Angiotensin II Stimulation of DPP4 Activity Regulates Megalin in the Proximal Tubules.

Proteinuria is a marker of incipient kidney injury in many disorders, including obesity. Previously, we demonstrated that megalin, a receptor endocytotic protein in the proximal tubule, is downregulated in obese mice, which was prevented by inhibition of dipeptidyl protease 4 (DPP4). Obesity is thought to be associated with upregulation of intra-renal angiotensin II (Ang II) signaling via the Ang II Type 1 receptor (AT1R) and Ang II suppresses megalin expression in proximal tubule cells in vitro. Therefore, we tested the hypothesis that Ang II will suppress megalin protein via activation of DPP4. We used Ang II (200 ng/kg/min) infusion in mice and Ang II (10(-8) M) treatment of T35OK-AT1R proximal tubule cells to test our hypothesis. Ang II-infused mouse kidneys displayed increases in DPP4 activity and decreases in megalin. In proximal tubule cells, Ang II stimulated DPP4 activity concurrent with suppression of megalin. MK0626, a DPP4 inhibitor, partially restored megalin expression similar to U0126, a mitogen activated protein kinase (MAPK)/extracellular regulated kinase (ERK) kinase kinase (MEK) 1/2 inhibitor and AG1478, an epidermal growth factor receptor (EGFR) inhibitor. Similarly, Ang II-induced ERK phosphorylation was suppressed with MK0626 and Ang II-induced DPP4 activity was suppressed by U0126. Therefore, our study reveals a cross talk between AT1R signaling and DPP4 activation in the regulation of megalin and underscores the significance of targeting DPP4 in the prevention of obesity related kidney injury progression.

Surgical treatment of benign prostatic hyperplasia: Thulium enucleation versus single-port transvesical robotic simple prostatectomy.

Objective: The objective of this work is to compare our outcomes using thulium laser enucleation of prostate (ThuLEP) to the single-port robot-assisted simple prostatectomy (SP RASP) in the surgical management of benign prostatic hyperplasia (BPH). Methods: A retrospective cohort study was conducted from January 2017 through December 2021 of men who underwent SP RASP and ThuLEP performed by a single surgeon with an enucleation experience of >300 cases and extensive robotic experience. The primary outcome was changed in International Prostate Symptom Score (IPSS) postoperatively. Secondary outcomes were operative time, length of stay (LOS), change in post-void residuals (PVR), de novo stress- or urge-urinary incontinence (SUI, UUI), and rate of complications. Results: One hundred two patients underwent surgery during the study period: 33 RASP and 69 ThuLEP. There was no difference in preoperative characteristics, including age and body mass index, between both groups. Changes in IPSS scores postoperatively were not significant between SP RASP versus ThuLEP (-17 vs. -14, p = 0.2956). SP RASP had a longer operative time (180 vs. 90 min, p < 0.0001). There was no difference in LOS (0 vs. 0 days, p = 0.2904). There was no difference in change in PVR (-96 vs. -91 mL, p = 0.8504). SP RASP patients had significantly less postoperative SUI than ThuLEP (0 vs. 13 patients, p = 0.0083), while there was no difference in UUI between both groups (4 vs. 2 patients, p = 0.0843). There was no difference in 30-day complication rate (21.2% vs. 21.7%, p = 0.9517), although there were three ThuLEP patients with Clavien-Dindo Class III or higher complication. Conclusions: There was no difference in change in IPSS scores between the two groups. ThuLEP is associated with shorter postoperative catheter days and decreased operative times. Hospital LOS was equivalent. SP RASP demonstrates significantly improved continence rates. Though SP RASP is within the initial learning curve at our institution, early results demonstrate the role for this modality alongside ThuLEP in the treatment of large gland BPH.

Forty-Three-Year-Old Female with Dopamine Secreting Pheochromocytoma of the Adrenal Gland.

We report on a 43-year-old, asymptomatic female who presented with incidental finding of left adrenal mass. MRI gave concerns for possible pheochromocytoma but markers for pheochromocytoma were not elevated as expected. 24-hour urine dopamine levels (6988 µg/day) were significantly elevated. The patient successfully underwent robotic assisted radical left adrenalectomy and was diagnosed with a dopamine secreting pheochromocytoma. Pathology revealed increased malignant potential associated with the tumor. The patient underwent full metastatic workup, which was negative. At two years of follow-up there was no recurrence and normalization of lab values.