Automated Peritoneal Dialysis With Remote Patient Monitoring: Clinical Effects and Economic Consequences for Poland.

OBJECTIVES: Remote patient monitoring (RPM) of patients treated with automated peritoneal dialysis (APD) at home allows clinicians to supervise and adjust the dialysis process remotely. This study aimed to review recent scientific studies on the use of RPM in patients treated with APD and based on extracted relevant data assess possible clinical implications and potential economic value of introducing such a system into practice in Poland. METHODS: A systematic literature review was performed in the MEDLINE, EMBASE, and Cochrane databases. The model of clinical effects and costs associated with APD was built as a cost-effectiveness analysis with a 10-year time horizon from the Polish National Health Fund perspective. Cost-effectiveness analysis compared 2 strategies: APD with RPM versus APD without RPM. RESULTS: Thirteen publications assessing the clinical value of RPM among patients with APD were found. The statistical significance of APD with RPM compared with APD without RPM was identified for the main clinical outcomes: frequency and length of hospitalizations, APD technique failure, and death. An incremental cost-effectiveness ratio was equal to €27 387 per quality-adjusted life-year. The obtained incremental cost-effectiveness ratio is below the willingness-to-pay threshold for the use of medical technologies in Poland (€36 510 per quality-adjusted life-year), which means that APD with RPM was a cost-effective technology. CONCLUSIONS: RPM in patients starting APD is a clinical option that is worth considering in Polish practice because it has the potential to decrease the frequency of APD technique failure and shorten the length of hospitalization.

A Comparative Analysis of Nutritional Assessment Using Global Leadership Initiative on Malnutrition Versus Subjective Global Assessment and Malnutrition Inflammation Score in Maintenance Hemodialysis Patients.

OBJECTIVE: Malnutrition is a prevalent condition in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the performance of the recently developed GLIM (Global Leadership Initiative on Malnutrition) in MHD by assessing the agreement, accuracy, sensitivity, specificity, and survival prediction of GLIM when compared to 7-point subjective global assessment (7p-SGA) and malnutrition inflammation score (MIS). DESIGN AND METHODS: We investigated 2 cohorts: MHDltaly (121 adults from Italy; 67 ± 16 years, 65% men, body mass index 25 ± 5 kg/m2) and MHDBrazil (169 elderly [age > 60 years] from Brazil; 71 ± 7 years, 66% men, body mass index 25 ± 4 kg/m2), followed for all-cause mortality for median 40 and 17 months, respectively. We applied the 2-step approach from GLIM: (1) screening and (2) confirming malnutrition by phenotypic and etiologic criteria. For 7p-SGA and MIS, a score ≤5 and ≥8, respectively, defined malnutrition. RESULTS: Malnutrition was present in 38.8% by GLIM, 25.6% by 7p-SGA, and 29.7% by MIS in the MHDItaly cohort, and in 47.9% by GLIM, 59.8% by 7p-SGA, and 49.7% by MIS in the MHDBrazil cohort. Cohen's kappa coefficient (κ) showed only "fair" agreement between GLIM and SGA (MHDItaly: κ = 0.26, P = .003; MHDBrazil: κ = 0.22, P = .003) and between GLIM and MIS (MHDItaly: κ = 0.33, P < .001; MHDBrazil: κ = 0.25, P = .001). Cox regression analysis showed that all 3 methods were able to predict mortality in crude analysis; however in the adjusted model, the association seemed more consistent and stronger in magnitude for 7p-SGA and MIS. CONCLUSION: In MHD patients, GLIM showed low agreement, sensitivity, and accuracy in identifying malnourished subjects by either 7p-SGA or MIS. Considering the specific wasting characteristics that predominate in MHD, the well-established 7p-SGA and MIS methods may be more useful in this clinical setting.

Hypoalbuminemia: a price worth paying for improved dialytic removal of middle-molecular-weight uremic toxins?

Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic toxins and may improve outcomes in patients with end-stage kidney disease (ESKD), but it requires complex equipment and comes with risks associated with infusion of large volumes of substitution solution. New high-flux hemodialysis membranes with improved diffusive permeability profiles do not have these limitations and offer an attractive alternative to HDF. However, both strategies are associated with increased albumin loss into the dialysate, raising concerns about the potential for decreased serum albumin concentrations that have been associated with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in ESKD, including protein energy wasting, inflammation, volume expansion, renal loss and loss into the dialysate; of these factors, loss into the dialysate is not necessarily the most important. Furthermore, recent studies suggest that mild hypoalbuminemia per se is not an independent predictor of increased mortality in dialysis patients, but in combination with inflammation it is a poor prognostic sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and mortality may depend on the presence or absence of inflammation. In this review we summarize recent findings on the role of dialysate losses in hypoalbuminemia and the importance of concomitant inflammation on outcomes in patients with ESKD. Based on these findings, we discuss whether hypoalbuminemia may be a price worth paying for increased dialytic removal of middle-molecular-weight uremic toxins.

Serum albumin, inflammation, and nutrition in end-stage renal disease: C-reactive protein is needed for optimal assessment.

Low serum albumin (S-Alb) is a frequent feature of end-stage renal disease (ESRD) that independently predicts mortality. Serum albumin has mainly been considered a biomarker of visceral protein and immunocompetence status, fundamental to nutritional assessment. However, low S-albumin level is associated with persistent systemic inflammation and many bodies of evidence show that S-Alb has a limited role as a marker of nutritional status. We reported that a low S-Alb concentration was an independent risk factor for poor outcome in ESRD only in the presence of systemic inflammation. Moreover, the relationships between inflammatory biomarkers and outcome are confounded also by alterations in body composition (such as obese sarcopenia) and oxidative stress. Taken together, S-Alb alone should not be used as a proxy of the nutritional status in a dialysis patient. Its association with dietary intake is poor and low S-Alb values are most often non-nutritional in origin. When analyzing S-Alb to predict mortality risk in ESRD, it should always be combined with measurement of hsCRP.

Incidence, predictors and clinical management of hyperkalaemia in new users of mineralocorticoid receptor antagonists.

BACKGROUND: Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA-associated hyperkalaemia in real-world settings and the extent of subsequent MRA discontinuation are poorly quantified. METHODS AND RESULTS: Observational study including all Stockholm citizens initiating MRA therapy during 2007-2010. Hyperkalaemias were identified from all potassium (K+ ) measurements in healthcare. MRA treatment lengths and dosages were obtained from complete collection of pharmacy dispensations. We assessed the 1-year incidence and clinical hyperkalaemia predictors, and quantified drug prescription changes after an episode of hyperkalaemia. Overall, 13 726 new users of MRA were included, with median age of 73 years, 53% women and median plasma K+ of 3.9 mmol/L. Within a year, 18.5% experienced at least one detected hyperkalaemia (K+ > 5.0 mmol/L), the majority within the first 3 monthsnthsnthsnthsnths of therapy. As a comparison, hyperkalaemia was detected in 6.4% of propensity-matched new beta-blocker users. Chronic kidney disease (CKD), older age, male sex, heart failure, peripheral vascular disease, diabetes and concomitant use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and diuretics were associated with increased hyperkalaemia risk. After hyperkalaemia, 47% discontinued MRA and only 10% reduced the prescribed dose. Discontinuation rates were higher after moderate/severe (K+ > 5.5 mmol/L) and early in therapy (<3 months from initiation) hyperkalaemias. CKD participants carried the highest risk of MRA discontinuation in adjusted analyses. When MRA was discontinued, most patients (76%) were not reintroduced to therapy during the subsequent year. CONCLUSION: Among real-world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD.

Clinical global assessment of nutritional status as predictor of mortality in chronic kidney disease patients.

