Intravenous tocilizumab for Takayasu arteritis with aortic aneurysms, bilateral renal artery stenosis, and atypical aortic coarctation in a 2-year-old girl.

Takayasu arteritis (TAK) is classified as large vessel vasculitis, and continuous inflammation of the vessel results in aneurysm or stenosis, which leads to various serious complications. Recently, a TAKT [TAK treated with tocilizumab (TCZ)] study showed that subcutaneous TCZ, a humanised anti-interleukin-6 receptor monoclonal antibody, is an effective treatment in patients with TAK above 12 years of age; however, the effectiveness of TCZ for juvenile TAK under 12 years old remains unclear. Here, we described the case of a 2-year-old girl with TAK, which was successfully treated with intravenous TCZ. She was diagnosed with TAK type V (Numano's angiographic classification system) with aortic aneurysms, bilateral renal arteries stenosis, and atypical descending aortic coarctation based on contrast-enhanced computed tomography findings. Treatment was started with 2 mg/kg/day prednisolone (PSL) and methotrexate instead of methylprednisolone pulse due to renovascular hypertension. She was immediately afebrile and her C-reactive protein level decreased, although it was elevated 4 weeks after starting PSL. Intravenous TCZ of 8 mg/kg/2 weeks was added because the progression of aneurysms or stenosis might lead to a poor prognosis. PSL was steadily reduced under intravenous TCZ. Magnetic resonance imaging showed that aortic aneurysms, renal arteries stenosis, and aortic coarctation ameliorated 4 months after starting TCZ, with the amelioration maintained at 1 year after starting TCZ. Aneurysms and stenosis improved; therefore, TCZ may be effective for the treatment of inflammation of vessels, aneurysms, and stenosis. It is desirable to examine the effect of TCZ on TAK patients under 12 years of age.

Resveratrol Supplants Captopril's Protective Effect on Cardiac Remodeling in a Hypertension Model Elicited by Renal Artery Stenosis.

Background: Renovascular hypertension elicits cardiac damage and remodeling. Two-kidney, one-clip (2K1C) is an experimental model used to study hypertension pathophysiology. In this model, the renin-angiotensin-system (RAS) is overactive due to renal artery stenosis, leading to cardiac remodeling. Redox mechanisms underlying RAS activation mediate hypertension-induced cardiovascular damage. Preclinical studies and clinical trials demonstrated resveratrol's protective effects in cardiovascular diseases, mainly attributed to its antioxidant properties. We hypothesized resveratrol alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor would be beneficial against cardiac damage caused by renovascular hypertension. Objective: We investigated the benefits of resveratrol against cardiac remodeling in 2K1C rats compared with captopril. Methods: Male Wistar rats underwent unilateral renal stenosis - 2K1C Goldblatt model of hypertension. Systolic Blood Pressure (SBP) was measured before and 6 weeks after surgery. Hypertensive 2K1C rats presented SBP≥160 mmHg. From the 6th week after the surgery, the animals received oral resveratrol (20 mg/kg), captopril (12 mg/kg), or their combination for 3 times per week for 3 weeks. Whole heart hypertrophy was evaluated. Histological assays assessed left ventricle hypertrophy and fibrosis. Results: Renovascular hypertension caused cardiac hypertrophy, accompanied by increased myocyte diameter and collagen deposition. Resveratrol reduced 2K1C rats' SBP and whole heart hypertrophy, independently of captopril. Resveratrol caused a higher reduction in ventricular hypertrophy than captopril. Collagen deposition was greater reduced by 2K1C treated only with resveratrol than with captopril alone or combined with resveratrol. Conclusion: Independent of captopril, resveratrol prompts cardioprotective effects on cardiomyocyte remodeling and fibrosis resulting from renovascular hypertension in 2K1C rats.

Expression of Cyr61 in ApoE-/- mice with chronic unilateral renal artery ligation.

