Solute Clearance Research Articles

Combining Diffusion, Convection and Absorption: A Pilot Study of Polymethylmethacrylate versus Polysulfone Membranes in the Removal of P-Cresyl Sulfate by Postdilution On-Line Hemodiafiltration

Dialytic clearance of p-cresyl sulfate (pCS) and other protein-bound toxins is limited by diffusive and convective therapies, and only a few studies have examined how to improve their removal by adsorptive membranes. This study tested the hypothesis that high-flux polymethylmethacrylate (PMMA) dialysis membranes with adsorptive capacity increase pCS removal compared to polysulfone membranes, in a postdilution on-line hemodiafiltration (OL-HDF) session. Thirty-five stable hemodialysis patients randomly completed a single study of 4 h OL-HDF with PMMA (BG2.1U, Toray®, Tokyo, Japan) and polysulfone (TS2.1, Toray®) membranes. The primary endpoint was serum pCS reduction ratios (RRs) obtained with each dialyzer. Secondary outcomes included RRs of other solutes such as β2-microglobulin, the convective volume obtained after each dialysis session, and the dialysis dose estimated by ionic dialysance (Kt) and urea kinetics (Kt/V). The RRs for pCS were higher with the PMMA membrane than those obtained with polysulfone membrane (88.9% vs. 58.9%; p < 0.001), whereas the β2-microglobulin RRs (67.5% vs. 81.0%; p < 0.001), Kt (60.2 ± 8.7 vs. 65.5 ± 9.4 L; p = 0.01), Kt/V (1.9 ± 0.4 vs. 2.0 ± 0.5; p = 0.03), and the convection volume (18.8 ± 2.8 vs. 30.3 ± 7.8 L/session; p < 0.001) were significantly higher with polysulfone membrane. In conclusion, pCS removal by OL-HDF was superior with high-flux PMMA membranes, appearing to be a good dialysis strategy for improving dialytic clearance of pCS, enabling an acceptable clearance of β2-microglobulin and small solutes.

Trimethylamine-N-oxide (TMAO) and clinical outcomes in patients with end-stage kidney disease receiving peritoneal dialysis.

Trimethylamine-N-oxide (TMAO) is a gut bacteria-derived metabolite of l-carnitine and choline. A high concentration of TMAO has been proven to relate to cardiovascular disease (CVD), all-cause mortality and chronic kidney disease progression. We aimed to investigate the relation between the value of serum TMAO and outcomes for peritoneal dialysis (PD) patients. This is a prospective cohort study with data retrospectively analysed. All incident PD patients were enrolled and followed up. Log-rank test, competing risk survival analysis and COX regression were performed to test the effect of serum TMAO on developing first-episode peritonitis, all-cause and CVD mortality. A wide distribution of serum TMAO concentration was observed in 513 PD patients, with a median level of 72.3 (43.7, 124.7) µmol/L. Patients with lower TMAO concentration were more likely to be without diabetes and hypertension. Patients with lower TMAO concentration showed better residual kidney function and solute clearance at baseline. Participants in the higher three TMAO quartiles showed an increased risk for first-episode peritonitis (p = 0.039). By competing risk survival analysis, after adjusting for age, sex, diabetes mellitus, CVD, body mass index, albumin, high-sensitive C-reactive protein, potassium, phosphorus, residual kidney function, normalised protein equivalent of total nitrogen appearance and calendar year of catheter implantation, patients in the higher three TMAO quartiles had a statistically or marginally higher risk for first-episode peritonitis compared with patients in the lowest quartile, with hazard ratio (HR) 1.65 (1.05, 2.58), 1.46 (0.92, 2.31) and 1.66 (1.05, 2.61), respectively. In the COX model, patients in the third quartile TMAO group had significantly higher CVD mortality risk compared with the lowest quartile group, as HR 2.27 (1.02, 5.05) after adjusting for various factors. As for all-cause mortality, TMAO did not show any associated effects. Serum TMAO concentration is associated with the risk of first-episode peritonitis and CVD mortality in PD patients. No obvious association between serum TMAO and all-cause mortality was observed.

Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney Disease.

The clearance of solutes removed by tubular secretion may be altered out of proportion to the GFR in CKD. Recent studies have described considerable variability in the secretory clearance of waste solutes relative to the GFR in patients with CKD. To test the hypothesis that secretory clearance relative to GFR is reduced in patients approaching dialysis, we used metabolomic analysis to identify solutes in simultaneous urine and plasma samples from 16 patients with CKD and an eGFR of 7±2 ml/min per 1.73 m2 and 16 control participants. Fractional clearances were calculated as the ratios of urine to plasma levels of each solute relative to those of creatinine and urea in patients with CKD and to those of creatinine in controls. Metabolomic analysis identified 39 secreted solutes with fractional clearance >3.0 in control participants. Fractional clearance values in patients with CKD were reduced on average to 65%±27% of those in controls. These values were significantly lower for 18 of 39 individual solutes and significantly higher for only one. Assays of the secreted anions phenylacetyl glutamine, p-cresol sulfate, indoxyl sulfate, and hippurate confirmed variable impairment of secretory clearances in advanced CKD. Fractional clearances were markedly reduced for phenylacetylglutamine (4.2±0.6 for controls versus 2.3±0.6 for patients with CKD; P<0.001), p-cresol sulfate (8.6±2.6 for controls versus 4.1±1.5 for patients with CKD; P<0.001), and indoxyl sulfate (23.0±7.3 versus 7.5±2.8; P<0.001) but not for hippurate (10.2±3.8 versus 8.4±2.6; P=0.13). Secretory clearances for many solutes are reduced more than the GFR in advanced CKD. Impaired secretion of these solutes might contribute to uremic symptoms as patients approach dialysis.

Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part II-Imaging Techniques and Clinical Applications.

The glymphatic system is a recently discovered network unique to the central nervous system that allows for dynamic exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF). As detailed in part I, ISF and CSF transport along paravascular channels of the penetrating arteries and possibly veins allow essential clearance of neurotoxic solutes from the interstitium to the CSF efflux pathways. Imaging tests to investigate this neurophysiologic function, although challenging, are being developed and are reviewed herein. These include direct visualization of CSF transport using postcontrast imaging techniques following intravenous or intrathecal administration of contrast material and indirect glymphatic assessment with detection of enlarged perivascular spaces. Application of MRI techniques, including intravoxel incoherent motion, diffusion tensor imaging, and chemical exchange saturation transfer, is also discussed, as are methods for imaging dural lymphatic channels involved with CSF efflux. Subsequently, glymphatic function is considered in the context of proteinopathies associated with neurodegenerative diseases and traumatic brain injury, cytotoxic edema following acute ischemic stroke, and chronic hydrocephalus after subarachnoid hemorrhage. These examples highlight the substantial role of the glymphatic system in neurophysiology and the development of certain neuropathologic abnormalities, stressing the importance of its consideration when interpreting neuroimaging investigations. © RSNA, 2021.

Anticoagulation in patients with acute kidney injury undergoing kidney replacement therapy.

Kidney replacement therapy (KRT) is used to provide supportive therapy for critically ill patients with severe acute kidney injury and various other non-renal indications. Modalities of KRT include continuous KRT (CKRT), intermittent hemodialysis (HD), and sustained low efficiency daily dialysis (SLED). However, circuit clotting is a major complication that has been investigated extensively. Extracorporeal circuit clotting can cause reduction in solute clearances and can cause blood loss, leading to an upsurge in treatment costs and a rise in workload intensity. In this educational review, we discuss the pathophysiology of the clotting cascade within an extracorporeal circuit and the use of various types of anticoagulant methods in various pediatric KRT modalities.

