Unilateral Renal Artery Stenosis Research Articles

Оценка чувствительности методов диагностики в выявлении гемодинамически значимых односторонних стенозов почечных артерий

Objective. Assessment of renal artery stenosis significance in patients with resistant arterial hypertension using non-invasive diagnostic methods and to compare them with the results of selective angiography and methods of physiological assessment of renal artery stenoses.Materials and methods. Prospectively, 156 patients with drug-resistant arterial hypertension and signs of renal artery stenosis detected by doppler ultrasonography of renal arteries were included in the study. Subsequently, 25 patients were excluded from the study due to multiple variant renal blood supply and bilateral renal artery stenosis. The remaining patients (n=131) underwent selective angiography of renal arteries, and 66 of them additionally underwent CTA of renal arteries with intravenous contrast. If the artery narrowing was 90% or more (n=27) in diameter, the stenosis was considered hemodynamically significant and further stenting of the affected artery was performed, and in case of 60-90% stenosis (n=52) additional assessment of functional significance of the stenosis was performed by measuring translesional pressure gradient, fractional blood flow reserve, instantaneous blood flow reserve (iFR) and Pd/ Pa ratio. Results. Among all patients (n=131), in whom the doppler ultrasonography of renal arteries showed signs of unilateral renal artery stenosis, after angiography combined with additional methods of functional significance assessment, hemodynamically significant renal artery stenosis was confirmed in 41% of cases (n=54). Thus, the sensitivity of doppler ultrasonography of renal arteries in detection of hemodynamically significant stenoses was 74%, prognostic value of positive 78% and negative result 64% (p<0,001). According to CTA (n=66) renal artery stenosis was confirmed in 56 patients. The results of CTA of renal arteries in 88% of cases coincided with the results of selective angiography, and using additional functional methods hemodynamically significant stenosis was confirmed in 32 (48%) patients. The sensitivity of CTA in detection of hemodynamically significant stenoses of renal arteries was 69%, specificity 91%, prognostic value of positive and negative results was 91 and 68% respectively. According to selective angiography, out of 131 patients, 24 patients had no renal artery stenosis, 28 patients had stenosis <60%, 27 patients had renal artery stenosis >90% and 52 patients had stenosis 60-90%. Patients with stenosis <60% were not considered candidates for renal artery stenting.

Hemodynamic analysis of unilateral and bilateral renal artery stenosis based on fluid-structure interaction

Renal artery stenosis (RAS) hypertension is a common type of secondary hypertension. This paper aimed to explore how unilateral renal artery stenosis (Uni-RAS) and bilateral renal artery stenosis (Bi-RAS) caused renovascular hypertension with the fluid-structure interaction (FSI) method. Based on a real RAS model, 20 ideal models with different stenosis degrees were established by modifying the stenosis segment. The hemodynamic parameters at different degrees of stenosis, mass flow rate (MFR), pressure drop (PD), fractional flow reserve (FFR), oscillatory shear index (OSI), and relative residence time (RRT), were numerically calculated by the computational fluid dynamics (CFD) method. The numerical results showed that RAS caused the decrease of MFR, and the increase of PD and the proportion of high OSI and high RRT. In the case of RAS, it could not be regarded as a reference indicator for causing renovascular hypertension that the value of FFR was greater than 0.9. In addition, the results of the statistical analysis indicated that Uni-RAS and Bi-RAS were statistically different for MFR, PD and the proportion of high RRT.

Successful Application of PTRA in a Patient with AKI Due to Severe Unilateral Renal Artery Stenosis: A Case Report with 4-Year Follow-up and Review of Literature

