Bioimpedance Spectroscopy‐Based Fluid Status in Combined Dialysis Compared With Hemodialysis and Peritoneal Dialysis: A Cross‐Sectional Study

Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used in Japan for PD patients with decreased residual renal function. However, fluid status in PD+HD patients has not been well studied. In this cross‐sectional study, we compared fluid status in 41 PD+HD patients with that in 103 HD and 92 PD patients using the bioimpedance spectroscopy. Extracellular water normalized to patient height (NECW, kg/m) was the highest in pre‐HD (8.3 ± 1.6) followed by PD (7.9 ± 2.7), PD+HD (7.5 ± 2.5), and post‐HD patients (6.9 ± 1.5) (P < 0.01). By multiple linear regression analysis, PD+HD was associated with a significantly lower NECW than pre‐HD (β = ?0.8, P = 0.03) and similar to PD (β = ?0.5, P = 0.24) and post‐HD (β = 0.6, P = 0.08) after adjustment for age, sex, diabetic nephropathy, ischemic heart disease, dialysis period, and daily urine volume. There was no correlation between NECW and daily urine volume in all dialysis groups. Average daily fluid removal (a sum of urine volume and ultrafiltration volume by dialysis) was positively correlated with NECW in PD+HD and pre‐HD, but not in PD and post‐HD patients. Our results suggest that fluid status in PD+HD patients with decreased residual renal function is acceptable as compared with that in HD and PD patients.     

Peritoneal Protein Losses Depend on More Than Just Peritoneal Dialysis Modality and Peritoneal Membrane Transporter Status

Peritoneal protein clearance (PPCl) depends upon vascular supply and size selective permeability. Some previous reports suggested PPCl can distinguish fast peritoneal membrane transport due to local or systemic inflammation. However, as studies have been discordant, we wished to determine factors associated with an increased PPCl. Consecutive patients starting peritoneal dialysis (PD) who were peritonitis-free were studied. Data included a baseline peritoneal equilibration test (PET), measurement of dialysis adequacy, 24-h dialysate PPCl and body composition measured by multifrequency bioimpedance. 411 patients, mean age 57.2 ± 16.6 years, 60.8% male, 39.4% diabetic, 20.2% treated by continuous ambulatory peritoneal dialysis (CAPD) were studied. Mean PET 4-h Dialysate/Serum creatinine was 0.73 ± 0.13, with daily peritoneal protein loss 4.6 (3.3–6.4) g, and median PPCl 69.6 (49.1–99.6) mL/day. On multivariate analysis, PPCl was most strongly associated with CAPD (β 0.25, P < 0.001), extracellular water (ECW)/total body water (TBW) ratio (β 0.21, P < 0.001), skeletal muscle mass index (β 0.21, P < 0.001), log N-terminal brain natriuretic peptide (NT-proBNP) (β 0.17, P = 0.001), faster PET transport (β 0.15, P = 0.005), and normalized nitrogen appearance rate (β 0.13, P = 0.008). In addition to the longer dwell times of CAPD, greater peritoneal creatinine clearance and faster PET transporter status, we observed an association between increased PPCl and ECW expansion, increased NT-proBNP, estimated dietary protein intake and muscle mass, suggesting a link to sodium intake and sodium balance, increasing both ECW and conduit artery hydrostatic pressure resulting in greater vascular protein permeability. This latter association may explain reports linking PPCl to patient mortality.     

Neighborhood Socioeconomic Status and Cognitive Trajectories in a Diverse Longitudinal Cohort

Objectives: Although individual-level socioeconomic status is associated with poor outcomes, less is known regarding how the social context might affect cognitive outcomes. We examined the effect of neighborhood socioeconomic status (NSES) on baseline cognitive function and trajectories of decline.

Methods: The sample (N = 480) came from a longitudinal cohort recruited to study cognitive function. Mixed effects models examined the influence of NSES on baseline and rate of change in executive function, semantic memory, and episodic memory.

Results: NSES was positively associated with semantic memory scores at baseline, but not with executive function or episodic memory in adjusted models, nor was it associated with cognitive change in longitudinal analyses. In exploratory analyses, for individuals with dementia, those with higher NSES declined faster in executive function and semantic memory than did those with lower NSES.

Conclusions: Results suggest that NSES has limited effects independent of personal characteristics; however, findings showed a complex relation of NSES and decline, with NSES effects observed only for individuals with dementia. Results are discussed in the context of cognitive reserve.

Clinical Implications: Clinical assessments of individuals who present with cognitive impairment might benefit from an understanding of the neighborhood context from which patients come.     

