暂无摘要。

UNASSIGNED: The Mayo imaging classification model (MICM) requires a prestep qualitative assessment to determine whether a patient is in class 1 (typical) or class 2 (atypical), where patients assigned to class 2 are excluded from the MICM application.
UNASSIGNED: We developed a deep learning-based method to automatically classify class 1 and 2 from magnetic resonance (MR) images and provide classification confidence utilizing abdominal T 2 -weighted MR images from 486 subjects, where transfer learning was applied. In addition, the explainable artificial intelligence (XAI) method was illustrated to enhance the explainability of the automated classification results. For performance evaluations, confusion matrices were generated, and receiver operating characteristic curves were drawn to measure the area under the curve.
UNASSIGNED: The proposed method showed excellent performance for the classification of class 1 (97.7%) and 2 (100%), where the combined test accuracy was 98.01%. The precision and recall for predicting class 1 were 1.00 and 0.98, respectively, with F 1 -score of 0.99; whereas those for predicting class 2 were 0.87 and 1.00, respectively, with F 1 -score of 0.93. The weighted averages of precision and recall were 0.98 and 0.98, respectively, showing the classification confidence scores whereas the XAI method well-highlighted contributing regions for the classification.
UNASSIGNED: The proposed automated method can classify class 1 and 2 cases as accurately as the level of a human expert. This method may be a useful tool to facilitate clinical trials investigating different types of kidney morphology and for clinical management of patients with autosomal dominant polycystic kidney disease (ADPKD).

暂无摘要。

Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group (p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure (p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.

Polycystic kidney disease is the most prevalent hereditary kidney disease globally and is mainly linked to the overexpression of a gene called PKD1. To date, there is no effective treatment available for polycystic kidney disease, and the practicing treatments only provide symptomatic relief. Discovery of the compounds targeting the PKD1 gene by inhibiting its expression under the disease condition could be crucial for effective drug development. In this study, a molecular docking and molecular dynamic simulation, QSAR, and MM/GBSA-based approaches were used to determine the putative inhibitors of the Pkd1 enzyme from a library of 1379 compounds. Initially, fourteen compounds were selected based on their binding affinities with the Pkd1 enzyme using MOE and AutoDock tools. The selected drugs were further investigated to explore their properties as drug candidates and the stability of their complex formation with the Pkd1 enzyme. Based on the physicochemical and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties, and toxicity profiling, two compounds including olsalazine and diosmetin were selected for the downstream analysis as they demonstrated the best drug-likeness properties and highest binding affinity with Pkd1 in the docking experiment. Molecular dynamic simulation using Gromacs further confirmed the stability of olsalazine and diosmetin complexes with Pkd1 and establishing interaction through strong bonding with specific residues of protein. High biological activity and binding free energies of two complexes calculated using 3D QSAR and Schrodinger module, respectively further validated our results. Therefore, the molecular docking and dynamics simulation-based in-silico approach used in this study revealed olsalazine and diosmetin as potential drug candidates to combat polycystic kidney disease by targeting Pkd1 enzyme.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary polycystic kidney disease characterized by renal enlargement, resulting in renal failure. In Indonesia, the exact prevalence of ADPKD is unknown due to limited reports on the disease. The aim of this study was to report a case of a patient with ADPKD with multiple complications. A 54-year-old male presented to the emergency room of Dr. Soetomo Academic General Hospital, Surabaya, Indonesia, with a chief complaint of dark-red-colored urine for one week. There was a progressive abdominal enlargement over the past five years, which had become more tense and rigid for the past one month. The patient had a history of fatigue and hypertension with routine follow-up. Physical examination on admission showed normal vital signs, and the abdominal assessment revealed a palpable hard mass approximately 4 cm in size in the right upper abdomen. Laboratory test indicated anemia, leukocytosis, lymphopenia, proteinuria, hematuria, leukocyturia, and elevated serum creatinine and urea levels. Abdominal imaging using ultrasonography, computed tomography (CT) scan, and magnetic resonance imaging (MRI) revealed bilateral kidney and liver enlargement containing multiple cysts, suggesting polycystic kidney and liver disease. There was a ruptured cyst in the middle of the left kidney pole with minimal ascites found in the CT scan. The MRI exhibited the presence of multiple cysts in both kidneys, partially filled with blood. The patient was diagnosed with ADPKD, gross hematuria, acute or chronic kidney disease (CKD), urinary tract infection (UTI), normochromic-normocytic anemia, and metabolic acidosis. Dietary control with high-calorie, high-protein, and low-salt diet; fluid balance; and other symptomatic medications were initiated. It is critical to be aware of risk factors associated with the rapid progression of ADPKD in order to be able to provide a favorable impact on the disease prevention and management.