Increasing the Clearance of Protein-Bound Uremic Solutes by Introducing an Activated Carbon Block into the Dialysate Stream

Increasing the Clearance of Protein-Bound Uremic Solutes by Introducing an Activated Carbon Block into the Dialysate Stream

Kidney Tubulointerstitial Fibrosis and Tubular Secretion

Tubular secretion plays an important role in the efficient elimination of endogenous solutes and medications, and lower secretory clearance is associated with risk of kidney function decline. We evaluated whether histopathologic quantification of interstitial fibrosis and tubular atrophy (IFTA) is associated with lower tubular secretory clearance in persons undergoing kidney biopsy. Cross-sectional. The Boston Kidney Biopsy Cohort is a study of persons undergoing native kidney biopsies for clinical indications. Semiquantitative score of IFTA reported by 2 trained pathologists. We measured plasma and urine concentrations of 9 endogenous secretory solutes using a targeted liquid chromatography/mass spectrometry assay. We used linear regression to test associations of urine-to-plasma ratios (UPRs) of these solutes with IFTA score after controlling for estimated glomerular filtration rate (eGFR) and albuminuria. Among 418 participants, mean age was 53 years, 51% were women, 64% were White, and 18% were Black. Mean eGFR was 50mL/min/1.73m2, and median urinary albumin-creatinine ratio was 819mg/g. Compared with individuals with≤25% IFTA, those with>50% IFTA had 12%-37% lower UPRs for all 9 secretory solutes. Adjusting for age, sex, race, eGFR, and urine albumin and creatinine levels attenuated the associations, yet a trend of lower secretion across groups remained statistically significant (P<0.05 for trend) for 7 of 9 solutes. A standardized composite secretory score incorporating UPR for all 9 secretory solutes using the min-max method showed similar results (P<0.05 for trend). Single time point and spot measures of secretory solutes. Greater IFTA severity is associated with lower clearance of endogenous secretory solutes even after adjusting for eGFR and albuminuria.

Catheter Port Reversal in Citrate Continuous Veno-Venous Hemofiltration

IntroductionKnowledge of effects of catheter port reversal (CathPR), when blood is withdrawn from the venous port and returned via the arterial port, often used in dysfunctional catheters in renal replacement therapy, is limited in the setting of citrate continuous veno-venous hemofiltration (CVVH).MethodsIn this open trial, post-filter ionized calcium (PfiCa), post-filter citrate concentration (PfCC), catheter recirculation, and solute clearance were measured before, during, and after 6 hours of CathPR, in well-functioning catheters. All other settings, including citrate settings, were left constant during the study.ResultsTwenty-three patients were included. Mean PfiCa before CathPR of 0.36 mmol/L (SD 0.06) decreased to 0.31 (0.04) after 2 hours (P = 0.002), 0.31 (0.04) (P = 0.002) at 4 hours, and 0.31 (0.04) at 6 hours (P = 0.001). Return to normal increased mean PfiCa to 0.34 (0.06) (P = 0.006). Mean PfCC rose from 592 mg/L (SD 164) before CathPR to 649 mg/L (190) after 2 hours (P = 0.045), to 696 mg/L (192) after 4 hours (P < 0.001), and to 657 mg/L (214) after 6 hours (P = 0.018). Return to normal decreased mean PfCC to 598 mg/L (184) (P = 0.024). Mean recirculation increased during CathPR (from 4.3% [0–8.7] before to 13.8% [9.7–22.2], P < 0.001). Urea, potassium, and creatinine clearances dropped significantly, but calcium clearance was unaffected.ConclusionCathPR caused a significant decrease in PfiCA and increase in PfCC. Calcium handling differs from other solutes because of increases caused in citrate concentration and subsequent effects on calcium chelation. In citrate CVVH, CathPR in dysfunctional catheters should be limited in time, with intensive follow-up. Trial registration: ClinicalTrials.gov: NCT024600416. Registered 9 November 2015.

APOE4-mediated Alzheimer disease and "Vascular"-"Meningeal Lymphatic" components: towards a novel therapeutic era?