Neighborhood Deprivation, Individual Socioeconomic Status, and Frailty in Older Adults

OBJECTIVES: To assess how individual socioeconomic status and neighborhood deprivation affect frailty.
DESIGN: Nationally representative population-based study, the English Longitudinal Study of Aging (ELSA), analyzed cross-sectionally.
PARTICIPANTS: Four thousand eight hundred eighteen individuals aged 65 and older.
MEASUREMENTS: Outcome was a frailty index (FI), based on 58 potential deficits, with a theoretical range from 0 to 1; exposures were individual wealth and neighborhood deprivation (lack of local resources, financial and otherwise), based on a set of standard indicators.
RESULTS: The FI score varied independently according to wealth and neighborhood deprivation. The mean FI score for an individual in the highest 20% of wealth and least deprived 20% of neighborhoods was 0.09 (95% confidence interval (CI)=0.09–0.09) and for an individual in the lowest 20% of wealth and most deprived 20% of neighborhoods was 0.17 (95% CI=0.16–0.17).
CONCLUSION: Frailty in older adults is independently associated with individual and neighborhood socioeconomic factors. Older adults who are poor and live in deprived neighborhoods are most vulnerable. Policies and interventions intended to prevent or reduce frailty must take into account individual circumstances and the broader social settings in which individuals are located.     

Peritoneal Protein Clearance and not Peritoneal Membrane Transport Status Predicts Survival in a Contemporary Cohort of Peritoneal Dialysis Patients

Background and objectives: Fast peritoneal membrane transport status may be due to inflammation or increased peritoneal membrane surface area. We evaluated the ability of peritoneal protein clearance (Pcl) to distinguish fast peritoneal membrane transport status as a consequence of peritoneal membrane inflammation and assess its impact on patient survival.Design, setting, participants, & measurements: Patients who initiated peritoneal dialysis at our center since January 1998 and had a baseline peritoneal equilibration test, measurement of dialysis adequacy, and 24-h dialysate Pcl were included. Demography, comorbidities, and biochemical data were prospectively collected. Follow-up was until death or the end of the period studied. Multivariate regression analysis identified factors that were associated with Pcl. A Cox proportional hazards model was used to identify factors that were associated with survival.Results: A total of 192 patients (56% men, mean age 54.3 ± 15.3; 32% with diabetes) were included. On univariate analysis, Pcl was negatively correlated with serum albumin and positively correlated with age, dialysate/plasma creatinine ratio (D/Pcr), the presence of peripheral vascular disease, and urine volume. On multivariate analysis, serum albumin, D/Pcr, urine volume, and peripheral vascular disease remained significant. Predictors of mortality were age, comorbidity grade, and Pcl but not D/Pcr.Conclusions: In this cohort, peritoneal transport status no longer predicted survival, whereas Pcl remained a predictor. Increased large-pore protein loss may reflect the severity of underlying cardiovascular disease, portending a poor prognosis for these patients.Fast peritoneal membrane transport status (fPTS) is defined by the measurement of the diffusive peritoneal transport rate for small solutes such that the dialysate-to-plasma creatinine ratio (D/Pcr) is ≥0.81 at 4 h (1). It may be present at the initiation of peritoneal dialysis (PD) but may develop with time on treatment (2,3). Studies of continuous ambulatory PD (CAPD) patients have demonstrated baseline fPTS to be an independent predictor of mortality and technique failure (4). Explanations for this association include reduced peritoneal membrane ultrafiltration capacity owing to more rapid dissipation of the glucose osmotic gradient and resultant fluid reabsorption (5). This results in extracellular fluid volume expansion and hypertension (5). Because of an association between fPTS and hypoalbuminemia, it has been postulated that fPTS may be a manifestation of local or systemic inflammation while serving as a surrogate marker for the increased mortality seen with the malnutrition, inflammation, and atherosclerosis syndrome (6). Against this explanation is emerging evidence that fPTS does not seem to be associated with reduced survival and technique failure in contemporary cohorts (7–9).To resolve this problem, it has been postulated that fPTS may have two potential etiologies: Increased vascularity of the membrane associated with an increased anatomic membrane area or the result of inflammation and vascular injury. In both instances, fPTS will be due to increased blood flow and increased effective small-pore area in contact with dialysate (10). One way to distinguish these processes, according to the three-pore model of membrane function, is to dissociate the small solute transport rate, proportional to the small-pore area, from peritoneal protein clearance (Pcl), which, depending on the protein size, will be a function of both small pores and large pores (11). Protein leak across large pores, equivalent to large-pore flow, will be determined by their relative number, which will be increased during inflammation or by increased hydrostatic pressure across the capillary (12).Heaf et al. (13) showed that patients whose membranes have increased large-pore flow (JvL) using the personal dialysis capacity (PDC) test have inferior survival; however, the membrane area parameter (A0/δx), a measure essentially equivalent to solute transport, was not included in a multivariate survival model (13). In a subsequent study, Van Biesen et al. (14) found that large-poor flow was associated with survival only when corrected for A0/δx such that a higher JvL for a given membrane area decreased survival, yet interpretation of these results is also confounded by the potential for internal mathematical coupling between JvL and A0/δx when using the PDC test, because the former is derived from the product of the pressure gradient and the ultrafiltration coefficient, LpS, and this in turn is derived from A0/δx (12). Both of these studies found a high level of correlation between small solute transport rates (either 4-h D/Pcr or A0/δx) and JvL. This might represent true biologic coupling, yet the use of shared parameters in the PDC test makes this unclear (15).Here we determined the association between patient survival and both solute transport and Pcl, measured and calculated independently, in a prospective, single-center cohort that had previously reported worse outcomes in patients with fPTS (16). We explored the relationship among peritoneal protein leak, comorbidity, and BP.     

