Search

We recently developed a therapeutic biopolymer composed of an elastin-like polypeptide (ELP) fused to vascular endothelial growth factor (VEGF) and showed long-term renoprotective effects in experimental renovascular disease after a single intra-renal administration. Here, we sought to determine the specificity, safety, efficacy, and mechanisms of renoprotection of ELP-VEGF after systemic therapy in renovascular disease. We tested whether kidney selectivity of the ELP carrier would reduce off-target binding of VEGF in other organs. In vivo bio-distribution after systemic administration of ELP-VEGF in swine was determined in kidneys, liver, spleen, and heart. Stenotic-kidney renal blood flow and glomerular filtration rate were quantified in vivo using multi-detector computed tomography (CT) after six weeks of renovascular disease, then treated with a single intravenous dose of ELP-VEGF or placebo and observed for four weeks. CT studies were then repeated and the pigs euthanized. Ex vivo studies quantified renal microvascular density (micro-CT) and fibrosis. Kidneys, liver, spleen, and heart were excised to quantify the expression of angiogenic mediators and markers of progenitor cells. ELP-VEGF accumulated predominantly in the kidney and stimulated renal blood flow, glomerular filtration rate, improved cortical microvascular density, and renal fibrosis, and was accompanied by enhanced renal expression of VEGF, downstream mediators of VEGF signaling, and markers of progenitor cells compared to placebo. Expression of angiogenic factors in liver, spleen, and heart were not different compared to placebo-control. Thus, ELP efficiently directs VEGF to the kidney after systemic administration and induces long-term renoprotection without off-target effects, supporting the feasibility and safety of renal therapeutic angiogenesis via systemic administration of a novel kidney-specific bioengineered compound., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The antiphospholipid syndrome is a common autoimmune disease caused by pathogenic antiphospholipid antibodies, leading to recurrent thrombosis and/or obstetrical complications. Importantly for nephrologists, antiphospholipid antibodies are associated with various renal manifestations including large renal vessel thrombosis, renal artery stenosis, and a constellation of intrarenal lesions that has been termed antiphospholipid nephropathy. This last condition associates various degrees of acute thrombotic microangiopathy, proliferative and fibrotic lesions of the intrarenal vessels, and ischemic modifications of the renal parenchyma. The course of the disease can range from indolent nephropathy to devastating acute renal failure. The pejorative impact of antiphospholipid antibody-related renal complication is well established in the context of systemic lupus erythematous or after renal transplantation. In contrast, the exact significance of isolated antiphospholipid nephropathy remains uncertain. The evidence to guide management of the renal complications of antiphospholipid syndrome is limited. However, the recent recognition of the heterogeneous molecular mechanisms underlying the progression of intrarenal vascular lesions in antiphospholipid syndrome have opened promising tracks for patient monitoring and targeted therapeutic intervention., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Randomized trials have shown a neutral effect of percutaneous revascularization compared with optimal medical therapy in patients with atherosclerotic renovascular disease (ARVD). However, there are few data to define what constitutes optimal medical therapy. We present a retrospective analysis of 529 ARVD patients. Separate analyses were performed comparing outcomes in patients prescribed/not prescribed beta blocker and antiplatelet agents. Analyses were adjusted for effects of baseline covariates on probability of treatment and on clinical outcome. Over a median follow-up period of 3.8 years, antiplatelet therapy was associated with a reduced risk for death (relative risk, 0.52 [95% confidence interval {CI}: 0.31-0.89]; P = .02). Beta blocker therapy was associated with a reduced for death (relative risk, 0.45 [95% CI: 0.21-0.97]; P = .04) and nonfatal cardiovascular events (relative risk, 0.74 [95% CI: 0.60-0.90]; P = .003). Although limited by small patient numbers, this study suggests that in ARVD, treatment with antiplatelet therapy and beta blockade may associate with a prognostic benefit., (Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Acute renal embolism (ARE) is a rare cause of acute abdominal pain. However, there are only a few studies on the clinical course of ARE. We attempted to investigate the clinical manifestations and long-term follow-up results of ARE., Methods: From September 2006 to August 2012, 47 patients, who were diagnosed with ARE by computed tomography (CT), were enrolled. Patient demographic and clinical data were retrospectively reviewed. For the long-term outcomes, change in the serum creatinine (s-Cr) level, change in renal infarction on follow-up CT, recurrent embolism, and dialysis-free survival were investigated., Results: The mean age of patients was 61 years (range, 29-89 years), and 51% of the patients were men. All the patients presented with abdominal or flank pain. The sites of ARE were the right kidney in 57% of the patients, the left kidney in 36% of the patients, and both the kidneys in 6% of the patients. The infarction volume was less than 50% of renal volume in 54% of infarcted kidneys. Six patients had a concurrent infarction in other organs (3 cases of splenic infarction and 3 cases of cerebral infarction). Etiology of embolism was cardiogenic in 55% and idiopathic in 45%. Mean s-Cr level was 1.2 mg/dL (range, 0.6-3.7 mg/dL). s-Cr elevation >0.5 mg/dL was detected in 19% of patients during the follow-up (6 of 31 patients; mean duration, 31 months). Follow-up CT was performed in 23 patients (mean duration, 29 months). The infarcted lesions showed atrophic changes in all the cases except for 1 case. During the mean follow-up period of 41 months (1-118 months), recurrent embolism developed in 8 patients (6 cases of cerebral artery embolism, 1 case of superior mesenteric artery embolism, and 1 case of renal artery embolism). Dialysis was necessary in 1 patient, and dialysis-free survival rates were 91%, 82%, and 64% at 1 year, 3 years, and 5 years, respectively., Conclusions: Although ARE causes irreversible loss of renal mass, it rarely leads to end-stage renal disease or long-term mortality. Therefore, the treatment should focus on the prevention of subsequent embolism to other vital organs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The purpose of this study was to assess the hyperemic effects of papaverine and dopamine in the renal microcirculation of hypertensive patients with renal artery stenosis (RAS). Although a poor correlation between angiographic lesion assessment and its hemodynamic significance is known, angiography is a major criterion for the decision of renal artery stenting. Assessment of the hyperemic translesional pressure gradient was recently shown to be conducive in identifying patients who may benefit from renal revascularization. The study included 14 patients (mean age, 66 ± 11.2 years) with resistant hypertension and moderate RAS. Using a pressure-sensing catheter, systolic, diastolic, and mean translesional pressure gradients, and the distal pressure (Pd):aortic pressure (Pa) ratio (Pd/Pa) were analyzed at baseline and after administration of 40 mg papaverine and 50 μg/kg dopamine. We did not observe significant changes in DG. Dopamine administration resulted in significant changes in systolic and mean translesional pressure gradients and Pd/Pa when compared with baseline (P < .05 for all). Changes in these parameters were caused by a decrease in systolic Pd in comparison with baseline conditions (119 ± 34 mm Hg vs. 101 mm Hg; P < .05). Systolic Pd pressure after papaverine (104 mm Hg) did not change significantly. Systolic and diastolic Pa values did not differ from baseline after either dopamine or papaverine bolus administration.This study indicates that, compared with papaverine, the intrarenal bolus of dopamine in hypertensive patients with RAS remains a more powerful hyperemic agent., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