A three-dimensional graphic design representation of the potential role of meningeal vessels in Alzheimer disease. Although there are major differences between APOE4(+) and APOE4(−) Alzheimer disease cases (described in detail in the Comment article by Mentis and colleagues), the figure depicts the clearance of macromolecules and other solutes from meningeal lymphatic vessels. Cover image: Ella Maru Studio.

Impaired cerebrospinal fluid transport due to idiopathic subdural hematoma in pig: an unusual case

BackgroundWe report the effects of the presentation of an idiopathic subdural hematoma (SDH) in an adult domestic pig on the glymphatic system, a brain-wide solute clearance system. This accidental finding is based on our recently published study that described this system for the first time in large mammals. Our current results define the need to investigate cerebrovascular pathologies that could compromise glymphatic function in gyrencephalic animal models as a tool to bridge rodent and human glymphatic studies.Case presentationThe pig underwent intracisternal infusion of a fluorescent tracer under general anesthesia to delineate cerebrospinal fluid (CSF) pathways, and was euthanized at the end of 3 h of tracer circulation. During brain isolation, a hematoma measuring approximately 15 × 35 mm in size beneath the dura was evident overlying fronto-parietal brain surface. Interestingly, CSF tracer distribution was markedly reduced on dorsal, lateral and ventral surfaces of the brain when compared with a control pig that was infused with the same tracer. Furthermore, regional distribution of tracer along the interhemispheric fissure, lateral fissure and hippocampus was 4–5-fold reduced in comparison with a control pig. Microscopically, glial-fibrillary acidic protein and aquaporin-4 water channel immunoreactivities were altered in the SDH pig brain.ConclusionsThis is the first case of impaired glymphatic pathway due to an idiopathic SDH in a pig. Potential etiology could involve an acceleration-deceleration injury inflicted prior to arrival at our housing facility (e.g., during animal transportation) leading to disruption of bridging veins along the superior sagittal sinus and impairing CSF pathways in the whole brain. This accidental finding of globally impaired glymphatic function sheds light on a novel consequence of SDH, which may play a role in the enhanced cognitive decline seen in elderly presenting with chronic SDH.

Phase offset between arterial pulsations and subarachnoid space pressure fluctuations are unlikely to drive periarterial cerebrospinal fluid flow.

Circulation of fluid through the central nervous system maintains fluid homeostasis and is involved in solute clearance. The glymphatic system is hypothesised to facilitate waste clearance in the brain, with inflow via periarterial spaces, bulk flow through the parenchyma, and outflow via perivenous spaces. The driving force for this mechanism is unknown. Previous modelling in the spinal cord suggests that timing offsets between arterial and subarachnoid space pressure pulses can enable net inflow in perivascular spaces (PVS). This study adapted the spinal pulse offset mechanism to the brain and simulated movement of tracer particles used in experiments. Both bulk flow and diffusive movement of tracer were simulated. Intracranial pressure pulses were applied to one end of a 300-μm-long perivascular space combined with a moving arterial wall simulating arterial pulsations. The simulations indicate the pulse offset mechanism can enable net inflow via PVS; however, it is unknown whether the temporal offset required is physiologically realistic. Increasing the positive component of the ICP (intracranial pressure) pulse increased net flow. Tracer particles driven by bulk flow reached the outlet of the PVS with a net speed of ~ 16μm/s when the permeability was two orders of magnitude higher than values in the literature. These particles were unable to penetrate into the parenchyma in the absence of diffusion. Dispersion dominated tracer movement in the parenchyma. Further research is required to reconcile discrepancies between these results, and both experimental and computational studies.

Strategies for Continuous Renal Replacement Therapy De-escalation.

Strategies for Continuous Renal Replacement Therapy De-escalation.

Improving Clearance for Renal Replacement Therapy.

The adequacy of hemodialysis is now assessed by measuring the removal of a single solute, urea. The urea clearance provided by current dialysis methods is a large fraction of the blood flow through the dialyzer, and, therefore, cannot be increased much further. However, other solutes, which are less effectively cleared than urea, may contribute more to the residual uremic illness suffered by patients on hemodialysis. Here, we review a variety of methods that could be used to increase the clearance of such nonurea solutes. New clinical studies will be required to test the extent to which increasing solute clearances improves patients' health.

