111 resultados para Kidney Failure, Acute


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BACKGROUND Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. METHODS AND RESULTS This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%. CONCLUSIONS In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.

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PURPOSE Little data is available on noninvasive MRI-based assessment of renal function during upper urinary tract (UUT) obstruction. In this study, we determined whether functional multiparametric kidney MRI is able to monitor treatment response in acute unilateral UUT obstruction. MATERIAL AND METHODS Between 01/2008 and 01/2010, 18 patients with acute unilateral UUT obstruction due to calculi were prospectively enrolled to undergo kidney MRI with conventional, blood oxygen level-dependent (BOLD) and diffusion-weighted (DW) sequences on emergency admission and after release of obstruction. Functional imaging parameters of the obstructed and contralateral unobstructed kidneys derived from BOLD (apparent spin relaxation rate [R2*]) and DW (total apparent diffusion coefficient [ADCT], pure diffusion coefficient [ADCD] and perfusion fraction [FP]) sequences were assessed during acute UUT obstruction and after its release. RESULTS During acute obstruction, R2* and FP values were lower in the cortex (p=0.020 and p=0.031, respectively) and medulla (p=0.012 and p=0.190, respectively) of the obstructed compared to the contralateral unobstructed kidneys. After release of obstruction, R2* and FP values increased both in the cortex (p=0.016 and p=0.004, respectively) and medulla (p=0.071 and p=0.044, respectively) of the formerly obstructed kidneys to values similar to those found in the contralateral kidneys. ADCT and ADCD values did not significantly differ between obstructed and contralateral unobstructed kidneys during or after obstruction. CONCLUSIONS In our patients with acute unilateral UUT obstruction due to calculi, functional kidney MRI using BOLD and DW sequences allowed for the monitoring of pathophysiologic changes of obstructed kidneys during obstruction and after its release.

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OBJECTIVE To determine the diagnostic value of a serologic microagglutination test (MAT) and a PCR assay on urine and blood for the diagnosis of leptospirosis in dogs with acute kidney injury (AKI). DESIGN Cross-sectional study. Animals-76 dogs with AKI in a referral hospital (2008 to 2009). PROCEDURES Dogs' leptospirosis status was defined with a paired serologic MAT against a panel of 11 Leptospira serovars as leptospirosis-associated (n = 30) or nonleptospirosis-associated AKI (12). In 34 dogs, convalescent serologic testing was not possible, and leptospirosis status was classified as undetermined. The diagnostic value of the MAT single acute or convalescent blood sample was determined in dogs in which leptospirosis status could be classified. The diagnostic value of a commercially available genus-specific PCR assay was evaluated by use of 36 blood samples and 20 urine samples. RESULTS Serologic acute testing of an acute blood sample had a specificity of 100% (95% CI, 76% to 100%), a sensitivity of 50% (33% to 67%), and an accuracy of 64% (49% to 77%). Serologic testing of a convalescent blood sample had a specificity of 92% (65% to 99%), a sensitivity of 100% (87% to 100%), and an accuracy of 98% (88% to 100%). Results of the Leptospira PCR assay were negative for all samples from dogs for which leptospirosis status could be classified. CONCLUSIONS AND CLINICAL RELEVANCE Serologic MAT results were highly accurate for diagnosis of leptospirosis in dogs, despite a low sensitivity for early diagnosis. In this referral setting of dogs pretreated with antimicrobials, testing of blood and urine samples with a commercially available genus-specific PCR assay did not improve early diagnosis.

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CONTEXT Lipoid congenital adrenal hyperplasia (CAH) is the most severe form of CAH leading to impaired production of all adrenal and gonadal steroids. Mutations in the gene encoding steroidogenic acute regulatory protein (StAR) cause lipoid CAH. OBJECTIVE We investigated three unrelated patients of Swiss ancestry who all carried novel mutations in the StAR gene. All three subjects were phenotypic females with absent Müllerian derivatives, 46,XY karyotype, and presented with adrenal failure. METHODS AND RESULTS StAR gene analysis showed that one patient was homozygous and the other two were heterozygous for the novel missense mutation L260P. Of the heterozygote patients, one carried the novel missense mutation L157P and one had a novel frameshift mutation (629-630delCT) on the second allele. The functional ability of all three StAR mutations to promote pregnenolone production was severely attenuated in COS-1 cells transfected with the cholesterol side-chain cleavage system and mutant vs. wild-type StAR expression vectors. CONCLUSIONS These cases highlight the importance of StAR-dependent steroidogenesis during fetal development and early infancy; expand the geographic distribution of this condition; and finally establish a new, prevalent StAR mutation (L260P) for the Swiss population.

