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Rationale and Objectives: Multidetector computed tomography (MDCT) is useful for measuring in the research setting single-kidney perfusion and function using iodinated contrast time-attenuation curves. Obesity promotes deposition of intrarenal fat, which might decrease tissue attenuation and thereby interfere with quantification of renal function using MDCT. The purpose of this study was to test the hypothesis that background subtraction adequately accounts for intrarenal fat deposition in mildly obese human subjects during renal contrast enhanced dynamic CT.Materials and Methods: We prospectively recruited seventeen human subjects stratified as lean or mildly obese based on body mass index below or over 30 kg/m2, respectively. Renal perfusion was quantified from CT-derived indicator-dilution curves after background subtraction. Dual-energy MDCT images were postprocessed to generate iodine and virtual-noncontrast datasets, and the ratios between kidney/aorta CT numbers and iodine values calculated as surrogates of renal function.Results: Subcutaneous adipose tissue was increased in obese subjects. Virtual-noncontrast maps revealed in obese patients a decrease in basal cortical and medullary attenuation. Overall, basal attenuation inversely correlated with body mass index, in line with renal fat deposition. Contrarily, the kidney/aorta CT attenuation (after background subtraction) and kidney/aorta iodine ratios were similar between lean and obese subjects and correlated directly. These observations show that following background subtraction, the CT number reliably reflects basal tissue attenuation.Conclusion: Therefore, our findings support our hypothesis that background subtraction enables reliable assessment of kidney function in mildly obese subjects using MDCT, despite decreased basal attenuation due to renal adiposity. [ABSTRACT FROM AUTHOR]

A gradually developing reduction in renal blood flow from atherosclerotic renovascular disease results in loss of kidney volume and a decrease in glomerular filtration rate that eventually becomes irreversible. Whether this process fundamentally reflects tissue hypoxia has been difficult to establish. Studies of human renovascular disease have indicated that reductions in blood flow of up to 30% to 40% can be tolerated with preservation of normal oxygenation and structural integrity. These observations are consistent with remarkable stability of poststenotic kidney function during sustained medical antihypertensive drug therapy in moderate renovascular disease. With more severe and sustained reductions, however, cortical oxygenation decreases and the magnitude of medullary hypoxia expands. These changes are associated with increasing renal venous levels of inflammatory cytokines, angiogenic markers, and infiltration of inflammatory cells, including tissue macrophages and T cells. Although restoring large-vessel blood flow can improve oxygenation, some of these processes reflect microvascular rarefication, remain activated, and do not depend on hemodynamic factors alone. Elucidation of tissue injury pathways associated with hypoxia opens the possibility of adjunctive therapeutic measures beyond renal revascularization. These include cell-based regeneration, mitochondrial protection, and/or angiogenic cytokine therapy to restore or preserve renal function in ischemic nephropathy. [ABSTRACT FROM AUTHOR]

Background Altered vascular structure or function in several diseases may impair renal perfusion. Multi-detector computed tomography (MDCT) is a non-invasive tool to assess single-kidney perfusion and function based on dynamic changes in tissue attenuation during contrast media transit. However, changes in basal tissue attenuation might hamper these assessments, despite background subtraction. Evaluation of iodine concentration using the dual-energy (DECT) MDCT mode allows excluding effects of basal values on dynamic changes in tissue attenuation. We tested whether decreased basal kidney attenuation secondary to intrarenal fat deposition in swine obesity interferes with assessment of renal perfusion using MDCT. Methods Domestic pigs were fed a standard (lean) or a high-cholesterol/carbohydrate (obese) diet (n = 5 each) for 16 weeks, and both kidneys were then imaged using MDCT/DECT after iodinated contrast injection. DECT images were post-processed to generate iodine and virtual-non-contrast (VNC) datasets, and the MDCT kidney/aorta CT number (following background subtraction) and DECT iodine ratios calculated during the peak vascular phase as surrogates of renal perfusion. Intrarenal fat was subsequently assessed with Oil-Red-O staining. Results VNC maps in obese pigs revealed decreased basal cortical attenuation, and histology confirmed increased renal tissue fat deposition. Nevertheless, the kidney/aorta attenuation and iodine ratios remained similar, and unchanged compared to lean pigs. Conclusions Despite decreased basal attenuation secondary to renal adiposity, background subtraction allows adequate assessment of kidney perfusion in obese pigs using MDCT. These observations support the feasibility of renal perfusion assessment in obese subjects using MDCT. [ABSTRACT FROM AUTHOR]