2 Renal Anemia Treatment In Peritoneal Dialysis Patients: A Multicenter Slovenian Study

Abdominal surgery is considered problematic if performed on dialysis patients who are on peritoneal dialysis. There is a common clinical practice to switch these patients to hemodialysis postoperatively for a period of time. Our attempt was to keep these patients on peritoneal dialysis after abdominal surgery, using a modified protocol of low volume exchanges. During the last two years, three of our patients on peritoneal dialysis underwent abdominal surgery. In one patient, laparoscopic cholecystectomy was performed, and abdominal hernia repair was performed in the other two. The day after the operation, we started with low volume (500 mL) exchanges with solutions with 1.36% glucose. During the daytime we prescribed four exchanges, and during the nighttime we put patients on automatic peritoneal dialysis (APD), also with low volume exchanges. After 5 days, the volume of exchanges was gradually increased and after 3 weeks all three patients were on their standard preoperative dialysis regime. Periodically, we controlled the adequacy of dialysis with Kt/V, which was not changed during these procedures. There were no complications postoperatively. We conclude that this modified protocol of peritoneal dialysis was useful and safe in all our patients and there was no need to switch patients to hemodialysis. Further clinical experience with a large number of patients might confirm the usefulness of low volume exchange protocol.     

Risk Factors for Encapsulating Peritoneal Sclerosis in Long‐Term Peritoneal Dialysis: A Retrospective Observational Study

Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long‐term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long‐term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non‐EPS. To evaluate the impact of PD‐associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum β2MG levels in the EPS and non‐EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non‐EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long‐term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD‐associated peritonitis could be critical in preventing EPS.     