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To systematically investigate putative causes of non-coronary high-sensitive troponin elevations in patients presenting to a tertiary care emergency department. In this cross-sectional analysis, patients who received serial measurements of high-sensitive troponin T between 1 August 2010 and 31 October 2012 at the Department of Emergency Medicine were included. The following putative causes were considered to be associated with non-acute coronary syndrome-related increases in high-sensitive troponin T: acute pulmonary embolism, renal insufficiency, aortic dissection, heart failure, peri-/myocarditis, strenuous exercise, rhabdomyolysis, cardiotoxic chemotherapy, high-frequency ablation therapy, defibrillator shocks, cardiac infiltrative disorders (e.g., amyloidosis), chest trauma, sepsis, shock, exacerbation of chronic obstructive pulmonary disease, and diabetic ketoacidosis. During the study period a total of 1,573 patients received serial measurements of high-sensitive troponin T. Of these, 175 patients were found to have acute coronary syndrome leaving 1,398 patients for inclusion in the study. In 222 (30 %) of patients, no putative cause described in the literature could be attributed to the elevation in high-sensitive troponin T observed. The most commonly encountered mechanism underlying the troponin T elevation was renal insufficiency that was present in 286 patients (57 %), followed by cerebral ischemia in 95 patients (19 %), trauma in 75 patients (15 %) and heart failure in 41 patients (8 %). Non-acute coronary syndrome-associated elevation of high-sensitive troponin T levels is commonly observed in the emergency department. Renal insufficiency and acute cerebral events are the most common conditions associated with high-sensitive troponin T elevation.

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Congenital distal renal tubular acidosis (dRTA) from mutations of the B1 subunit of the V-ATPase is considered an autosomal recessive disease. We analyzed a dRTA kindred with a truncation-mutation of B1 (p.Phe468fsX487) previously shown to have failure of assembly into the V1 domain of the V-ATPase. All heterozygous carriers in this kindred have normal plasma bicarbonate concentrations, thus evaded the diagnosis of RTA. However, inappropriately high urine pH, hypocitraturia, and hypercalciuria are present either individually or in combination in the heterozygotes at baseline. Two of the heterozygotes studied also have inappropriate urinary acidification with acute ammonium chloride loading and impaired urine-blood pCO2 gradient during bicarbonaturia indicating presence of H+ gradient and flux defects. In normal human renal papillae, wild type B1 is located primarily on the plasma membrane but papilla from one of the heterozygote who had kidney stones had renal tissue secured from surgery showed B1 in both plasma membrane as well as a diffuse intracellular staining. Titrating increasing amounts of the mutant B1 subunit did not exhibit negative dominance over the expression, cellular distribution, or H+-pump activity of the wild type B1 in mammalian HEK293 cells and in V-ATPase-deficient S. cerevisiae. This is the first demonstration of renal acidification defects and nephrolithiasis in heterozygous carriers of mutant B1 subunit; which cannot be attributable to negative dominance. We propose that heterozygosity may lead to mild real acidification defects due to haploinsufficiency. B1 heterozygosity should be considered in patients with calcium nephrolithiasis and urinary abnormalities such as alkalinuria or hypocitraturia.