We hypothesized that chronic specific endothelin-A (ET-A) receptor blockade therapy would reverse renal dysfunction and injury in advanced experimental renovascular disease. To test this, unilateral renovascular disease was induced in 19 pigs, and after 6 weeks, single-kidney hemodynamics and function was quantified in vivo using computed tomography. All pigs with renovascular disease were divided such that seven were untreated, seven were treated with ET-A blockers, and five were treated with ET-B blockers. Four weeks later, all pigs were restudied in vivo, and then killed and ex vivo studies performed on the stenotic kidney to quantify microvascular density, remodeling, renal oxidative stress, inflammation, and fibrosis. Renal blood flow, glomerular filtration rate, and redox status were significantly improved in the stenotic kidney after ET-A but not ET-B blockade. Furthermore, only ET-A blockade therapy reversed renal microvascular rarefaction and diminished remodeling, which was accompanied by a marked decreased in renal inflammatory and fibrogenic activity. Thus, ET-A but not ET-B blockade ameliorated renal injury in pigs with advanced renovascular disease by stimulating microvascular proliferation and decreasing the progression of microvascular remodeling, renal inflammation, and fibrosis in the stenotic kidney. These effects were functionally consequential as ET-A blockade improved single kidney microvascular endothelial function, renal blood flow, and glomerular filtration rate, and decreased albuminuria.