Purpose: To identify risk factors for progression to renal replacement therapy (RRT) and all-cause mortality in patients who underwent renal artery (RA) stent placement for atherosclerotic renal artery stenosis (RAS).Materials and Methods: A retrospective study from June 1996 to June 2009 identified 1,052 patients who underwent RA stent placement. Glomerular filtration rate at time of RA stent placement was estimated from serum creatinine level and divided into chronic kidney disease (CKD) stages 1-5. Univariate and multivariable Cox proportional hazards models were used to determine which factors were associated with each endpoint.Results: Times to progression to all-cause mortality and RRT were similar for CKD stages 1/2/3A and served as the reference group. In multivariable analysis, high-grade proteinuria (P < .001) and higher CKD stage (5 vs 1/2/3A [P < .001], 4 vs 1/2/3A [P < .001], 3B vs 1/2/3A [P = .02]) remained independently associated with increased risk of progression to RRT. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use was associated with decreased risk of progression to RRT (P = .03). Higher CKD stage (5 vs 1/2/3A [P < .001], 4 vs 1/2/3A [P = .004]), carotid artery disease (P < .001), diabetes mellitus (P = .002), and high-grade proteinuria (P < .001) remained independently associated with all-cause mortality. Statin use was associated with decreased risk of all-cause mortality (P < .001).Conclusions: Patients with atherosclerotic RAS who undergo RA stent placement and have high-grade proteinuria and CKD stage 3B/4/5 have increased risk of progression to RRT. Patients with high-grade proteinuria, CKD stage 3B/4/5, carotid artery disease, or diabetes have increased risk for all-cause mortality after renal artery stent placement. Patients receiving ACEI/ARBs have a decreased risk of progression to RRT, and patients receiving statins have a decreased risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

Renal function in patients with atherosclerosis and renal artery stenosis (ARAS) deteriorates more frequently than in nonatherosclerotic RAS. We hypothesized that ARAS aggravates stenotic-kidney micro vascular loss compared to RAS. Domestic pigs were randomized to normal, RAS, and ARAS (RAS fed a high-cholesterol diet) groups (n = 7 each). Ten weeks later stenotic-kidney oxygenation, renal blood flow, and glomerular filtration rate (GFR) were evaluated in vivo, and micro vascular density by micro-computed tomography. Blood pressure in both RAS and ARAS was elevated; and stenotic-kidney renal blood flow and GFR similarly decreased. RAS decreased the density of small-size cortical microvessels (<200 μm), whereas ARAS extended the decrease to medium-sized microvessels (200–300 μm). Cortical hypoxia and interstitial fibrosis increased in both RAS and ARAS but correlated inversely with micro vascular density only in RAS. Atherosclerosis aggravates loss of stenotic-kidney microvessels, yet additional determinants likely contribute to cortical hypoxia and fibrosis in swine ARAS. [ABSTRACT FROM AUTHOR]

Occlusion of the renal arteries can threaten the viability of the kidney when severe, in addition to accelerating hypertension and circulatory congestion. Renal artery stenting procedures have evolved from a treatment mainly for renovascular hypertension to a maneuver capable of recovering threatened renal function in patients with 'ischemic nephropathy' and improving management of congestive heart failure. Improved catheter design and techniques have reduced, but not eliminated, hazards associated with renovascular stenting. Expanded use of endovascular stent grafts to treat abdominal aortic aneurysms has introduced a new indication for renal artery stenting to protect the renal circulation when grafts cross the origins of the renal arteries. Although controversial, prospective randomized trials to evaluate the added benefit of revascularization to current medical therapy for atherosclerotic renal artery stenosis until now have failed to identify major benefits regarding either renal function or blood pressure control. These studies have been limited by selection bias and have been harshly criticized. While studies of tissue oxygenation using blood-oxygen-level-dependent (BOLD) magnetic resonance establish that kidneys can adapt to reduced blood flow to some degree, more severe occlusive disease leads to cortical hypoxia associated with microvascular rarefaction inflammatory injury, and fibrosis. Current research is directed toward identifying pathways of irreversible kidney injury due to vascular occlusion and to increase the potential for renal repair after restoring renal artery patency. The role of nephrologists likely will focus upon recognizing the limits of renal adaptation to vascular disease and identifying kidneys truly at risk for ischemic injury at a time point when renal revascularization can still be of benefit to recovering kidney function. [ABSTRACT FROM AUTHOR]