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INTRODUCTION Treatment failure in acute myeloid leukemia is probably caused by the presence of leukemia initiating cells, also referred to as leukemic stem cells, at diagnosis and their persistence after therapy. Specific identification of leukemia stem cells and their discrimination from normal hematopoietic stem cells would greatly contribute to risk stratification and could predict possible relapses. RESULTS For identification of leukemic stem cells, we developed flow cytometric methods using leukemic stem cell associated markers and newly-defined (light scatter) aberrancies. The nature of the putative leukemic stem cells and normal hematopoietic stem cells, present in the same patient's bone marrow, was demonstrated in eight patients by the presence or absence of molecular aberrancies and/or leukemic engraftment in NOD-SCID IL-2Rγ-/- mice. At diagnosis (n=88), the frequency of the thus defined neoplastic part of CD34+CD38- putative stem cell compartment had a strong prognostic impact, while the neoplastic parts of the CD34+CD38+ and CD34- putative stem cell compartments had no prognostic impact at all. After different courses of therapy, higher percentages of neoplastic CD34+CD38- cells in complete remission strongly correlated with shorter patient survival (n=91). Moreover, combining neoplastic CD34+CD38- frequencies with frequencies of minimal residual disease cells (n=91), which reflect the total neoplastic burden, revealed four patient groups with different survival. CONCLUSION AND PERSPECTIVE Discrimination between putative leukemia stem cells and normal hematopoietic stem cells in this large-scale study allowed to demonstrate the clinical importance of putative CD34+CD38- leukemia stem cells in AML. Moreover, it offers new opportunities for the development of therapies directed against leukemia stem cells, that would spare normal hematopoietic stem cells, and, moreover, enables in vivo and ex vivo screening for potential efficacy and toxicity of new therapies.

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BACKGROUND Adaptive servo-ventilation (ASV) is a well-established treatment of central sleep apnea (CSA) related to congestive heart failure (CHF). Few studies have evaluated the effectiveness and adherence in patients with CSA of other etiologies, and even less is known about treatment of CSA in patients of post ischemic stroke. METHODS A single-centre retrospective analysis of ASV treatment for CSA in post-acute ischemic stroke patients without concomitant CHF was performed. Demographics, clinical data, sleep studies, ventilator settings, and adherence data were evaluated. RESULTS Out of 154 patients on ASV, 15 patients had CSA related to ischemic stroke and were started on ASV a median of 11 months after the acute cerebrovascular event. Thirteen out of the 15 patients were initially treated with continuous positive airway pressure (11/15) and bilevel positive airway pressure (2/15) therapy with unsatisfactory control of CSA. ASV significantly improved AHI (46.7 ± 24.3 vs 8.5 ± 12/h, P = 0.001) and reduced ESS (8.7 ± 5.7 vs 5.6 ± 2.5, P = 0.08) with a mean nightly use of ASV of 5.4 ± 2.4 h at 3 months after the initiation of treatment. Results were maintained at 6 months. CONCLUSION ASV was well tolerated and clinically effective in this group of patients with persistent CSA after ischemic stroke.

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BackgroundHepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data.MethodsVia questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications.ResultsEarly treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 ¿M) and NTBC-levels in the therapeutic range (20¿40 ¿M). Side effects of NTBC are mild and often transient.Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood).ConclusionBased on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

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PurposeTo assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy.MethodsData from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC). Secondary endpoints included local (LC) and regional (RC) controls, distant metastasis free survival (DMFS), laryngectomy free survival (LFS), overall survival (OS), and acute and late toxicities. Time-to-event endpoints were estimated using Kaplan-Meier method, and univariate and multivariate analyses were performed using Cox proportional hazards models. Recurrent gross tumor volume (RTV) on post-treatment diagnostic imaging was analyzed in relation to corresponding CTV (in-volume, > 95% of RTV inside CTV; marginal, 20¿95% inside CTV; out-volume, < 20% inside CTV).ResultsFifty patients (stage III: 14, IVa: 33, IVb: 3) completed treatment and were included in the analysis (median follow-up of 4.2 years). Three-year LRC, DMFS and overall survival (OS) were 77%, 96% and 63%, respectively. Grade 2 and 3 acute toxicity were 38% and 62%, respectively; grade 2 and 3 late toxicity were 23% and 15%, respectively. We identified 10 patients with LRF (8 local, 1 regional, 1 local¿+¿regional). Six out of 10 RTVs were fully included in both elective and high-dose CTVs, and 4 RTVs were marginal to the high-dose CTVs.ConclusionThe treatment of locally advanced HL-SCC with definitive IMRT and concurrent systemic therapy provides good LRC rates with acceptable toxicity profile. Nevertheless, the analysis of LRFs in relation to CTVs showed in-volume relapses to be the major mode of recurrence indicating that novel strategies to overcome radioresistance are required.