Primary congenital abdominal aortic aneurysm is an extremely rare entity, with only 15 patients reported in the literature. Options for repair are often limited secondary to branch vessel size and other anatomic limitations. We present a neonate diagnosed with an abdominal aortic aneurysm on prenatal ultrasound. A postpartum computed tomography angiogram revealed an extensive type IV thoracoabdominal aortic aneurysm extending to the aortic bifurcation and resulting in bilateral renal artery stenosis. The unique features of this patient and challenges in management are discussed., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Transplant renal artery stenosis (TRAS) is a common occurrence following kidney transplantation with an incidence rate ranging from 6% to 23%. A single-center retrospective study was conducted to examine the use of drug-eluting stents (DES) in eligible patients with hemodynamically significant TRAS. Between March 2008 and January 2011, 12 patients were diagnosed with TRAS with reference vessel diameter measuring <5 mm and underwent endovascular intervention (EVI) with DES placement. TRAS was detected within the first year posttransplantation in a majority of these patients (83%) and manifested as hypertension (100%), allograft dysfunction (100%) and edema (58%). Procedural success rate was 100%. Patients were followed for a mean period of 16 ± 10 months. Blood pressure improved from a mean of 156/82 to 138/73 mmHg at the end of the follow-up period. In 11/12 patients, serum creatinine improved from 3.1 ± 1.3 mg/dL to 2.3 ± 0.5 mg/dL at the end of the follow-up period. TRAS of early onset is readily amenable to EVI with stent placement resulting in improvement in blood pressure control and allograft function., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: Antiphospholipid antibodies (aPL) can be associated with numerous infectious and particularly Q fever. Data on the pathogenicity of aPL in the course of acute Q fever are scarce., Case Report: We report the case an acute Coxiella burnetii infection associated with clinical and biological manifestations of the aPL syndrome, including a renal infarction. Along with antibiotic treatment, anticoagulation and intravenous immunoglobulins, the clinical outcome was favourable. Antiphospholipid antibodies and Q fever antibody titers had a closely related evolution., Conclusion: Arterial thrombosis associated with Q fever and aPL is exceptional. The nosology and potential mechanisms are discussed.

Acute renal artery embolism is an uncommon clinical diagnosis. We present a case report of a patient who was treated with transcatheter thrombolysis and a literature review and discussion of this condition and its management.

Heparin-induced thrombocytopenia is a rare but serious complication of heparin therapy. Most of cases are related to unfractionated heparin, but a few are due to low molecular weight heparin sometimes associated with unfractionated heparin. A patient with pulmonary contusions after chest injury developed a catheter related subclavian vein thrombosis on day 16. He was treated by increasing doses of low molecular weight heparin. Aortic and renal thromboses occurred on day 21. Surgical thrombectomy, performed after starting alternative anticoagulation treatment led to complete arterial recovery. In case of suspicion of heparin-induced thrombocytopenia, with unfractionated or low-molecular-weight heparin, heparin treatment must be discontinued before the results of biological tests become available. Arterial and/or venous thrombosis is a serious complication of heparin-induced thrombocytopenia. The treatment has two aims: first, to restore arterial patency by clot removal by thrombectomy, bypass or thrombolysis, and second, to avoid new thrombosis formation by substitutive anticoagulation treatment: danaparoid may have cross-reaction with heparin, or lepirudin has anaphylactic risks and needs biological follow-up. Heparin-induced thrombocytopenia and thrombosis can be complicated by death or disabilities such as amputations, stroke, renal or bowel infarction. Once HIT has been diagnosed heparin should never be given again, but if cardiopulmonary bypass is required, it might be reintroduced during operation only if serum antibodies have disappeared.

Ischemic nephropathy is recognized as a distinct cause of renal insufficiency and it is defined as a significant reduction in glomerular filtration rate in patients with hemodynamically significant renovascular occlusive disease. We argue the epidemiologic and clinical manifestations of atherosclerotic renovascular disease, and we evaluate the pronostic agents. Published studies of the outcome of revascularization for renal-artery stenosis have been excellent, offering a durable patency and functional improvement but they have had numerous limitations. The atherosclerosis is a systemic disease and it provides the general prognosis of patients. We conclude that ischemic renal disease is a nephropathy of smoker men, with proteinuria excretion similar to nephropathy with unilateral stenosis. The age of patients is the clinical feature that decide the treatment: surgery, angioplasty/stent or medical management. Comparative analysis of percutaneous transluminal angioplasty and operation for renal revascularization and medically treated patients have proved that the advanced chronic renal insufficiency is associated with an unfavourable response of treatment of the ischemic nephropathy. But, in this nephropathy the revascularization can be the better therapy for selected patients. The revascularization with angioplasty/stent for patients with unilateral renal stenosis and chronic renal insufficiency has a doubtful effectiveness, as the chronic renal failure is result of nephroangiosclerosis.