Effect of increased blood flow rate on renal anemia and hepcidin concentration in hemodialysis patients

BackgroundIncreasing the blood flow rate (BFR) is a useful method for increasing Kt/V and the clearance for low molecular solutes. Hemodialysis patients are often anemic due to hypoerythropoiesis and their chronic inflammatory state. Hepcidin, a hormone that regulates iron homeostasis, is considered as an indicator of iron deficiency in patients with end-stage renal disease. This study aimed to investigate the effects of an increased BFR during hemodialysis on serum hepcidin levels and anemia.MethodsBetween April 2014 and March 2016, 22 chronic dialysis patients (11 men [50.0 %]; mean [± standard deviation] age, 72 ± 12 years) undergoing maintenance hemodialysis treatment, thrice weekly, were enrolled and followed prospectively for 24 months. In April 2014, the BFR was 200 mL/min; in April 2015 this was increased to 400 mL/min, which was within acceptable limits. The dialysate flow rate remained stable at; 500mlL/min. Blood samples were collected in March 2015 and 2016. The primary endpoint was the comparison of the amounts of erythropoiesis-stimulating agent (ESA) required.ResultsThe increased BFR increased the Kt/V and contributed to significantly decreased urea nitrogen (UN) (p = 0.015) and creatinine (Cr) (p = 0.005) levels. The dialysis efficiency was improved by increasing the BFR. Ferritin (p = 0.038), hepcidin (p = 0.041) and high-sensitivity interleukin-6 (p = 0.038) levels were also significantly reduced. The ESA administered was significantly reduced (p = 0.004) and the Erythropoietin Resistant Index (ERI) significantly improved (p = 0.031). The reduction rates in UN (p < 0.001), Cr (p < 0.001), and beta-2 microglobulin (p = 0.017) levels were significantly greater post the BFR increase compared to those prior to the BFR increase. However, hepcidin was not affected by the BFR change.ConclusionsIncreasing BFR was associated with hemodialysis efficiency, and led to reduce inflammatory cytokine interleukin-6, but did not contribute to reduce C-reactive protein. This reduced hepcidin levels, ESA dosage and ERI. Hepcidin levels were significantly correlated with ferritin levels, and it remains to be seen whether reducing hepcidin leads to improve ESA and iron availability during anemia management.

Harmonic solutions for a class of non-autonomous piecewise linear oscillators

The study deals with the existence and uniqueness conditions of harmonic solutions of a class of piecewise linear oscillators with a general periodic excitation. Based on the relationship between natural frequency and driving frequency, we divide the discussion of the harmonic solutions into resonant case and non-resonant case. For resonant case, the existence conditions dependent on periodic excitation and clearance of harmonic solutions are given based on the Poincaré-Bohl fixed point theorem. Moreover, we give a necessary and sufficient condition of bounded solutions, where harmonic solutions, n-subharmonic solutions, and quasi-periodic solutions can occur simultaneously. For non-resonant case, the existence of harmonic solutions are analyzed based on contract mapping. The uniqueness of harmonic solutions for resonant and non-resonant cases are proven by variational method and reduction to absurdity. Numerical examples are presented to illustrate the theoretical results.