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BACKGROUND To cover the shortage of cadaveric organs, new approaches to expand the donor pool are needed. Here we report on a case of domino liver transplantation (DLT) using an organ harvested from a compound heterozygous patient with primary hyperoxaluria (PHO), who underwent combined liver and kidney transplantation. The DLT recipient developed early renal failure with oxaluria. The time to the progression to oxalosis with renal failure in such situations is unknown, but, based on animal data, we hypothesize that calcineurin inhibitors may play a detrimental role. METHODS A cadaveric liver and kidney transplantation was performed in a 52-year-old male with PHO. His liver was used for a 64-year-old patient with a non-resectable, but limited cholangiocarcinoma. RESULTS While the course of the PHO donor was uneventful, in the DLT recipient early post-operative, dialysis-dependent renal failure with hyperoxaluria developed. Histology of a kidney biopsy revealed massive calcium oxalate crystal deposition as the leading aetiological cause. CONCLUSIONS DLT using PHO organs for marginal recipients represents a possible therapeutic approach regarding graft function of the liver. However, it may negatively alter the renal outcome of the recipient in an unpredictable manner, especially with concomitant use of cyclosporin. Therefore, we suggest that, although DLT should be promoted, PHO organs are better excluded from such procedures.

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Experimentally renal tissue hypoxia appears to play an important role in the pathogenesis of chronic kidney disease (CKD) and arterial hypertension (AHT). In this study we measured renal tissue oxygenation and its determinants in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) under standardized hydration conditions. Four coronal slices were selected, and a multi gradient echo sequence was used to acquire T2* weighted images. The mean cortical and medullary R2* values ( = 1/T2*) were calculated before and after administration of IV furosemide, a low R2* indicating a high tissue oxygenation. We studied 195 subjects (95 CKD, 58 treated AHT, and 42 healthy controls). Mean cortical R2 and medullary R2* were not significantly different between the groups at baseline. In stimulated conditions (furosemide injection), the decrease in R2* was significantly blunted in patients with CKD and AHT. In multivariate linear regression analyses, neither cortical nor medullary R2* were associated with eGFR or blood pressure, but cortical R2* correlated positively with male gender, blood glucose and uric acid levels. In conclusion, our data show that kidney oxygenation is tightly regulated in CKD and hypertensive patients at rest. However, the metabolic response to acute changes in sodium transport is altered in CKD and in AHT, despite preserved renal function in the latter group. This suggests the presence of early renal metabolic alterations in hypertension. The correlations between cortical R2* values, male gender, glycemia and uric acid levels suggest that these factors interfere with the regulation of renal tissue oxygenation.

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AIMS We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. CONCLUSION A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required.

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AIMS Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure. METHODS AND RESULTS We assessed serum CAF levels in 196 patients who participated in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Muscle wasting was identified using dual-energy X-ray absorptiometry (DEXA) in 38 patients (19.4%). Patients with muscle wasting demonstrated higher CAF values than those without (125.1 ± 59.5 pmol/L vs. 103.8 ± 42.9 pmol/L, P = 0.01). Using receiver operating characteristics (ROC), we calculated the optimal CAF value to identify patients with muscle wasting as >87.5 pmol/L, which had a sensitivity of 78.9% and a specificity of 43.7%. The area under the ROC curve was 0.63 (95% confidence interval 0.56-0.70). Using simple regression, we found that serum CAF was associated with handgrip (R = - 0.17, P = 0.03) and quadriceps strength (R = - 0.31, P < 0.0001), peak oxygen consumption (R = - 0.5, P < 0.0001), 6-min walk distance (R = - 0.32, P < 0.0001), and gait speed (R = - 0.2, P = 0.001), as well as with parameters of kidney and liver function, iron metabolism and storage. CONCLUSION CAF shows good sensitivity for the detection of skeletal muscle wasting in patients with heart failure. Its assessment may be useful to identify patients who should undergo additional testing, such as detailed body composition analysis. As no other biomarker is currently available, further investigation is warranted.

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PURPOSE Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.