Abstract: Abnormal circadian blood pressure (BP) pattern is common after kidney transplantation but its relationship to long term allograft function is unclear. Of 119 kidney recipients who had ambulatory BP monitoring 1 year from transplantation, 36 patients without history of rejection were selected. Twenty-nine recipients were followed for 4 years and seven for 3 years. Iothalamate glomerular filtration rate (GFR) was obtained at 3 weeks then annually. Dippers (n = 10) had day-night systolic BP (SBP) drop (ΔSBP) of ≥10%, nondippers (n = 15) had ΔSBP 0%–9%, whereas reverse dippers (n = 11) had nocturnal rise in SBP. Compared with dippers, reverse and nondippers had a higher Banff cv score at 1 year (P = .03), lower GFR at last follow-up (73.7 ± 18.1, 55.7 ± 16.3, and 56.6 ± 21 mL/min/1.73 m2 for dippers, non-, and reverse dippers, respectively, P = .05) and higher kidney function loss (8.0 ± 20, −9 ± 17, and 1 ± 14 mL/min/1.73 m2 for dippers, non-, and reverse dippers, respectively, P = .02). GFR at 4 years and at last follow-up independently correlated with ΔSBP at 1 year (r = 0.46, P = .01; r = 0.34, P = .03). The current study indicates that abnormal circadian BP pattern at 1 year identifies a group of kidney recipients at risk for increased kidney function loss and lower GFR 3–4 years from transplantation. [Copyright &y& Elsevier]

Abstract: Elevated arterial blood pressure is common after kidney transplantation and contributes to shortened patient and allograft survivals and increased fatal and nonfatal cardiovascular events. Unfortunately, current evidence indicates that arterial blood pressure remains poorly controlled in kidney transplant recipients. One concern is how best to evaluate treated levels of arterial pressure in transplant recipients as office and clinic measurements often differ from blood pressure readings obtained using ambulatory blood pressure monitoring. Some antihypertensive drugs interact with immunosuppressive medications and adversely affect electrolyte balance and kidney function, which complicates the management of kidney transplant patients. Target blood pressure readings have been suggested by different guidelines, but patient-specific management plan is still lacking. Understanding the basic mechanisms responsible for the persistent hypertension after kidney transplantation is helpful in drafting patient-directed management plan that includes both pharmacologic and nonpharmacologic interventions to achieve target blood pressure control. In this review, we propose a multilayered treatment plan that addresses hypertension in both the early and late posttransplant periods, bearing in mind complications of antihypertensive medications, interactions with immunosuppressive drugs, patient comorbidities, and patient-specific cardiovascular risk factors in the posttransplant period. [Copyright &y& Elsevier]

Abstract: Renal injury distal to an atherosclerotic renovascular obstruction reflects multiple intrinsic factors producing parenchymal tissue injury. Atherosclerotic disease pathways superimposed on renal arterial obstruction may aggravate damage to the kidney and other target organs, and some of the factors activated by renal artery stenosis may in turn accelerate the progression of atherosclerosis. This cross-talk is mediated through amplified activation of renin-angiotensin system, oxidative stress, inflammation, and fibrosis—pathways notoriously involved in renal disease progression. Oxidation of lipids also accelerates the development of fibrosis in the stenotic kidney by amplifying profibrotic mechanisms and disrupting tissue remodeling. The extent to which actual ischemia modulates injury in the stenotic kidney has been controversial, partly because the decrease in renal oxygen consumption usually parallels a decrease in renal blood flow, and because renal vein oxygen pressure in the affected kidney is not decreased. However, recent data using novel methodologies demonstrate that intra-renal oxygenation is heterogeneously affected in different regions of the kidney. Activation of such local injury within the kidney may lead to renal dysfunction and structural injury, and ultimately unfavorable and irreversible renal outcomes. Identification of specific pathways producing progressive renal injury may enable development of targeted interventions to block these pathways and preserve the stenotic kidney. [Copyright &y& Elsevier]

