Atherosclerotic Renovascular Disease Research Articles

Improving outcomes in atherosclerotic renovascular disease: importance of clinical presentation and multi-disciplinary review.

Atherosclerotic renal artery stenosis may cause hypertension, chronic kidney disease and heart failure, but large randomized control trials to date have shown no major additional benefit of renal revascularization over optimal medical management. However, these trials did not consider outcomes specifically in relation to clinical presentations. Given that atherosclerotic renal artery stenosis is a heterogenous condition, measures of success likely differ according to the clinical presentation. Our retrospective study objectives were to determine the effects of revascularization when applied to specific clinical presentations and after careful multi-disciplinary team review. All patients presenting to our centre and its referring hospitals with radiological findings of at least one renal artery stenosis > 50% between January 2015 and January 2020 were reviewed at the renovascular multi-disciplinary team meeting with revascularization considered in accordance with international guidelines, notably for patients with anatomically significant renal artery stenosis, adequately sized kidney and presentations with any of; deteriorating kidney function, heart failure syndrome, or uncontrollable hypertension. Optimal medical management was recommended for all patients which included lipid lowering agents, anti-platelets and anti-hypertensives targeting blood pressure ≤ 130/80mmHg. The effect of revascularization was assessed according to the clinical presentation; blood pressure and number of agents in those with renovascular hypertension, delta glomerular filtration rate in those with ischaemic nephropathy and heart failure re-admissions in those with heart failure syndromes. During this 5-year period, 127 patients with stenosis ≥ 50% were considered by the multidisciplinary team,with 57 undergoing revascularization (17 primarily for severe hypertension, 25 deteriorating kidney function, 6 heart failure syndrome and 9 for very severe anatomical stenosis). Seventy-ninepercent of all revascularized patients had a positive outcome specific to their clinical presentation, with 82% of those with severe hypertension improving blood pressure control, 72% with progressive ischaemic nephropathy having attenuated GFR decline, and no further heart failure admissions in those with heart failure. Seventy-eight percent of patients revascularized for high grade stenosis alone had better blood pressure control with 55% also manifesting renal functional benefits. Multi-disciplinary team discussion successfully identified a group of patients more likely to benefit from revascularization based on 3 key factors: clinical presentation, severity of the renal artery lesion and the state of the kidney beyond the stenotic lesion. In this way, a large proportion of patients can clinically improve after revascularization if their outcomes are considered according to the nature of their clinical presentation.

A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension.

In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office BP<130/80mmHg in most and against target office BP<120/70mmHg in all patients with CKD; recommendations for use of spironolactone or chlortalidone for patients with resistant hypertension with eGFR higher or lower than 30ml/min/1.73m2, respectively; use of an SGLT2-inhibitor for patients with CKD and eGFR ≥20ml/min/1.73m2; use of finerenone for patients with CKD, type 2 DM, albuminuria, eGFR ≥25ml/min/1.73m2 and serum potassium<5.0mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts of ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD.

Kidney Intrinsic Mechanisms as Novel Targets in Renovascular Hypertension.

Almost a hundred years have passed since obstruction of the renal artery has been recognized to raise blood pressure. By now chronic renovascular disease (RVD) due to renal artery stenosis is recognized as a major source of renovascular hypertension and renal disease. In some patients, RVD unaccompanied by noteworthy renal dysfunction or blood pressure elevation may be incidentally identified during peripheral angiography. Nevertheless, in others, RVD might present as a progressive disease associated with diffuse atherosclerosis, leading to loss of renal function, renovascular hypertension, hemodynamic compromise, and a magnified risk for cardiovascular morbidity and mortality. Atherosclerotic RVD leads to renal atrophy, inflammation, and hypoxia but represents a potentially treatable cause of chronic renal failure because until severe fibrosis sets in the ischemic kidney, it retains a robust potential for vascular and tubular regeneration. This remarkable recovery capacity of the kidney begs for early diagnosis and treatment. However, accumulating evidence from both animal studies and randomized clinical trials has convincingly established the inadequate efficacy of renal artery revascularization to fully restore renal function or blood pressure control and has illuminated the potential of therapies targeted to the ischemic renal parenchyma to instigate renal regeneration. Some of the injurious mechanisms identified as potential therapeutic targets included oxidative stress, microvascular disease, inflammation, mitochondrial injury, and cellular senescence. This review recapitulates the intrinsic mechanisms that orchestrate renal damage and recovery in RVD and can be harnessed to introduce remedial opportunities.

