Greater access to transplantation should be a priority: A view of the Dialysis PATIENTS Demonstration Act.

Fragmentation of care has been cited as a rationale toward moving to new care models with care coordination and a focus on value-based care delivery. This trend is gathering momentum in end-stage renal disease (ESRD) care given evident care gaps and the variety of healthcare entities that touch patients with ESRD in the course of their treatment. Although care models supported by chronic condition special needs plans and ESRD seamless care organizations (ESCOs) have advanced care and cost-effectiveness, their shortcomings limit their ability to support larger patient populations. New care models and potential organizational structures, such as those proposed in the Dialysis Patient Access To Integrated-care, Empowerment, Nephrologists, Treatments, and Services (PATIENTS) Demonstration Act, provide another approach toward reducing fragmentation of care, increasing patient health, and helping define better approaches to care for patients with ESRD so that they have the opportunity to be better transplant candidates. We recognize that this type of innovation represents change without certainty. We also believe that multiple levels of accountability, ongoing support for transplantation, and continued freedom of access to transplant professionals who participate in Medicare would prioritize patient health, quality of life, and choice with regard to transplantation with this care model.

Filling the gap in CKD: The health care workforce and faculty development.

Given limited resources, adding another chronic illness to the panoply of chronic disease care is problematic. Nevertheless, chronic kidney disease (CKD) is increasing in recognition and prevalence across the world, and a management strategy for this growing population is necessary. A diverse group of health care professionals interacts with patients with CKD and their family members, including nurses, nurse practitioners, dieticians, social workers, pharmacists, physicians, physical therapists, physician assistants, and public health workers. All these individuals have the opportunity to reinforce CKD management. This potentially would bring a broader health care workforce to bear on CKD, reducing the impact of the nephrology workforce shortage. To realize such a strategy, it is necessary to bolster CKD awareness and knowledge in the diverse health care workforce. A faculty development program that extends CKD awareness to existing health care workers also has the possibility of migrating into the learner curriculum in health professional schools. This approach would expand CKD education, creating a skilled diverse health care workforce.

The rationale, implementation, and effect of the Medicare CKD education benefit.

Although it affects <1% of the US population, stage 4 chronic kidney disease (CKD) has increased in prevalence in the United States, grown 67% between the early 1990s and the first part of this decade. It is important to consider new strategies to slow or halt this increase. A frameshift in patient care delivery is underway in kidney health care in the United States with a Medicare education benefit for patients with stage 4 CKD. This Medicare benefit is a unique program that has the potential to inform patients and families about CKD and prepare them for transitions in health states and kidney health care. For the greatest value of this benefit to be realized, it is critical for the health care community to accurately gauge patient understanding of CKD and provide curricula that are comprehensible and actionable for patients. This type of benefit is patient centered, yet it will succeed only with a willingness to review its effectiveness and revise it if needed.

Retrograde occlusive arteriography of hemodialysis access: failure to detect inflow lesions?

Once thought to be a minor player in hemodialysis (HD) access dysfunction relative to outflow stenosis, inflow stenosis has recently come to be viewed as a major cause of access failure. Indeed, recent literature has shown that up to 40% of all accesses referred for dysfunction have an inflow lesion. Imaging of the inflow segment has been traditionally performed by interventional nephrologists via retrograde occlusive arteriography (ROA). Recent advances in our understanding of ROA have cast the technique in a negative light, with the possibility of vascular complications and poor diagnostic yield coming to the fore. Using a prospectively collected, vascular access database, we identified 18 consecutive patients who received imaging of inflow lesions by ROA and direct arteriogram (DA). The mean percent luminal stenoses were found to be 59.89 ± 24 and 79.06 ± 17.8 (p = 0.009) for the ROA vs. DA groups, respectively. Using multiple regression analysis, DA was found to be associated with detecting higher degree of luminal stenosis (ß = 19.17, 95% CI 6.28-32.05, p = 0.006). This small case series provides evidence on the theoretical concern that ROA does not adequately evaluate inflow lesions. We may conclude that by relying solely on ROA, interventional nephrologists may be failing to detect a subset of hemodynamically significant inflow lesions.