BACKGROUND: The value of subjective global assessment (SGA) as nutritional assessor of protein-energy wasting (PEWSGA) in chronic kidney disease (CKD) patients depends on its mortality predictive capacity. We investigated associations of PEWSGA with markers of nutritional status and all-cause mortality in CKD patients. METHODS: In 1031 (732 CKD1-5 non-dialysis and 299 dialysis) patients, SGA and body (BMI), lean (LBMI) and fat (FBMI) body mass indices, % handgrip strength (% HGS), serum albumin, and high sensitivity C-reactive protein (hsCRP) were examined at baseline. The five-year all-cause mortality predictive strength of baseline PEWSGA and during follow-up were investigated. RESULTS: PEWSGA was present in 2% of CKD1-2, 16% of CKD3-4, 31% of CKD5 non-dialysis and 44% of dialysis patients. Patients with PEWSGA (n = 320; 31%) had higher hsCRP and lower BMI, LBMI, FBMI, %HGS and serum albumin. But, using receiver operating characteristics-derived cutoffs, these markers could not classify (by kappa statistic) or explain variations of (by multinomial logistic regression analysis) presence of PEWSGA. In generalized linear models, SGA independently predicted mortality after adjustments of multiple confounders (RR: 1.17; 95% CI: 1.11-1.23). Among 323 CKD5 patients who were re-assessed after median 12.6 months, 222 (69%) remained well-nourished, 37 (11%) developed PEWSGA de novo, 40 (12%) improved while 24 (8%) remained with PEWSGA. The latter independently predicted mortality (RR: 1.29; 95% CI: 1.13-1.46). CONCLUSIONS: SGA, a valid assessor of nutritional status, is an independent predictor of all-cause mortality both in CKD non-dialysis and dialysis patients that outperforms non-composite nutritional markers as prognosticator.

Chronic kidney disease is associated with poorer in-hospital outcomes in patients hospitalized with infections: Electronic record analysis from China.

Predominantly based on studies from high-income countries, reduced estimated glomerular filtration rate (eGFR) has been associated with increased risk of infections and infection-related hospitalizations (IRHs). We here explore in-hospital outcomes of IRHs in patients with different kidney function. A total of 6,283 adults, not on renal replacement therapy, with a discharge diagnosis of infection, and with an eGFR 1-12 months before index hospitalization, were included from four hospitals in China. We compared in-hospital outcomes (death, intensive care unit (ICU) admission, length of hospital stay (LOHS) and medical expenses), between patients with and without chronic kidney disease (CKD, defined as eGFR ≤ 60 ml/min per 1.73 m2 of body surface area) by mixed-effects logistic regression model or generalized linear model. The odds for in-hospital mortality (adjusted odds ratios (OR) = 1.41; 95% CI 1.02-1.96) and ICU admission (OR = 2.18; 95% CI 1.64-2.91) were higher among patients with CKD. The median LOHS was significantly higher for CKD patients (11 days vs. 10 days in non-CKD, P < 0.001), and inferred costs were 20.0% higher adjusted for inflation rate based on costs in 2012 (P < 0.001). Patients with CKD hospitalized with infections are at increased risk of poorer in-hospital outcomes, conveying higher medical costs.

Changes of peritoneal transport parameters with time on dialysis: assessment with sequential peritoneal equilibration test.

BACKGROUND: Sequential peritoneal equilibration test (sPET) is based on the consecutive performance of the peritoneal equilibration test (PET, 4-hour, glucose 2.27%) and the mini-PET (1-hour, glucose 3.86%), and the estimation of peritoneal transport parameters with the 2-pore model. It enables the assessment of the functional transport barrier for fluid and small solutes. The objective of this study was to check whether the estimated model parameters can serve as better and earlier indicators of the changes in the peritoneal transport characteristics than directly measured transport indices that depend on several transport processes. METHODS: 17 patients were examined using sPET twice with the interval of about 8 months (230 ± 60 days). RESULTS: There was no difference between the observational parameters measured in the 2 examinations. The indices for solute transport, but not net UF, were well correlated between the examinations. Among the estimated parameters, a significant decrease between the 2 examinations was found only for hydraulic permeability LpS, and osmotic conductance for glucose, whereas the other parameters remained unchanged. These fluid transport parameters did not correlate with D/P for creatinine, although the decrease in LpS values between the examinations was observed mostly for patients with low D/P for creatinine. CONCLUSIONS: We conclude that changes in fluid transport parameters, hydraulic permeability and osmotic conductance for glucose, as assessed by the pore model, may precede the changes in small solute transport. The systematic assessment of fluid transport status needs specific clinical and mathematical tools beside the standard PET tests.

