Patient perspective on telemedicine replacing physical consultations in urology during the COVID-19 lockdown in Denmark.

OBJECTIVE: In March-April 2020, during the coronavirus disease 2019 (COVID-19) pandemic lockdown in Denmark, the Danish Health Authorities recommended that, where possible, face-to-face patient-physician consultations be replaced by telephone consultations. The aim of this study was to obtain patients' evaluation of their telemedicine experience. METHODS: Patients who were candidates for telemedicine consultations were recruited based on their urological ailment, necessity for follow-up and comorbidity. New referrals including patients with suspicion of cancer were not candidates for telemedicine. In total, 548 patients had their appointment altered during the period from 13 March to 30 April 2020. Postal questionnaires were sent to 548 patients and 300 (54.7%) replied. RESULTS: In total, 280 patient answered, 224 (80%) men and 56 (20%) women, mean age 69 years (range 18-91) of whom 180 (64.3%) had a benign and 100 (35.7%) a malignant diagnosis. Twenty (6.7%) respondents did not remember their telephone consultation and were therefore excluded. Telephone consultation satisfaction was reported by 230 (85.0%) patients, but they would not prefer video consultations over telephone consultations, and only 102 (36.4%) would prefer telephone consultations in the future. Patients' age, sex and distance to the hospital did not seem to be associated with telephone consultation satisfaction (age p = 0.17; sex p = 0.99; distance p = 0.27, respectively). In total, 226 (80.7%) were medically assessed as being at risk for COVID, but 74 (26.4%) subjectively evaluated themselves as being at risk. CONCLUSIONS: In general (85.0%), urological patients were satisfied with telephone consultations.

Natriuretic peptides relax human intrarenal arteries through natriuretic peptide receptor type-A recapitulated by soluble guanylyl cyclase agonists.

AIM: Natriuretic peptides, BNP and ANP increase renal blood flow in experimental animals. The signalling pathway in human kidney vasculature is unknown. It was hypothesized that BNP and ANP cause endothelium-independent relaxation of human intrarenal arteries by vascular natriuretic peptide receptor-A, but not -B and -C, which is mimicked by agonists of soluble guanylyl cyclase sGC. METHODS: Human (n = 54, diameter: 665 ± 29 µm 95% CI) and control murine intrarenal arteries (n = 83, diameter 300 ± 6 µm 95% CI) were dissected and used for force recording by four-channel wire myography. Arterial segments were pre-contracted, then subjected to increasing concentrations of BNP, ANP, phosphodiesterase 5-inhibitor sildenafil, sGC-activator BAY 60-2770 and -stimulator BAY 41-2272. Endothelial nitric oxide synthase (eNOS) dependence was examined by use of L-NAME and eNOS knockout respectively. Molecular targets (NPR A-C, sGC, phosphodiesterase-5 and neprilysin) were mapped by PCR, immunohistochemistry and RNAscope. RESULTS: BNP, ANP, sildenafil, sGC-activation and -stimulation caused concentration-dependent relaxation of human and murine intrarenal arteries. BNP responses were independent of eNOS and were not potentiated by low concentration of phosphodiesterase-5-inhibitor, sGC-stimulator or NPR-C blocker. PCR showed NPR-A and C, phosphodiesterase-5, neprilysin and sGC mRNA in renal arteries. NPR-A mRNA and protein was observed in vascular smooth muscle and endothelial cells in arteries, podocytes, Bowmans capsule and vasa recta. NPR-C was observed in tubules, glomeruli and vasculature. CONCLUSION: Activation of transmembrane NPR-A and soluble guanylyl cyclase relax human preglomerular arteries similarly to phosphodiestase-5 inhibition. The human renal arterial bed relaxes in response to cGMP pathway.

Percutaneous cryoablation of a solitary, soft-tissue metastasis from renal cell carcinoma: a new local minimal invasive curative treatment.

Cryoablation is a well-established treatment option, proven to be successful in treating local renal cell carcinoma (RCC). We treated a 67-year-old man in an outpatient setting with late onset of a 25 mm solitary soft-tissue metastasis of from RCC with cryoablation. The treatment was performed under sedation and in local anaesthesia. There were no complications during the procedure. The patient did not experience any adverse effects to the treatment. He was able to resume his normal daily routines the day after his treatment. A follow-up CT scan at 3, 8 and 12 months after treatment reported sufficient cryoablation and no sign of recurrence or other metastases.

Periarterial fat from two human vascular beds is not a source of aldosterone to promote vasoconstriction.

