Patients with ESRD undergoing dialysis have highly complex medication regimens and disproportionately higher total cost of care compared with the general Medicare population. As shown by several ...studies, dialysis-dependent patients are at especially high risk for medication-related problems. Providing medication reconciliation and therapy management services is critically important to avoid costs associated with medication-related problems, such as adverse drug events and hospitalizations in the ESRD population. The Medicare Modernization Act of 2003 included an unfunded mandate stipulating that medication therapy management be offered to high-risk patients enrolled in Medicare Part D. Medication management services are distinct from the dispensing of medications and involve a complete medication review for all disease states. The dialysis facility is a logical coordination center for medication management services, like medication therapy management, and it is likely the first health care facility that a patient will present to after a care transition. A dedicated and adequately trained clinician, such as a pharmacist, is needed to provide consistent, high-quality medication management services. Medication reconciliation and medication management services that could consistently and systematically identify and resolve medication-related problems would be likely to improve ESRD patient outcomes and reduce total cost of care. Herein, this work provides a review of available evidence and recommendations for optimal delivery of medication management services to ESRD patients in a dialysis facility-centered model.
Background. Incident and prevalent (I&P) rates in dialysis end-stage renal disease (ESRD) patients in Taiwan increased rapidly following the launch of National Health Insurance (NHI) in 1995. Our aim ...was to explore the impact of NHI on the status and trends of ESRD epidemiology in Taiwan. Methods. This study was conducted using retrospective cohort analysis of data collected from the Taiwan national dialysis registry. Results. From 1990 to 2001, I&P rates of ESRD patients increased 2.6 times from 126 to 331 per million populations (pmp) and 3.46 times from 382 to 1322 pmp, respectively. Increasing ESRD was seen in patients who were middle-aged, elderly and who had diabetic nephropathy as their primary renal disease. The mean age of I&P patients increased by 7.2 years and 7.1 years, respectively. All of these parameters increased markedly in 1995, the year of NHI implementation. First-year mortality decreased to 7.8 per 1000 patient-months in 1994, and then increased to 18.0 in 2001. The cumulative survival rate of the elderly subgroup (age >65) in the incident 1990–1994 cohort was greater than in the 1995–1999 cohort. These data indicated that NHI implementation significantly influenced the inflow and the mortality of ESRD patients. Conclusion. In addition to presenting ESRD epidemiology in Taiwan, this study demonstrated that NHI implementation stimulated the growth of treated ESRD populations. Preventive plans mounted against chronic kidney diseases will be essential to reduce the growth of ESRD patient numbers and consequent economic burdens.
With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited ...data exists on its safety and efficacy.
We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function.
A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332-6254).
Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.
Cardiac failure is directly affected by left ventricular (LV) dysfunction, and particularly LV systolic dysfunction is strongly associated with survival in ESRD patients. The aim of this study was to ...determine the prognostic value of reduced LV ejection fraction (LVEF) measured at the time of initiation of hemodialysis (HD) in incident HD patients.
1254 consecutive ESRD patients who electively started HD therapy were screened by echocardiography within 1 month after its inception. They were divided into five groups according to LVEF levels with a decrease of 0.1 each and were followed up for up to 7 years. Survival was examined with the Kaplan-Meier method and compared using the log-rank test.
Among the 1254 patients, LVEF levels ≥0.6, 0.5 to 0.6, 0.4 to 0.5, 0.3 to 0.4, and <0.3 were seen in 842 (67.1%), 247 (19.7%), 107 (8.5%), 41 (3.3%), and 17 (1.4%) patients, respectively. On Kaplan-Meier analysis, 7-year event-free rates from cardiovascular death were 84.2, 83.7, 73.6, 59.4, and 30.9% in order of groups with decreasing LVEF of 0.1 each, respectively. Seven-year event-free rates from all-cause death were 69.2, 61.7, 57.1, 45.9, and 23.1% in the respective groups. Even after adjustment for other risk factors, decreasing LVEF was a strong independent predictor for cardiovascular death.
Reduced LVEF on starting HD therapy could stratify risk of cardiovascular and all-cause mortality in ESRD patients. Screening by echocardiography at start of HD therapy might be recommended to predict prognosis in patients with ESRD.
There are conflicting research results about the survival differences between hemodialysis and peritoneal dialysis, especially during the first 2 years of dialysis treatment. Given the challenges of ...conducting randomized trials, differential rates of modality switch and transplantation, and time-varying confounding in cohort data during the first years of dialysis treatment, use of novel analytical techniques in observational cohorts can help examine the peritoneal dialysis versus hemodialysis survival discrepancy.
