Toll-like receptor 4 mutation mitigates gut microbiota-mediated hypertensive kidney injury.

Hypertension-associated dysbiosis is linked to several clinical complications, including inflammation and possible kidney dysfunction. Inflammation and TLR4 activation during hypertension result from gut dysbiosis-related impairment of intestinal integrity. However, the contribution of TLR4 in kidney dysfunction during hypertension-induced gut dysbiosis is unclear. We designed this study to address this knowledge gap by utilizing TLR4 normal (TLR4N) and TLR4 mutant (TLR4M) mice. These mice were infused with high doses of Angiotensin-II for four weeks to induce hypertension. Results suggest that Ang-II significantly increased renal arterial resistive index (RI), decreased renal vascularity, and renal function (GFR) in TLR4N mice compared to TLR4M. 16 S rRNA sequencing analysis of gut microbiome revealed that Ang-II-induced hypertension resulted in alteration of Firmicutes: Bacteroidetes ratio in the gut of both TLR4N and TLR4M mice; however, it was not comparably rather differentially. Additionally, Ang-II-hypertension decreased the expression of tight junction proteins and increased gut permeability, which were more prominent in TLR4N mice than in TLR4M mice. Concomitant with gut hyperpermeability, an increased bacterial component translocation to the kidney was observed in TLR4N mice treated with Ang-II compared to TLR4N plus saline. Interestingly, microbiota translocation was mitigated in Ang-II-hypertensive TLR4M mice. Furthermore, Ang-II altered the expression of inflammatory (IL-1ß, IL-6) and anti-inflammatory IL-10) markers, and extracellular matrix proteins, including MMP-2, -9, -14, and TIMP-2 in the kidney of TLR4N mice, which were blunted in TLR4M mice. Our data demonstrate that ablation of TLR4 attenuates hypertension-induced gut dysbiosis resulting in preventing gut hyperpermeability, bacterial translocation, mitigation of renal inflammation and alleviation of kidney dysfunction.

Impacts of center and clinical factors in antihypertensive medication use after kidney transplantation.

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first-line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age > 18 years) with AHM fill records from a pharmaceutical claims warehouse (2007-2016) to describe use and correlates of AHM use during months 7-12 post-transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta-blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non-DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC-8) guidelines (2014-2016), compared with an earlier period (2007-2013). The median odds ratios generated from case-factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.

Antidepressant medication use before and after kidney transplant: implications for outcomes - a retrospective study.

We examined a novel database wherein national US transplant registry identifiers were linked to records from a large pharmaceutical claims warehouse (2008-2015) to characterize antidepressant use before and after kidney transplantation, and associations [adjusted hazard ratio (aHR) 95% CI] with death and graft failure. Among 72 054 recipients, 12.6% filled antidepressant medications in the year before transplant, and use was more common among women and patients who were white, unemployed, and had limited functional status. Pre-transplant antidepressant use was associated with 39% higher 1-year mortality (aHR 1.39, 95% CI 1.18-1.64) and 15% higher all-cause graft loss risk (aHR 1.15, 95% CI 1.02-1.30). More than 50% of patients who filled antidepressants pre-transplant continued fill post-transplant. Antidepressant use in the first year after transplant was associated with twofold higher risk of death (aHR 1.94, 95% CI 1.60-2.35), 38% higher risk of death-censored graft failure, and 61% higher risk of all-cause graft failure in the subsequent year. Pre-listing antidepressant use was also associated with increased mortality, but transplantation conferred a survival benefit regardless of prelisting antidepressant use status. While associations may in part reflect underlying behaviors or comorbidities, kidney transplant candidates and recipients treated with antidepressant medications should be monitored and supported to reduce the risk of adverse outcomes.

Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice.

To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass correlation analysis, "center effect" explained most of the variation in TMG (58%), ALEM (66%), other (51%), and no induction (58%) use. Median odds ratios generated from case-factor adjusted models (7.66-11.19) also supported large differences in the likelihood of induction choices between centers. The wide variation in induction therapy choice across US transplant centers is not dominantly explained by differences in patient or donor characteristics; rather, it reflects center choice and practice.