Mouse adipocytes have been reported to release aldosterone and reduce endothelium-dependent relaxation. It is unknown whether perivascular adipose tissue (PVAT) releases aldosterone in humans. The present experiments were designed to test the hypothesis that human PVAT releases aldosterone and induces endothelial dysfunction. Vascular reactivity was assessed in human internal mammary and renal segmental arteries obtained at surgery. The arteries were prepared with/without PVAT, and changes in isometric tension were measured in response to the vasoconstrictor thromboxane prostanoid receptor agonist U46619 and the endothelium-dependent vasodilator acetylcholine. The effects of exogenous aldosterone and of mineralocorticoid receptor (MR) antagonist eplerenone were determined. Aldosterone concentrations were measured by ELISA in conditioned media incubated with human adipose tissue with/without angiotensin II stimulation. Presence of aldosterone synthase and MR mRNA was examined in perirenal, abdominal, and mammary PVAT by PCR. U46619 -induced tension and acetylcholine-induced relaxation were unaffected by exogenous and endogenous aldosterone (addition of aldosterone and MR blocker) in mammary and renal segmental arteries, both in the presence and absence of PVAT. Aldosterone release from incubated perivascular fat was not detectable. Aldosterone synthase expression was not consistently observed in human adipose tissues in contrast to that of MR. Thus, exogenous aldosterone does not affect vascular reactivity and endothelial function in ex vivo human arterial segments, and the tested human adipose tissues have no capacity to synthesize/release aldosterone. In perspective, physiologically relevant effects of aldosterone on vascular function in humans are caused by systemic aldosterone originating from the adrenal gland.

Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin.

The proteinase prostasin is a candidate mediator for aldosterone-driven proteolytic activation of the epithelial sodium channel (ENaC). It was hypothesized that the aldosterone-mineralocorticoid receptor (MR) pathway stimulates prostasin abundance in kidney and urine. Prostasin was measured in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial. Prostasin protein level was assessed by immunoblotting in (1) human and rat urines with/without nephrotic syndrome, (2) human nephrectomy tissue, (3) urine and kidney from aldosterone synthase-deficient (AS-/-) mice and ANGII- and aldosterone-infused mice, and in (4) kidney from adrenalectomized rats. Serum aldosterone concentration related to prostasin concentration in urine but not in plasma. Plasma prostasin concentration increased significantly after spironolactone compared to control. Urinary prostasin and albumin related directly and were reduced by spironolactone. In patients with nephrotic syndrome, urinary prostasin protein was elevated compared to controls. In rat nephrosis, proteinuria coincided with increased urinary prostasin, unchanged kidney tissue prostasin, and decreased plasma prostasin while plasma aldosterone was suppressed. Prostasin protein abundance in human nephrectomy tissue was similar across gender and ANGII inhibition regimens. Prostasin urine abundance was not different in AS-/- and aldosterone-infused mice. Prostasin kidney level was not different from control in adrenalectomized rats and AS-/- mice. We found no evidence for a direct relationship between mineralocorticoid receptor signaling and kidney and urine prostasin abundance. The reduction of urinary prostasin in spironolactone-treated patients is most likely the result of an improved glomerular filtration barrier function and generally reduced proteinuria.

Initial experience with hand-assisted laparoscopic donor nephrectomy: a single-centre experience over 5 years.

OBJECTIVE: The objective of this study was to evaluate outcome after hand-assisted live donor nephrectomy with a retroperitoneal approach during a 5 year period. MATERIALS AND METHODS: All donor nephrectomies at Odense University Hospital, Denmark, from January 2008 to December 2012 were identified retrospectively, and the medical records were examined. RESULTS: In total, 108 patients were enrolled: 68 females, with a median age of 50 years (range 24-68 years), and 40 males, with a median age of 51 years (32-70 years). The median body mass index (BMI) was 25 kg/m² (19-33 kg/m²) in females and 27 kg/m² (21-38 kg/m²) in males. The median intraoperative bleeding was 175 ml. The median warm ischaemia time was 3.2 min (1.5-6.7 min). The median operative time was 230 min (161-360 min). The median hospital stay was 4 days (2-10 days). Thirty donors (28%) had 34 early complications. Six donors (6%) needed reoperation. Late complications were seen in seven (7%). Sixteen donors (15%) were obese (BMI ≥30 kg/m²), which was associated with significant complications (p < .0001). There was a significantly higher complication rate in donors who were smokers and ingested alcohol above the Danish recommended limits (p < .0001). Fifteen donors (13%) developed hypertension postoperatively within the first year. There was no mortality. A total of 104 (96%) of the recipients had a functional transplant after 1 year. CONCLUSION: Hand-assisted donor nephrectomy is a safe procedure. Potential candidates should be advised to stop smoking and to avoid alcohol before surgery, especially those with a BMI of 30 kg/m² or higher.

[Diagnosis and treatment of symptomatic hydronephrosis in pregnancy]. / Diagnose og behandling af symptomgivende hydronefrose i graviditeten.

Hydronephrosis in pregnancy is common in the second and third trimester. Only a few cases are symptomatic, caused by a ureteric stone or by the pregnancy itself. The clinical dilemma is when to treat and when not to treat. We propose a multidisciplinary management based on renal ultrasonography to verify hydronephrosis and renography to diagnose obstructive hydronephrosis. Obstruction with a high intra-renal pressure must be treated to avoid kidney dysfunction. Patients with pyonephrosis need immediate treatment.

The epithelial sodium channel γ-subunit is processed proteolytically in human kidney.