Prevalence of CKD and comorbid illness in elderly patients in the United States: results from the Kidney Early Evaluation Program (KEEP).

BACKGROUND: Elderly individuals with chronic kidney disease (CKD) have high rates of comorbid conditions, including cardiovascular disease and its risk factors, and CKD-related complications. In individuals aged > or = 65 years, we sought to describe the prevalence of CKD determined from laboratory test results in the Kidney Early Evaluation Program (KEEP; n = 27,017) and National Health and Nutrition Examination Survey (NHANES) 1999-2006 (n = 5,538) and the prevalence of diagnosed CKD determined from billing codes in the Medicare 5% sample (n = 1,236,946). In all 3 data sources, we also explored comorbid conditions and CKD-related complications. METHODS: CKD was identified as decreased estimated glomerular filtration rate (<60 mL/min/1.73 m(2)) or increased albumin-creatinine ratio in KEEP and NHANES; CKD was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes in Medicare. Investigated comorbid conditions included diabetes, hypertension, high cholesterol level, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and cancer, and CKD-related complications included anemia, hypocalcemia, hyperphosphatemia, and hyperparathyroidism. RESULTS: The prevalence of CKD was approximately 44% in both KEEP and NHANES participants, and the prevalence of diagnosed CKD was 7% in Medicare beneficiaries. In all 3 data sets, the prevalence of CKD or diagnosed CKD was higher in participants aged > or = 80 years and those with comorbid conditions. For KEEP and NHANES participants, the prevalence of most comorbid conditions and CKD complications increased with decreasing estimated glomerular filtration rate. For participants with CKD stages 3-5, a total of 29.2% (95% CI, 27.8-30.6) in KEEP and 19.9% (95% CI, 17.0-23.1) in NHANES had anemia, 0.7% (95% CI, 0.4-0.9) and 0.6% (95% CI, 0.3-1.3) had hypocalcemia, 5.4% (95% CI, 4.7-6.1) and 6.4% (95% CI, 5.1-8.0) had hyperphosphatemia, and 52.0% (95% CI, 50.4-53.6) and 30.0% (95% CI, 25.9-34.3) had hyperparathyroidism, respectively. CONCLUSIONS: CKD is common in the elderly population and is associated with high frequencies of concomitant comorbid conditions and biochemical abnormalities. Because CKD is not commonly diagnosed, greater emphasis on physician education may be beneficial.

Association of Chronic Condition Special Needs Plan With Hospitalization and Mortality Among Patients With End-Stage Kidney Disease.

Importance: While several studies have demonstrated the benefit of enrollment in chronic condition special needs plans (C-SNPs) for other chronic diseases (eg, diabetes), there is no evaluation of the association of C-SNPs with outcomes among patients with end-stage kidney disease (ESKD). Objective: To examine whether and to what degree C-SNP enrollment was associated with improved clinical outcomes and quality of life in patients with ESKD. Design, Setting, and Participants: This multicenter cohort study included 2718 patients who were newly enrolled in an ESKD C-SNP between January 1, 2013, and September 30, 2017, and receiving dialysis from DaVita Kidney Care. Patients were followed up until death, loss to follow-up, or end of study (ie, December 31, 2018). Enrollees in C-SNP were matched via multiple clinical and demographic characteristics with 2 different control populations, as follows: (1) those in the same facilities (n = 2545) or (2) those in similar counties (n = 1986). Patients enrolled in CareMore C-SNPs (n = 206) were excluded from the study. Data analysis was conducted June to December 2019. Exposures: Standard ESKD care with dialysis plus access to an integrated care team who worked with the patient and the dialysis team, comprehensive health assessments done by the integrated care team, and access to select benefits (such as vision and dental care) as a C-SNP enrollee. Main Outcomes and Measures: Hospitalizations, mortality, laboratory values indicative of metabolic control, and Kidney Disease Quality of Life 36-item (KDQOL-36) survey scores. Results: The 2545 C-SNP enrollees in the facility-matched analysis had a mean (SD) age of 57.2 (12.9) years, and included 968 (38.0%) women, 1328 (52.2%) Hispanic individuals, and 553 (21.7%) African American individuals. The 1986 C-SNP enrollees in the county-matched analysis had a mean (SD) age of 57.8 (12.2) years, with 705 (35.5%) women, 1085 (54.6%) Hispanic individuals, and 472 (23.8%) African American individuals. Compared with patients not enrolled in C-SNP, enrollees had lower hospitalization rates, with incidence rate ratios of 0.90 (95% CI, 0.84-0.97; P = .006) in the facility-matched analysis and 0.76 (95% CI, 0.70-0.83; P < .001) in the county-matched analysis. Compared with patients not enrolled in C-SNP, enrollees had decreased mortality risk in the same facilities (hazard ratio, 0.77; 95% CI, 0.68-0.88; P < .001) and in the same counties (hazard ratio, 0.77; 95% CI, 0.66-0.88; P < .001). No significant differences were observed between C-SNP enrollees and matched patients in metabolic laboratory values or KDQOL-36 survey scores. Conclusions and Relevance: This cohort study found a positive association of C-SNP enrollment with lower rates of hospitalization and mortality. The findings suggest that the additional services and benefits C-SNPs provide may improve outcomes compared with standard of care for patients with ESKD.