Endovascular treatments of atherosclerotic renovascular disease: a narrative review and literature search.

In recent years, endovascular treatments have become more common in patients with renal artery stenosis and aneurysm. Although the treatment algorithms are not universally accepted, endovascular therapy can be readily utilized for the appropriate indications in the context of surgical treatment for renovascular diseases. The most important factor to consider is that the correct indication is applied for such treatment. Although the applied procedures are believed to have minimal risk, any complications that occur may result in major problems. Moreover, the pathology that is being treated (e.g., hypertension, high serum creatinine concentration, or low glomerular filtration rate) must be well defined. As stent and balloon technologies continue to be developed, more positive results are expected in the coming years. In the present study, we reviewed the endovascular treatment algorithms for atherosclerotic renovascular disease and performed a narrative review of the current literature.

#6682 RENAL ARTERY STENOSIS: A SINGLE CENTRE STUDY

Abstract Background and Aims Renal artery stenosis (RAS) is present from 1% to 5% in people affected by arterial hypertension and it is often associated with peripheral artery disease and coronary artery disease; as the matter of fact, it is commonly found in people undergoing cardiac catheterization (18-20%) or angiography for aorto-iliac and lower extremities diseases. The major cause of renal artery stenosis is an atherosclerotic lesion localized in the proximal segment or to the ostium. Clinical presentations are renovascular hypertension and ischemic nephropathy. The aim of the study is to define either endovascular treatment gives a significant benefit on renal function and blood pressure control, when associated to medical therapy. Method This is a retrospective study focused on patients who underwent renal artery angioplasty and stenting in the last ten years, from November 2011 to April 2021 in the Nephrology Department, at Sant'Andrea Hospital, La Spezia (Italy). The primary outcome was kidney function, while secondary outcomes were blood pressure and the number of antihypertensive drugs one year after the revascularization. Patients included in the study had uncontrolled and refractory arterial hypertension (PA ≥140/90 mmHg) and/or progressive worsening of renal function, secondary to bilateral or unilateral stenosis in one functional kidney, that was identified at the color-doppler ultrasound examination by a peak systolic velocity (PSV) &amp;gt;200 ml/min and an aortic-renal ratio &amp;gt;3,5. We found 36 patients who had these characteristics. They were all affected by chronic kidney disease (CKD) (mean±SD eGFR 25,3±15,3 ml/min/1,73 m2) equally divided into stage 3 (33%, eGFR 30-60 ml/min/1,73 m2), stage IV (31% eGFR 15-29 ml/min/1,73 m2) and stage V (36%, eGFR &amp;lt;15 ml/min/1,73 m2). Results Kidney function, measured as serum creatinine (SCr) (mg/dl), improved immediately after the revascularization (mean ± SD SCr after vs before 2,52 ± 1,61 vs 3,31 ± 2,47 mg/dl p&amp;lt;0.05), after 30 days (mean ± SD SCr after vs before creat. 2,36 ± 1,53 vs 3,19 ± 2,39 mg/dl p&amp;lt;0.05) and after one year (mean ± SD SCr after vs before creat. 2,04 ± 1,16 vs 2,99 ± 2,40 mg/dl p&amp;lt;0.05) (Fig. 1). Regarding arterial hypertension, a significant reduction of both systolic (SBP) and diastolic (DBP) blood pressure was detected in the subgroup of people under 75 years old (mean ± SD SBP after vs before, 144,62 ± 12,55 vs 168,18 ± 36,40 mmHg, p&amp;lt; 0,01; after one year vs before, 143,95 ± 21,10 vs 167,83 ± 38,16 mmHg, p&amp;lt;0.05) (mean ± SD DBP after vs before, 73,62 ± 9,62 vs 83,07 ± 21,75 mmHg, p&amp;lt; 0,05; after one year vs before 75,20 ± 9,02 vs 83,33 ± 23,10 mmHg, p = 0.07) (Fig. 2). The number of antihypertensive drugs dropped immediately after the angioplasty (mean ± SD tablets after vs before 2,28 ± 1,11 vs 3,21 ± 1,43, p&amp;lt;0.01), while after one year there was not a significant increase of therapy (mean ± SD tablets after one year vs before, 3,00 ± 1,41 vs 3,23 ± 1,42, p = 0,47), even if blood pressure was better controlled than before the procedure with the same amount of tablets (Fig. 3). Conclusion Although our population was quite small, we demonstrated the advantages of renal artery revascularization in atherosclerotic renovascular disease, as demonstrated by kidney function and blood pressure control. Our results contrast the larger studies considered, that found no relevant clinical benefit on renal function and incidence of major adverse cardiovascular and renal events by comparing patients treated with medical therapy alone or with medical therapy plus angioplasty. The different conclusions are probably due to our strict adhesion to the endovascular treatment indications, which consider the revascularization as the optimal strategy for a well-defined population.