This study examined a cohort of incident dialysis patients who initiated dialysis in DaVita dialysis facilities between July of 2001 and June of 2004 and were followed for 24 months. This study used the causal modeling technique of marginal structural models to examine the survival differences between peritoneal dialysis and hemodialysis over the first 24 months, accounting for modality change, differential transplantation rates, and detailed time-varying laboratory measurements.
On dialysis treatment day 90, there were 23,718 incident dialysis-22,360 hemodialysis and 1,358 peritoneal dialysis-patients. Incident peritoneal dialysis patients were younger, had fewer comorbidities, and were nine and three times more likely to switch dialysis modality and receive kidney transplantation over the 2-year period, respectively, compared with hemodialysis patients. In marginal structural models analyses, peritoneal dialysis was associated with persistently greater survival independent of the known confounders, including dialysis modality switch and transplant censorship (i.e., death hazard ratio of 0.52 95% confidence limit 0.34-0.80).
Peritoneal dialysis seems to be associated with 48% lower mortality than hemodialysis over the first 2 years of dialysis therapy independent of modality switches or differential transplantation rates.
Recombinant human erythropoietin (r-HuEpo) has been used for the treatment of renal anemia. With the loss of its patent protection, there has been an upsurge of more affordable biosimilar agents, ...increasing patient access to treatment for these conditions. The complexity of the manufacturing process for these recombinant proteins, however, can result in altered properties that may significantly affect patient safety. As it is not known whether various r-HuEpo products can be safely interchanged, we studied 30 patients with chronic kidney disease treated by subcutaneous injection with biosimilar r-HuEpo and who developed a sudden loss of efficacy. Sera from 23 of these patients were positive for r-HuEpo-neutralizing antibodies, and their bone marrow biopsies indicated pure red-cell aplasia, indicating the loss of erythroblasts. Sera and bone marrow biopsies from the remaining seven patients were negative for anti-r-HuEpo antibodies and red-cell aplasia, respectively. The cause for r-HuEpo hyporesponsiveness was occult gastrointestinal bleeding. Thus, subcutaneous injection of biosimilar r-HuEpo can cause adverse immunological effects. A large, long-term, pharmacovigilance study is necessary to monitor and ensure patient safety for these agents.
Among patients who had acute kidney injury (AKI) during hospitalization, there is a need to improve risk prediction such that those at highest risk for subsequent loss of kidney function are ...identified for appropriate follow-up.
To evaluate the association of post-AKI proteinuria with increased risk of future loss of renal function.
The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study was a multicenter prospective cohort study including 4 clinical centers in North America included 1538 patients enrolled 3 months after hospital discharge between December 2009 and February 2015.
Urine albumin-to-creatinine ratio (ACR) quantified 3 months after hospital discharge.
Kidney disease progression defined as halving of estimated glomerular filtration rate (eGFR) or end-stage renal disease.
Of the 1538 participants, 769 (50%) had AKI durring hospitalization. The baseline study visit took place at a mean (SD) 91 (23) days after discharge. The mean (SD) age was 65 (13) years; the median eGFR was 68 mL/min/1.73 m2; and the median urine ACR was 15 mg/g. Overall, 547 (37%) study participants were women and 195 (13%) were black. After a median follow-up of 4.7 years, 138 (9%) participants had kidney disease progression. Higher post-AKI urine ACR level was associated with increased risk of kidney disease progression (hazard ratio HR, 1.53 for each doubling; 95% CI, 1.45-1.62), and urine ACR measurement was a strong discriminator for future kidney disease progression (C statistic, 0.82). The performance of urine ACR was stronger in patients who had had AKI than in those who had not (C statistic, 0.70). A comprehensive model of clinical risk factors (eGFR, blood pressure, and demographics) including ACR provided better discrimination for predicting kidney disease progression after hospital discharge among those who had had AKI (C statistic, 0.85) vs those who had not (C statistic, 0.76). In the entire matched cohort, after taking into account urine ACR, eGFR, demographics, and traditional chronic kidney risk factors determined 3 months after discharge, AKI (HR, 1.46; 95% CI, 0.51-4.13 for AKI vs non-AKI) or severity of AKI (HR, 1.54; 95% CI, 0.50-4.72 for AKI stage 1 vs non-AKI; HR, 0.56; 95% CI, 0.07-4.84 for AKI stage 2 vs non-AKI; HR, 2.24; 95% CI, 0.33-15.29 for AKI stage 3 vs non-AKI) was not independently associated with more rapid kidney disease progression.