Complete reversal of epithelial to mesenchymal transition requires inhibition of both ZEB expression and the Rho pathway.

BACKGROUND: Epithelial to Mesenchymal Transition (EMT) induced by Transforming Growth Factor-beta (TGF-beta) is an important cellular event in organogenesis, cancer, and organ fibrosis. The process to reverse EMT is not well established. Our purpose is to define signaling pathways and transcription factors that maintain the TGF-beta-induced mesenchymal state. RESULTS: Inhibitors of five kinases implicated in EMT, TGF-beta Type I receptor kinase (TbetaRI), p38 mitogen-activated protein kinase (p38 MAPK), MAP kinase kinase/extracellular signal-regulated kinase activator kinase (MEK1), c-Jun NH-terminal kinase (JNK), and Rho kinase (ROCK), were evaluated for reversal of the mesenchymal state induced in renal tubular epithelial cells. Single agents did not fully reverse EMT as determined by cellular morphology and gene expression. However, exposure to the TbetaRI inhibitor SB431542, combined with the ROCK inhibitor Y27632, eliminated detectable actin stress fibers and mesenchymal gene expression while restoring epithelial E-cadherin and Kidney-specific cadherin (Ksp-cadherin) expression. A second combination, the TbetaRI inhibitor SB431542 together with the p38 MAPK inhibitor SB203580, was partially effective in reversing EMT. Furthermore, JNK inhibitor SP600125 inhibits the effectiveness of the TbetaRI inhibitor SB431542 to reverse EMT. To explore the molecular basis underlying EMT reversal, we also targeted the transcriptional repressors ZEB1 and ZEB2/SIP1. Decreasing ZEB1 and ZEB2 expression in mouse mammary gland cells with shRNAs was sufficient to up-regulate expression of epithelial proteins such as E-cadherin and to re-establish epithelial features. However, complete restoration of cortical F-actin required incubation with the ROCK inhibitor Y27632 in combination with ZEB1/2 knockdown. CONCLUSIONS: We demonstrate that reversal of EMT requires re-establishing both epithelial transcription and structural components by sustained and independent signaling through TbetaRI and ROCK. These findings indicate that combination small molecule therapy targeting multiple kinases may be necessary to reverse disease conditions.

WITHDRAWN: Endothelium in the allograft.

The paper entitled "Endothelium in the allograft" by Bryan N Becker et al, which was published online on 9 September 2009, has been withdrawn at the authors' request. Kidney International advance online publication, 9 September 2009; doi:10.1038/ki.2009.333.

KDOQI US commentary on the KDIGO clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in CKD.