Survival implications of opioid use before and after liver transplantation.

Implications of prescription opioid use for outcomes after liver transplantation (LT) have not been described. We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2014; n = 29,673). Opioid fills on the waiting list were normalized to morphine equivalents (MEs), and exposure was categorized as follows: > 0-2 ME/day (level 1), > 2-10 ME/day (level 2), > 10-70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio [aHR], 95% LCL aHR 95% UCL ) of pretransplant ME level with patient and graft survival over 5 years after transplant were quantified by multivariate Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Overall, 9.3% of recipients filled opioids on the waiting list. Compared with no use, level 3 (aHR 1.06 1.281.55 ) and 4 (aHR 1.16 1.521.98 ) opioid use during listing were associated with increased mortality over 5 years after transplant. These associations were driven by risk after the first transplant anniversary, such that mortality >1-5 years increased in a graded manner with higher use on the waiting list (level 2, aHR, 1.00 1.271.62 ; level 3, aHR, 1.08 1.381.77 ; level 4, aHR, 1.49 2.012.72 ). Similar patterns occurred for graft failure. Of recipients with the highest level of opioids on the waiting list, 65% had level 3 or 4 use in the first year after transplant, including 55% with use at these levels from day 90-365 after transplant. Opioid use in the first year after transplant also bore graded associations with subsequent death and graft loss >1-5 years after transplant. Opioid use history may be relevant in assessing and providing care to LT candidates. Liver Transplantation 23 305-314 2017 AASLD.

Immunobiology in VCA.

Transplantation of vascularized composite tissue is a relatively new field that is an amalgamation of experience in solid organ transplantation and reconstructive plastic and orthopedic surgery. What is novel about the immunobiology of VCA is the addition of tissues with unique immunologic characteristics such as skin and vascularized bone, and the nature of VCA grafts, with direct exposure to the environment, and external forces of trauma. VCAs are distinguished from solid organ transplants by the requirement of rigorous physical therapy for optimal outcomes and the fact that these procedures are not lifesaving in most cases. In this review, we will discuss the immunobiology of these systems and how the interplay can result in pathology unique to VCA as well as provide potential targets for therapy.

Monitoring and long-term outcomes in vascularized composite allotransplantation.

PURPOSE OF REVIEW: The field of vascularized composite allotransplantation (VCA) is young, with less than 150 transplants worldwide. However, we now possess as much as 14 years of clinical follow-up. There are similarities and distinct differences between solid-organ transplantation (SOT) and VCA. This review will summarize how VCA recipients are monitored, outcomes observed, and what aspects are unique to VCA. RECENT FINDINGS: Of about 90 documented cases, 10% of VCA recipients are out more than 10 years and 14% are out 5 or more years. There have been both graft losses and patient mortality. In most cases, these losses have been acute, most within the first year, and all within 3 years. Unlike SOT, VCA grafts function well during severe rejection. Chronic rejection-like sequelae are less frequent than in SOT, but do appear. Immunosuppression ranges from standard protocols to novel trials aimed at immunosuppression minimization. Patient selection greatly affects the outcome. Graft loss after year 1 is associated with compliance issues. SUMMARY: Functional outcomes have exceeded expectations. VCA recipients enjoy a quality of life not achievable with conventional reconstruction. Outstanding long-term results of more than a decade have been achieved. Monitoring of VCA patients will require new strategies to incorporate external visualization and effects of environment on rejection. Graft loss has occurred early, suggesting we focus improvement on this time period. More follow-up is needed to determine the rates and targets of chronic rejection, and the characteristics of VCA unique to face vs. hand transplantation.

Diabetic Nephropathy and Gaseous Modulators.