Introduction: Renal artery stenosis (RAS) is defined by a decrease in the internal diameter of one or both of the renal arteries. This can lead to renal insufficiency. RAS mostly occurs due to atherosclerosis; however, other conditions can cause this complication. Case Presentation: We present a 66-year-old man who was initially presented with abrupt bilateral lower limbs and scrotal edema in Shahid Beheshti Hospital of Qom. The patient had been regularly visiting the nephrology clinic for mild CKD. Due to the increased levels of creatinine (Cr) and urea in serum, he underwent angiography with suspicion of RAS, and 99% stenosis was confirmed in the left renal artery. Immediately after the diagnosis, we subjected the patient to angioplasty. After removing the arterial stenosis, the patient passed 8 liters of urine during one day, and his symptoms, including generalized edema, weight gain, and dyspnea, were improved gradually. The patient was discharged after 8 days of hospitalization with dramatically improved kidney function and relatively good general conditions. Conclusions: This patient had an uncommon presentation for a unilateral RAS and significant narrowing in the healthy renal artery. Angioplasty and stenting yielded a satisfactory result as a definite and effective treatment, and the patient enjoyed a relatively normal life with preserved kidney function during 4 years of follow-up.

An Interesting Presentation of Unilateral Renal Artery Stenosis

An Interesting Presentation of Unilateral Renal Artery Stenosis

Bilateral renal artery stenosis impacts postoperative complications after major vascular surgery

BackgroundIncidental atherosclerotic renal artery stenosis (RAS) is common in patients undergoing vascular surgery and has been shown to be associated with postoperative AKI among patients undergoing major non-vascular surgeries. We hypothesized that patients with RAS undergoing major vascular procedures would have a higher incidence of AKI and postoperative complications than those without RAS. MethodsA single-center retrospective cohort study of 200 patients who underwent elective open aortic or visceral bypass surgery (100 with postoperative AKI; 100 without AKI) were identified. RAS was then evaluated by review of pre-surgery CTAs with readers blinded to AKI status. RAS was defined as ≥50 % stenosis. Univariate and multivariable logistic regression was used to assess association of unilateral and bilateral RAS with postoperative outcomes. Results17.4 % (n = 28) of patients had unilateral RAS while 6.2 % (n = 10) of patients had bilateral RAS. Patients with bilateral RAS had similar preadmission creatinine and GFR as compared to unilateral RAS or no RAS. 100 % (n = 10) of patients with bilateral RAS had postoperative AKI compared with 45 % (n = 68) of patients with unilateral or no RAS (p < 0.05). In adjusted logistic regression models, bilateral RAS predicted severe AKI (OR 5.82; CI 1.33, 25.53; p = 0.02), in-hospital mortality (OR 5.71; CI 1.03, 31.53; p = 0.05), 30-day mortality (OR 10.56; CI 2.03, 54.05; p = 0.005) and 90-day mortality (OR 6.88; CI 1.40, 33.87; p = 0.02). ConclusionsBilateral RAS is associated with increased incidence of AKI as well as in-hospital, 30-day, and 90-day mortality suggesting it is a marker of poor outcomes and should be considered in preoperative risk stratification.

Using Ultrahigh b -Value Diffusion-Weighted Imaging to Noninvasively Assess Renal Fibrosis in a Rabbit Model of Renal Artery Stenosis.

This study aimed to investigate the feasibility of diffusion-weighted imaging with ultrahigh b values ( ub DWI) for the evaluation of renal fibrosis (RF) induced by renal artery stenosis (RAS) in a rabbit model. Thirty-two rabbits underwent left RAS operation, whereas 8 rabbits received sham surgery. All rabbits underwent ub DWI ( b = 0-4500 s/mm 2 ). The standard apparent diffusion coefficient (ADC st ), molecular diffusion coefficient ( D ), perfusion fraction ( f ), perfusion-related diffusion coefficient ( D *) and ultrahigh apparent diffusion coefficient (ADC uh ) were longitudinally assessed before operation and at weeks 2, 4, and 6 after operation. The degree of interstitial fibrosis and the expression of aquaporin (AQP) 1 and AQP2 were determined through pathological examination. In the stenotic kidney, the ADC st , D , f , and ADC uh values of the renal parenchyma significantly decreased compared with those at baseline (all P < 0.05), whereas the D * values significantly increased after RAS induction ( P < 0.05). The ADC st , D , D *, and f were weakly to moderately correlated with interstitial fibrosis as well as with the expression of AQP1 and AQP2. Furthermore, the ADC uh negatively correlated with interstitial fibrosis ( ρ = -0.782, P < 0.001) and positively correlated with AQP1 and AQP2 expression ( ρ = 0.794, P < 0.001, and ρ = 0.789, P < 0.001, respectively). Diffusion-weighted imaging with ultrahigh b values shows the potential for noninvasive assessment of the progression of RF in rabbits with unilateral RAS. The ADC uh derived from ub DWI could reflect the expression of AQPs in RF.