Proteinuria level is a valuable risk-stratification tool in the post-AKI period. These results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI.
Cross-sectional health-related quality of life (HR-QOL) measures are associated with mortality in hemodialysis (HD) patients. The impact of changes in HR-QOL on outcomes remains unclear. We describe ...the association of prior changes in HR-QOL with subsequent mortality among HD patients.
A total of 13 784 patients in the Dialysis Outcomes and Practice Patterns Study had more than one measurement of HR-QOL. The impact of changes between two measurements of the physical (PCS) and mental (MCS) component summary scores of the SF-12 on mortality was estimated with Cox regression.
Mean age was 62 years (standard deviation: 14 years); 59% were male and 32% diabetic. Median time between HR-QOL measurements was 12 months interquartile range (IQR): 11, 14. Median initial PCS and MCS scores were 37.5 (IQR: 29.4, 46.2) and 46.4 (IQR: 37.2, 54.9); median changes in PCS and MCS scores were -0.2 (IQR: -5.5, 4.7) and -0.1 (IQR: -6.8, 5.9), respectively. The adjusted hazard ratio (HR) for a 5-point decline in HR-QOL score was 1.09 95% confidence interval (CI): 1.06-1.12 for PCS and 1.05 (95% CI: 1.03-1.08) for MCS. Adjusting for the second QOL score, the change was not associated with mortality: HR = 1.01 (95% CI: 0.98-1.05) for delta PCS and 1.01 (95% CI: 0.98-1.03) for delta MCS. Categorizing the first and second scores as predictors, only the second PCS or MCS score was associated with mortality.
In our study, only the most recent HR-QOL score was associated with mortality. Hence, the predictive power of a measurement of HR-QOL is not affected by changes in HR-QOL prior to that measurement; more frequent HR-QOL measurements are needed to improve the prediction of outcomes in HD. Further studies are needed to determine the optimal frequency and appropriate instrument to be used for serial measurements.
To investigate serum level of high mobility group box protein-1 (HMGB1) and prognosis of patients with end-stage renal disease (ESRD) on hemodialysis (HD) and peritoneal dialysis (PD).This ...prospective cohort observational study included a total of 253 ESRD patients who came to our hospital for HD or PD from February 2013 to February 2015. Enzyme linked immunosorbent assay (ELISA) method was used to detect the serum level of HMGB1, interleukin (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-α). The kidney disease quality of life short form (KDQOL-SF) and kidney disease targeted area (KDTA) was applied for evaluating the quality of life. Kaplan-Meier (K-M) curve was performed for survival time.Serum level of HMGB1 in patients on HD was higher than PD. HMGB1 levels were gradually decreased with the treatment of HD or PD. Furthermore, HMGB1 was positively correlated with IL-6 and TNF-α. Moreover, patients with higher HMGB1 had more complications than patients with lower HMGB1, but there was no difference for the survival rate. In addition, the quality of life was associated with different dialysis methods.The serum level of HMGB1 and prognosis of ESRD patients was associated with different dialysis methods.
Genetic etiologies have been identified among approximately 10% of adults with chronic kidney disease. However, data are lacking regarding the prevalence of monogenic etiologies especially among ...members of minority groups. The objective of this study was to characterize the genetic markers among members of an Israeli minority group with end-stage kidney disease (ESKD).
A national-multicenter cross-sectional study of Israeli Druze patients receiving maintenance dialysis for ESKD. an Arabic-speaking Near-Eastern transnational population isolate. All study participants underwent exome sequencing.
& Participants: We recruited 94 adults with ESKD, which comprised 97% of the total 97 dialysis-treated Druze individuals throughout Israel during the study period.
Demographics and clinical characteristics of kidney disease
Genetic markers.
Whole exome sequencing and their relationship of markers to clinical phenotypes.
We identified genetic etiologies in 17 of 94 participants (18%). None had a previous molecular diagnosis. A novel, population-specific, WDR19 homozygous pathogenic variant (p.Cys293Tyr) was the most common genetic diagnosis. Other monogenic etiologies included PKD1, PKD2, type IV collagen mutations, as well as monogenic forms of non-communicable diseases. The pre-exome clinical diagnosis corresponded to the final molecular diagnosis in less than half of the participants.
This study was limited to Druze, so its generalizability may be limited.
Exome sequencing identified a genetic diagnosis in approximately 18% of in Druze with ESKD. These results support conducting genetic analyses in minority populations with high rates of CKD and for whom phenotypic disease specificity may be low.
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