MO703URINE VOLUME AS A MARKER OF RESIDUAL KIDNEY FUNCTION IN PERITONEAL DIALYSIS PATIENTS: QUANTITATIVE ASSESSMENT

Abstract Background and Aims In dialysis patients, urine volume is an easy-to-obtain marker of residual kidney function but information is lacking of its potential value as an estimate of the renal contribution to total clearance of small solutes. We explored whether correlations of urine volume with different estimations of the residual renal function for urea, creatinine, and phosphorus, could be used to assess renal solute clearances and renal mass removal for investigated solutes. Method In an observational study of 94 non-anuric (urine output ≥ 100 mL per 24 hours) patients (54% men, median age 59 [45 - 68] year, BMI 25.8 [21.4 - 27.7] kg/m2) undergoing automated (n = 59) or continuous ambulatory (n = 35) peritoneal dialysis (PD), we evaluated renal, peritoneal and total (renal plus peritoneal) solute removal (g/week) and clearance (L/week) in relation to urine volume (L/day). Urine volume, renal clearances, ratio of urine solute to serum solute concentration, removed mass of each solute and the ratio of mass removed by urine (renal clearance) over total mass removed by urine and dialysate (total clearance) for urea, creatinine and phosphorus were estimated from 24 h collections of urine and dialysate and determination of solute concentrations in serum, urine and dialysate. Statistical dependence between variables was tested using Spearman’s correlation coefficient (rho). Data are expressed as median with interquartile range. Results Median 24-hour urine output was 560 [323 – 938] mL. Renal mass removal for urea, creatinine and phosphorus was 10.1 [4.5 – 17.1], 3.5 [1.8 – 5.6] and 1.0 [0.4 – 1.7] g/week, respectively. The average contribution of residual renal removal to the total mass removed was 28% [17% - 41%] for urea, 56% [30% - 72%] for creatinine and 44% [24% - 58%] for phosphorus. Serum creatinine correlated weakly and negatively with urine volume (rho = -0.26, p &amp;lt; 0.05), but no such relationship was observed for urea and phosphorus. Only urine concentration of creatinine correlated weakly with urine volume with rho = -0.28 and p &amp;lt; 0.01. Urine concentration over plasma concentration did not correlate with urine volume for any solute. Renal urea clearance (20.1 [11.4 - 35.7] L/week) correlated positively with creatinine renal clearance (43.0 [18.9 - 75.1] L/week), (rho = 0.92), and with phosphorus renal clearance (17.3 [7.6 - 32.9] L/week), (rho = 0.89, p &amp;lt; 0.001; Fig. 1A), while renal creatinine clearance correlated positively with phosphorus renal clearance (rho = 0.86, p&amp;lt;0.001). Urine volume correlated positively with urea, creatinine and phosphorus clearances at rho 0.78, 0.63 and 0.73, respectively (all p&amp;lt; 0.001), and with renal removal of mass of urea, creatinine, and phosphorus with rho= 0.83, 0.68 and 0.74 (Fig. 1B), respectively; all p&amp;lt;0.001. Conclusion In PD patients, solute renal clearances and renal mass removal for urea, creatinine and phosphorus may be predicted from urine volume. Among renal clearances for urea, creatinine, and phosphorus two of them may be assessed based on measurements of the third one.

MO681PERITONEAL DIALYSIS TIME ON THERAPY AND REGIONAL DIFFERENCES IN DEATH, TRANSFER TO HEMODIALYSIS AND KIDNEY TRANSPLANTATION: RESULTS FROM THE PDOPPS

