Human - murine concordance of molecular signatures in nerve-sparing murine partial bladder outlet obstruction (NeMO)

Recently we demonstrated the utility of a nerve-sparing mid-urethra model of partial outlet obstruction (NeMO) that has high consistency and minimal mortalities, unlike the traditional model proximal to the bladder neck. Our goal was to uncover potential therapeutic targets by investigating the genome wide transcriptional changes and pathways altered in NeMO to compare with published human bladder obstruction data. We performed RNAseq and analysed the differentially upregulated and downregulated genes for associated pathways, transcription factor binding site analysis (TFBS), upstream regulators and Gene Set Enrichment Analysis (GSEA). NeMO increased bladder mass, relative bladder mass and hyperactivity, and decreased voiding efficiency. In NeMO vs. sham, 831 genes were differentially expressed (adjusted p<0.05) and correlated significantly with at least one physiologic parameter. Gene ontology revealed an enrichment for matrix pathways in the upregulated genes, and for cardiac contraction, oxidative phosphorylation and pyruvate metabolism in downregulated genes. TFBS analysis revealed a differential regulation of up vs downregulated genes, with KLF4 strongly associated with the downregulated genes. Downregulated genes of Human bladder obstruction were also associated with the TFBS of KLF4. GSEA of the NeMO gene set confirmed the DAVID results, but also showed a cluster of cytokine activation genes. In human bladder underactive obstruction, cytokines were also highly upregulated. The common cytokine pathway upregulation provided an example of the use of RNAseq for uncovering potential new therapeutic targets. As TNF and the innate immune pathways were strongly implicated in both human and mouse, and TNF is produced by macrophages, we depletion macrophages with clodronate (CL) during NeMO. Although CL did not block hypertrophy, it significantly decreased NeMO-induced hyperactive voiding (p<0.01) and increased voiding efficiency (p<0.05). The expression of several cytokines/chemokines correlated significantly with bladder functional parameters such as residual volumes, and hyperactivity. Conclusions: Gene expression signatures of NeMO were consistent with human bladder obstruction, supporting the use of the nerve-sparing mouse obstruction model for therapeutic exploration.

Minimally invasive surgery for benign prostatic hyperplasia: causes, forms, and prevention of urinary disorders (literature review)

Benign prostatic hyperplasia (BPH) ranks 4th among all diagnoses in the group of men 50 years of age and older. With an increase in prostate volume of more than 20 cm³, patients develop lower urinary tract symptoms (LUTS), which negatively affect the quality of life of men. Currently, minimally invasive endovideosurgical methods of treating BPH have proven themselves successfully: transurethral resection (TUR) of monopolar or bipolar type, transurethral bipolar enucleation of the prostate (TUEP), holmium laser enucleation of the prostate (HoLEP). However, despite the clinical efficiency of endoscopic operations, the incidence of postoperative complications remains quite significant. After surgical intervention, the main causes of urinary disorders are detrusor overactivity or a decrease in its functional activity, as well as bladder obstruction. Prolonged bladder catheterization in the postoperative period prevents early recovery of independent urination, which is a risk factor for the development of urinary disorders. Stress urinary incontinence has a significant impact on patients, both physically and mentally. For the treatment of postoperative stress urinary incontinence, behavioral therapy, drug treatment of disorders, minimally invasive methods of treatment are used: injections of hyaluronic acid into the submucous layer of the urethra, botulinum toxin into the detrusor, as well as the technique of sacral neuromodulation. Surgical methods include the implantation of a synthetic sphincter or the installation of male sling.