Moyamoya disease presenting with tubular dysfunction in a child: pitfalls in diagnosing an atypical hyponatremic-hypertensive syndrome

BackgroundMoyamoya disease, a cause of pediatric stroke, has been shown to affect furthermore extra-cranial districts, mostly the kidney arterial site, resulting in steno-occlusive changes. Unilateral renal artery stenosis accounts for 8%-10% out of cases of renovascular hypertension in childhood, however it rarely underlies a hyponatremic-hypertensive syndrome (HHS).Case presentationWe describe an 18-month-old boy with a recent history of polyuria and polydipsia, who presented an acute febrile gastroenteritis with neurological impairment, severe dehydration, hyponatremia, hypokalemia, kidney tubular dysfunction, and elevated aldosterone and renin even with a normal blood pressure. Fluid and electrolytes correction was performed, with complete recovery. An abdominal ultrasound displayed a smaller right kidney. A brain magnetic resonance and an electroencephalogram did not show any relevant abnormalities. Five months later, the child experienced a left-side hemiparesis after a traumatic concussion, and a severe hypertension. A brain tomography documented a cerebral ischemia. Brain and kidney angiographic studies displayed puff of smoke findings of internal right carotid artery branches and a steno-occlusive pattern of right renal artery, respectively. Hence, moyamoya disease with HHS secondary to unilateral renal artery stenosis was diagnosed. After an unsuccessful antiplatelet and antihypertensive pharmacological treatment, the boy underwent a renal angioplasty and a cerebral STA-MCA bypass (direct superficial temporal artery-to-middle cerebral artery bypass), resulting in a significant improvement of both neurological and kidney disease.ConclusionsAlthough the association between unilateral renal artery stenosis and HHS has been previously shown, this is the first report of atypical HHS, with hypertension preceded by tubular dysfunction, recognized in the framework of moyamoya disease.

Defining Hemodynamic Significance of Renal Artery Stenosis: Insights From a Porcine Model of Graded Renal Artery Stenosis

To investigate the renal pressure-flow relationship and its relation to renin release, because the renal perfusion pressure below which renal flow starts to decline and renin secretion isupregulatedis unclear. A porcine model of graded unilateral renal artery stenosis was created. The severity of the stenosis was expressed as the ratio between distal renal pressure (Pd) and aortic pressure (Pa). Pd and renal flow velocity were continuously measured using a combined pressure-flow wire (Combowire®). Hemodynamic measurements and blood sampling for renin, angiotensin and aldosterone were performed in baseline conditions and during progressive balloon inflation in the renal artery leading to Pd decrease per 5% increment. Resistive index (RI)was computed as (1-(End Diastolic V/Peak Systolic V))*100. For a 5% decrease in renal perfusion pressure (95% of aortic pressure or 5% decrease compared to Pa), peak systolic velocity started to decrease. A significant decrease in average peak flow velocitywas observed when distal renal perfusion pressure decreased by 25% and was associated with activation of ipsilateral renin secretion. The RI decreased already for minimal changes in Pd/Pa ratio. In an animal model of unilateral graded renal artery stenosis, a 25% decrease in perfusion pressure results in a significant decrease in distal renal flow, causing upregulation of renin secretion.

Evaluation of Renal Fibrosis Using Magnetization Transfer Imaging at 1.5T and 3T in a Porcine Model of Renal Artery Stenosis.

