***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Renal tissue hypoxia is a final pathway in the development and progression of chronic kidney disease ( CKD ) , but whether renal oxygenation predicts renal function decline in humans has not been proven . Therefore , we performed a prospect i ve study and measured renal tissue oxygenation by blood oxygenation level-dependent magnetic resonance imaging ( BOLD-MRI ) in 112 patients with CKD , 47 with hypertension without CKD , and 24 healthy control individuals . Images were analyzed with the twelve-layer concentric objects method that divided the renal parenchyma in 12 layers of equal thickness and reports the mean R2 * value of each layer ( a high R2 * corresponds to low oxygenation ) , along with the change in R2 * between layers called the R2 * slope . Serum creatinine values were collected to calculate the yearly change in estimated glomerular function rate ( MDRD eGFR ) . Follow up was three years . The  change in eGFR in CKD , hypertensive and control individuals was -2.0 , 0.5 and -0.2 ml/min/1.73m2/year , respectively . In multivariable regression analysis adjusted for age , sex , diabetes , RAS-blockers , eGFR , and proteinuria the yearly eGFR change correlated negatively with baseline 24 hour proteinuria and the mean R2 * value of the cortical layers , and positively with the R2 * slope , but not with the other covariates . Patients with CKD and high outer R2 * or a flat R2 * slope were three times more likely to develop an adverse renal outcome ( renal replacement therapy or over a 30 % increase in serum creatinine ) . Thus , low cortical oxygenation is an independent predictor of renal function decline . This finding should stimulate studies exploring the therapeutic impact of improving renal oxygenation on renal disease progression BACKGROUND AND OBJECTIVES Atherosclerotic renal artery stenosis ( ARAS ) can reduce renal blood flow , tissue oxygenation , and GFR . In this study , we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function , pressor hormones , and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization .  DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Nonr and omized inpatient studies were performed in patients with unilateral ARAS ( > 60 % occlusion ) before and 3 months after revascularization ( n=10 ) or medical therapy ( n=20 ) or patients with essential hypertension ( n=32 ) under identical conditions . The primary study outcome was change in single-kidney GFR . Individual kidney hemodynamics and volume were measured using multidetector computed tomography . Tissue oxygenation ( using R(2 ) * as a measure of deoxyhemoglobin ) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin ( NGAL ) , monocyte chemoattractant protein-1 ( MCP-1 ) , and plasma renin activity were measured . RESULTS Total GFR did not change over 3 months in either group , but the stenotic kidney ( STK ) GFR rose over time in the stent compared with the medical group ( + 2.2[-1.8 to 10.5 ] versus -5.3[-7.3 to -0.3 ] ml/min ; P=0.03 ) . Contralateral kidney ( CLK ) GFR declined in the stent group ( 43.6±19.7 to 36.6±19.5 ml/min ; P=0.03 ) . Fractional tissue hypoxia fell in the STK ( fraction R(2 ) * > 30/s : 22.1%±20 % versus 14.9%±18.3 % ; P<0.01 ) after stenting . Renal vein biomarkers correlated with the degree of hypoxia in the STK : NGAL(r=0.3 ; P=0.01 ) and MCP-1(r=0.3 ; P=0.02 ; more so after stenting ) . Renal vein NGAL was inversely related to renal blood flow in the STK ( r=-0.65 ; P<0.001 ) . Biomarkers were highly correlated between STK and CLK , NGAL ( r=0.94 ; P<0.001 ) , and MCP-1 ( r=0.96 ; P<0.001 ) . CONCLUSIONS These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR . Furthermore , they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS . Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines PURPOSE To prospect ively determine the 3-year stability and potential changes of functional parameters in renal allograft recipients obtained from diffusion-weighted imaging ( DWI ) and blood oxygenation level-dependent ( BOLD ) MRI . MATERIAL S AND METHODS Nine renal allograft recipients underwent DWI and BOLD-MRI twice , once 7 ± 3 months after transplantation , and again 32 ± 2 months after the first MRI . DWI yielded an apparent diffusion coefficient ( ADC ) and the perfusion contribution ( F(P ) ) . BOLD imaging yielded R2 , providing an estimation of renal oxygenation . Coefficients of variation between ( CV(b ) ) and within subjects ( CV(w ) ) were calculated . RESULTS The parameters were stable after 32 months in eight of the nine patients , who had well-functioning allografts . Mean diffusion values were very similar in the first and second scan . CV(w ) and CV(b ) for ADC values were less than 3.5 % and 5.9 % , respectively , in cortex and medulla , but were higher for F(P ) ( 15%-18 % ) . CV(w ) and CV(b ) of R2 were also low ( medulla : CV(w ) = 10.8 % , CV(b ) = 11.4 % ; cortex : CV(w ) and CV(b ) = 7.2 % ) . R2 increased significantly ( P = 0.035 ) in cortex but not in medulla , suggesting reduced cortical oxygen content . One subject with decreased glomerular filtration rate demonstrated strongly altered parameters . CONCLUSION In the absence of graft dysfunction , DWI and BOLD imaging yield consistent results over 3 years in stable human renal allograft recipients Background — Atherosclerotic renal artery stenosis reduces renal blood flow ( RBF ) and amplifies stenotic kidney hypoxia . Revascularization with percutaneous transluminal renal angioplasty ( PTRA ) and stenting often fails to recover renal function , possibly because of ischemia/reperfusion injury developing after PTRA . Elamipretide is a mitochondrial-targeted peptide that binds to cardiolipin and stabilizes mitochondrial function . We tested the hypothesis that elamipretide plus PTRA would improve renal function , oxygenation , and RBF in patients with atherosclerotic renal artery stenosis undergoing PTRA . Methods and Results — Inpatient studies were performed in patients with severe atherosclerotic renal artery stenosis scheduled for PTRA . Patients were treated before and during PTRA with elamipretide ( 0.05 mg/kg per hour intravenous infusion , n=6 ) or placebo ( n=8 ) . Stenotic kidney cortical/medullary perfusion and RBF were measured using contrast-enhanced multidetector CT , and renal oxygenation by 3-T blood oxygen level−dependent magnetic resonance imaging before and 3 months after PTRA . Age and basal glomerular filtration rate did not differ between groups . Blood oxygen level−dependent imaging demonstrated increased fractional hypoxia 24 hours after angiography and stenting in placebo ( + 47 % ) versus elamipretide ( −6 % ) . These were reverted to baseline 3 months later . Stenotic kidney RBF rose ( 202±29–262±115 mL/min ; P=0.04 ) 3 months after PTRA in the elamipretide-treated group only . Over 3 months , systolic blood pressure decreased , and estimated glomerular filtration rate increased ( P=0.003 ) more in the elamipretide group than in the placebo group ( P=0.11 ) . Conclusions — Adjunctive elamipretide during PTRA was associated with attenuated postprocedural hypoxia , increased RBF , and improved kidney function in this pilot trial . These data support a role for targeted mitochondrial protection to minimize procedure-associated ischemic injury and to improve outcomes of revascularization for human atherosclerotic renal artery stenosis . Clinical Trial Registration — URL : https://www . clinical trials.gov . Unique identifier : NCT01755858 PURPOSE To prospect ively assess the oxygenation state of renal transplants and determine the feasibility of using blood oxygen level-dependent ( BOLD ) magnetic resonance ( MR ) imaging to differentiate between acute tubular necrosis ( ATN ) , acute rejection , and normal function . MATERIAL S AND METHODS This HIPAA-compliant study had institutional human subjects review committee approval , and written informed consent was obtained from all patients . BOLD MR imaging was performed in 20 patients ( age range , 21 - 70 years ) who had recently received renal transplants . Six patients had clinical ly normal functioning transplants , eight had biopsy-proved rejection , and six had biopsy-proved ATN . R2 * ( 1/sec ) measurements were obtained in the medulla and cortex of transplanted kidneys . R2 * is a measure of the rate of signal loss in a specific region and is related to the amount of deoxyhemoglobin present . Statistical analysis was performed by using a two- sample t test . Threshold R2 * values were identified to discriminate between transplanted kidneys with ATN , those with acute rejection , and those with normal function . RESULTS R2 * values for the medulla were significantly lower in the acute rejection group ( R2 * = 15.8/sec + /- 1.5 ) than in normally functioning transplants ( R2 * = 23.9/sec + /- 3.2 ) and transplants with ATN ( R2 * = 21.3/sec + /- 1.9 ) . The differences between the acute rejection and normal function groups ( P = .001 ) , as well as between the acute rejection and ATN groups ( P < .001 ) , were significant . Acute rejection could be differentiated from normal function and ATN in all cases by using a threshold R2 * value of 18/sec . R2 * values for the cortex were higher in ATN ( R2 * = 14.2/sec + /- 1.4 ) than for normally functioning transplants ( R2 * = 12.7/sec + /- 1.6 ) and transplants with rejection ( R2 * = 12.4/sec + /- 1.2 ) . The difference in R2 * values in the cortex between ATN and rejection was statistically significant ( P = .034 ) , although there was no threshold value that enabled differentiation of all cases of ATN from cases of normal function or acute rejection . CONCLUSION R2 * measurements in the medullary regions of transplanted kidneys with acute rejection were significantly lower than those in normally functioning transplants or transplants with ATN . These results suggest that marked changes in intrarenal oxygenation occur during acute transplant rejection Acute experimental reduction of renal blood flow decreases the renal blood oxygenation level – dependent ( BOLD ) MRI signal in animals .  Angiotensin II also reduces renal blood flow , but the ability of BOLD MRI to dynamically detect this response has not yet been investigated in humans . Six healthy male volunteers underwent an individual dose-finding study to identify the intravenous doses of angiotensin II , norepinephrine , and sodium nitroprusside necessary to induce a 15-mm Hg peak mean arterial blood pressure change . MRI studies followed within 3 weeks , when angiotensin II ( 8.8±1.4 ng/kg ) , norepinephrine ( 52±12 ng/kg ) , and sodium nitroprusside ( 2.0±0.3 & mgr;g/kg ) were given twice in an unblocked , r and omized sequence while imaging experiments were performed on a 1.5-T Siemens Sonata . A multiecho echo-planar imaging sequence was used to acquire T2 * maps with a temporal resolution of 1 respiratory cycle . Averaged over a renal cortex dominated region of interest , angiotensin II caused a shortening of T2 * between 6 % and 10 % . Sodium nitroprusside and norepinephrine , although of equal potency concerning blood pressure responses , did not alter the renal BOLD signal . The renal BOLD response to angiotensin II appeared with short onset latency ( as early as 10 seconds after peripheral intravenous angiotensin II bolus administration ) suggesting that this response is a consequence of altered perfusion rather than increased renal oxygen consumption . The methods described here are suitable to assess renal responsiveness to angiotensin II and may , thus , be of great value in human hypertension research Blood oxygenation level-dependent ( BOLD ) MRI was shown to allow non-invasive observation of renal oxygen 
    Output:
    
Increases in its outcome measure R2 * ( transverse relaxation rate expressed as per second ) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation , whereas decreases in R2 * indicate higher oxygenation .
BOLD-MRI has shown that patients suffering from chronic kidney disease ( CKD ) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls .
Additionally , CKD patients with the lowest cortical oxygenation have the worst renal outcome .