Abstract Background and Aims Comparing and interpreting regional differences in peritoneal dialysis (PD) time on therapy needs to consider differences in the rates of permanent transfer to hemodialysis (HDT), death or kidney transplantation. Here we describe these outcomes among countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), as well as reasons for PD discontinuation. Method PDOPPS is a prospective cohort study of randomly selected patients across national samples of PD facilities from Australia/New Zealand (A/NZ), Canada, Japan, Thailand, the UK, and the US. Fine and Gray models were used on a population of 7115 patients, of varying PD vintages at study entry [median (IQR) vintage = 0.82 yrs (0.21, 2.03)], to analyse the cumulative incidence from PD start of transplantation, HDT, or death (on PD or within 7 days of transfer to HD). This allows for the determination of the % of patients remaining on PD at each PD vintage referred to as Time on Therapy (ToT). Models were left truncated to account for PD vintage at time of study enrollment. HDT was defined as no return from HD therapy within 12 weeks of transferring to HD. Cox models were used to calculate hazard ratios (HR) for death accounting for facility clustering and adjusted for patient age, sex, US black race, heart disease, diabetes, psychiatric disorder, prior HD experience, urine volume, and transplant waitlist referral. Results Mean patient age ranged from 56 yrs in Thailand to 64 yrs in Japan (Figure). Overall, 1261 patients transferred to HD, 76 patients transferred to HD/PD hybrid therapy, 900 patients died and 506 were transplanted during follow-up. By 3 years, the % of patients remaining on PD ranged from 25% in UK, 34-40% in A/NZ, Canada and US, to 47% in Thailand, and 54% in Japan (Figure). The much lower % of patients on PD at 3 yrs in the UK vs Japan was largely due to the high % of patients transplanted in the UK vs Japan: % transplanted ranged from 2% in Japan and Thailand to 32% in the UK at 3 yrs. When defining a ‘poor outcome’ as either death or HDT: (1) the % of patients still on PD or having been transplanted were quite similar across all 6 countries, and (2) death was a much larger proportion of this ‘poor outcome’ in Thailand vs other countries. Similar risks of HDT were seen across all countries except Thailand which displayed much lower risks of HDT. This finding changed little with covariate adjustment (not shown). Infection, reported as primary HDT cause, varied from 30% (Canada) to 66% (Thailand) of cases, and insufficient solute or water clearance as primary HDT cause ranged from 6% (Thailand) to 44% (Japan) of cases (not shown). In Cox models, the adjusted HR of death, compared to the US, was higher in Thailand [1.55 (1.17-2.06)], lower in Canada [0.75 (0.61-0.92)], A/NZ [0.60 (0.47-0.78)], and Japan [0.36 (0.27-0.48)], and close to 1 in UK [0.98 (0.75-1.28)]. Conclusion Time on PD therapy differed considerably across countries. This was mainly due to large country differences in proportion transplanted, so that transplantation has a greater impact on country variability in ToT than HDT and death. Risk of death varied greatly across countries, particularly when accounting for case-mix. With the exception of Thailand, differences between countries in risk of HDT were modest. Marked differences in recorded reasons for HDT merit additional study.

MO1007RELATIONSHIP BETWEEN DIALYSIS ADEQUACY, ULTRAFILTRATION RATE AND SURVIVAL IN YOUNG HEMODIALYSIS (HD) PATIENTS HAVING INITIATED CHRONIC HD IN CHILDHOOD*

Abstract Background and Aims Hemodialysis (HD) adequacy is currently assessed based on weight-normalized small solute clearance (spKt/V), with same targets in both adult and pediatric patients on chronic thrice weekly hemodialysis, despite lack of pediatric studies to support this. It has been hypothesised that pediatric patients of small size may require higher spKt/V targets, due to higher ratio of body surface area (BSA) to body weight and/or greater post-dialysis urea rebound. Ultrafiltration rates (UFR) &amp;gt;10-13 mL/kg/h, associated with increased mortality in adults, are furthermore routinely exceeded in pediatric patients with uncertain consequences. We aimed to characterize how different delivered HD adequacy metrics and UFR are associated with survival in a large cohort of patients who started HD in childhood. Method Retrospective analysis on a cohort of patients &amp;lt;30y on chronic HD since childhood (&amp;lt;19y), having received thrice-weekly HD 2004-2016 in outpatient DaVita dialysis centers. Mean delivered dialysis dose (spKt/V) and alternative measures of HD adequacy and fluid balance, including eKt/V, body-surface normalized Kt (Kt/BSA) and ultrafiltration rate (UFR), were investigated as predictors of survival in a Weibull regression model. Results A total of 1780 patients were included (age at initiation of HD: 0-12y: n=321, &amp;gt;12-18y: n=1459), with median spKtV=1.55, eKt/V=1.31, Kt/BSA=31.2 L/m2 and UFR=10.6 mL/kg/h. Kt/BSA was a better predictor of survival than spKt/V or eKt/V (P&amp;lt;0.001 versus P=0.002, respectively). UFR was associated with survival (P&amp;lt;0.001), with increased mortality &amp;lt;10/&amp;gt;18 mL/kg/h. Associations remained significant after adjusting for age, ethnicity, and etiology of kidney disease. Conclusion We found that targeting Kt/BSA&amp;gt;30 L/m2 in children and young adults on maintenance HD is associated with improved long-term outcomes, corresponding to spKt/V&amp;gt;1.4 (&amp;gt;12 years) and &amp;gt;1.6 (&amp;lt;12 years), respectively. Relatively high UFR of 10-18 ml/kg/h appears to be risk-free in this HD population.