Renal fibrosis is an important marker in the progression of chronic kidney disease, and renal biopsy is the current reference standard for detecting its presence. Currently, non-invasive methods have only been partially successful in detecting renal fibrosis. Magnetization transfer imaging (MTI) allows estimates of renal fibrosis but may vary with scanning conditions. We hypothesized that MTI-derived renal fibrosis would be reproducible at 1.5T and 3T MRI and over time in fibrotic kidneys. Fifteen pigs with unilateral renal artery stenosis (RAS, n = 9) or age-matched sham controls (n = 6) underwent MTI-MRI at both 1.5T and 3T 6 weeks post-surgery and again 4 weeks later. Magnetization transfer ratio (MTR) measurements of fibrosis in both kidneys were compared between 1.5T and 3T, and the reproducibility of MTI at the two timepoints was evaluated at 1.5T and 3T. MTR at 3T with 600 Hz offset frequency successfully distinguished between normal, stenotic, and contralateral kidneys. There was excellent reproducibility of MTI at 1.5T and 3T over the two timepoints and no significant differences between MTR measurements at 1.5T and 3T. Therefore, MTI is a highly reproducible technique which is sensitive to detect changes in fibrotic compared to normal kidneys in the RAS porcine model at 3T.

Assessment of hemodynamic significance of renal artery stenoses in endovascular treatment of resistant vasorenal arterial hypertension

Objective. To determine the significance of renal artery stenosis according to different methods of assessing the functional significance of stenosis and to evaluate the safety and efficacy of stenting of unilateral renal artery stenosis after 6 months and 1 year according to office BP and ABPM.Materials and methods. The study included 44 patients with resistant arterial hypertension and renal artery stenosis (mean age 69 ± 11 years), while receiving multicomponent antihypertensive therapy, including diuretic. After assessing the degree of RA stenosis according to selective angiography and additional methods of assessing the functional significance of RA stenosis (iFR, Pd/Pa, translesional gradient and FFR) the patients underwent RA stenting. The safety of the procedure was assessed by creatinine and glomerular filtration rate dynamics (MDRD equation). The effectiveness of the procedure was study according to office blood pressure (BP) and ambulatory BP monitoring (ABPM).Results. According to the results of angiography, the patients were divided into two groups: group A – patients with subtotal PA stenosis (&gt; 90%) and group B – patients with moderate stenosis (60-90%), who underwent additional assessment of the functional significance of stenosis. The immediate angiographic result in both groups was optimal (the degree of residual stenosis was less than 5%). In group B, after stent implantation in the PA, there was a decrease of the translesional gradient by 38 ± 10 mm Hg (p &lt; 0,0001), FFR &gt; 0,8(p &lt; 0.0001). iFR &gt; 0.89, Pd/Pa&gt;0.9 (p = 0,093). In both groups, there was a significantly significant reduction in arterial blood pressure at distant times, according to clinical BP measurement and ABPM.Conclusion. The measurement of such parameters as translesional gradient and fractional reserve is the most reliable in assessing the hemodynamic significance of PA stenosis in comparison with iFR and Pd/Pa measurements in patients with moderate PA stenosis. PA stenting in patients with uncontrolled resistant AH and severe renal artery lesions, as well as moderate stenosis confirmed by additional methods of stenosis functional significance assessment is reasonable to consider in order to enhance the antihypertensive effect.

Correlation of renal cortical blood perfusion and BP response after renal artery stenting.