Abstract: Management of atherosclerotic renal artery stenosis has become more complex with advances in both medical therapy and endovascular procedures. Results from recent trials fail to demonstrate major benefits of endovascular stenting in addition to optimal medical therapy. The general applicability of these results to many patients is limited by short-term follow-up and selection biases in recruitment. Many patients at highest risk were excluded from these studies and some were included with trivial lesions. Identification of patients with hemodynamically significant lesions remains a challenge and has led to more stringent criteria for Doppler ultrasound, measurement of translesional gradients and quantitative angiography. Although many patients can now be managed with medical therapy, it should be recognized that long-term reduction in antihypertensive drug requirements and recovery of kidney function are limited to those undergoing renal revascularization. As with any major vascular lesion, follow-up for disease stability and/or progression is essential. The ambiguity of present trial data may lead some to overlook selected subgroups that would benefit from restoring renal blood supply through revascularization. Further studies to more precisely identify kidneys that can recover function and/or are beyond meaningful recovery are essential. Considering the comorbid risks for the atherosclerotic population, it will remain imperative for clinicians to consider the hazards, costs and benefits carefully for each patient to determine the role and timing for both medical therapy and revascularization. [Copyright &y& Elsevier]

Improved technology for detection of and endovascular procedures for renal artery stenosis due to atherosclerosis has been associated with increases in renal artery intervention. Hypertension with accelerated target organ injury, reduced kidney function, and episodic circulatory congestion in patients with renovascular disease predict reduced patient survival. Recent studies indicate that activation of pressor mechanisms depends upon hemodynamic gradients that are often overrated by visual estimates. Although activation of the renin-angiotensin system initiates renovascular hypertension, additional mechanisms perpetuate vascular remodeling and kidney injury that may not depend upon large vessel occlusion. Major advances in medical therapy have led to initiation of at least 4 major prospective trials comparing optimal medical therapy with or without stenting. Up to now, outcome data fail to support broad application of renal revascularization, including results from a recent large, prospective trial from the United Kingdom, despite small groups of patients that experience major clinical benefit. The ambiguity of these results partly reflect poor characterization of the severity of vascular lesions and competing risks within the population related to aging and pre-existing disease. Many patients currently undergoing renal artery interventions derive little net benefit and some are exposed to significant complications, including atheroembolic disease. Determining the appropriate role for renal artery interventions will depend on developing better methods for judging the role of large vessel occlusive disease regarding tissue oxygenation, activation of profibrotic pathways, and irreversible injury in the post-stenotic kidney. [Copyright &y& Elsevier]

Purpose: To present clinical outcomes with the use of embolic protection devices (EPDs) and renal artery stents in patients with chronic renal insufficiency (CRI) and renal artery stenosis (RAS). Materials and Methods: A retrospective study was conducted in 23 patients with RAS and CRI who were treated with renal artery stent placement with an EPD. Follow-up data were obtained through medical records. Results: In 23 patients (18 men; 78%) with an average age of 69.4 years ± 11 (range, 46–86 y), 32 renal arteries were treated for worsening renal function (n = 17; 74%) or uncontrolled hypertension and worsening renal function (n = 6; 26%). Nine FilterWire EZ devices were used in eight patients (35%) and 17 SpideRX devices were used in 15 patients (65%). The average follow-up was 8 months ± 5. After the stent procedure, the mean systolic blood pressure decreased significantly (P < .05) whereas the diastolic pressure remained unchanged. There was a significant increase in the mean estimated glomerular filtration rate from 32.9 mL/min ± 12.9 at baseline to 41.3 mL/min ± 13.7 at last follow-up (P < .05). In 96% of patients, there was improvement or stabilization of kidney function. In six of the 17 SpideRX devices (35%), macroscopically evident embolic material was observed in the device after stent placement. There were two minor and two major complications. Conclusions: Renal artery stent placement combined with the use of a SpideRX or FilterWire EZ device is associated with an good clinical outcome with a reasonable safety profile. [Copyright &y& Elsevier]