Cyr61 is a member of the CCN family of proteins that is expressed in atherosclerotic lesions and regulated by angiotensin II. It is unknown whether renal artery stenosis (RAS) increases Cyr61 expression. Male ApoE-/- mice were randomized to surgically induced RAS, RAS + treatment with either irbesartan, aliskiren or amlodipine or sham-surgery. RAS resulted in increased plasma angiotensin II levels, a mild, sustained increase in systolic blood pressure and increased aortic lipid deposition compared to sham-surgery. Surgically induced RAS led to the formation of atheroma in the infrarenal aorta and there was consistent and intense staining for Cyr61 within the atheroma. Treatment with irbesartan, aliskiren and amlodipine were associated with decreased aortic lipid deposition and decreased staining for Cyr61 in aortic atheroma. Serum levels of Cyr61 were not increased in mice or humans with RAS. In summary, Cyr61 expression in aortic atheroma but not serum is increased by RAS in ApoE-/- mice and is reduced by agents that lower blood pressure.

Diabetes Mellitus and Noncardiac Atherosclerotic Vascular Disease-Pathogenesis and Pharmacological Treatment Options.

Diabetes mellitus (DM) is also a cause of cardiovascular (CV) disease (CVD). Addressing the atherosclerotic CVD (ASCVD) burden in DM should reduce premature death and improve quality of life. Diabetes mellitus-associated ASCVD can lead to complications in all vascular beds (carotids as well as coronary, lower extremity, and renal arteries). This narrative review considers the diagnosis and pharmacological treatment of noncardiac atherosclerotic vascular disease (mainly in patients with DM). Based on current knowledge and the fact that modern DM treatment guidelines are based on CV outcome trials, it should be noted that patients with noncardiac CVD may not have the same benefits from certain drugs compared with patients who predominantly have cardiac complications. This leads to the conclusion that in the future, consideration should be given to conducting well-designed trials that will answer which pharmacological treatment modalities will be of greatest benefit to patients with noncardiac ASCVD.

Recovery of Renal Function following Kidney-Specific VEGF Therapy in Experimental Renovascular Disease.

BACKGROUND: Chronic renovascular disease (RVD) can lead to a progressive loss of renal function, and current treatments are inefficient. We designed a fusion of vascular endothelial growth factor (VEGF) conjugated to an elastin-like polypeptide (ELP) carrier protein with an N-terminal kidney-targeting peptide (KTP). We tested the hypothesis that KTP-ELP-VEGF therapy will effectively recover renal function with an improved targeting profile. Further, we aimed to elucidate potential mechanisms driving renal recovery. METHODS: Unilateral RVD was induced in 14 pigs. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified by multidetector CT imaging. Pigs then received a single intrarenal injection of KTP-ELP-VEGF or vehicle. CT quantification of renal hemodynamics was repeated 4 weeks later, and then pigs were euthanized. Ex vivo renal microvascular (MV) density and media-to-lumen ratio, macrophage infiltration, and fibrosis were quantified. In parallel, THP-1 human monocytes were differentiated into naïve macrophages (M0) or inflammatory macrophages (M1) and incubated with VEGF, KTP-ELP, KTP-ELP-VEGF, or control media. The mRNA expression of macrophage polarization and angiogenic markers was quantified (qPCR). RESULTS: Intrarenal KTP-ELP-VEGF improved RBF, GFR, and MV density and attenuated MV media-to-lumen ratio and renal fibrosis compared to placebo, accompanied by augmented renal M2 macrophages. In vitro, exposure to VEGF/KTP-ELP-VEGF shifted M0 macrophages to a proangiogenic M2 phenotype while M1s were nonresponsive to VEGF treatment. CONCLUSIONS: Our results support the efficacy of a new renal-specific biologic construct in recovering renal function and suggest that VEGF may directly influence macrophage phenotype as a possible mechanism to improve MV integrity and function in the stenotic kidney.

Renal arteriography with endovascular ultrasound for the management of renal infarction patients.