Diabetic nephropathy (DN) remains the leading cause of vascular morbidity and mortality in diabetes patients. Despite the progress in understanding the diabetic disease process and advanced management of nephropathy, a number of patients still progress to end-stage renal disease (ESRD). The underlying mechanism still needs to be clarified. Gaseous signaling molecules, so-called gasotransmitters, such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), have been shown to play an essential role in the development, progression, and ramification of DN depending on their availability and physiological actions. Although the studies on gasotransmitter regulations of DN are still emerging, the evidence revealed an aberrant level of gasotransmitters in patients with diabetes. In studies, different gasotransmitter donors have been implicated in ameliorating diabetic renal dysfunction. In this perspective, we summarized an overview of the recent advances in the physiological relevance of the gaseous molecules and their multifaceted interaction with other potential factors, such as extracellular matrix (ECM), in the severity modulation of DN. Moreover, the perspective of the present review highlights the possible therapeutic interventions of gasotransmitters in ameliorating this dreaded disease.

Role of AI and Radiomic Markers in Early Diagnosis of Renal Cancer and Clinical Outcome Prediction: A Brief Review.

Globally, renal cancer (RC) is the 10th most common cancer among men and women. The new era of artificial intelligence (AI) and radiomics have allowed the development of AI-based computer-aided diagnostic/prediction (AI-based CAD/CAP) systems, which have shown promise for the diagnosis of RC (i.e., subtyping, grading, and staging) and prediction of clinical outcomes at an early stage. This will absolutely help reduce diagnosis time, enhance diagnostic abilities, reduce invasiveness, and provide guidance for appropriate management procedures to avoid the burden of unresponsive treatment plans. This survey mainly has three primary aims. The first aim is to highlight the most recent technical diagnostic studies developed in the last decade, with their findings and limitations, that have taken the advantages of AI and radiomic markers derived from either computed tomography (CT) or magnetic resonance (MR) images to develop AI-based CAD systems for accurate diagnosis of renal tumors at an early stage. The second aim is to highlight the few studies that have utilized AI and radiomic markers, with their findings and limitations, to predict patients' clinical outcome/treatment response, including possible recurrence after treatment, overall survival, and progression-free survival in patients with renal tumors. The promising findings of the aforementioned studies motivated us to highlight the optimal AI-based radiomic makers that are correlated with the diagnosis of renal tumors and prediction/assessment of patients' clinical outcomes. Finally, we conclude with a discussion and possible future avenues for improving diagnostic and treatment prediction performance.

BK viral disease in renal transplantation.

PURPOSE OF REVIEW: BK virus is one of the most frequent causes of graft loss after renal transplantation, with BK virus-associated nephropathy occurring in roughly 8% of patients, and graft loss rates reported as high as 50%. This review is meant to highlight the literature on BK viral disease following renal transplantation published in the most recent year. RECENT FINDINGS: Prevention of BK virus-associated graft loss requires early diagnosis of BK viral replication, which is best achieved by screening for BK viral DNA in the blood. Screening intervals more frequently than the currently recommended 3 months appear to offer increased efficacy. Reduction in immunosuppression remains the mainstay for treatment of BK viral disease, with consideration given to antiviral drug therapy with leflunomide. Acute rejection may be minimized by a short course of intravenous immunoglobulin. Sirolimus appears to be a promising addition to the therapeutic armamentarium. For patients requiring re-transplantation after BK virus-associated graft loss, viral clearance from the bloodstream prior to re-transplantation should be achieved to attain optimal results. SUMMARY: BK virus is a major pathogen affecting renal allografts, although intensive surveillance and targeted dose reduction in immunosuppression with the consideration of additional antiviral drug therapy can minimize graft loss resulting from infection.

Effect of increasing dialysate flow rate on diffusive mass transfer of urea, phosphate and beta2-microglobulin during clinical haemodialysis.