Atherosclerotic renovascular disease: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and the Working Group Hypertension and the Kidney of the European Society of Hypertension (ESH).

Atherosclerotic renovascular disease (ARVD) is the most common type of renal artery stenosis. It represents a common health problem with clinical presentations relevant to many medical specialties and carries a high risk for future cardiovascular and renal events, as well as overall mortality. The available evidence regarding the management of ARVD is conflicting. Randomized controlled trials failed to demonstrate superiority of percutaneous transluminal renal artery angioplasty (PTRA) with or without stenting in addition to standard medical therapy compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD, but they carried several limitations and met important criticism. Observational studies showed that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes (i.e. flash pulmonary oedema, resistant hypertension or rapid loss of kidney function). This clinical practice document, prepared by experts from the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and from the Working Group on Hypertension and the Kidney of the European Society of Hypertension (ESH), summarizes current knowledge in epidemiology, pathophysiology and diagnostic assessment of ARVD and presents, following a systematic literature review, key evidence relevant to treatment, with an aim to support clinicians in decision making and everyday management of patients with this condition.

Correction to: Renal Artery Stenting in Consecutive High-Risk Patients With Atherosclerotic Renovascular Disease: A Prospective 2-Center Cohort Study.

Correction to: Renal Artery Stenting in Consecutive High-Risk Patients With Atherosclerotic Renovascular Disease: A Prospective 2-Center Cohort Study.

Endovascular Versus Medical Management of Atherosclerotic Renovascular Disease: Update and Emerging Concepts.

Atherosclerotic renovascular disease is the most frequent cause of renovascular hypertension and its prevalence increases with age and in specific subset of patients, such as those with end-stage chronic kidney disease, heart failure, and coronary artery disease. Besides hypertension, atherosclerotic renovascular disease is responsible for several clinical manifestations, including life-threatening conditions, such as recurrent flash pulmonary edema, rapidly progressive chronic kidney disease, or acute kidney injury. Atherosclerotic renovascular disease is usually part of a more diffuse atherosclerotic process and requires a combination therapy including antihypertensive, antiplatelet and lipid-lowering agents, as well as optimization of antidiabetic treatment, if needed. Besides medical therapy, percutaneous renal angioplasty was supposed to be the most effective therapy for atherosclerotic renovascular disease, by leading to blood flow restoration. However, despite an apparently solid rationale, several randomized clinical trials failed to confirm the favorable effects of percutaneous renal angioplasty on blood pressure control, kidney function, cardiovascular and renal outcomes, previously reported in observational, retrospective and single-center cohorts, switching off the enthusiasm for this procedure. Several studies' limitations may partly account for this failure, including heterogeneity of diagnostic techniques, overestimation of the degree of renal artery stenosis, inappropriate timing of revascularization, multiple protocol revisions, frequent crossovers, and most importantly exclusion of patients at higher likelihood to respond to angioplasty. The purpose of this review is to summarize studies' potential weaknesses and provide guidance to the clinician for identification of patients who may benefit most from revascularization.

Atherosclerotic renovascular disease and cardiovascular risk: new concepts.