BACKGROUND: Renal infarction (RI) is a rare disease with poor prognosis. Appropriate secondary prevention treatment is essential and requires an exhaustive etiological assessment. We aimed to determine whether invasive endovascular explorations may improve the diagnostic process and change the secondary prevention treatment strategy in RI patients. METHODS: We report a retrospective observational study of 25 RI patients referred to Tours University Hospital between 2011 and 2018 for etiological investigation including renal arteriography and intravascular ultrasonography (IVUS). We sought for antithrombotic treatment regimen, vital status, bleeding and ischemic outcomes during the median follow-up of 59 months. RESULTS: Invasive explorations showed local arterial disease in 14 patients (56%). This led to a diagnosis or change in diagnosis in 9 patients (36%) and to a change in antithrombotic strategy in 56% of cases, with an increased prescription of antiplatelet therapy. No patient died, only two patients (8%) had persistent mild renal insufficiency. One IVUS complication was reported and treated without any significant long-term consequences. CONCLUSION: Invasive endovascular investigations of RI may modify the secondary prevention treatment through a better assessment of the aetiology of RI. Multicentric randomized studies are necessary to advocate the hypothesis that invasive exploration of renal artery can improve long-term prognosis.

Fetal congenital midaortic syndrome with unilateral renal artery stenosis prenatally presenting with polyhydramnios and postpartum as hyponatremic hypertensive syndrome.

The midaortic syndrome (MAS) is a rare anomaly, characterised by narrowing of the distal aorta and its major branches. The most common symptom is severe arterial hypertension. The combination of hyponatremia, polyuria and renovascular hypertension caused by a unilateral renal artery stenosis is described as hyponatremic hypertensive syndrome. We report a case of MAS with unilateral renal artery stenosis in a preterm female neonate. A pregnant woman at 34 weeks of gestation was referred with fast growing abdominal circumference and pain. The ultrasound revealed severe polyhydramnios and fetal myocardial hypertrophy. Within the first 48 hours of the neonatal period, the diagnosis of MAS was made. We conclude that symptomatic MAS, caused by unilateral renal artery stenosis, resulting in increased renin-angiotensin-aldosterone system activity and subsequent polyuria of the non-stenotic kidney, lead to clinically significant polyhydramnios.

Advancements in medical and surgical treatments of Takayasu arteritis-induced renal arteritis: a systematic review.

BACKGROUND: Takayasu arteritis-induced renal arteritis (TARA), commonly seen in Takayasu arteritis (TA), has become one of the main causes of poor prognosis and early mortality in patients with TA. TARA progressing into Takayasu arteritis-induced renal artery stenosis (TARAS), could lead to severe complications including malignant hypertension, cardiac-cerebral vascular disease, and ischemic nephropathy. Since there existed no guidelines on treatments, this study aimed to review the comprehensive treatments for TARA. METHODS: We searched systematically in databases including PubMed, Ovid-Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and SinoMed, from inception to May 2018. Literature selection, data extraction, and statistical analysis were performed. RESULTS: Eighty-two literatures were recruited focusing on medical treatments (n = 34) and surgical treatments (n = 48). We found that combined medical treatments of glucocorticoids and conventional synthetic disease-modifying anti-rheumatic drugs could reach high rates of remission in patients with TARA, and biological disease-modifying anti-rheumatic drugs were preferred for refractory patients. After remission induction, surgical treatment could help reconstruct renal artery and recover renal function partly. Percutaneous transluminal angioplasty was the first choice for patients with TARAS, while open surgery showed a good long-term survival. CONCLUSIONS: Patients with TARA should benefit both from medical treatments and from surgical treatments comprehensively and sequentially. Multidisciplinary team coordination is recommended especially in patients with severe complications.

Endothelin: 30 Years From Discovery to Therapy.

Discovered in 1987 as a potent endothelial cell-derived vasoconstrictor peptide, endothelin-1 (ET-1), the predominant member of the endothelin peptide family, is now recognized as a multifunctional peptide with cytokine-like activity contributing to almost all aspects of physiology and cell function. More than 30 000 scientific articles on endothelin were published over the past 3 decades, leading to the development and subsequent regulatory approval of a new class of therapeutics-the endothelin receptor antagonists (ERAs). This article reviews the history of the discovery of endothelin and its role in genetics, physiology, and disease. Here, we summarize the main clinical trials using ERAs and discuss the role of endothelin in cardiovascular diseases such as arterial hypertension, preecclampsia, coronary atherosclerosis, myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) caused by spontaneous coronary artery dissection (SCAD), Takotsubo syndrome, and heart failure. We also discuss how endothelins contributes to diabetic kidney disease and focal segmental glomerulosclerosis, pulmonary arterial hypertension, as well as cancer, immune disorders, and allograft rejection (which all involve ETA autoantibodies), and neurological diseases. The application of ERAs, dual endothelin receptor/angiotensin receptor antagonists (DARAs), selective ETB agonists, novel biologics such as receptor-targeting antibodies, or immunization against ETA receptors holds the potential to slow the progression or even reverse chronic noncommunicable diseases. Future clinical studies will show whether targeting endothelin receptors can prevent or reduce disability from disease and improve clinical outcome, quality of life, and survival in patients.