Plasma Volume,Albumin, and Fluid Status in Peritoneal Dialysis Patients

Background and objectives: Peritoneal dialysis (PD) patients may be overhydrated especially when inflammation is present. We hypothesized that patients with a plasma albumin below the median value would have measurable overhydration without a proportional increase in plasma volume (PV).Design, setting, participants, & measurements: We investigated a cross-sectional sample of 46 prevalent PD patients powered to detect a proportional increase in PV associated with whole body overhydration and hypoalbuminemia. PV was determined from ¹²⁵I-labeled albumin dilution, absolute total body water from D dilution (TBW_D), and relative hydration from multifrequency bioimpedance analysis (BIA; Xitron 4200) expressed as the extracellular water (ECW):TBW_BIA ratio.Results: Whereas patients with plasma albumin below the median (31.4 g/dl) were overhydrated as determined both by BIA alone (ECW:TBW_BIA 0.49 versus 0.47, P < 0.036) and the difference between estimated TBW_BIA and measured TBW_D (3.55 versus 0.94 L, P = 0.012), corrected PV was not different (1463 versus 1482 ml/m², NS). Mean PV was not different from predicted, and its variance did not correlate with any other clinical measures. Multivariate analysis showed that the only independent predictor of whole body overhydration was reduced plasma albumin.Conclusions: Hypoalbuminemia is an important determinant of tissue overhydration in PD patients. This overhydration is not associated with an increased plasma volume. Attempts to normalize the ECW:TBW ratio in hypoalbuminemic, inflamed PD patients may lead to hypovolemia and loss of residual renal function.Evidence from various sources suggests that in a significant proportion of peritoneal dialysis (PD) patients there is difficulty in achieving euvolemia. Observational studies have found that low levels of salt and water removal, independent of residual renal function, are associated with worse survival (1,2). It is not clear, however, whether this association is causal, with excess tissue hydration or expanded plasma volume (PV) accelerating organ dysfunction, or simply evidence that there are difficulties in achieving euvolemia due to confounding factors such as cardiac dysfunction, inflammation, or poor dietary intake (3–5). Individual variability in peritoneal membrane function may also contribute to this problem, although there is now increasing evidence that poor ultrafiltration associated with high solute transport rates can be avoided by using automated PD and icodextrin (6,7).One of the challenges in establishing cause and effect is the difficulty in measuring volume status in PD patients. Bioimpedance analysis (BIA) has been the most widely applied method and has been the main source of evidence that a significant proportion of PD patients are fluid loaded (8). In particular, the abnormal ratio of reactance (an indicator of body cell mass) to resistance (inversely proportional to the total body water [TBW]) implies patients are overhydrated for a given muscle mass. When extrapolated to actual volumes using commercial algorithms, this is frequently expressed as an abnormally high extracellular water (ECW):TBW ratio. This is clearly a relevant biometric as it predicts survival (9) and detects interventions intended to alter fluid status, (5) but suffers a number of problems. First, the ratio will be affected both by muscle wasting and abnormal tissue hydration, and compared with normal subjects, it is the former that is most abnormal (10). Second, the use of algorithms to estimate TBW volume assumes normal hydration of tissues, and we have recently demonstrated in a cohort of hemodialysis (HD) patients, followed over 12 months, that when combining BIA with absolute measurement of TBW using D dilution, patients with greater degrees of comorbidity have overhydrated tissues (11). Third, BIA fails to distinguish between intravascular and interstitial ECW excess. This is especially relevant in PD patients in whom plasma albumin is frequently depressed due to peritoneal protein losses and inflammation when it is possible to hypothesize that mal-distribution of ECW may occur due to lower plasma oncotic pressure. If so, by attempting to normalize the ECW:TBW in hypoalbuminemic patients, it is possible that PV might be reduced below normal, and there is ample evidence from both observational and intervention studies that volume depletion is a risk factor for loss in residual renal function (5,12,13).The purpose of this study was first to demonstrate that abnormal body composition observed in hypoalbuminemic patients is indeed associated with excess tissue hydration and second to test the hypothesis that this overhydration is not associated with a proportional increase in plasma volume.     

Hypertension and Socioeconomic Status in South Central Uganda: A Population-Based Cohort Study

Background:Limited studies exploring the impact of socioeconomic status (SES) on hypertension in Africa suggest a positive association between higher SES and hypertension. The economic development in sub-Saharan African countries has led to changes in SES and associated changes in lifestyle, diet, and physical activity, which may affect the relationship between hypertension and SES differently compared with higher income countries. This cross-sectional study from a large population-based cohort, the Rakai Community Cohort Study (RCCS), examines SES, hypertension prevalence, and associated risk factors in the rural Rakai Region in south-central Uganda.Methods:Adults aged 30–49 years residing in 41 RCCS fishing, trading, and agrarian communities, were surveyed with biometric data obtained between 2016 and 2018. The primary outcome was hypertension (systolic blood pressure (BP) ≥ 130 mmHg or diastolic BP ≥ 80 mmHg). Modified Poisson regression assessed the adjusted prevalence ratios (PR) of hypertension associated with SES; body mass index (BMI) was explored as a potential mediator.Results:Among 9,654 adults, 20.8% had hypertension (males 21.2%; females 20.4 %). Participants with hypertension were older (39.0 ± 6.0 vs. 37.8 ± 5.0; p < 0.001). Higher SES was associated with overweight or obese BMI categories (p < 0.001). In the multivariable model, hypertension was associated with the highest SES category (aPR 1.23; confidence interval 1.09–1.38; p = 0.001), older age, male sex, alcohol use, and living in fishing communities and inversely associated with smoking and positive HIV serostatus. When BMI was included in the model, there was no association between SES and hypertension (aPR 1.02; CI 0.90–1.15, p = 0.76).Conclusion:Hypertension is common in rural Uganda among individuals with higher SES and appears to be mediated by BMI. Targeted interventions could focus on lifestyle modification among highest-risk groups to optimize public health impact.Key Messages What is already known about this subject?

• Hypertension is an important modifiable risk factor for cardiovascular disease.
• There are few large epidemiological studies that investigate the relationship between hypertension and socioeconomic status in low-income countries.

What are the new findings?

• Hypertension is common among adults in rural South–Central Uganda, particularly among those with higher socioeconomic status.
• BMI is a mediator of the relationship between hypertension and socioeconomic status.

How might it impact on clinical practice in the foreseeable future?

• These findings suggest that public health interventions and community efforts to prevent chronic cardiovascular disease and hypertension should focus on lifestyle modification by elucidating obesity risk perception and health risk awareness, particularly among those of higher socioeconomic status.