KDIGO (Kidney Disease: Improving Global Outcomes) is an international initiative with a key mission of developing clinical practice guidelines in the area of chronic kidney disease (CKD). KDIGO recently published evidence-based clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus infection in individuals with CKD. The process of adaptation of international guidelines is an important task that, although guided by general principles, needs to be individualized for each region and country. Therefore, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) convened a multidisciplinary group to comment on the application and implementation of the KDIGO guidelines for patients with CKD in the United States. This commentary summarizes the process undertaken by this group in considering the guidelines in the context of health care delivery in the United States. Guideline statements are presented, followed by a succinct discussion and annotation of the rationale for the statements. Research recommendations that are of particular interest to the United States are then summarized to highlight future areas of inquiry that would enable updating of the guidelines.

CKD stage-to-stage progression in native and transplant kidney disease.

BACKGROUND: Kidney half-life and inter-stage progression rates in native chronic kidney disease (CKD) and CKD-transplant (CKD-T) remain unknown. METHODS: We examined stage-to-stage progression/regression rates in patients with CKD (n = 601) and CKD-T (n = 431) between 1991 and 2001. Kidney function was estimated by Cockcroft-Gault and MDRD eGFR formulae. Kaplan-Meier analyses determined progression and regression half-lives, defined as the time required for 50% of kidneys to advance towards a higher or lower stage of CKD, respectively. RESULTS: Most (67%) of the patients were in stage 3. Patients with native CKD were more likely to progress compared to CKD-T (inter-stage progression rates 12 vs 4 cases per 100 patient-years, P < 0.0001). Accordingly, estimated glomerular filtration rate (eGFR)-based progression half-lives were significantly shorter in CKD compared to CKD-T [6 vs 9.6 years, P < 0.0001, hazard ratio (HR) 3.1, 95% confidence interval (CI) = 2.5-3.7]. Creatinine clearance (CCR)-based stage half-lives were 7.2 months shorter in each group (5.4 and 9 years in CKD and CKD-T, respectively). Despite slower progression rates in patients with transplant kidney disease, adjusted patient survival rates were significantly decreased in CKD-T compared to CKD. Only Scr and CCR-based formulae were significantly associated with patient and allograft outcomes in the CKD-T group. Moreover, death rates were not different in stage 3 compared to stage 2 CKD-T, suggesting that eGFR and the current staging classification have a limited value to predict patient death in this cohort. CONCLUSION: Kidney half-lives per stage of CKD may be a novel tool to examine disease progression.

Alemtuzumab induction and recurrence of glomerular disease after kidney transplantation.

BACKGROUND: An increase in the incidence of autoimmune diseases has been described in patients receiving alemtuzumab. METHODS: To determine whether induction with alemtuzumab increases recurrence of glomerular disease, we performed a retrospective study in 443 patients with biopsy-proven glomerular diseases undergoing kidney transplantation. Patients receiving alemtuzumab (n=161) were compared with those receiving interleukin (IL)-2-receptor antagonists (n=217) or antithymocyte globulin (n=64). RESULTS: Biopsy-proven glomerular disease recurrence was similar in patients induced with alemtuzumab or IL-2 receptor antagonists. Patients receiving antithymocyte antibody had a lower recurrence rate than patients treated with other induction agents, with borderline significance (hazard ratio [HR] 0.13, 95% confidence interval [95% CI] 0.02-0.98, P=0.047). Patients with systemic lupus treated with alemtuzumab had a similar re-emergence of autoreactive antibodies to patients treated with other agents. Recurrent disease increased the risk of allograft failure (HR 2.36, 95% CI 1.28-4.32, P=0.0056). The development of acute rejection and the use of deceased (vs. living) donor kidneys were also significant factors influencing graft survival. A greater risk of mortality was detected in those patients with recurrent glomerular disease (HR 3.76, 95% CI 1.37-10.35, P=0.01), whereas increased age at transplantation (HR 1.05) and the use of deceased (vs. living) donor kidneys (HR 3.20) also increased mortality. No specific induction agent significantly affected graft loss or mortality when using adjusted or unadjusted hazard ratios. CONCLUSIONS: In this retrospective analysis, induction with alemtuzumab did not increase the rate of re-emergence of autoantibodies or biopsy-proven recurrence of glomerular disease. A slight reduction in the incidence of recurrence was observed in patients treated with thymoglobulin, yet this observation can only be validated in a prospective randomized trial.