Factors influencing access to education, decision making, and receipt of preferred dialysis modality in unplanned dialysis start patients.

OBJECTIVES: Unplanned dialysis start (UPS) leads to worse clinical outcomes than planned start, and only a minority of patients ever receive education on this topic and are able to make a modality choice, particularly for home dialysis. This study aimed to determine the predictive factors for patients receiving education, making a decision, and receiving their preferred modality choice in UPS patients following a UPS educational program (UPS-EP). METHODS: The Offering Patients Therapy Options in Unplanned Start (OPTiONS) study examined the impact of the implementation of a specific UPS-EP, including decision support tools and pathway improvement on dialysis modality choice. Linear regression models were used to examine the factors predicting three key steps: referral and receipt of UPS-EP, modality decision making, and actual delivery of preferred modality choice. A simple economic assessment was performed to examine the potential benefit of implementing UPS-EP in terms of dialysis costs. RESULTS: The majority of UPS patients could receive UPS-EP (214/270 patients) and were able to make a decision (177/214), although not all patients received their preferred choice (159/177). Regression analysis demonstrated that the initial dialysis modality was a predictive factor for referral and receipt of UPS-EP and modality decision making. In contrast, age was a predictor for referral and receipt of UPS-EP only, and comorbidity was not a predictor for any step, except for myocardial infarction, which was a weak predictor for lower likelihood of receiving preferred modality. Country practices predicted UPS-EP receipt and decision making. Economic analysis demonstrated the potential benefit of UPS-EP implementation because dialysis modality costs were associated with modality distribution driven by patient preference. CONCLUSION: Education and decision support can allow UPS patients to understand their options and choose dialysis modality, and attention needs to be focused on ensuring equity of access to educational programs, especially for the elderly. Physician practice and culture across units/countries is an important predictor of UPS patient management and modality choice independent of patient-related factors. Additional work is required to understand and improve patient pathways to ensure that modality preference is enacted. There appears to be a cost benefit of delivering education, supporting choice, and ensuring that the choice is enacted in UPS patients.

Assessment of arterial stiffness for clinical and epidemiological studies: methodological considerations for validation and entry into the European Renal and Cardiovascular Medicine registry.

Epidemiological studies have highlighted the role of arterial stiffness as a risk factor for development of cardiovascular (CV) diseases. Moreover, aortic stiffness has been shown to be a significant predictive factor of all-cause and CV mortality in different populations including patients with end-stage renal disease. Pulse-wave velocity (PWV) is the most widely used technique to assess arterial stiffness. Although PWV can be measured on any artery or between any arterial sites, only carotid-to-femoral PWV, representing stiffness of the aorta and iliofemoral axes, has been shown to have predictive value for morbidity and mortality. The several available commercial devices differ according to the type of signal (pressure, distension, flow) or by recording both sites simultaneously or using ECG synchronization. It is also possible to directly measure arterial diameter changes during the cardiac cycle and link them to local pulse-pressure changes, which provides the pressure-diameter relationship and stress-strain relationship if arterial wall thickness is also measured. These techniques are based on high-precision vascular echo tracking or magnetic resonance imaging and applanation tonometry. This paper summarizes the basic principles of arterial haemodynamics and various methodologies to assess stiffness and the latest consensus recommendations for clinical applications.

Activity-related energy expenditure of patients undergoing hemodialysis.