BackgroundThis study aimed to observe the correlation between renal cortical blood perfusion (CBP) parameters and BP response in patients with severe renal artery stenosis (RAS) who underwent stenting.MethodsThis was a single-center retrospective cohort study. A total of 164 patients with unilateral severe RAS after successful percutaneous transluminal renal artery stenting in Beijing Hospital from October 2017 to December 2020 were included. According to the results of BP evaluated at 12 months, all patients were divided into the BP response group (n = 98) and BP nonresponse group (n = 66). The baseline clinical and imaging characteristics and follow-up data about 24 h ABPM and CBP were recorded and analyzed. Pearson correlation analysis was used to evaluate the relationship between CBP parameters and 24 h average SBP. Univariate and multivariate logistic regression analysis was used to evaluate the risk factors for BP response.ResultsAmong 164 patients with severe RAS, there were 100 males (61.0%), aged 37–75 years, with an average of 56.8 ± 18.4 years, and average artery stenosis of 84.0 ± 12.5%. The BP nonresponse patients had a longer duration of hypertension, more current smoking subjects and diabetic patients, lower eGFR, increased number of hypertensive agents, and rate of insulin compared with the BP response group (P < 0.05). After PTRAS, patients in the BP response group were associated with significantly lower BP and improved CPB, characterized by increased levels of maximum intensity (IMAX), area under ascending curve (AUC1), area under the descending curve (AUC2), shortened rising time (RT), mean transit time (mTT), and prolonged time to peak intensity (TTP; P < 0.05). However, the BP nonresponse group was only associated with significantly reduced RT (P < 0.05) compared with baseline data. During an average follow-up of 11.5 ± 1.7 months, the BP response group was associated with significantly lower levels of SBP, DBP, 24 h average SBP, and 24 h average DBP compared with the nonresponse group (P < 0.05). Pearson correlation analysis showed that the the pre-operative CBP parameters, including IMAX (r = 0.317), RT (r = 0.249), AUC1 (r = 0.614), AUC2 (r = 0.558), and postoperative CBP parameters, including RT (r = 0.283), AUC1 (r = 0.659), and AUC2 (r = 0.674) were significantly positively correlated with the 24 h average SBP, while the postoperative TTP (r = −0.413) and mTT (r = −0.472) were negatively correlated with 24 h average SBP (P < 0.05). Multivariate Logistic regression analysis found that diabetes (OR = 1.294), NT-proBNP (OR = 1.395), number of antihypertensive agents (OR = 2.135), pre-operation IMAX (OR = 1.534), post-operation AUC2 (OR = 2.417), and baseline dDBP (OR = 2.038) were related factors for BP response (all P < 0.05).ConclusionPatients in the BP nonresponse group often have diabetes, a longer duration of hypertension, significantly reduced glomerular filtration rate, and heavier renal artery stenosis. CBP parameters are closely related to 24 h average SBP, and pre-operation IMAX and post-operation AUC2 are markers for a positive BP response.

Abstract 075: The Kidney-OVLT Neuroaxis Mediates Neurogenic Hypertension And Polydipsia In 2-Kidney, 1-Clip Rats

Renal afferent nerves mediate activation of the sympathetic nervous system and hypertension in rats with unilateral renal artery stenosis (2K1C-HTN). However, the central neural structures that mediate this response are unclear. The organum vasculosum of the lamina terminalis (OVLT), has also been implicated in the regulation of mean arterial pressure (MAP) and sympathetic activity in preclinical models of hypertension. We tested the hypothesis that afferent renal nerves and the OVLT share a common neural pathway required for the development of 2K1C-HTN. Two experiments were conducted. 1: Male rats (n=5-9) were implanted with telemeters to measure MAP. 1-week later they received a clip on the left renal artery and were subjected to afferent renal denervation (ARDN) by periaxonal capsaicin (2K1C-ARDN) or sham (2K1C-sham) treatment of the clipped kidney. 2: Male rats (n=6-8) were subjected to lesioning of the OVLT (OVLTx) or sham operation. 1-week later telemeters were implanted and 7 days later the left renal artery was stenosed by application of a silver clip. In both experiments, MAP was measured continuously for 6 weeks, and water intake (WI) was measured once a week. Neurogenic pressor activity (NPA) was assessed by measuring the peak MAP response to ganglionic blockade. EXPT 1 Results: At the end of the protocol, MAP was 165±5 mmHg in 2K1C-sham compared to 131±10mmHg in 2K-1C-ARDN rats (p&lt;0.001). WI increased in 2K1C-sham rats peaking at 110±13 ml/day at week 2. In contrast, WI was markedly reduced in 2K1C-ARDN rats at this same time point (41±3 ml/day). NPA was increased in 2K1C-sham (-50 ± 4 mmHg) but was reduced in 2K1C-ARDN (-25 ± 3 mmHg) rats (p&lt;0.05). EXPT 2 Results: At end of the protocol MAP was 162±6 mmHg in sham-2K1C rats compared to 135±8 mmHg in OVLTx-2K1C rats (p&lt;0.001). WI peaked at 74±9 ml/day in sham lesion-2K1C compared to 52±9 ml/day in OVLTx-2K1C rats at week 2 (p&lt;0.05). NPA was increased in sham-2K1C rats (-51 ± 3 mmHg) but was reduced in OVLTx-2K1C rats (-31 ± 4 mmHg) (p&lt;0.05). Since both ARDN and OVLTx attenuated MAP, WI, and NPA similarly in 2K1C rats, we hypothesize that afferent renal nerves and the OVLT are linked in a common neural pathway required for the development of hypertension following renal artery stenosis.