Renal vascular hypertension (RVHT) is one of the most common secondary forms of hypertension. It is estimated that 1% to 5% of all cases of hypertension can be attributed to RVHT. RVHT is generally caused by progressive stenosis of the renal artery most often due to atherosclerosis, and less often caused by fibromuscular dysplasia. Atherosclerotic renal artery stenosis (ARAS) can lead to the development of resistant hypertension and can also cause progressive impairment of renal function. ARAS can also result in serious cardiac complications, such as flash pulmonary edema or congestive heart failure. Most patients with ARAS are characterized by the presence of left ventricular hypertrophy and diastolic dysfunction. The disease progression is associated with an increase in left ventricular mass index and cardiac dilatation. Atherosclerotic renovascular disease is recognized as a relevant risk factor for cardiovascular morbidity and mortality. Studies published so far documented ARAS as a predictor of higher cardiovascular risk and showed that mortality after incidental ARAS diagnosis is much higher than that observed in the general population. Proper recognition of the patients with ARAS who would benefit from interventional treatment is crucial, particularly for identification of patients with true resistant hypertension, flash pulmonary edema, and progressive impairment of renal function.

Autologous Extracellular Vesicles Attenuate Cardiac Injury in Experimental Atherosclerotic Renovascular Disease More Effectively Than Their Parent Mesenchymal Stem/Stromal Cells.

Atherosclerotic renovascular disease (RVD) leads to hypertension, chronic kidney disease (CKD), and heart disease. Intrarenal delivery of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) attenuate renal injury and suppress release of inflammatory cytokines in porcine RVD. We hypothesized that this strategy would also be useful for cardioprotection. Pigs with renovascular hypertension and metabolic syndrome were studied 4 weeks after treatment with a single intrarenal infusion of autologous MSCs, EVs, or vehicle. Cardiac structure and function were assessed in vivo, and myocardial remodeling and expression of the pro-fibrotic factor growth factor receptor-bound protein-2 (Grb2) were measured ex-vivo. Inflammatory cytokine levels were measured in the systemic circulation and myocardial tissue. Blood pressure was elevated in all RVD groups, but serum creatinine increased in RVD and decreased in both RVD + MSCs and RVD + EVs. RVD-induced diastolic dysfunction (lower E/A ratio) was normalized in both MSCs- and EVs- treated pigs. Intrarenal delivery of MSCs and EVs also attenuated RVD-induced myocardial fibrosis, collagen deposition, and Grb2 expression, yet EVs restored capillary density and inflammation more effectively than MSCs. These observations suggest that autologous EVs attenuate cardiac injury in experimental RVD more effectively than their parent MSCs.

Cardiovascular Disease Prevention in Patients With Atherosclerotic Renovascular Disease-Induced Resistant Hypertension: Further Considerations for 24-Hour BloodPressure Profiles.

Cardiovascular Disease Prevention in Patients With Atherosclerotic Renovascular Disease-Induced Resistant Hypertension: Further Considerations for 24-Hour BloodPressure Profiles.

With a Little Help From My Friends: the Role of the Renal Collateral Circulation in Atherosclerotic Renovascular Disease.

The collateral circulation can adapt to bypass major arteries with limited flow and serves a crucial protective role in coronary, cerebral, and peripheral arterial disease. Emerging evidence indicates that the renal collateral circulation can similarly adapt and thereby limit kidney ischemia in atherosclerotic renovascular disease. These adaptations predominantly include recruitment of preexisting microvessels for arteriogenesis, with de novo vessel formation playing a limited role. Yet, adaptations of the renal collateral circulation in renovascular disease are often insufficient to fully compensate for the limited flow within an obstructed renal artery and may be hampered by the severity of obstruction or patient comorbidities. Experimental strategies have attempted to circumvent limitations of collateral formation and improve the prognosis of patients with various ischemic vascular territories. These have included pharmacological approaches such as endothelial growth factors, renin-angiotensin-aldosterone system blockade, and If channel-blockers, as well as interventions like preconditioning, exercise, enhanced external counter-pulsation, and low-energy shock-wave therapy. However, few of these strategies have been implemented in atherosclerotic renovascular disease. This review summarizes current understanding regarding the development of renal collateral circulation in atherosclerotic renovascular disease. Studies are needed to apply lessons learned in other vascular beds in the setting of atherosclerotic renovascular disease to develop new treatment regimens for this patient group.