BACKGROUND: Diffusive clearance depends on blood and dialysate flow rates and the overall mass transfer area coefficient (K(o)A) of the dialyzer. Although K(o)A should be constant for a given dialyzer, urea K(o)A has been reported to vary with dialysate flow rate possibly because of improvements in flow distribution. This study examined the dependence of K(o)A for urea, phosphate and ß(2)-microglobulin on dialysate flow rate in dialyzers containing undulating fibers to promote flow distribution and two different fiber packing densities. METHODS: Twelve stable haemodialysis patients underwent dialysis with four different dialyzers, each used with a blood flow rate of 400 mL/min and dialysate flow rates of 350, 500 and 800 mL/min. Clearances of urea, phosphate and ß(2)-microglobulin were measured and K(o)A values calculated. RESULTS: Clearances of urea and phosphate, but not ß(2)-microglobulin, increased significantly with increasing dialysate flow rate. However, increasing dialysate flow rate had no significant effect on K(o)A or K(o) for any of the three solutes examined, although K(o) for urea and phosphate increased significantly as the average flow velocity in the dialysate compartment increased. CONCLUSIONS: For dialyzers with features that promote good dialysate flow distribution, increasing dialysate flow rate beyond 600 mL/min at a blood flow rate of 400 mL/min is likely to have only a modest impact on dialyzer performance, limited to the theoretical increase predicted for a constant K(o)A.

Impact of Functional Status on Outcomes of Simultaneous Pancreas-kidney Transplantation: Risks and Opportunities for Patient Benefit.

BACKGROUND: The impact of functional status on survival among simultaneous pancreas-kidney transplant (SPKT) candidates and recipients is not well described. METHODS: We examined national Scientific Registry of Transplant Recipients (SRTR) data for patients listed for SPKT in the United States (2006-2019). Functional status was categorized by center-reported Karnofsky Performance Score (KPS). We used Cox regression to quantify associations of KPS at listing and transplant with subsequent patient survival, adjusted for baseline patient and transplant factors (adjusted hazard ratio, 95% LCLaHR95%UCL). We also explored time-dependent associations of SPKT with survival risk after listing compared with continued waiting in each functional status group. RESULTS: KPS distributions among candidates (N = 16 822) and recipients (N = 10 316), respectively, were normal (KPS 80-100), 62.0% and 57.8%; capable of self-care (KPS 70), 23.5% and 24.7%; requires assistance (KPS 50-60), 12.4% and 14.2%; and disabled (KPS 10-40), 2.1% and 3.3%. There was a graded increase in mortality after listing and after transplant with lower functional levels. Compared with normal functioning, mortality after SPKT rose progressively for patients capable of self-care (aHR, 1.001.181.41), requiring assistance (aHR, 1.061.311.60), and disabled (aHR, 1.101.552.19). In time-dependent regression, compared with waiting, SPKT was associated with 2-fold mortality risk within 30 days of transplant. However, beyond 30 days, SPKT was associated with reduced mortality, from 52% for disabled patients (aHR, 0.260.480.88) to 70% for patients with normal functioning (aHR, 0.260.300.34). CONCLUSIONS: While lower functional status is associated with increased mortality risk among SPKT candidates and recipients, SPKT can provide long-term survival benefit across functional status levels in those selected for transplant.

Cannabis Dependence or Abuse in Kidney Transplantation: Implications for Posttransplant Outcomes.

BACKGROUND: Cannabis is categorized as an illicit drug in most US states, but legalization for medical indications is increasing. Policies and guidance on cannabis use in transplant patients remain controversial. METHODS: We examined a database linking national kidney transplant records (n = 52 689) with Medicare claims to identify diagnoses of cannabis dependence or abuse (CDOA) and associations [adjusted hazard ratio (aHR) with 95% upper and lower confidence limits (CLs)] with graft, patient, and other clinical outcomes. RESULTS: CDOA was diagnosed in only 0.5% (n = 254) and 0.3% (n = 163) of kidney transplant recipients in the years before and after transplant, respectively. Patients with pretransplant CDOA were more likely to be 19 to 30 years of age and of black race, and less likely to be obese, college-educated, and employed. After multivariate and propensity adjustment, CDOA in the year before transplant was not associated with death or graft failure in the year after transplant, but was associated with posttransplant psychosocial problems such as alcohol abuse, other drug abuse, noncompliance, schizophrenia, and depression. Furthermore, CDOA in the first year posttransplant was associated with an approximately 2-fold increased risk of death-censored graft failure (aHR, 2.29; 95% CL, 1.59-3.32), all-cause graft loss (aHR, 2.09; 95% CL, 1.50-2.91), and death (aHR, 1.79; 95% CL, 1.06-3.04) in the subsequent 2 years. Posttransplant CDOA was also associated with cardiovascular, pulmonary, and psychosocial problems, and with events such as accidents and fractures. CONCLUSIONS: Although associations likely, in part, reflect associated conditions or behaviors, clinical diagnosis of CDOA in the year after transplant appears to have prognostic implications for allograft and patient outcomes. Recipients with posttransplant CDOA warrant focused monitoring and support.