P8.047: An Arrow for Two Targets: Kidney Donation in Unilateral Renal Artery Stenosis

P8.047: An Arrow for Two Targets: Kidney Donation in Unilateral Renal Artery Stenosis

313.3: Domino Kidney Transplant Following Nephrectomy for Renal Artery Stenosis With Arterial Reconstruction and Viability Assessment Using Ex Vivo Normothermic Perfusion: A Case Series

Introduction: Ex vivo normothermic perfusion (EVNP) is increasingly recognised as a viability tool to increase organ utilisation. We report use of EVNP to assess graft perfusion of potential domino transplants following therapeutic nephrectomy and backbench arterial reconstruction in four cases of refractory hypertension secondary to renal artery stenosis (RAS) unsuitable for endovascular treatment. Case Detail: Patient A and Patient B had isolated unilateral RAS presumed secondary to fibromuscular dysplasia. Pre-operative imaging and functional assessment revealed a split function of the affected kidneys to be 38% and 43%, for Patient A and Patient B, respectively. Patient C and Patient D had a wider distribution of vascular occlusive disease. Patient C had an occluded left renal artery with an atrophic left kidney and no evidence of function on isotope imaging. Following unsuccessful angioplasty and stenting, Patient D had developed in stent occlusion; subsequent imaging demonstrated hypo-perfused right kidney with 6% estimated split function. Outcome: Following nephrectomy, all kidneys were prepared on the backbench for EVNP. For Patient A and Patient B, a common stem was created using spatulation of the renal artery and reconstruction with collateral vessels (plus saphenous vein patch in Patient B). Both grafts perfused well with excellent global perfusion and urine output (EVNP assessment score=1). Beyond the stent stenosis, the renal artery from Patient C was short but allowed cannulation following dilatation. Patient D required separate cannulation (to renal artery and main collateral) with 14G cannula. Patient C and Patient D demonstrated high resistance and poorer perfusion (EVNP assessment score=4). The kidneys from Patient A and Patient B were successfully transplanted into two dialysis-dependent patients who achieved primary function and eGFR of 58 and 62ml/min/1.73m2, respectively. Discussion: The demonstration of adequate arterial reconstruction plus excellent graft perfusion whilst on EVNP, alongside favourable pre-operative functional imaging, provided confidence to transplant two marginal domino grafts.

MO077: Systemic Therapy with a Single-Dose Kidney-Targeted Bioengineered VEGF Construct Improves Stenotic Kidney Hemodynamics in Experimental Renovascular Disease