Purpose: To describe restenosis and clinical outcomes with drug-eluting stents (DESs) and compare them to those of bare metal stents (BMSs) in the treatment of symptomatic atherosclerotic renal artery stenosis (RAS) in the same patients. Methods and Materials: A retrospective study was performed of all patients with RAS treated with a DES (Taxus Express 2 or Cypher). DESs were used for RASs with luminal vessel diameters of 4 mm or smaller and BMSs were used for those larger than 4 mm. Results: Sixteen patients (eight women; mean age, 72 years ± 8) underwent treatment of 27 RASs for worsening renal function (n = 10) and uncontrolled hypertension (n = 6). Eighteen RASs were treated with 23 DESs (Cypher, n = 12; Taxus, n = 11) and nine were treated with BMSs. The average follow-up was 22 months ± 10. After the procedure, the mean systolic blood pressure decreased significantly (P < .05), with no change in the mean diastolic pressure, serum creatinine, or number of antihypertensive medications. By Kaplan-Meier estimates, the 1- and 2-year patency rates for DESs were 78% and 68%, respectively; and for BMSs, the respective rates were 58% and 47% (P = NS). The average diameters of RASs were 3.4 mm ± 0.6 in the DES group and 5.3 mm ± 0.6 in the BMS group (P < .05). There were two technical failures (7.7%) in the DES group. There was one minor complication and a non–flow-limiting dissection. Conclusions: DESs were used to treat RASs with good technical results and low restenosis rates compared with BMSs despite the smaller artery diameters in the DES group. [Copyright &y& Elsevier]

Hypertension produced by renal artery occlusive disease is an important secondary form of hypertension. Clinicians commonly encounter forms of renal arterial disease of varying severity, many of which are of little hemodynamic significance when first detected. Experimental studies emphasize that transient activation of the renin-angiotensin-aldosterone system is necessary for initiation of renovascular hypertension. At some point, angiotensin II activates additional mechanisms responsible for sustained increased blood pressure including sodium retention, endothelial dysfunction, and vasoconstriction related to production of reactive oxygen species. Widespread application of agents that block the renin-angiotensin system, including angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, render many patients with unilateral renal arterial disease manageable primarily by medical means for many years. In the setting of high a priori likelihood of renovascular disease, recognizing the potential for disease progression during medical therapy and individually evaluating the risks and benefits of renal revascularization are important tasks. Recent prospective studies show limited, but real, benefit regarding blood pressure control for patients with atherosclerotic disease. Whether earlier renal revascularization offers benefits regarding improved morbidity and mortality from cardiovascular end point reduction is an important question to be addressed in multicenter, prospective, randomized trials. Our paradigm stresses the fact that patients with renovascular hypertension require intensive blood pressure control and cardiovascular risk factor intervention, both before and after revascularization. Hence, management of such patients requires close attention and periodic review regarding restenosis and progression of vascular disease. [ABSTRACT FROM AUTHOR]

Percutaneous transluminal renal angioplasty (PTRA) is the primary treatment for renal fibromuscular dysplasia (RFMD). Surgical revascularization is limited to patients who fail or are unsuitable for PTRA. All patients who were operated on with RFMD since the indications for renal PTRA were expanded in our institution were retrospectively reviewed. Outcome included patency, hypertension, and renal function. Twenty-six patients had reconstruction of 32 renal arteries between 1998 and 2004. The mean age was 47.1?±?14 years; the majority (81%) were female. Six patients had bilateral disease and three had a solitary kidney. Operations were done for hypertension in 25 patients, renal artery aneurysm in 8, and chronic dissection in 1, alone or in combination. Six patients had a failed PTRA and 20 were unsuitable for it. Aortorenal bypass was done most often (n?=?28) and saphenous vein was the preferred conduit (n?=?25). The distal anastomosis was to the main renal artery in 13 patients and to the branch arteries in 19. Ex vivo repair was needed in five patients. Five intraoperative revisions were done because of abnormalities on duplex scan. One patient died unexpectedly 42 days after operation from myocardial infarction. Extrarenal complications occurred in five patients. Median follow-up was 2.4 (range, 42 days to 6.3) years and was available in all but one patient (96%). Two bypasses occluded at 3 and 376 days, which resulted in loss of the kidneys. One graft stenosis was treated successfully with PTRA at 239 days. All failures occurred in men. One-year cumulative primary patency was 89?±?8% and was not adversely affected by prior PTRA or complex repair. Hypertension at 1 year was cured in 27% of the patients and improved in 60%. No patient developed acute or chronic renal failure. Surgical reconstruction for RFMD has excellent short-term patency. Failed PTRA or complex reconstructions did not adversely affect outcome. [ABSTRACT FROM AUTHOR]

Editorial. Discusses the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure's guidelines for the management of hypertension. Blood pressure classification for adults; Blood pressure treatment goals; Antihypertensive therapy; Combination drug therapy.

Examines the effects of revascularization in atherosclerotic renal artery disease. Improvement of blood pressure control; Exposure of patients with accelerating hypertension to risks of surgical revascularization; Implications on the balance of clinical judgment on risks and benefits.