Alport Syndrome (AS) is the most common genetic glomerular disease, and it is caused by COL4A3, COL4A4, and COL4A5 pathogenic variants. The classic phenotypic spectrum associated with AS ranges from isolated hematuria to chronic kidney disease (CKD) with extrarenal abnormalities. Atypical presentation of the disorder is possible, and it can mislead the diagnosis. Polycystic kidney disease (PKD), which is most frequently associated with Autosomal Dominant PKD (ADPKD) due to PKD1 and PKD2 heterozygous variants, is emerging as a possible clinical manifestation in COL4A3-A5 patients. We describe a COL4A5 novel familial frameshift variant (NM_000495.5: c.1095dup p.(Leu366ValfsTer45)), which was associated with AS and PKD in the hemizygous proband, as well as with PKD, IgA glomerulonephritis and focal segmental glomerulosclerosis (FSGS) in the heterozygous mother. Establishing the diagnosis of AS can sometimes be difficult, especially in the context of misleading family history and atypical phenotypic features. This case study supports the emerging genotypic and phenotypic heterogeneity in COL4A3-A5-associated disorders, as well as the recently described association between PKD and collagen type IV (Col4) defects. We highlight the importance of the accurate phenotyping of all family members and the relevance of next-generation sequencing in the differential diagnosis of hereditary kidney disease.

BACKGROUND: We focused on neutrophil gelatinase-associated lipocalin (NGAL) and autosomal dominant polycystic kidney disease (ADPKD) progression.
METHODS: ADPKD patients with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 were included. Serum NGAL level and NGAL to eGFR ratio (NGR), height-adjusted total kidney volume (hTKV) were assessed initially. Patients were followed-up for 5 years.
RESULTS: Sixty one patients were enrolled and initial eGFR was 73.6 (48.9-101.5) ml/min/1.73m2. EGFR declined by 3.7 mL/min/1.73m2 per year. Thirty four patients (55.7%) exhibited rapid progression. Rapid progression group had lower serum NGAL levels (p < 0.001) and higher hTKV (p < 0.001). Lower serum NGAL level was a risk factor for rapid progression (p < 0.001). NGR was not associated with rapid progression. Serum NGAL level was predictive in for rapid progression ROC analysis (cut-off <10.62 ng/mL).
CONCLUSIONS: Relatively lower serum NGAL levels can predict worse outcomes in ADPKD and can provide risk stratification in patients with ADPKD.

Autosomal polycystic kidney disease (ADPKD) is the most common genetic form of kidney failure, reflecting unmet needs in management. Prescription of the only approved treatment (tolvaptan) is limited to persons with rapidly progressing ADPKD. Rapid progression may be diagnosed by assessing glomerular filtration rate (GFR) decline, usually estimated (eGFR) from equations based on serum creatinine (eGFRcr) or cystatin-C (eGFRcys). We have assessed the concordance between eGFR decline and identification of rapid progression (rapid eGFR loss), and measured GFR (mGFR) declines (rapid mGFR loss) using iohexol clearance in 140 adults with ADPKD with ≥3 mGFR and eGFRcr assessments, of which 97 also had eGFRcys assessments. The agreement between mGFR and eGFR decline was poor: mean concordance correlation coefficients (CCCs) between the method declines were low (0.661, range 0.628 to 0.713), and Bland and Altman limits of agreement between eGFR and mGFR declines were wide. CCC was lower for eGFRcys. From a practical point of view, creatinine-based formulas failed to detect rapid mGFR loss (-3 mL/min/y or faster) in around 37% of the cases. Moreover, formulas falsely indicated around 40% of the cases with moderate or stable decline as rapid progressors. The reliability of formulas in detecting real mGFR decline was lower in the non-rapid-progressors group with respect to that in rapid-progressor patients. The performance of eGFRcys and eGFRcr-cys equations was even worse. In conclusion, eGFR decline may misrepresent mGFR decline in ADPKD in a significant percentage of patients, potentially misclassifying them as progressors or non-progressors and impacting decisions of initiation of tolvaptan therapy.

UNASSIGNED: Tolvaptan is the only US Food and Drug Administration-approved drug to slow the progression of autosomal dominant polycystic kidney disease (ADPKD), but it requires strict clinical monitoring due to potential serious adverse events.
UNASSIGNED: We aimed to share our experience in developing and implementing an electronic health record (EHR)-based application to monitor patients with ADPKD who were initiated on tolvaptan.
UNASSIGNED: The application was developed in collaboration with clinical informatics professionals based on our clinical protocol with frequent laboratory test monitoring to detect early drug-related toxicity. The application streamlined the clinical workflow and enabled our nursing team to take appropriate actions in real time to prevent drug-related serious adverse events. We retrospectively analyzed the characteristics of the enrolled patients.
UNASSIGNED: As of September 2022, a total of 214 patients were enrolled in the tolvaptan program across all Mayo Clinic sites. Of these, 126 were enrolled in the Tolvaptan Monitoring Registry application and 88 in the Past Tolvaptan Patients application. The mean age at enrollment was 43.1 (SD 9.9) years. A total of 20 (9.3%) patients developed liver toxicity, but only 5 (2.3%) had to discontinue the drug. The 2 EHR-based applications allowed consolidation of all necessary patient information and real-time data management at the individual or population level. This approach facilitated efficient staff workflow, monitoring of drug-related adverse events, and timely prescription renewal.
UNASSIGNED: Our study highlights the feasibility of integrating digital applications into the EHR workflow to facilitate efficient and safe care delivery for patients enrolled in a tolvaptan program. This workflow needs further validation but could be extended to other health care systems managing chronic diseases requiring drug monitoring.