Long-Term Outcomes After Renal Revascularization for Atherosclerotic Renovascular Disease in the ASTRAL Trial

Long-Term Outcomes After Renal Revascularization for Atherosclerotic Renovascular Disease in the ASTRAL Trial

Atherosclerotic Renovascular Disease: A KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference

The diagnosis and management of atherosclerotic renovascular disease (ARVD) is complex and controversial. Despite evidence from the ASTRAL (2009) and CORAL (2013) randomized controlled trials showing that percutaneous renal artery revascularization did not improve major outcomes compared with best medical therapy alone over 3-5 years, several areas of uncertainty remain. Medical therapy, including statin and antihypertensive medications, has evolved in recent years, and the use of renin-angiotensin-aldosterone system blockers is now considered the primary means to treat hypertension in the setting of ARVD. However, the criteria to identify kidneys with renal artery stenosis that have potentially salvageable function are evolving. There are also data suggesting that certain high-risk populations with specific clinical manifestations may benefit from revascularization. Here, we provide an overview of the epidemiology, diagnosis, and treatment of ARVD based on consensus recommendations from a panel of physician experts who attended the recent KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference on central and peripheral arterial diseases in chronic kidney disease. Most focus is provided for contentious issues, and we also outline aspects of investigation and management of ARVD that require further research.

Inflammation and Oxidative Damage in Ischaemic Renal Disease.

Ischaemic renal disease as result of atherosclerotic renovascular disease activates a complex biological response that ultimately leads to fibrosis and chronic kidney disease. Large randomised control trials have shown that renal revascularisation in patients with atherosclerotic renal artery disease does not confer any additional benefit to medical therapy alone. This is likely related to the activation of complex pathways of oxidative stress, inflammatory cytokines and fibrosis due to atherosclerotic disease and hypoxic injury due to reduced renal blood flow. New evidence from pre-clinical trials now indicates a role for specific targeted therapeutic interventions to counteract this complex pathogenesis. This evidence now suggests that the focus for those with atherosclerotic renovascular disease should be a combination of revascularisation and renoprotective therapies that target the renal tissue response to ischaemia, reduce the inflammatory infiltrate and prevent or reduce the fibrosis.

A Case Report of Recurrent Flash Pulmonary Edema: The Pickering Syndrome

Flash Pulmonary Edema (FPE) is a type of recurrent pulmonary edema that usually develops in patients with critical bilateral renal artery stenosis (RAS) or renal artery stenosis to a solitary kidney. A recent recommendation from the 20th European Meeting on Hypertension proposes naming this clinical entity Pickering Syndrome. Currently, it is one of the few clear indications for endovascular procedures in atherosclerotic renovascular disease. We present a case of a 45-year old female with Pickering syndrome and good outcome after revascularization.

Microvascular Loss and Remodeling in Human Kidneys Distal to Severe Atherosclerotic Renovascular Disease

Microvascular Loss and Remodeling in Human Kidneys Distal to Severe Atherosclerotic Renovascular Disease

Peristenotic Collateral Circulation in Atherosclerotic Renovascular Disease: Association With Kidney Function and Response to Treatment.