The authors reflect on the importance of early referral for chronic kidney disease (CKD). The authors inferred that CKD is an unrecognized public health concern in the U.S. They believed that the vital component of the CKD classification system provided by the National Kidney Foundation Inc. is the glomerular filtration rate estimate. They averred that the value of early detection and targeted treatment options to lessen morbidity, mortality, and progression to kidney failure is still unknown.

Looks into the close relationship between kidney failure and cardiovascular disease. Emphasis on the prevalence of cardiovascular risk factors based on estimated kidney function; Utilization of the Modification of Diet in Renal Disease equation to estimate the burden of reduced kidney function in the general population; Belief of the authors that there are major opportunities for the medical community to actively benefit patients with chronic kidney disease who often have multiple cardiovascular risk factors.

Abstract Objective Renal function deterioration is an important determinant of mortality in patients treated for complex aortic aneurysms. We have previously determined that catheter and guidewire manipulation in diseased aortas during fenestrated-branched endovascular aneurysm repair (F-BEVAR) is associated with risk of renal function deterioration. The aim of this study was to describe the impact of atherothrombotic aortic wall thrombus (AWT) on renal function deterioration among patients treated by F-BEVAR for pararenal and extent IV thoracoabdominal aortic aneurysms. Methods Clinical data of 212 patients treated for complex aortic aneurysms with F-BEVAR were entered into a prospectively maintained database (2007-2015). AWT was evaluated by computed tomography angiography using volumetric measurements in nonaneurysmal aortic segments. AWT was classified as mild, moderate, or severe using objective assessment of the number of affected segments, thrombus type, thickness, area, and circumference. Acute kidney injury (AKI) was defined using Risk, Injury, Failure, Loss of kidney function, and End-stage renal disease (RIFLE) criteria, and renal function deterioration was defined by a decline in estimated glomerular filtration rate (eGFR) >30% from baseline. Patient survival and renal outcomes were assessed at dismissal, at 6 to 8 weeks, at 6 months, and annually, including AKI, serum creatinine concentration, eGFR, chronic kidney disease stage, need for renal replacement therapy, and presence of kidney infarction. Results There were 169 male (80%) and 43 female (20%) patients with a mean age of 75 ± 7 years. Aneurysm extent was pararenal in 157 patients and extent IV thoracoabdominal aortic aneurysm in 55 patients. A total of 700 renal-mesenteric arteries were incorporated (3.1 ± 1 vessels/patient). AWT was classified as mild in 98 patients (46%), moderate in 75 (35%), and severe in 39 (19%). At 30 days, 45 patients (21%) developed AKI. Decline in eGFR and kidney infarction were associated with higher AWT volume index and severe AWT classification (P <.05). There was no association of AWT with 30-day mortality, which was 0.5% for the entire cohort. Mean follow-up was 29 ± 23 months. Freedom from renal function deterioration was 73% ± 6% for mild, 81% ± 6% for moderate, and 66% ± 8% for severe AWT patients at 3 years (P =.012) and 46% ± 9% and 82% ± 4% for those with or without AKI after the initial procedure (P <.001). Overall, 41 patients (19%) had progression of chronic kidney disease stage, but none of the patients required renal replacement therapy. Survival was 73% ± 5% for mild, 72% ± 6% for moderate, and 69% ± 10% for severe AWT patients at 3 years (P =.67). Conclusions AWT is a significant predictor of AKI and continued decline in renal function after the initial F-BEVAR procedure. Longer follow-up time is needed to determine the actual impact of AWT on survival. [ABSTRACT FROM AUTHOR]

The metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. Mitochondria can be overwhelmed by substrate excess, leading to inefficient energy production and thereby tissue hypoxia. Mitochondrial dysfunction is emerging as an important determinant of renal damage, but whether it contributes to MetS-induced renal injury remains unknown. We hypothesized that early MetS induces kidney mitochondrial abnormalities and dysfunction, which would be notable in the vulnerable renal medulla. Pigs were studied after 16 weeks of diet-induced MetS, MetS treated for the last 4 weeks with the mitochondria-targeted peptide elamipretide (0.1 mg/kg SC q.d), and Lean controls (n = 7 each). Single-kidney renal blood flow, glomerular filtration rate, and oxygenation were measured in-vivo, whereas cortical and medullary mitochondrial structure and function and renal injurious pathways were studied ex-vivo. Blood pressure was slightly elevated in MetS pigs, and their renal blood flow and glomerular filtration rate were elevated. Blood oxygen level-dependent magnetic resonance imaging demonstrated that this was associated with medullary hypoxia, whereas cortical oxygenation remained intact. MetS decreased renal content of the inner mitochondrial membrane cardiolipin, particularly the tetra-linoleoyl (C18:2) cardiolipin species, and altered mitochondrial morphology and function, particularly in the medullary thick ascending limb. MetS also increased renal cytochrome-c-induced apoptosis, oxidative stress, and tubular injury. Chronic mitoprotection restored mitochondrial structure, ATP synthesis, and antioxidant defenses and decreased mitochondrial oxidative stress, medullary hypoxia, and renal injury. These findings implicate medullary mitochondrial damage in renal injury in experimental MetS, and position the mitochondria as a therapeutic target. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ARBs) may induce an acute decrease of glomerular filtration rate (GFR) in the stenotic kidney in renal artery stenosis, but most patients tolerate these drugs well. We hypothesized that angiotensin-converting enzyme inhibitors/ARBs stabilize stenotic kidney function during prolonged treatment by conferring protective effects. We tested this in control domestic pigs and pigs with renal artery stenosis untreated or treated with Valsartan, or triple therapy (seven pigs in each group) for 4 weeks starting 6 weeks after stenosis induction. Renal function, oxygenation, tubular function, and microcirculation were assessed by multi-detector computed tomography (CT), blood oxygen level-dependent magnetic-resonance imaging, and micro-CT. Valsartan and triple therapy decreased blood pressure similarly; however, Valsartan did not change the GFR of the stenotic kidney compared with renal artery stenosis and was similar to triple therapy. Both Valsartan and triple therapy stimulated microvascular density and improved tubular function. Valsartan also caused a greater increase of angiogenic factors and a decrease in oxidative stress, which were related to higher cortical perfusion and tubular response than triple therapy. Thus, Valsartan did not decrease stenotic kidney GFR, but improved cortical perfusion and microcirculation. These beneficial effects may partly offset the hemodynamic GFR reduction in renal artery stenosis and preserve kidney function. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To test the hypothesis that kidney function and metabolic risk factors are associated with glomerular density on renal biopsy samples from healthy adults. PATIENTS AND METHODS: This study compared glomerular density with predonation kidney function, blood pressure, and metabolic risk factors In living kidney donors at Mayo Clinic in Rochester, MN, from May 10, 1999, to February 4, 2009. During Implantation of the kidney allograft, an 18-gauge core needle biopsy sample of the renal cortex was obtained, sectioned, and examined by pathologists. Glomerular density was determined by the number of glomeruli (normal and sclerotic) divided by area of cortex. RESULTS: The study sample of 1046 kidney donors had a mean of 21 glomeruli (0.8 sclerotic glomeruli) and a glomerular density of 2.3 glomeruli per square millimeter. In a subset of 54 donors, glomerular density Inversely correlated with the mean glomerular area (r,=-0.28). independent predictors of decreased glomerular density were older age, increased glomerular filtration rate, family history of end-stage renal disease, increased serum uric acid, and Increased body mass index, Increased urine albumin excretion, hypertension, decreased high-density lipoprotein cholesterol, and metabolic syndrome were also associated with decreased glomerular density after age-sex adjustment. These associations were not explained by the presence of glomerulosclerosis, tubular atrophy, interstitial fibrosis, or arteriosclerosis on the renal biopsy sample. In older donors, decreased glomerular density was attenuated by an increased prevalence of glomerulosclerosis and tubular atrophy. CONCLUSION: Decreased glomerular density is associated with many different kidney function and metabolic risk factors among relatively healthy adults and may represent an early state of increased risk of parenchymal Injury. [ABSTRACT FROM AUTHOR]