Determinants of long-term outcome in patients after percutaneous stent-assisted intervention for renal artery steno-occlusive atherosclerotic disease.

INTRODUCTION: The effect of stent­assisted percutaneous transluminal angioplasty (PTA) for renal artery stenosis (RAS) on systolic (SBP) and diastolic blood pressure (DBP) as well as renal function, in comparison with medical therapy, is still debatable. Data on determinants of cardiovascular (CV) outcome after PTA are lacking. OBJECTIVES: We aimed to identify determinants of major cardiac and cerebral events (MACCEs) following PTA for RAS. PATIENTS AND METHODS: A total of 248 PTAs for RAS were performed in 211 patients with difficult­to­treat hypertension and/or progressive renal impairment. The primary outcomes were procedural success, in­hospital complications, renal function (estimated glomerular filtration rate [eGFR]), change in SBP or DBP, and an incidence of MACCEs during a median of 47 months (interquartile range [IQR], 18-78 months). RESULTS: Procedural success and complication rates were 99.2% and 4.7%, respectively. We observed significant differences in SBP, DBP, and eGFR at 12 months as compared with baseline. A total of 63 MACCEs (30.6%) were noted in 206 patients with available follow­up data. The receiver operating characteristic curve analysis indicated the following best cutoff values for the risk of CV death: an increase in eGFR by at least 11 ml/min/1.73 m2 and a decrease in SBP and DBP by at least 20 mm Hg and 5 mm Hg, respectively. At 12­month follow­up, an increase in eGFR of at least 11 ml/min/1.73 m2 was independently associated with a reduced risk of death (hazard ratio [HR], 0.42; 95% CI, 0.19-0.90; P = 0.02) and MACCEs (HR, 0.54; 95% CI, 0.32-0.93; P = 0.03), while a decrease of DBP by 5 mm Hg or higher, with a reduced risk of stroke (HR, 0.1; 95% CI, 0.02-0.39; P = 0.001). CONCLUSIONS: This study confirms the efficacy and safety of PTA as well as its significant effect on changes in blood pressure and eGFR values. Patients with an increase in eGFR of at least 11 ml/min/1.73 m2 have a significant risk reduction of MACCEs and CV death, while those with a decrease in DBP of at least 5 mm Hg, of stroke.

Early Rapid Decline in Kidney Function in Medically Managed Patients With Atherosclerotic Renal Artery Stenosis.

Background Early rapid declines of kidney function may occur in patients with atherosclerotic renal artery stenosis with institution of medical therapy. The causes and consequences are not well understood. Methods and Results Patients enrolled in the medical therapy-only arm of the CORAL (Cardiovascular Outcomes With Renal Artery Lesions) study were assessed for a rapid decline (RD) in estimated glomerular filtration rate (eGFR), defined as a ≥30% decrease from baseline to either 3 months, 6 months, or both. In the medical therapy-only cohort, eGFR was available in 359 subjects at all time points, the subjects were followed for a median of 4.72 years, and 66 of 359 (18%) subjects experienced an early RD. Baseline log cystatin C (odds ratio, 1.78 [1.11-2.85]; P=0.02), age (odds ratio, 1.04 [1.00-1.07]; P<0.05), and Chronic Kidney Disease Epidemiology Collaboration creatinine eGFR (odds ratio, 1.86 [1.15-3.0]; P=0.01) were associated with an early RD. Despite continued medical therapy only, the RD group had an improvement in eGFR at 1 year (6.9%; P=0.04). The RD and nondecline groups were not significantly different for clinical events and all-cause mortality (P=0.78 and P=0.76, respectively). Similarly, renal replacement therapy occurred in 1 of 66 (1.5%) of the RD patients and in 6 of 294 (2%) of the nondecline patients. The regression to the mean of improvement in eGFR at 1 year in the RD group was estimated at 5.8±7.1%. Conclusions Early rapid declines in kidney function may occur in patients with renal artery stenosis when medical therapy is initiated, and their clinical outcomes are comparable to those without such a decline, when medical therapy only is continued.