Disease progression and outcomes in type 1 diabetic kidney transplant recipients based on posttransplantation CKD staging.

BACKGROUND: Disease progression rates and outcomes per stage of kidney disease in kidney transplant recipients with type 1 diabetes mellitus are unknown. STUDY DESIGN: Single-center retrospective cohort study. SETTINGS & PARTICIPANTS: 276 kidney transplant recipients with type 1 diabetes mellitus and a functioning graft at 1 year posttransplantation. PREDICTORS: Stage of chronic kidney disease at 1 year posttransplantation, donor source, and other clinical characteristics (covariates). OUTCOMES & MEASUREMENTS: Slope of creatinine clearance, weighted average slopes of creatinine clearance in a subgroup of 60 patients, death-censored allograft and patient survival rates. RESULTS: The median rate of creatinine clearance decrease after the first posttransplantation year was -1.6 mL/min/y (95% confidence interval [CI], -1.97 to -1.30) during a median follow-up of 8.4 years (95% CI, 8.13 to 8.84). The slope was significantly greater in stages 1 to 2 (-1.7 mL/min/y; 95% CI, -2.2 to -1.4) than stage 3 (-1.2 mL/min/y; 95% CI, -1.9 to -0.6; P = 0.0003). However, chronic kidney disease stage and donor source had no significant effect on death-censored allograft survival and patient survival rates. There were 23 deaths and 31 allograft losses in patients with stages 1 to 2 compared with 19 deaths and 18 allograft losses in those with stage 3. Univariate and multivariable Cox regression analyses showed that semiquantitative proteinuria of 1 or greater, mean arterial pressure, hematocrit of 33% or less, and calcineurin-inhibitor use were associated with decreased allograft survival, and age and hemoglobin A(1c) level of 7% or greater were significant risk factors for patient death regardless of donor type and stage of kidney function. LIMITATIONS: Generalizability to other settings; study power. CONCLUSION: All forms of kidney transplantation in patients with type 1 diabetes mellitus progressed at similar rates regardless of chronic kidney disease stage at 1 year posttransplantation. Age, anemia, hemoglobin A(1c) level, proteinuria, hypertension, and calcineurin-inhibitor use were associated with decreased allograft and patient outcomes.

Preemptive transplantation for patients with diabetes-related kidney disease.

BACKGROUND: Preemptive kidney transplantation (PreKT) before initiation of chronic dialysis has been examined recently with favorable results as the most effective treatment for kidney failure. Given that few of these studies are disease specific, the present analyses investigated the outcomes of PreKT by transplantation option and diabetes type. METHODS: The impact of PreKT on posttransplantation mortality and graft failure was examined in 23 238 adults with type 1 and type 2 diabetes mellitus (DM), receiving either living or deceased donor kidneys or undergoing simultaneous pancreas-kidney (SPK) transplantation between January 1, 1997, and December 31, 2002. RESULTS: The PreKTs were provided to 14.4% of patients with type 1 DM and 6.7% of patients with type 2 DM. Cox regression models were used to estimate the effect of PreKT on the adjusted risk ratio (RR) of graft failure and mortality. After adjusting for multiple factors, PreKT in this era was associated with lower RR of mortality only among type 1 and type 2 diabetic recipients of transplants from living donors and SPK transplant recipients with type 1 DM (RR, 0.50-0.65; P<.007 for each). The effect on graft failure was less pronounced, significant only for preemptive SPK transplant recipients (RR, 0.79; P=.01 vs nonpreemptive SPK transplant recipients). CONCLUSIONS: These analyses suggest that PreKT has significant benefits for subsets of patients with types 1 and 2 DM and end-stage renal disease. It also suggests a time trend toward less benefit from preemptive transplants from deceased donors in more recent years compared with the early 1990s. This observation and the discrepancies between RR of graft loss and RR of mortality deserve further study.

Trends in kidney transplantation rates and disparities.