The significance of peristenotic collateral circulation (PCC) development around a stenotic renal artery is unknown. We tested the hypothesis that PCC is linked to loss of kidney function and recovery potential in patients with atherosclerotic renovascular disease (ARVD). Thirty-four patients with ARVD were assigned to medical-therapy with or without revascularization based on clinical indications. The PCC was visualized using multidetector computed tomography and defined relative to segmental arteries in patients with essential hypertension. PCC number before and 3 months after treatment was correlated with various renal parameters. Thirty-four stenotic kidneys from 30 patients were analyzed. PCC number correlated inversely with kidney volume. ARVD-stenotic kidneys with baseline PCC (collateral ARVD [C-ARVD], n=13) associated with elevated 24-hour urine protein and stenotic kidney vein level of tumor necrosis factor-α, lower single-kidney volume and blood flow, and greater hypoxia than in stenotic kidneys with no PCC (no collateral ARVD [NC-ARVD], n=17). Revascularization (but not medical-therapy alone) improved stenotic kidney function and reduced inflammation in both NC-ARVD and C-ARVD. In C-ARVD, revascularization also increased stenotic kidney volume, blood flow, and oxygenation to levels comparable to NC-ARVD, and induced PCC regression. However, revascularization improved systolic blood pressure, plasma renin activity, and filtration fraction only in NC-ARVD. Therefore, patients with C-ARVD have greater kidney dysfunction, atrophy, hypoxia, and inflammation compared with patients with NC-ARVD, suggesting that PCC does not effectively protect the stenotic kidney in ARVD. Renal artery revascularization improved in C-ARVD stenotic kidney function, but not hypertension or renin-angiotensin system activation. These observations may help direct management of patients with ARVD.

Selection of Patients for Angioplasty for Treatment of Atherosclerotic Renovascular Disease: Predicting Responsive Patients

Atherosclerotic renal artery stenosis (ARAS) can cause secondary hypertension, progressive decline in renal function, and cardiac complications. Recent randomized controlled trials including the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study have not reported the benefit of renal artery stenting compared with medical therapy alone to improve renal function or reduce cardiovascular and renal events in the enrolled patients with ARAS. However, observational evidence indicating the benefits of angioplasty in the selected high-risk patients with ARAS has been increasing. Thus, the timely correction of stenosis through angioplasty may have a beneficial effect in selected patients. However, optimal patient selection for angioplasty has been debated and can be challenging at times. Clinicians must identify the responsive patients who would benefit from angioplasty through risk stratification and the prediction of outcomes. Efforts have been made for the determination of predictors that can identify the subgroups of patients who would benefit from angioplasty. Lower age, more severe stenosis, preserved renal perfusion, and absence of diabetes or generalized atherosclerosis have been reported as the predictors for the improvement of hypertension after angioplasty. Global renal ischemia, rapidly declining renal function over 6-12 months, progressive shrinkage of the affected kidney, lower resistive index, and lower levels of albuminuria have been reported as predictors of improved or preserved renal function after angioplasty. This review discusses the identification of ARAS patients who will potentially respond well to angioplasty.

In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure

Atherosclerotic renovascular disease (ARVD) reduces tissue perfusion and eventually leads to loss of kidney function with limited therapeutic options. Here we describe results of Phase 1a escalating dose clinical trial of autologous mesenchymal stem cell infusion for ARVD. Thirty-nine patients with ARVD were studied on two occasions separated by three months. Autologous adipose-derived mesenchymal stem cells were infused through the renal artery in 21 patients at three different dose levels (1, 2.5 and 5.0× 105 cells/kg) in seven patients each. We measured renal blood flow, glomerular filtration rate (GFR) (iothalamate and estimated GFR), renal vein cytokine levels, blood pressure, and tissue oxygenation before and three months after stem cell delivery. These indices were compared to those of 18 patients with ARVD matched for age, kidney function and blood pressure receiving medical therapy alone that underwent an identical study protocol. Cultured mesenchymal stem cells were also studied invitro. For the entire stem cell treated-cohort, mean renal blood flow in the treated stenotic kidney significantly increased after stem cell infusion from (164 to 190 ml/min). Hypoxia, renal vein inflammatory cytokines, and angiogenic biomarkers significantly decreased following stem cell infusion. Mean systolic blood pressure significantly fell (144 to 136 mmHg) and the mean two-kidney GFR (Iothalamate) modestly but significantly increased from (53 to 56 ml/min). Changes in GFR and blood pressure were largest in the high dose stem cell treated individuals. No such changes were observed in the cohort receiving medical treatment alone. Thus, our data demonstrate the potential for autologous mesenchymal stem cell to increase blood flow, GFR and attenuate inflammatory injury in post-stenotic kidneys. The observation that some effects are dose-dependent and related to in-vitro properties of mesenchymal stem cell may direct efforts to maximize potential therapeutic efficacy.