OBJECTIVES: The aim of this study was to evaluate the activity-related energy expenditure (AEE) of patients undergoing hemodialysis (HD) and to compare it with that of healthy controls. DESIGN: This was a cross-sectional study. SETTING: This was an in-center study conducted at the Dialysis Unit, Nephrology Division, Federal University of São Paulo-Oswaldo Ramos Foundation, Brazil. PATIENTS AND METHODS: AEE was evaluated in 32 patients undergoing HD (20 men, aged: 46.3 ± 12.2 years). A subgroup consisting of 22 patients was pair-matched by gender and age with 22 sedentary, healthy individuals. AEE was measured over a period of 5 days using a portable physical activity monitor. Body fat and lean body mass were assessed by dual energy X-ray absorptiometry and body cell mass by bioelectrical impedance analysis. RESULTS: AEE correlated positively with lean body mass and body cell mass, and negatively with age, body fat, and body mass index. From the multiple regression analysis, it was found that age and lean body mass (r(2) = 0.32) or body cell mass (r(2) = 0.30) were the best among the variables that explained variations in AEE. AEE of HD patients in comparison with healthy controls was found to be lower on dialysis days (234 [9.5 to 1,145] kcal/day vs. 565 [214 to 1,319] kcal/day, median [range]; P < .01) as well as on nondialysis days (369 [89.5 to 1,242] kcal/day vs. 565 [214 to 1,319] kcal/day; P = .02). Total energy expenditure of the HD patients on dialysis days (2,051 ± 289 kcal/day) as well as nondialysis days (2,202 ± 283 kcal/day) was also found to be lower in comparison with controls (2,514 ± 307 kcal/day; P < .01). The average contribution of the AEE toward total energy expenditure in HD patients was 15%, whereas in controls it was 24% (P = .03). CONCLUSION: As compared with sedentary, healthy individuals, AEE was reported to be considerably lower in HD patients.

Systemic and local inflammation in peritoneal dialysis: mechanisms, biomarkers and effects on outcome.

Thanks to the technological development in peritoneal dialysis (PD) during the last three decades, the most important problem nowadays for the nephrologists is the maintenance of the long-term function of the peritoneal membrane. Although PD may exert an early survival benefit as compared with hemodialysis (HD), long-term PD is often associated with histopathological alterations in the peritoneal membrane that are linked to peritoneal ultrafiltration deficit and increased mortality risk. These alterations are closely related to the presence of a chronic activated (local and systemic) inflammatory response. PD itself may have other factors associated that could further modulate the inflammatory response, such as the bioincompatibility of dialysis solutions, fluid overload and changes in the body composition. Understanding the pathophysiology of inflammation in PD is essential for the adoption of adequate strategies to improve both membrane and patient survival.

Is UCP2 gene polymorphism associated with decreased resting energy expenditure in nondialyzed chronic kidney disease patients?

OBJECTIVE: The deletion/deletion (del/del) polymorphism of uncoupling protein 2 (UCP2) was associated with decreased energy expenditure in diabetic and obese patients. There is evidence of decreased resting energy expenditure (REE) in chronic kidney disease (CKD) patients not yet on dialysis. However, whether REE is associated with the UCP2 polymorphism was not previously investigated in this population. This study evaluated whether the del/del polymorphism of the UCP2 gene is associated with lower REE in nondialyzed CKD patients. DESIGN: This was a cross-sectional study. PATIENTS AND METHODS: Forty-four nondialyzed CKD patients (29 male; aged 52 +/- 12 years; creatinine clearance, 37 +/- 13 mL/min/1.73 m(2) [values are mean +/- SD unless otherwise noted]) were included. Their REE was assessed by indirect calorimetry, and body composition by bioelectrical impedance. High-sensitivity C-reactive protein (hs-CRP) was also evaluated. The insertion/deletion (ins/del) polymorphism of the UCP2 gene was determined in all participants. To test whether the deletion/deletion (del/del) polymorphism of the UCP2 gene was associated with lower REE, the REE of carriers of the del/del genotype (n = 24; group Del) was compared with that of carriers of the insertion and ins/del genotype (n = 20; group Ins). MAIN OUTCOME MEASURE: The main outcome measure was REE. RESULTS: The REE of group Del was similar to that of the group Ins (1379 +/- 239 kcal/day vs. 1360 +/- 289 kcal/day, respectively, P = NS). This result was maintained even after the REE was adjusted for lean body mass by analysis of covariance. In addition, in a multiple-regression analysis using REE as the dependent variable, only lean body mass and hs-CRP were significant predictors of REE. CONCLUSION: The results suggest that the del/del polymorphism of the UCP2 gene is not associated with lower REE in nondialyzed CKD patients.