The epithelial sodium channel (ENaC) of the kidney is necessary for extracellular volume homeostasis and normal arterial BP. Activity of ENaC is enhanced by proteolytic cleavage of the γ-subunit and putative release of a 43-amino acid inhibitory tract from the γ-subunit ectodomain. We hypothesized that proteolytic processing of γENaC occurs in the human kidney under physiologic conditions and that proteinuria contributes to aberrant proteolytic activation. Here, we used monoclonal antibodies (mAbs) with specificity to the human 43-mer inhibitory tract (N and C termini, mAbinhibit, and mAb4C11) and the neoepitope generated after proteolytic cleavage at the prostasin/kallikrein cleavage site (K181-V182 and mAbprostasin) to examine human nephrectomy specimens. By immunoblotting, kidney cortex homogenate from patients treated with angiotensin II type 1 receptor antagonists (n=6) or angiotensin-converting enzyme inhibitors (n=6) exhibited no significant difference in the amount of full-length or furin-cleaved γENaC or the furin-cleaved-to-full-length ratio of γENaC compared with homogenate from patients on no medication (n=5). Patients treated with diuretics (n=4) displayed higher abundance of full-length and furin-cleaved γENaC, with no significant change in the furin-cleaved-to-full-length γENaC ratio. In patients with proteinuria (n=6), the inhibitory tract was detected only in full-length γENaC by mAbinhibit. Prostasin/kallikrein-cleaved γENaC was detected consistently only in tissue from patients with proteinuria and observed in collecting ducts. In conclusion, human kidney γENaC is subject to proteolytic cleavage, yielding fragments compatible with furin cleavage, and proteinuria is associated with cleavage at the putative prostasin/kallikrein site and removal of the inhibitory tract within γENaC.

Prostaglandin I2 and prostaglandin E2 modulate human intrarenal artery contractility through prostaglandin E2-EP4, prostacyclin-IP, and thromboxane A2-TP receptors.

Cyclooxygenase inhibitors decrease renal blood flow in settings with decreased effective circulating volume. The present study examined the hypothesis that prostaglandins, prostaglandin E2 (PGE2) and prostacyclin (PGI2), induce relaxation of human intrarenal arteries through PGE2-EP and PGI2-IP receptors. Intrarenal arteries were microdissected from human nephrectomy samples (n=53, median diameter ≈362 µm, 88% viable, 76% relaxed in response to acetylcholine). Rings were suspended in myographs to record force development. In vessels with K(+)-induced tension (EC70: -log [mol/L]=1.36±0.03), PGE2 and PGI2 induced concentration-dependent relaxation (-log EC50: PGE2=7.1±0.3 and PGI2=7.7). The response to PGE2 displayed endothelium dependence and desensitization. Relaxation by PGE2 was mimicked by an EP4 receptor agonist (CAY10598, EC50=6.7±0.2). The relaxation after PGI2 was abolished by an IP receptor antagonist (BR5064, 10(-8) mol/L). Pretreatment of quiescent arteries with PGE2 for 5 minutes (10(-6) mol/L) led to a significant right shift of the concentration-response to norepinephrine (EC50 from 6.6±0.1-5.9±0.1). In intrarenal arteries with K(+)-induced tone, PGE2 and PGI2 at 10(-5) mol/L elicited increased tension. This was abolished by thromboxane receptor (TP) antagonist (S18886, 10(-6) mol/L). A TP agonist (U46619, n=6) evoked tension (EC50=8.1±0.2) that was inhibited by S18886. Polymerase chain reaction and immunoblotting showed EP4, IP, and TP receptors in intrarenal arteries. In conclusion, PGE2 and PGI2 may protect renal perfusion by activating cognate IP and EP4 receptors associated with smooth muscle cells and endothelium in human intrarenal arteries and contribute to increased renal vascular resistance at high pathological concentrations mediated by noncognate TP receptor.

Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo.

Voltage-gated Ca(2+) (Cav) channels play an essential role in the regulation of renal blood flow and glomerular filtration rate (GFR). Because T-type Cav channels are differentially expressed in pre- and postglomerular vessels, it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed with the use of two T-type Cav knockout (Cav3.1(-/-) and Cav3.2(-/-)) mouse strains. Continuous recordings of blood pressure and heart rate, para-aminohippurate clearance (renal plasma flow), and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild-type (WT) and Cav3.1(-/-) and Cav3.2(-/-) mice. The contractility of afferent and efferent arterioles was determined in isolated perfused blood vessels. Efferent arterioles from Cav3.2(-/-) mice constricted significantly more in response to a depolarization compared with WT mice. GFR was increased in Cav3.2(-/-) mice with no significant changes in renal plasma flow, heart rate, and blood pressure. Cav3.1(-/-) mice had a higher renal plasma flow compared with WT mice, whereas GFR was indistinguishable from WT mice. No difference in the concentration response to K(+) was observed in isolated afferent and efferent arterioles from Cav3.1(-/-) mice compared with WT mice. Heart rate was significantly lower in Cav3.1(-/-) mice compared with WT mice with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intrarenal arteries in response to a small depolarization. In conclusion, Cav3.2 channels support dilatation of efferent arterioles and affect GFR, whereas Cav3.1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Cav3.2 and Cav3.1, respectively, may account for the observed effects.