A 77 year old man with coronary artery disease was referred to our institution for recurrent (flash) episodes of pulmonary edema due to malignant hypertension. A selective contrast-enhanced angiography showed severe bilateral renal artery stenosis. We also found a high level of plasma renin production identifying intense renin-angiotensin system activation. We first considered revascularisation. Percutaneous intervention initially failed and thereafter the patient denied surgical revascularisation. We have then recommended medical therapy, namely a beta-blocker after adequate correction of fluid retention. We used CARVEDILOL which has no nephrotoxicity and effectively inhibit the renin-angiotensin system. The patient feels significant functional and clinical improvement with no fluid retention relapse with a follow-up of more than 18 months.

Renal arterial thrombosis, usually in association with aortic thrombosis, has been reported as a result of prolonged neonatal umbilical artery catheterization. A case of renal artery thrombosis attributable to umbilical artery catheterization, resulting in malignant renovascular hypertension, in a 15-day-old neonate, treated by catheter-directed thrombolysis through the involuting umbilical artery, was studied. Resolution of systemic hypertension and partial return of right renal function followed rapid thrombus dissolution.

The effects of ACE inhibitors on the stenosed kidney in patients with unilateral arterial stenosis are not well characterised. While there are conflicting reports, some experimental and clinical evidence suggest that the stenosed kidney may undergo atrophy: secondary to effective blood pressure lowering and decreased perfusion pressure distally, or due to other mechanism/s. Such a loss of renal function may go unrecognised. In view of the widespread use of ACE inhibitors, the fate of the stenosed kidney needs to be more accurately known.

Management of acute renal artery occlusion remains a therapeutic challenge. We report our experience with 10 cases of acute renal artery occlusion treated primarily by local infusion of fibrinolytic agents. Renal artery occlusion occurred as a result of thrombosis of a stenosed vessel in three cases, from renal artery embolism in two cases, as a complication of percutaneous transluminal angioplasty in four cases, and in association with aortic occlusion in one case. Flank pain was present in all cases and hematuria in four cases. Acute renal failure was seen at the time of presentation in four cases (one case from bilateral occlusion and three cases from an associated nonfunctioning contralateral kidney). Diagnosis was confirmed by renal isotope scanning and arteriography in all cases. All patients were treated by selective infusion of streptokinase or urokinase into the occluded renal arteries. In five cases this was combined with balloon catheter angioplasty. Therapy was initiated within 24 hours from the onset of symptoms in three cases, within 3 days in four cases, within 6 days in two cases, and after 5 weeks in one case. Successful revascularization was initially achieved in 7 of the 10 cases by arteriographic criteria. Rethrombosis occurred in one patient after 3 days and fibrinolytic therapy was repeated successfully. Renal function was restored in one of the four patients presenting with acute renal failure. One complication necessitating resection occurred as a result of fibrinolytic therapy in the form of acute mesenteric embolism with descending colon infarction. No major bleeding complications were encountered and there were no deaths in this group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Because the signs and symptoms of acute renal artery occlusion mimic those of many more common diseases, prompt diagnosis is aided by an awareness that an occlusive renovascular event may have occurred. No routine, noninvasive laboratory test can confirm the diagnosis. Renal arteriography is the procedure of choice after excretory urograms have ruled out an obstructive uropathy. Early assessment of kidney viability is important. The endpoints of emergency treatment are to decrease symptoms, decrease diastolic blood pressure to less than or equal to 105 mm Hg, and to maintain urine output at greater than 50 mL/h. Restoration of a lower blood pressure must not be so prompt that renal perfusion decreases too rapidly. Definitive surgical treatment versus medical management of the renal artery occlusion remains a controversial topic. Where surgery is not feasible, medical management consists of streptokinase acutely followed by heparin and then chronic coumarin therapy.