Renal revascularization by percutaneous transluminal angioplasty improves blood pressure and stenotic kidney function in selected groups of patients, but the reversibility of intrarenal and microvascular remodeling remains unknown. Here, we tested the hypothesis that renal angioplasty improves the function and structure of renal microcirculation in experimental chronic renal artery stenosis. Stenotic kidney function, hemodynamics, and endothelial function were assessed in vivo in pigs after 10 weeks of unilateral renal artery stenosis. Renal microvascular remodeling, angiogenic pathways, and fibrosis were measured ex vivo. Angioplasty and stenting carried out 4 weeks before measurement decreased blood pressure, improved glomerular filtration rate, and improved microvascular endothelial function. It also promoted the expression of angiogenic factors and decreased renal apoptosis due to stenosis, compared with a sham intervention. The spatial density of renal microvessels, however, was partially improved after angioplasty. Renal blood flow was incompletely restored compared with the kidneys of sham-treated animals, as was interstitial fibrosis. Renal microvascular media-to-lumen ratio remained unchanged by angioplasty. Thus, our study shows that revascularization of a stenotic renal artery restores the glomerular filtration rate and renal endothelial function 4 weeks later. Renal hemodynamics and structure, however, are incompletely resolved. [ABSTRACT FROM AUTHOR]

New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation.Background.Post-transplant diabetes (PTDM) is a common and serious complication of kidney transplantation. The implications of developing hyperglycemia of lesser severity are not well understood.Methods.In this study we used American Diabetes Association (ADA) criteria to assess the incidence of abnormal glycemia post-transplant, the variables that relate to this complication, and the relationship between hyperglycemia and cardiovascular (CV) disease. Included in the study were 490 kidney recipients, transplanted from 1998 to 2003, without a history of diabetes, and with a pretransplant fasting glucose<126 mg/dL.Results.Within one week post-transplant, 45% of recipients had impaired fasting glycemia (IFG, glucose 100–125 mg/dL), and 21% PTDM (glucose≥126). One year post-transplant, 33% of patients had IFG, and 13% PTDM. Risk factors for hyperglycemia at one year included: older recipient, male gender, higher BMI, higher pretransplant glucose, and higher glucose one week post-transplant (allP<0.002 by multivariable analyses). During a follow-up period of 40± 14 months, 12% of recipients had CV events (cardiac, CVA, and/or peripheral). Increasing fasting glucose levels at one, four, and/or 12 months post-transplant were significantly related to CV events. Furthermore, these relationships were independent of other CV risk factors, including: older age, CV events pretransplant, male gender, dyslipidemia, and transplant year. Fasting glucose levels>100 mg/dL were associated with higher incidence of post-transplant cardiac (P= 0.001) and peripheral vascular disease events (P= 0.003).Conclusion.The incidence of post-transplant hyperglycemia and its CV impact have been underestimated. Pretransplant characteristics and, particularly, the glycemia during the first month post-transplant identified patients at risk of PTDM. Increasing glucose levels greater than 100 mg/dL, any time after the first month post-transplant, are associated with increasing CV risk. We postulate that aggressive detection and treatment of post-transplant hyperglycemia may significantly reduce CV morbidity and mortality after kidney transplantation. [ABSTRACT FROM AUTHOR]

Patient and graft outcomes from older living kidney donors are similar to those from younger donors despite lower GFR.Background.Donor age adversely affects deceased-donor kidney transplant outcomes, but its influence on living-donor transplantation is less well characterized.Methods.Living-donor kidney transplants at a single center between 1998 and 2000 were reviewed. Data were abstracted for 52 transplants from donors aged≥50 years and for a matched group of 104 transplants from donors aged<50 years. Survival indices were compared during the first three years' post-transplantation. Functional indices, including serial iothalamate clearances, were compared at 1, 12, and 24 months.Results.Predonation glomerular filtration rate (GFR) was lower among older donors (94± 12 vs. 108± 17 mL/min/SA) but post-transplant compensatory hypertrophy was similar (11.7± 26.3% vs. 7.7± 31.4%). Recipients of older-donor grafts were older (52.8± 16.5 vs. 46.1± 15.1 years) and more frequently unrelated to the donor (54% vs. 39%). Trends toward higher frequency of slow graft function, cytomegalovirus (CMV) infection, and polyomavirus nephropathy were observed for older-donor grafts. Three-year recipient, graft, and death-censored graft survivals were≥90% for both groups. At 1, 12, and 24 months, serum creatinine was higher and GFR was lower among recipients of older- compared with younger-donor grafts. Other functional indices (urine total protein, serum potassium and uric acid, hemoglobin, and number of antihypertensives) were not different. Donor age correlated with graft GFR at 1, 12, and 24 months for the entire study cohort by linear regression.Conclusion.Older donor age does not preclude excellent results from living-donor kidney transplantation but should be appreciated as being associated with relatively lower GFR. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Long-term risks for kidney donors" by G. Mjøen, S. Hallan, and A. Hartmann.