Personalized Management of Sodium and Volume Imbalance in Hemodialysis to Mitigate High Costs of Hospitalization.

The primary objective of hemodialysis (HD) is lowering concentrations of organic uremic toxins that accumulate in blood in end-stage kidney disease (ESKD) and redress imbalances of inorganic compounds in particular sodium and water. Removal by ultrafiltration of excess fluid that has accumulated during the dialysis-free interval is a vital aspect of each HD session. Most HD patients are volume overloaded, with ∼25% of patients having severe (>2.5 L) fluid overload (FO). The potentially serious complications of FO contribute to the high cardiovascular morbidity and mortality observed in the HD population. Weekly cycles imposed by the schedule of HD treatments create a deleterious and unphysiological "tide phenomenon" marked by sodium-volume overload (loading) and depletion (unloading). Fluid overload-related hospitalizations are frequent and costly, with average cost estimates of $ 6,372 per episode, amounting to some $ 266 million total costs over a 2-year period in a US dialysis population. Various strategies (e.g., dry weight management or use of fluids with different sodium concentrations) have been attempted to rectify FO in HD patients but have met with limited success largely due to imprecise and cumbersome, or costly, approaches. In recent years, conductivity-based technologies have been refined to actively restore sodium and fluid imbalance and maintain the predialysis plasma sodium set point (plasma tonicity) of each patient. By automatically controlling the dialysate-plasma sodium gradient based on the specific patient needs throughout a session, an individualized sodium dialysate prescription can be delivered. Maintaining precise sodium mass balance helps better control of blood pressure, reduces FO, and thus tends to prevent hospitalization for congestive heart failure. We present the case for personalized salt and fluid management via a machine-integrated sodium management tool. Results from proof-of-principle clinical trials indicate that the tool enables individualized sodium-fluid volume control during each HD session. Its application in routine clinical practice has the potential to mitigate the substantial economic burden of hospitalizations attributed to volume overload complications in HD. Additionally, such a tool would contribute toward reduced symptomology and dialysis-induced multiorgan damage in HD patients and to improving their treatment perception and quality of life which matters most to patients.

Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort.

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

Changing paradigms of renal replacement therapy in chronic kidney disease patients: ultrapure dialysis fluid and high-efficiency hemodiafiltration for all?

Ultrapurity of dialysis fluid is important for the biocompatibility of renal replacement therapy systems. Penne and collaborators have assessed the microbiological quality of water and dialysis fluid in dialysis facilities. No side effects were noted in 97 patients who received 11,258 online hemodiafiltration sessions. This study confirms that ultrapure water and dialysis fluid may be easily produced and used for online hemodiafiltration.

Vascular access use and outcomes: an international perspective from the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: A well-functioning vascular access (VA) is essential to efficient dialysis therapy. Guidelines have been implemented improving care, yet access use varies widely across countries and VA complications remain a problem. This study took advantage of the unique opportunity to utilize data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) to examine international trends in VA use and trends in patient characteristics and practices associated with VA use from 1996 to 2007. DOPPS is a prospective, observational study of haemodialysis (HD) practices and patient outcomes at >300 HD units from 12 countries and has collected data thus far from >35,000 randomly selected patients. METHODS: VA data were collected for each patient at study entry (1996-2007). Practice pattern data from the facility medical director, nurse manager and VA surgeon were also analysed. RESULTS: Since 2005, a native arteriovenous fistula (AVF) was used by 67-91% of prevalent patients in Japan, Italy, Germany, France, Spain, the UK, Australia and New Zealand, and 50-59% in Belgium, Sweden and Canada. From 1996 to 2007, AVF use rose from 24% to 47% in the USA but declined in Italy, Germany and Spain. Moreover, graft use fell by 50% in the USA from 58% use in 1996 to 28% by 2007. Across three phases of data collection, patients consistently were less likely to use an AVF versus other VA types if female, of older age, having greater body mass index, diabetes, peripheral vascular disease or recurrent cellulitis/gangrene. In addition, countries with a greater prevalence of diabetes in HD patients had a significantly lower percentage of patients using an AVF. Despite poorer outcomes for central vein catheters, catheter use rose 1.5- to 3-fold among prevalent patients in many countries from 1996 to 2007, even among non-diabetic patients 18-70 years old. Furthermore, 58-73% of patients new to end-stage renal disease (ESRD) used a catheter for the initiation of HD in five countries despite 60-79% of patients having been seen by a nephrologist >4 months prior to ESRD. Patients were significantly (P < 0.05) less likely to start dialysis with a permanent VA if treated in a faciity that (1) had a longer time from referral to access surgery evaluation or from evaluation to access creation and (2) had longer time from access creation until first AVF cannulation. The median time from referral until access creation varied from 5-6 days in Italy, Japan and Germany to 40-43 days in the UK and Canada. Compared to patients using an AVF, patients with a catheter displayed significantly lower mean Kt/V levels. CONCLUSIONS: Most countries meet the contemporary National Kidney Foundation's Kidney Disease Outcomes Quality Initiative goal for AVF use; however, there is still a wide variation in VA preference. Delays between the creation and cannulation must be improved to enhance the chances of a future permanent VA. Native arteriovenous fistula is the VA of choice ensuring dialysis adequacy and better patient outcomes. Graft is, however, a better alternative than catheter for patients where the creation of an attempted AVF failed or could not be created for different reasons.