MO228NATIVE KIDNEY BIOPSIES: DIAGNOCTIC VALUE AND COMPLICATIONS

Background and Aims Percutaneous renal biopsy is essential tool in nephrology but it is invasive procedure that can lead to complications, including gross hematuria, clinical significant haematoma and infection. The aim of the study was to determine the nature and incidence of PRB complications and the impact of biopsy results on treatment strategy. Method 82 patients (male – 42, female – 40) with a median age of 43.5 (Q1; Q3 – 34;71) years, BMI 26.4 (22.9; 30.6) were included in retrospective study of all native kidney biopsies performed at our institute from January 1, 2016 to December 31, 2019. An informed consent was mandatory in all patients. The indications for biopsies were nephrotic syndrome, 24-hour proteinuria ≥ 1g, nephritic syndrome, renal failure of unknown origin. The median duration of kidney disease was 9.5 (3.0; 26.6) months, serum creatinine level - 135 (87; 197) μmol/l, eGFR (CKD-EPI formula) – 52.9 (26.6; 83.7) ml/min/1.73 m2, 24-hour proteinuria – 2.8 (1.2; 5.4) g. All biopsies were percutaneous, ultrasound-guided and were performed under local anesthesia in prone position with a 16G needle. Medications that may increase bleeding risk (anticoagulants, antiplatelet agents, and nonsteroidal anti–inflammatory drugs) was stopped before PRB. Immediately after the biopsy, bed rest and vital signs monitoring was prescribed for 12 hours. In the absence of complications, a control kidneys ultrasound was performed 24 hours after biopsy; if complications were suspected, regarding to the local protocol. We prescribed prophylactic antibiotics to the patients with a hematoma volume &gt; 100 ml. All biopsy specimens were sent to tertiary laboratory of renal pathology and evaluated by light and immunofluorescence (IF) microscopy; electron microscopy was not used in our study. Biopsy samples were considered satisfactory for diagnosis if they contained five or more glomeruli. Results Post-biopsy complications included gross hematuria – 19 of 82 (23.5%) patients, haematomas ≤ 100 ml – 17 (20.7%), haematomas &gt; 100 ml – 8 (20.7%), pain in the puncture site requiring the administration of analgesics – 2 (2.4%). No death, infections, bladder obstruction or nephrectomy due to biopsy complications was registered. One (1.2%) patient required blood transfusion. We identified renal arteriovenous fistula which did not require special treatment in one (1.2%) patient 2 months after PRB. We found no differences in the incidence of post-biopsy haematomas by gender, age, or BMI. Haematomas were significantly more common in patients with higher mean blood pressure and serum creatinine levels (Fig.1, A, B). In one case (1.2%) the biopsy was inadequate. The results of PRB were varied, including unexpected findings. IgA nephropathy was found in 23 of 81 (28.4%) patients, focal segmental glomerulosclerosis – in 21 (25.9%), membranous nephropathy – in 9 (11.1%), pauci-immune crescentic glomerulonephritis – in 6 (7,4%), lupus nephritis – in 2 (2.4%), membranoproliferative glomerulonephritis – in 2 (2.4%) - one with polyclonal Ig+/C3+ on IF and one - with monoclonal IgG kappa+, C3 nephropathy – in 1 (1.2%), AL-amyloidosis – in 2 (2.4%), light chain deposit disease – in 1 (1.2%), hypertensive nephropathy – in 1 (1.2%), diabetic nephropathy – in 3 (3.7%), tubulointerstitial nephritis – 5 (6.2%), thrombotic microangiopathy – in 2 (2.4%), diffuse nephrosclerosis – in 2 (2.4%), renal tuberculosis – in 1 (1.2%). According to the results of the biopsy, pathogenetic treatment was first prescribed to 43 of 81 (53.1%) patients, changed – in 17 (21%), treatment remained unchanged – in 8 (9.9%) cases. Thirteen (16%) patients were referred for additional examination by a hematologist and rheumatologist. Conclusion Biopsy of native kidney is a high diagnostic value and safe procedure with a low risk of major complications. Treatment was changed significantly after biopsy in 74% of patients in our study.

Inverted bladder diverticulum with sigmoid colon herniation masquerading as bowel and bladder obstruction

Urinary bladder diverticula can be congenital or acquired, and the latter tends to occur in older men and results from urinary obstruction. Primary bladder diverticula are congenital, smooth walled, solitary in nature and rarely diagnosed in adults. An internal hernia (IH) is a protrusion of intestines or other abdominal organs through a normal or abnormal orifice in the peritoneum or mesentery, occasionally leading to strangulation or incarceration. Internal hernias (IH) are rare causes of acute abdomen and intestinal obstruction in adults. Here we present a case report detailing the authors' surgical experience with inverted bladder diverticulum, presenting as internal hernia with sigmoid colon herniating through it, with features of acute intestinal obstruction and urinary dysfunction.