Assessment of kidney proximal tubular secretion in critical illness.

BACKGROUNDSerum creatinine concentrations (SCrs) are used to determine the presence and severity of acute kidney injury (AKI). SCr is primarily eliminated by glomerular filtration; however, most mechanisms of AKI in critical illness involve kidney proximal tubules, where tubular secretion occurs. Proximal tubular secretory clearance is not currently estimated in the intensive care unit (ICU). Our objective was to estimate the kidney clearance of secretory solutes in critically ill adults.METHODSWe collected matched blood and spot urine samples from 170 ICU patients and from a comparison group of 70 adults with normal kidney function. We measured 7 endogenously produced secretory solutes using liquid chromatography–tandem mass spectrometry. We computed a composite secretion score incorporating all 7 solutes and evaluated associations with 28-day major adverse kidney events (MAKE28), defined as doubling of SCr, dialysis dependence, or death.RESULTSThe urine-to-plasma ratios of 6 of 7 secretory solutes were lower in critically ill patients compared with healthy individuals after adjustment for SCr. The composite secretion score was moderately correlated with SCr and cystatin C (r = –0.51 and r = –0.53, respectively). Each SD higher composite secretion score was associated with a 25% lower risk of MAKE28 (95% CI 9% to 38% lower) independent of severity of illness, SCr, and tubular injury markers. Higher urine-to-plasma ratios of individual secretory solutes isovalerylglycine and tiglylglycine were associated with MAKE28 after accounting for multiple testing.CONCLUSIONAmong critically ill adults, tubular secretory clearance is associated with adverse outcomes, and its measurement could improve assessment of kidney function and dosing of essential ICU medications.FUNDINGGrants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/NIH) K23DK116967, the University of Washington Diabetes Research Center P30DK017047, an unrestricted gift to the Kidney Research Institute from the Northwest Kidney Centers, and the Vanderbilt O’Brien Kidney Center (NIDDK 5P30 DK114809-03). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

One-year intradialytic leg exercises with resistance bands and fat mass increase in elderly hemodialysis patients: a retrospective study

BackgroundIntradialytic exercises are recommended to be available as a treatment for enhancing physical functioning. However, there have been few reports which evaluated the results of long-term mild intradialytic exercises in elderly patients. The purpose of this study is to investigate the changes in body weight, body composition, and laboratory data in elderly hemodialysis patients after 1-year intradialytic leg exercises with resistance bands.MethodsA retrospective study. Twenty-one outpatients, aged 65 or older (mean ± SD, 75.2 ± 5.1 years), received intradialytic leg exercises with resistance bands for a year were analyzed. The values of dry weight, body composition, and laboratory data were collected from the year-ago period, at baseline and 1 year after baseline. Fat and muscle mass were evaluated by using a multi-frequency bioimpedance device.ResultsPhysical performance changed and body weight increased after 1-year resistance band exercises. However, the participants gained fat mass, not muscle mass. Although the changes in biochemical data related to protein intake were equivocal, triglyceride levels increased significantly after 1-year exercises. An elevation in serum creatinine levels was observed, even if solute clearance increased significantly.ConclusionsOne-year intradialytic leg exercises with resistance bands may have a potential clinical benefit for body mass index even in elderly hemodialysis patients. However, optimal dietary modification is needed to achieve a balanced increase of muscle and fat mass. An increase of serum creatinine levels does not always mean muscle mass hypertrophy.