Project description:To investigate the transcriptome differences between wild-type and Vhl mutant mice in kidney stones process, we established CaOx-induced nephrolithiasis mouse model and performed RNA-sequencing.
Project description:Cystinuria is a rare renal genetic disease caused by mutations in cystine transporter genes and characterized by defective cystine reabsorption leading to kidney stones. In 14% of cases patients undergo nephrectomy, but given the difficulty to predict the evolution of the disease, the identification of markers of kidney damage would improve the follow up of patients with a higher risk. The aim of the present study is to develop a robust, reproducible and non-invasive methodology for proteomic analysis of urinary exosomes using high resolution mass spectrometry. A clinical pilot study, conducted on 8 cystinuria patients vs. 10 controls, highlighted 165 proteins, of which 38 were up-regulated, that separate cystinuria patients from controls, and further discriminate between severe and moderate forms of the disease. These proteins include markers of kidney injury, circulating proteins and a neutrophil signature. Analysis of selected proteins by immunobloting, performed on six additional cystinuria patients, validated the mass spectrometry data. To our knowledge, this is the first successful proteomic study in cystinuria unmasking potential role of inflammation in this disease. The workflow we have developed is applicable to investigate urinanry exosomes in different renal diseases and to search for diagnostic/prognostic markers.
Project description:Microarray analysis was used to assess the expression levels of lncRNAs and mRNAs in three pairs of Randall’s plaques tissues of CaOx renal stones patients and normal renal papillary tissues.Randall’s Plaques tissues of CaOx renal stones patients were obtained from patients with idiopathic CaOx renal stone who underwent percutaneous nephrolithotomy. Normal renal papillary tissues were obtained from patients with renal tumor who underwent nephrectomy, the tissues were obtained from papillary without tumor invasion. Randall’s Plaques tissues of CaOx renal stones patients were obtained from patients with idiopathic CaOx renal stone who underwent percutaneous nephrolithotomy. Normal renal papillary tissues were obtained from patients with renal tumor who underwent nephrectomy, the tissues were obtained from papillary without tumor invasion.
Project description:BACKGROUND:The long-held notion that, without urinary tract or circulatory infection, bladder urine and blood are sterile biofluids has been disproven. There have been no previous reports on the kidney pelvis urinary microbiome after bladder disinfection in kidney stone patients. This study aimed to determine whether a kidney pelvis urinary microbiome is present after eliminating the influence of the bladder urinary microbiome, whether the microbiome composition is different in patients with stone kidney pelvis (SKP) and non-stone kidney pelvis (NSKP), and the correlation between SKP and patient clinical characteristics. RESULTS:Comparisons of bacterial diversity and community structure exhibited that urine in bladder was similar to SKP and NSKP. However, the comparisons showed that urine samples were different from blood. The most common operational taxonomic units were shared by all three types of urine samples. Corynebacterium was significantly higher in SKP compared to NSKP. Several bacteria were associated with patient characteristics, including Lactobacillus, which was positively correlated with fasting blood glucose, and Prevotella was negatively correlated with BMI. Lactobacillus was significantly higher in SKP compared to blood but not in NSKP compared to blood. CONCLUSIONS:The composition of the kidney pelvis urinary microbiome after disinfection of the bladder and its similarity to the bladder microbiome indicate that bladder urine can be used to replace kidney pelvis urine in microbiome research. Additionally, the comparison of SKP and NSKP and clinical associations suggest that the occurrence of kidney stones is responsible for the SKP urinary microbiome.
Project description:Cystinuria is a rare renal genetic disease caused by mutations in cystine transporter genes and characterized by defective cystine reabsorption leading to kidney stones. In 14% of cases patients undergo nephrectomy, but given the difficulty to predict the evolution of the disease, the identification of markers of kidney damage would improve the follow up of patients with a higher risk. The aim of the present study is to develop a robust, reproducible and non-invasive methodology for proteomic analysis of urinary exosomes using high resolution mass spectrometry. A clinical pilot study, conducted on 8 cystinuria patients vs. 10 controls, highlighted 165 proteins, of which 38 were up-regulated, that separate cystinuria patients from controls, and further discriminate between severe and moderate forms of the disease. These proteins include markers of kidney injury, circulating proteins and a neutrophil signature. Analysis of selected proteins by immunobloting, performed on six additional cystinuria patients, validated the mass spectrometry data. To our knowledge, this is the first successful proteomic study in cystinuria unmasking potential role of inflammation in this disease. The workflow we have developed is applicable to investigate urinanry exosomes in different renal diseases and to search for diagnostic/prognostic markers.