Stroke and renal artery stenosis from Takayasu's arteritis diagnosed in a 57-year-old male patient.

Takayasu arteritis (TA) is a rare chronic granulomatous inflammatory arterial disease of unknown etiology that affects the aorta, its main branches and pulmonary artery. The clinical presentation is nonspecific, with signs and symptoms that vary according to the affected arterial segment. The most commonly affected vessel is the subclavian artery, while renal artery stenosis is relatively uncommon. We report a case of a 57-year-old male patient with late diagnosis of TA and various related complications including stroke in the left middle cerebral artery territory, predominant left renal artery stenosis, and hypertension with discrepancy of blood pressure between two arms due to predominant left subclavian artery stenosis. Thus, physicians should keep in their mind this late presentation after the age of 40 years. The aim is to increase the awareness of this condition because of early diagnosis and the timely introduction of treatment can lead to improved outcomes in this poorly understood clinical enigma.

Mitochondrial Protection Partly Mitigates Kidney Cellular Senescence in Swine Atherosclerotic Renal Artery Stenosis.

BACKGROUND/AIMS: Atherosclerotic renal artery stenosis (ARAS) may cause kidney injury and mitochondrial dysfunction, which is linked to cellular senescence. Elamipretide, a mitochondria-targeted peptide, improves renal function in ARAS, but whether it alleviates senescence is unknown. We hypothesized that elamipretide would reduce senescence stenotic kidney (STK) in ARAS. METHODS: Domestic pigs were randomized to control and unilateral ARAS untreated or treated with subcutaneous elamipretide (5d/wk) for 4 weeks starting after 6 weeks of ARAS or sham (n=6 each). After completion of treatment, STK renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed in-vivo using multi-detector computed-tomography. Renal fibrosis and oxidative stress were analyzed in trichrome- and dihydroethidium-stained slides, respectively. Mitochondrial markers involved in the electrontransport chain (COX4, ATP/ADP ratio), biogenesis (PGC1α, PPARα), dynamics (MFN2, DRP1), and mitophagy (parkin, p62) were measured in the kidney using ELISA, western-blot, and immunohistochemistry. Cellular senescence (senescence-associated ß-galactosidase and heterochromatin foci, phosphorylated-H2AX, and p16/21/53) and senescence-associated secretory phenotype (SASP; PAI-1, MCP-1, TGFß, and TNFα) markers were studied by microscopy, quantitative reverse transcription-polymerase chain reaction, and western-blot. RESULTS: Blood pressure was elevated whereas STK-RBF and GFR were decreased in ARAS pigs, and tissue scarring was increased. ARAS induced STK cellular senescence and accumulated dysfunctional mitochondria, which were associated with cardiolipin loss, upregulated mitochondrial biogenesis, and defective mitophagy. Elamipretide normalized STK-RBF and GFR, alleviated fibrosis and oxidative stress, and restored mitochondrial cardiolipin, biogenesis, and mitophagy in ARAS, but did not change SASP markers, and attenuated only senescenceassociated ß-galactosidase activity and p53 gene expression. CONCLUSION: Mitochondrial protection improved renal function and fibrosis in the ARAS STK, but only partly mitigated cellular senescence. This finding suggests that mitochondrial dysfunction may not be a major determinant of cellular senescence in the early stage of ARAS.

Combination of Renal Angioplasty and Angiotensin-converting-enzyme Inhibitor Can Reduce Proteinuria in Patients with Bilateral Renal Artery Disease.