Abstract BACKGROUND AND AIMS We recently developed a construct of an elastin-like polypeptide fused to VEGF (ELP-VEGF) and showed its efficacy to target and protect the kidney after single systemic administration in a swine model of unilateral renovascular disease (RVD) via therapeutic angiogenesis. Despite a demonstrated renal efficacy, the possibility of off-target binding of VEGF to other organs and undesired effects exists. Thus, we augmented renal specificity by adding a kidney-targeting peptide (KTP) and showed that KTP-ELP accumulates in the kidney to a greater extent than ELP (rodents and swine). Furthermore, addition of KTP redirected ELP-VEGF, which was found at high levels in the liver, to the kidney (rodents). The current proof-of-concept study aims to define the renal therapeutic efficacy of the KTP-ELP-VEGF construct after systemic administration in RVD. METHOD RVD was induced in 12 pigs by unilateral renal artery stenosis and observed for 10 weeks. After 6 weeks, pigs were treated with a single IV dose of untargeted ELP-VEGF, KTP-ELP-VEGF (1 mg/kg, through ear vein) or placebo (n = 4 each). RBF, GFR and cortical perfusion were quantified in vivo using multi-detector CT before and 4 weeks after treatment/placebo. An additional four animals were used as normal controls. RESULTS Stenotic-kidney hemodynamics were similarly reduced in all RVD pigs 6 weeks after induction of renal artery stenosis. Administration of ELP-VEGF or KTP-ELP-VEGF led to significant improvements in RBF, GFR and cortical perfusion compared with pretreatment values, suggesting no interference with VEGF's biological activity. Notably, KTP-ELP-VEGF showed a slightly greater improvement in stenotic kidney hemodynamics than untargeted ELP-VEGF. CONCLUSION This study builds on our recent work and shows for the first time the biological activity and therapeutic efficacy of KTP-ELP-VEGF, expanding the potential of strategies using targeted renal treatments and offering the possibility of intra-renal and systemic routes of administration. The traits of KTP-ELP carriers strengthened drug-delivery strategies by minimizing off-target effects of VEGF or any other therapeutic cargo, which may help to extend applications to other forms of renal disease.

Selective kidney targeting increases the efficacy of mesenchymal stromal/stem cells for alleviation of murine stenotic-kidney senescence and damage.

Chronic ischemia triggers senescence in renal tubules and at least partly mediates kidney dysfunction and damage through a p16Ink4a -related mechanism. We previously showed that mesenchymal stromal/stem cells (MSCs) delivered systemically do not effectively decrease cellular senescence in stenotic murine kidneys. We hypothesized that selective MSC targeting to injured kidneys using an anti-KIM1 antibody (KIM-MSC) coating would enhance their ability to abrogate cellular senescence in murine renal artery stenosis (RAS). KIM-MSC were injected into transgenic INK-ATTAC mice, which are amenable for selective eradication of p16Ink4a+ cells, 4weeks after induction of unilateral RAS. To determine whether KIM-MSC abolish p16Ink4a -dependent cellular senescence, selective clearance of p16Ink4a+ cells was induced in a subgroup of RAS mice using AP20187 over 3weeks prior to KIM-MSC injection. Two weeks after KIM-MSC aortic injection, renal senescence, function, and tissue damage were assessed. KIM-MSC delivery decreased gene expression of senescence and senescence-associated secretory phenotype factors, and improved micro-MRI-derived stenotic-kidney glomerular filtration rate and perfusion. Renal fibrosis and tubular injury also improved after KIM-MSC treatment. Yet, their efficacy was slightly augmented by prior elimination of p16Ink4a+ senescent cells. Therefore, selective targeting of MSC to the injured kidney markedly improves their senolytic potency in murine RAS, despite incomplete eradication of p16+ cells. KIM-MSC may constitute a useful therapeutic strategy in chronic renal ischemic injury.

Reliable Assessment of Swine Renal Fibrosis Using Quantitative Magnetization Transfer Imaging.

Quantitative magnetization transfer (qMT) is useful for measurement of murine renal fibrosis at high and ultrahigh field strengths. However, its utility at clinical field strengths and in human-like kidneys remains unknown. We tested the hypothesis that qMT would successfully detect fibrosis in swine kidneys with unilateral renal artery stenosis (RAS) at 3.0 T. The qMT protocol is composed of MT scans with variable flip angles and offset frequencies, and of B0, B1, and T1 mapping. Pigs were scanned 10 weeks after RAS or control. A 2-pool model was used to fit the bound pool fraction f of the renal cortex (CO) and outer medulla (OM). Then qMT-derived f in 5 normal and 10 RAS pigs was compared with histological fibrosis determined using Masson's trichrome staining and to renal perfusion assessed with computed tomography. The qMT 2-pool model provided accurate fittings of data collected on swine kidneys. Stenotic kidneys showed significantly elevated f in both the CO (9.8% ± 2.7% vs 6.4% ± 0.9%, P = 0.002) and OM (7.6% ± 2.2% vs 4.7% ± 1.1%, P = 0.002), as compared with normal kidneys. Histology-measured renal fibrosis and qMT-derived f correlated directly in both the cortex (Pearson correlation coefficient r = 0.93, P < 0.001) and OM (r = 0.84, P = 0.002), and inversely with stenotic kidney perfusion (r = 0.85, P = 0.002). This study demonstrates the feasibility of qMT for measuring fibrosis in human-like swine kidneys, and the association between tissue macromolecule content and renal perfusion. Therefore, qMT may be useful as a tool for noninvasive assessment of renal fibrosis in subjects with RAS at clinical field strengths.