OBJECTIVE: To examine the likelihood of transplantation and trends over time among persons with end-stage renal disease (ESRD) in Wisconsin. METHODS: We examined the influence of patient- and community-level characteristics on the rate of kidney transplantation in Wisconsin among 22,387 patients diagnosed with ESRD between January 1, 1982 and October 30, 2005. We grouped patients by the year of ESRD onset in order to model the change in transplantation rates over time. RESULTS: After multivariate adjustment, all other racial groups were significantly less likely to be transplanted compared with whites, and the racial disparity increased over calendar time. Older patients were less likely to be transplanted in all periods. Higher community income and education level and a greater distance from patients' residence to the nearest dialysis center significantly increased the likelihood of transplantation. Males also had a significantly higher rate of transplantation than females. CONCLUSION: These results demonstrate a growing disparity in transplantation rates by demographic characteristics and a consistent disparity in transplantation by socioeconomic characteristics. Future studies should focus on identifying specific barriers to transplantation among different subpopulations in order to target effective interventions.

Noninvasive assessment of early kidney allograft dysfunction by blood oxygen level-dependent magnetic resonance imaging.

BACKGROUND: Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) is a noninvasive method to assess tissue oxygen bioavailability, using deoxyhemoglobin as an endogenous contrast agent. We hypothesized that BOLD-MRI could accurately discriminate different types of rejection early after kidney transplantation. METHODS: Twenty-three patients underwent imaging in the first four months posttransplant. Five had normal functioning transplants and 18 had biopsy-proven acute allograft dysfunction (acute tubular necrosis [ATN, n=5] and acute rejection [n=13] including borderline rejection: n=3; IA rejection: n=4; IIA rejection: n=6: C4d(+) rejection: n=9). RESULTS: Mean medullary R2* (MR2*) levels (a measure directly proportional to tissue deoxyhemoglobin levels) were significantly higher in normal functioning allografts (R2*=24.3/s+/-2.3) versus acute rejection (R2*=16.6/s+/-2.1) and ATN (R2*=20.9/s+/-1.8) (P<0.05). The lowest MR2* levels were observed in acute rejection episodes with vascular injury i.e. IIA and C4d (+). Similarly, the lowest medullary to cortical R2* ratios (MCR2*) were present in allografts with IIA (1.24+/-0.05) and C4d(+) rejection (1.26+/-0.06). ROC curve analyses suggested that MR2* and MCR2* values could accurately discriminate acute rejection in the early posttransplant period. CONCLUSIONS: BOLD-MRI demonstrated significant changes in medullary oxygen bioavailability in allografts with biopsy-proven ATN and acute rejection, suggesting that there may be a role for this noninvasive tool to evaluate kidney function early after transplantation.

In-center hemodialysis patients' use of the internet in the United States: a national survey.

BACKGROUND: Education is critical to help patients with chronic kidney disease self-manage their illness by thoroughly understanding their treatment options, medications, diet and fluids, and symptoms. METHODS: This study assesses in-center hemodialysis patients' use of the Internet in general and for health information seeking, both independently and by proxy-asking a family member or friend. Patients (n = 1,804) were recruited from 37 randomly selected dialysis clinics in 18 End-Stage Renal Disease Networks. Respondents completed a survey in English or Spanish. RESULTS: Across the entire sample, 34.7% had used the Internet themselves compared with 38% of disabled Americans. Internet use was more likely among patients who were younger, non-Hispanic, from the Southeast or Texas, and more highly educated. Median education level of English-reading respondents was 12th grade. Their total Internet health information use was 43.5% (24.7% independently, 18.8% by proxy). Median education level of Spanish-reading respondents was 6th grade; their total Internet health information use was only 25.5% (8.5% independently, 17% by proxy). Reasons for not using the Internet related more to not having access to a computer or knowledge (70.4%) than to lack of interest (21.3%). CONCLUSION: Alerting patients to Internet access at public libraries or providing a computer in dialysis clinic waiting rooms may help overcome this barrier. Proxy use may extend the reach of the Internet to patients who do not have access on their own.