Differences in solute removal by two high-flux membranes of nominally similar synthetic polymers.

BACKGROUND: Membranes fabricated from nominally similar polymers may be markedly different in chemical composition, morphology and geometry. To examine the relative importance of these factors to dialyzer performance, the removal of small and large uraemic toxins was determined for dialyzers containing 'polysulfone' membranes of different composition and morphology, with and without fibre undulations. METHODS: Total removal and instantaneous clearances of urea, phosphorus, beta(2)-microglobulin, leptin, angiogenin, complement factor D and immunoglobulin kappa light chain were determined in randomized cross-over studies. Total solute removal was assessed from the pre- to post-dialysis change in plasma concentration and the total amount of solute recovered in the dialysate. Trapping of solute at the membrane was determined as the difference between solute lost from plasma water and solute recovered in the dialysate. RESULTS: Total removal of urea and phosphorus was independent of the membrane composition and structure. Large molecule removal differed significantly between the two membranes, particularly for beta(2)-microglobulin. The importance of trapping at the membrane as a mechanism of beta(2)-microglobulin removal also differed significantly between the two membranes, with trapping being less important for the membrane with the greatest beta(2)-microglobulin removal. As molecular size increased, the contribution of trapping at the membrane to solute removal increased and the difference between the two membranes decreased. CONCLUSIONS: High-flux membranes fabricated from nominally similar polymers may differ significantly in their ability to remove low molecular weight protein uraemic toxins.

Center-driven and Clinically Driven Variation in US Liver Transplant Maintenance Immunosuppression Therapy: A National Practice Patterns Analysis.

BACKGROUND: Variation in the use of immunosuppression regimens after liver transplant has not been well described. METHODS: Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice. RESULTS: In the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; P<0.001), cancer within 6 months (aOR, 6.07; P<0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m2 (aOR, 1.98; P<0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; P=0.003). CONCLUSIONS: Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.

Prevalence and severity of urinary incontinence in kidney transplant recipients.

OBJECTIVE: To estimate the prevalence and severity of urinary incontinence and its impact on activities of daily living in kidney transplant recipients. METHODS: The continence status, severity, and impact of urinary incontinence on activities of daily living in female kidney transplant recipients was studied by using Sandvik's Incontinence Severity Index and the Incontinence Impact Questionnaire. Clinical and sociodemographic data from post-transplant incontinent and continent participants were compared by using chi(2), Student t, and Mann-Whitney U tests. RESULTS: One hundred of 123 female kidney transplant recipients completed the survey for a response rate of 81.3%. The prevalence of urinary incontinence in female kidney transplant recipients was 28%. The mean Sandvik's Incontinence Severity Index score was 5.1 (median 3.5; 95% confidence interval 3.6, 6.6). The mean Incontinence Impact Questionnaire score was 12.9 (median 4.8; 95% confidence interval 6.7, 18.9). Incontinent kidney transplant recipients recorded a greater daily fluid intake on their 3-day diaries than continent kidney transplant recipients (2,951.9 +/- 1,228.6 mL compared with 1,854.6 +/- 614.8 mL, P =.04). CONCLUSIONS: The prevalence rate of urinary incontinence from interviewed kidney transplant recipients was 28%, which had minimal impact on activities of daily living and may not be predicted by a history of incontinence before kidney failure. LEVEL OF EVIDENCE: II-3

High-Resolution Imaging Using the VisualSonics Vevo 2100 on Isolated, Perfused Porcine Kidneys on Mechanical Circulatory Support.