Recent large clinical trials failed to show clear benefits of percutaneous transluminal renal angioplasty (PTRA) as compared with medical therapy on patients with renal artery stenosis. It was also reported that proteinuria is an adverse prognostic factor after PTRA, and PTRA is less effective in patients with overt proteinuria. From the renoprotective point of view, to reduce proteinuria after PTRA is an important therapeutic goal in patients with renal artery stenosis with overt proteinuria. We hereby describe two patients successfully treated by combination therapy with PTRA and administration of angiotensin-converting enzyme (ACE) inhibitor for bilateral renal artery disease with overt proteinuria.

Reduced efficacy of transcatheter and surgical revascularization in Takayasu arteritis.

A 55-year-old woman with newly diagnosed Takayasu arteritis was followed for 7 years, during which time she underwent bare metal stenting, drug eluting stenting and coronary bypass grafting for critical coronary and renal artery stenoses. Interventions were initially successful but restenosis occurred within 24 months for all modalities. In contrast, native vessel disease was largely stable after the introduction of immunosuppressive therapy. We advocate a conservative revascularization approach in Takayasu arteritis in the absence of critical end organ ischemia and early optimization of medical therapy.

Calcium channel blockers are associated with improved survival and lower cardiovascular mortality in patients with renovascular disease.

BACKGROUND AND OBJECTIVE: Results of interventional trials in renovascular hypertension have been disappointing, and medical therapy is the current recommended gold standard. However, the comparative long-term benefits of different antihypertensive drug classes in atherosclerotic renal artery stenosis are not known. We aim to assess the effect of different antihypertensive drug classes on outcomes in renovascular hypertension DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Using Tayside Health Informatics Centre database, anonymized data over a 6-year period was analyzed. Biochemistry, prescribing data, morbidity, mortality, and demographic data were accessed via hospital medical records and electronic data stored in the Tayside Health Informatics Centre Safe Haven. General Registrar's Office data were used to identify patients who died from cardiovascular disease. Independent predictors of survival in each group were analyzed using Kaplan-Meier survival curves and Cox proportional hazard models, adjusted for a range of covariates, using time-updated drug analysis. Blood pressure data were obtained from primary and secondary care clinic blood pressure records for each patient. Adjustments for mean systolic blood pressure over the follow-up period and baseline blood pressure were made. RESULTS: A total of 579 patients with atherosclerotic renal artery stenosis were identified. In the unilateral renal artery stenosis cohort, calcium channel blockers but not ACE inhibitors/ARBs were associated with a significant reduction in all-cause (HR = 0.45, CI = 0.31, 0.65; P = <0.0001) and cardiovascular (HR = 0.51, CI = 0.29-0.90 P = 0.019) mortality. This was maintained after adjustment for blood pressure. In the bilateral renal artery stenosis cohort, both classes of drugs reduced all-cause but not cardiovascular mortality. Patients with moderate disease benefitted more than those with mild or severe disease. CONCLUSIONS: Calcium channel blockers are associated with significantly increased survival and lower cardiovascular mortality particularly in patients with moderate RAS disease.

Systemic biopolymer-delivered vascular endothelial growth factor promotes therapeutic angiogenesis in experimental renovascular disease.

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.

Successful Treatment of Transplant Renal Artery Thrombosis With Systemic Infusion of Recombinant-Tissue-Plasminogen Activator After Renal Transplant.

A 24-year-old man with end-stage renal disease secondary to congenital renal hypoplasia under-went a preemptive renal transplant. Although a vascular complication occurred during surgery, the operation was completed satisfactorily. However, postoperative Doppler ultrasound showed no perfusion of the renal artery, vein, and parenchyma, indicating a transplant renal artery thrombosis. A reoperation was promptly performed, with systemic infusion of recombinant-tissue-plasminogen activator during graft nephrectomy, followed by a reimplant that resulted in a salvage allograft. Immediate thrombolysis using systemically infused recombinant-tissue-plasminogen activator may be an effective treatment option for transplant renal artery thrombosis after renal transplant.

Antiphospholipid syndrome and kidney disease.

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.

Kidney disease in primary anti-phospholipid antibody syndrome.

APS is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for aPL. APS can be isolated (primary APS) or associated with other autoimmune diseases. The kidney is a major target organ in APS, and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal vasculature and renal veins). Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal involvement in patients with definite APS is treated with long-term anticoagulants as warfarin, but new treatments are being tried. The aim of this article is to review the links between primary APS and kidney disease.