2 recurrent mutations were discovered. The presence of 3 known polymorphisms was confirmed. Seven of the 8 new discovered mutations were heterozygous Discussion: The results of the present study demonstrated that the frequency of genetic abnormalities in the analyzed fragments of the PKD1 gene in the Lower Silesian population is smaller than previously reported. Moreover, we could not detect deletions and insertions, which are often present is these regions of the PKD1 gene, which may be due to the limited number of screened patients. We conclude that none of the discovered changes in the PKD1 gene had any effect on clinical phenotype of the disease [ABSTRACT FROM AUTHOR]

Turner syndrome is a chromosomal disorder that involves multiple organ systems and is typically associated with short stature. A multidisciplinary approach with regular screening and surveillance is key to managing this condition's multiple comorbidities. We present a case of a young girl with Turner syndrome and associated short stature on growth hormone treatment who presented with cystic renal disease found to be autosomal dominant kidney disease. We propose reevaluation of renal screening guidelines in this population due to the potential association of growth hormone and cyst proliferation., (Copyright © 2020 Baylor University Medical Center.)

Feline polycystic kidney disease (PKD), an inherited autosomal dominant disease, has been reported to occur mostly in Persian or Persian related cats, and to be associated with a mutation from C to A at position 10063 in exon 29 of the feline PKD1 gene (PKD1 mutation). Many clinical cases have been recognized in Japan, but the mutation rate in cats has not been reported. The objective of this study was to determine epidemiological characteristics and clinical features in cats with the PKD1 mutation. Referring veterinarians sent blood samples of 377 cats for the PKD1 gene evaluation. The blood samples were from 159 cats with renal cysts confirmed by ultrasonography, 60 cats without renal cysts, and 158 cats that did not undergo ultrasonography. In total, 150 cats carried the PKD1 mutation and the signalment, site and number of renal cysts, and results of blood test were evaluated in cats with the PKD1 mutation. The breeds with the highest rate of the PKD1 mutation were Persian (46%), Scottish Fold (54%) and American Shorthair cats (47%). However, mixed breed cats also showed high rates of the PKD1 mutation. Of cats with the mutation, the incidence of high plasma creatinine (≥1.6 mg/dl) was greater in cats ≥3 years old, although a few cats ≥9 years of age had low plasma creatinine (<1.6 mg/dl). The coincidence of renal and hepatic cysts was 12.6%, with the high prevalence in Persian cats (31%).