Despite many improvements in the field of renal transplantation, the key problem that persists is the lack of organs for all the patients who need kidneys. This problem continues despite the addition of extended criteria donors and donation after cardiac death. Compounding this issue is the high discard rate and there are no good means to truly predict renal function using current pretransplantation testing parameters. In an isolated renal perfusion model using porcine kidneys, we tested the proof of principle that a Vevo 2100 high-frequency high-resolution ultrasound system (Fujifilm VisualSonics, Inc., Toronto, Canada) could assess renal parenchymal perfusion and flow in the central renal vessels which could not assess by conventional ultrasound. Images and velocities were easily obtained during these studies. High-frequency ultrasound imaging may be a feasible and reproducible method for assessing renal parenchymal integrity and function pretransplantation. Further studies are required to determine the sensitivity and specificity of this approach in comparison with traditional renal biopsy pretransplantation with the goal of increasing the identification and use of donated kidneys for transplantation.

Models and methods for analyzing DCE-MRI: a review.

PURPOSE: To present a review of most commonly used techniques to analyze dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), discusses their strengths and weaknesses, and outlines recent clinical applications of findings from these approaches. METHODS: DCE-MRI allows for noninvasive quantitative analysis of contrast agent (CA) transient in soft tissues. Thus, it is an important and well-established tool to reveal microvasculature and perfusion in various clinical applications. In the last three decades, a host of nonparametric and parametric models and methods have been developed in order to quantify the CA's perfusion into tissue and estimate perfusion-related parameters (indexes) from signal- or concentration-time curves. These indexes are widely used in various clinical applications for the detection, characterization, and therapy monitoring of different diseases. RESULTS: Promising theoretical findings and experimental results for the reviewed models and techniques in a variety of clinical applications suggest that DCE-MRI is a clinically relevant imaging modality, which can be used for early diagnosis of different diseases, such as breast and prostate cancer, renal rejection, and liver tumors. CONCLUSIONS: Both nonparametric and parametric approaches for DCE-MRI analysis possess the ability to quantify tissue perfusion.

Dialysate flow rate and delivered Kt/Vurea for dialyzers with enhanced dialysate flow distribution.

BACKGROUND AND OBJECTIVES: Previous in vitro and clinical studies showed that the urea mass transfer-area coefficient (K(o)A) increased with increasing dialysate flow rate. This observation led to increased dialysate flow rates in an attempt to maximize the delivered dose of dialysis (Kt/V(urea)). Recently, we showed that urea K(o)A was independent of dialysate flow rate in the range 500 to 800 ml/min for dialyzers incorporating features to enhance dialysate flow distribution, suggesting that increasing the dialysate flow rate with such dialyzers would not significantly increase delivered Kt/V(urea). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multi-center randomized clinical trial to compare delivered Kt/V(urea) at dialysate flow rates of 600 and 800 ml/min in 42 patients. All other aspects of the dialysis prescription, including treatment time, blood flow rate, and dialyzer, were kept constant for a given patient. Delivered single-pool and equilibrated Kt/V(urea) were calculated from pre- and postdialysis plasma urea concentrations, and ionic Kt/V was determined from serial measurements of ionic dialysance made throughout each treatment. RESULTS: Delivered Kt/V(urea) differed between centers; however, the difference in Kt/V(urea) between dialysate flow rates of 800 and 600 ml/min was NS by any measure (95% confidence intervals of -0.064 to 0.024 for single-pool Kt/V(urea), -0.051 to 0.023 for equilibrated Kt/V(urea), and -0.029 to 0.099 for ionic Kt/V). CONCLUSIONS: These data suggest that increasing the dialysate flow rate beyond 600 ml/min for these dialyzers offers no benefit in terms of delivered Kt/V(urea).