Kidney stone disease.

Kidney stone disease is rapidly increasing with a strong relationship to metabolic syndrome. This review gives a brief overview of the current state and current treatment modalities. Increasing use of CT and ultrasound scans leads to increased diagnosis of asymptomatic kidney stones, which rarely require treatment. The trend in stone treatment goes towards endoscopic lithotripsy which together with ESWL enables a personalised approach. Obstructive stones with infection require urgent intervention to reduce mortality. Increased fluid intake, dietary changes as well as potassium citrate supplements are the most important elements in stone prevention in the common idiopathic stone disease.

Protective effect of sacubitril/valsartan (Entresto) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy.

Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II-angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n = 6). Next, four groups of pigs were followed for 15 days (n = 24) after PN (one-third right kidney, 60 min ischaemia) + Entresto (49/51 mg/day; n = 8), PN + vehicle (n = 8), sham + Entresto (49/51 mg/day; n = 4) and sham + vehicle (n = 4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25 ± 6 mL/min, left 31 ± 7 mL/min) accounted for the total GFR (56 ± 14 mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23 ± 6 mL/min, P < .05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.

Protection of kidney function and tissue integrity by pharmacologic use of natriuretic peptides and neprilysin inhibitors.

With variable potencies atrial-, brain-type and c-type natriuretic peptides (NP)s, best documented for ANP and its analogues, promote sodium and water excretion, renal blood flow, lipolysis, lower blood pressure, and suppress renin and aldosterone secretion through interaction predominantly with cGMP-coupled NPR-A receptor. Infusion of especially ANP and its analogues up to 50 ng/kg/min in patients with high risk of acute kidney injury (cardiac vascular bypass surgery, intraabdominal surgery, direct kidney surgery) protects kidney function (GFR, plasma flow, medullary flow, albuminuria, renal replacement therapy, tissue injury) at short term and also long term and likely additively with the diuretic furosemide. This documents a pharmacologic potential for the pathway. Neprilysin (NEP, neutral endopeptidase) degrades NPs, in particular ANP, and angiotensin II. The drug LCZ696, a mixture of the neprilysin inhibitor sacubitril and the ANGII-AT1 receptor blocker valsartan, was FDA approved in 2015 and marketed as Entresto®. In preclinical studies of kidney injury, LCZ696 and NPs lowered plasma creatinine, countered hypoxia and oxidative stress, suppressed proinflammatory cytokines, and inhibited fibrosis. Few randomized clinical studies exist and were designed with primary cardiac outcomes. The studies showed that LCZ696/entresto stabilized and improved glomerular filtration rate in patients with chronic kidney disease. LCZ696 is safe to use concerning kidney function and stabilizes or increases GFR. In perspective, combined AT1 and neprilysin inhibition is a promising approach for long-term renal protection in addition to AT1 receptor blockers in acute kidney injury and chronic kidney disease.

Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model.

BACKGROUND: The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. METHODS: The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. RESULTS: All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. CONCLUSION: In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms.

Laparo- and thoracoscopic aortic aneurysm neck optimization and treatment of potential endoleaks type IA and II in a porcine model.

BACKGROUND: Endovascular repair of aortic aneurysms has a higher incidence of late complications, and open conversion (OC) associated with high mortality may be required. As alternatives to OCs, we propose minimal invasive laparo-/thoracoscopic approaches, either to control endoleaks after endovascular repair, or to convert non-endovascular treatable cases due to a hostile neck anatomy by inserting a peri-aortic PTFE collar before endovascular repair. Such interventions may reduce complications and the necessity for OCs in the future. METHODS: In twelve pigs, were 10 had infra-/juxtrarenal AAAs, externally placed collars/aneuwraps around the proximal AAA neck and just below the left subclavian artery and division of the aortic side branches were carried out laparo-and thoracoscopically. RESULTS: For the laparoscopic and thoracoscopic procedures respectively, mean operative time was 143 ± 41 min and 86 ± 51 min and a mean of 2.6 and 2.25 aortic side branches were ligated/divided. For both procedures, the last half in the series were carried out significantly faster (p < 0.05) indicating a learning curve. Blood loss was minimal and no procedure related complications were seen. CONCLUSION: Using these minimal invasive endoscopic approaches, it seems feasible to externally band aneurysm necks and ligate aortic side branches in a pig model. These procedures could potentially be considered as alternatives to OCs in controlling endoleaks and in improving the safety of endovascular interventions. As endoscopic aortic surgery is challenging a learning curve is expected. Practicing the described procedures using this model, can be used as a learning tool prior to similar interventions on humans.

Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model.

BACKGROUND: A large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. METHODS: 10 pigs (group A) underwent infrarenal aortic dissection, balloon dilatation, infusion of elastase into the lumen and placement of a stenosing cuff around the aorta. 10 control pigs (group B) underwent a sham procedure. The subsequent 28 days the AP-diameters of the aneurysms were measured using ultrasound, hereafter the pigs were euthanized for inspection and AAA wall sampling for histological analysis. RESULTS: In group A, all pigs developed continuous expanding AAA's with a mean increase in AP-diameter to 16.26 ± 0.93 mm equivalent to a 57% increase. In group B the AP-diameters increased to 11.33 ± 0.13 mm equivalent to 9.3% which was significantly less than in group A (p < 0.001). In group A, a significant negative association between the preoperative weight and the resulting AP-diameters was found. Histology shoved more or less complete resolution of the elastic tissue in the tunica media in group A. The most frequent complication was a neurological deficit in the lower limbs. CONCLUSION: In pigs it's possible to induce continuous expanding AAA's based upon proteolytic degradation and pathological flow, resembling the real life dynamics of human aneurysms. Because the lumbars are preserved, it's also a potential model for further studies of novel endovascular devices and their complications.

[Scrotal Paget's disease].

A patient with extramammary Paget's disease (EMPD) had a plaque of the scrotum surgically removed. Histology and immunohistochemistry was consistent with primary EMPD. EMPD is a rare intraepidermal neoplasia mostly confined to regions of the skin with apocrine sweat glands. Clinical features include red plaques, which often will be mistakenly diagnosed as an infection or a rash. The treatment is surgical.

[Two cases of severe variceal haemorrhage from an ileal conduit].

Variceal haemorrhage from an ileal conduit is a rare but well-known complication to portal hypertension. Many treatments are described and a transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice if possible, because this addresses the underlying portal hypertension. We report two cases of haemorrhage from an ileal conduit, which illustrates that treatment must be individualized with attention to life expectancy, co-morbidities and degree of the portosystemic pressure gradient, but TIPS treatment has to be considered even if there is no history of liver disease.