Atheromatous unilateral renal artery stenosis presenting as pheochromocytoma mimic

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Evaluation of Endovascular Therapy for Unilateral Atherosclerotic Renal Artery Stenosis Using Measurements of Differential Renal Function

Abstract Background To evaluate the efficacy of endovascular therapy in patients with unilateral arteriosclerotic renal artery stenosis using nuclide renal dynamic imaging and to analyze the influencing factors that may affect the renal function. Methods A retrospective analysis was made on 60 patients with &amp;gt;70% unilateral arteriosclerotic renal artery stenosis who underwent renal artery stent implantation. Serum creatinine, urea nitrogen, renal artery color Doppler ultrasonography, and renal dynamic imaging results were obtained before and after 1 year of operation. A regression model was used to analyze the influencing factors. Results All patients underwent balloon dilatation and stenting of the affected renal artery. The immediate intervention success rate was 100%. The residual stenosis of the affected renal artery was less than 20%. No serious complications occurred during the perioperative period. After operation, systolic blood and diastolic blood pressures were improved (P &amp;lt; 0.01), the serum creatinine was stable (P = 0.25), and the degree of renal artery stenosis of the affected side was relieved significantly (P &amp;lt; 0.01). One year after operation, the patency rate of renal artery stent was 85%. Based on the changes of differential glomerular filtration rate of the affected side, 40 patients (66.7%) were improved while 20 patients (33.3%) were not. A linear regression analysis showed that the renal insufficiency of the affected side before operation was the only significant influencing factor (B = 0.50, P &amp;lt; 0.01). Conclusions Renal artery stenting is safe and effective in the treatment of unilateral renal artery stenosis. One-year patency rate is 85%. Two-thirds of the patients have an improved renal function after operation. The patients with preoperative renal insufficiency of affected side are more likely to benefit from renal artery stenting.

Impaired immunomodulatory capacity in adipose tissue-derived mesenchymal stem/stromal cells isolated from obese patients.

Immune‐modulatory properties of adipose tissue‐derived mesenchymal stem/stromal cells (MSCs) might be susceptible to metabolic disturbances. We hypothesized that the immune‐modulatory function of MSCs might be blunted in obese human subjects. MSCs were collected from abdominal subcutaneous fat of obese and lean subjects during bariatric or kidney donation surgeries, respectively. MSCs were co‐cultured in vitro for 24 h with M1 macrophages, which were determined as M1or M2 phenotypes by flow cytometry, and cytokines measured in conditioned media. In vivo, lean or obese MSCs (5 × 105), or PBS, were injected into mice two weeks after unilateral renal artery stenosis (RAS) or sham surgeries (n = 6 each). Fourteen days later, kidneys were harvested and stained with M1 or M2 markers. Lean MSCs decreased macrophages M1 marker intensity, which remained elevated in macrophages co‐cultured with obese MSCs. TNF‐α levels were four‐fold higher in conditioned media collected from obese than from lean MSCs. RAS mouse kidneys were shrunk and showed increased M1 macrophage numbers and inflammatory cytokine expression compared with normal kidneys. Lean MSCs decreased M1 macrophages, M1/M2 ratio and inflammation in RAS kidneys, whereas obese MSCs did not. MSCs isolated from lean human subjects decrease inflammatory M1 macrophages both in vivo and in vitro, an immune‐modulatory function which is blunted in MSCs isolated from obese subjects.