Improving outcomes for dialysis patients in the international Dialysis Outcomes and Practice Patterns Study.

The international Dialysis Outcomes and Practice Patterns Study (DOPPS) is well suited to evaluate levels of deviation from emerging and established guidelines to clinical practice of hemodialysis, over time and by country. The DOPPS can also evaluate whether the target levels that are chosen in the guidelines are in agreement with outcomes such as elevated risk for mortality, hospitalization, and vascular access failure. At a special DOPPS symposium during the 2004 congress of the American Society of Nephrology, the authors presented such findings; key points from that symposium are presented in this article, focusing on vascular access, mineral metabolism, dialysis dose, and anemia management. Although an observational study cannot prove causality, DOPPS suggests large opportunities to improve care and outcomes of dialysis patients. The international perspective of DOPPS assists in the new efforts for international guidelines. Some encouraging trends in recent years are documented in these areas.

Dose of dialysis: key lessons from major observational studies and clinical trials.

Analyses based on the National Cooperative Dialysis Study (NCDS) provided the impetus for routine quantification of delivered dialysis dose in hemodialysis practice throughout the world, by suggesting minimum targets for small solute (urea) clearance. Morbidity and mortality in dialysis populations remain high despite many technological advances in dialysis delivery. A number of observational studies reported association between higher dose of dialysis as measured by Kt/V urea or urea reduction ratio with lower mortality risk. During the 1990s, a steady increase in dialysis dose and a modest reduction in mortality on dialysis were observed. However, observational studies only reveal associations and are limited by selection bias and confounding. The Kidney Disease Outcomes Quality Initiative guidelines on dialysis adequacy are based on results of observational studies and expert opinion. Since the NCDS, the HEMO Study was the first major randomized clinical trial designed to study the effect of dose of dialysis and dialyzer flux on patient outcomes. Despite adequate separation of dose and flux, however, results of the trial did not prove a beneficial effect of higher dose. The Dialysis Outcomes and Practice Patterns Study (DOPPS), in a major international effort designed to examine the effect of practice patterns on outcomes, has made significant contributions to the topic of dialysis dose. The following review critically examines data from observational studies, including the DOPPS, and from the HEMO Study, emphasizing important lessons from both, and discusses future paradigms for achieving dialysis adequacy to improve patient outcomes.

Early readmission and length of hospitalization practices in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Rising hospital care costs have created pressure to shorten hospital stays and emphasize outpatient care. This study tests the hypothesis that shorter median length of stay (LOS) as a dialysis facility practice is associated with higher rates of early readmission. METHODS: Readmission within 30 days of each hospitalization was evaluated for participants in the Dialysis Outcomes and Practice Patterns Study, an observational study of randomly selected hemodialysis patients in the United States (142 facilities, 5095 patients with hospitalizations), five European countries (101 facilities, 2281 patients with hospitalizations), and Japan (58 facilities, 883 patients with hospitalizations). Associations between median facility LOS (estimated from all hospitalizations at the facility and interpreted as a dialysis facility practice pattern) and odds of readmission were assessed using logistic regression, adjusted for patient characteristics and the LOS of each index hospitalization. RESULTS: Risk of readmission was directly and significantly associated with LOS of the index hospitalization (adjusted odds ratio [AOR] 1.005 per day in median facility LOS, p = 0.007) and inversely associated with median facility LOS (AOR = 0.974 per day, p = 0.016). This latter association was strongest for US hemodialysis centers (AOR = 0.954 per day, p = 0.015). CONCLUSIONS: Dialysis facilities with shorter median hospital LOS for their patients have higher odds of readmission, particularly in the United States, where there is greater pressure to shorten LOS. The determinants and consequences of practices related to hospital LOS for hemodialysis patients should be further studied.

Health-related quality of life among dialysis patients on three continents: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Assessing health-related quality of life (HRQOL) can provide information on the types and degrees of burdens that afflict patients with chronic medical conditions, including end-stage renal disease (ESRD). Several studies have shown important international differences among ESRD patients treated with hemodialysis, but no studies have compared these patients' HRQOL. Our goal was to document international differences in HRQOL among dialysis patients and to identify possible explanations of those differences. METHODS: We examined data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, observational, international study of hemodialysis patients. We performed a cross-sectional analysis of DOPPS data from the United States, five countries in Europe (France, Germany, Italy, Spain, and the United Kingdom), and Japan. Linear mixed models were used to analyze differences in HRQOL, using the KDQOL-SFTM. Norm-based scores were used to minimize cultural response bias. Linear regression analysis was used to adjust for confounding factors. Other variables included demographic variables, comorbidities, primary cause of ESRD, complications of ESRD and treatment, and socioeconomic status. RESULTS: In all generic HRQOL subscales, patients on all three continents had much lower scores than their respective population norm values. Patients in the United States had the highest scores on the mental health subscale and the highest mental component summary scores. Japanese patients reported better physical functioning than did patients in the United States or Europe, but they also reported the greatest burden of kidney disease. Overall, these differences remained even after adjusting for possible confounders. CONCLUSION: On all three continents, ESRD and hemodialysis profoundly affect HRQOL. In the United States, the effects on mental health are smaller than in other countries. Japanese hemodialysis patients perceived that their kidney disease imposes a greater burden, but their physical functioning was significantly higher. Different distributions of socioeconomic factors and major comorbid conditions could explain little of this difference in physical functioning. Other possible factors, such as quality of dialysis and related health care, deserve careful study.