Agreement between different parameters of dialysis dose in achieving treatment targets: results from the NECOSAD study.

BACKGROUND: The recommended parameter of dialysis dose differs between K-DOQI and the European Best Practice Guidelines. It is not well known to what extent an agreement exists between the different parameters, nor if target and delivered dialysis dose are prescribed according to the urea reduction rate (URR), single-pool Kt/V (spKt/V) or equilibrated double-pool Kt/V (eKt/V) and which parameter is most strongly related to mortality. METHODS: In 830 haemodialysis patients from the NECOSAD cohort URR, spKt/V and eKt/V were calculated and compared according to a classification regarding the recommended treatment targets (70%, 1.4 and 1.2, respectively) as well as minimum delivered dialysis dose (65%, 1.2 and 1.05, respectively). Moreover, the relation between treatment dose and survival was assessed using Cox regression analysis. RESULTS: A spKt/V of ≥1.4 and URR ≥70% corresponded with eKt/V ≥1.20 (as reference method) in, respectively, 98.0 and 90.6% of patients. spKt/V of ≥1.2 and URR ≥65% corresponded with eKt/V ≥1.05 in, respectively, 95.5 and 91.2% of patients. Deviations from the reference method were significantly related to differences in urea distribution volume (spKt/V), treatment time (URR) and ultrafiltration volume (URR). The adjusted HR (95% CI) was 0.98 (0.96, 0.99) for URR, 0.51 (0.31, 0.84) for spKt/V and 0.46 (0.30, 0.80) for the eKt/V. CONCLUSION: The use of URR leads to larger disagreement with the reference method (eKt/V) treatment target as compared to spKt/V. Low urea distribution volume, short treatment time and low ultrafiltration volumes are predictive parameters for overestimation of dialysis dose when utilizing the alternative methods spKt/V and URR instead of eKt/V. Delivered eKt/V, spKt/V and URR were all positively related to survival.

Severe hemodialysis access-induced distal ischemia may be associated with poor survival.

BACKGROUND: Some hemodialysis patients develop hemodialysis access-induced distal ischemia due to insufficient loco-regional perfusion pressure and consequent poor arterial flow. We hypothesized that patients with severe hemodialysis access-induced distal ischemia had worse survival compared with patients with mild or no hemodialysis access-induced distal ischemia. METHODS: This single-center retrospective observational cohort study included three groups of prevalent hemodialysis patients with an upper extremity vascular access between 2006 and 2018. Symptomatic patients had signs and symptoms of hemodialysis access-induced distal ischemia and low digital brachial indices (<60%) and were divided into a mild (Grade I-IIa) and a severe hemodialysis access-induced distal ischemia (IIb-IV) group. The control group consisted of hemodialysis patients without signs of hemodialysis access-induced distal ischemia with digital brachial indices ≥60%. Factors potentially related to 4-year survival were analyzed. RESULTS: Mild hemodialysis access-induced distal ischemia-patients displayed higher digital brachial indices (n = 23, 41%, ±3) compared with severe hemodialysis access-induced distal ischemia-patients (n = 28, 24%, ±4), whereas controls had the highest values (n = 48, 80%, ±2; p < .001). A total of 44 patients (44%) died during follow-up. Digital brachial index (hazards ratio 0.989 [0.979-1.000] p = .046) was related to overall mortality following correction for presence of arterial occlusive disease (hazards ratio 2.28 [1.22-4.29], diabetes (hazards ratio 2.00 [1.07-3.72], and increasing age (hazards ratio 1.03 [1.01-1.06] as was digital pressure (hazards ratio 0.990 [0.983-0.998], p = .011). Overall survival was similar in mild hemodialysis access-induced distal ischemia and controls (2-year, 79% ±5; 4-year, 57% ±6, p = .818). In contrast, 4-year survival was >20% lower in patients with severe hemodialysis access-induced distal ischemia (2-year 62%± 10; 4-year 34% ± 10; p = .026). CONCLUSION: Presence of severe hemodialysis access-induced distal ischemia may be associated with poorer survival in hemodialysis patients. Lower digital brachial index values are associated with higher overall mortality, even following correction for other known risk factors.

Haemodialysis decreases finger pressures independent of artificial kidney blood flow.

BACKGROUND: During haemodialysis, some patients experience intensification of symptoms of haemodialysis access-induced distal ischaemia. Aim of this study is to compare the effects of two different regimens of arterial blood flow in patients with an arteriovenous access. METHODS: A questionnaire identified 10 patients that subjectively experienced ischaemic symptoms during haemodialysis. Systolic blood pressure, heart rate, finger pressure (P(dig)), finger temperature (T(dig)), oxygen saturation and ischaemic scores were monitored during two different arterial blood flow dialysis sessions. RESULTS: Before dialysis, P(dig) and T(dig) of the arteriovenous access hand were significantly lower compared with the other hand. Haemodialysis induced a drop of P(dig) in both hands. All changes in P(dig) occurred independent of the artificial kidney's blood flow level. CONCLUSION: Systemic hypotension following onset of haemodialysis further intensifies an already diminished hand perfusion. Measures preventing dialytic hypotension will likely attenuate symptoms associated with haemodialysis access-induced distal ischaemia during haemodialysis.

Synthetic ACTH in High Risk Patients with Idiopathic Membranous Nephropathy: A Prospective, Open Label Cohort Study.

New therapeutic agents are warranted in idiopathic membranous nephropathy. Synthetic ACTH may be advantageous with reported remission rates up to 85% and few side effects. We conducted a prospective open label cohort study from 2008 till 2010 (NCT00694863). We prospectively selected patients with idiopathic membranous nephropathy and high risk for progression (defined as ßeta-2-microglobulin (ß2m) excretion of >500 ng/min). For comparison, we selected matched historical controls treated with cyclophosphamide. The prospectively selected patients received intramuscular injections of synthetic ACTH during 9 months (maximal dose 1 mg twice a week). The primary endpoints concerned the feasibility and incidence of remissions as a primary event. Secondary endpoints included side effects of treatment and the incidence of remissions and relapses at long-term follow-up. Twenty patients (15 men) were included (age 54±14 years, serum creatinine 104 µmol/l [IQR 90­113], urine protein:creatinine ratio 8.7 g/10 mmol creatinine [IQR 4.3­11.1]). Seventeen patients (85%) completed treatment. 97% of injections were administered correctly. Cumulative remission rate was 55% (complete remission in 4 patients, partial remission 7 patients). In a group of historical controls treated with cyclophosphamide and steroids, 19 of 20 patients (95%) developed a remission (complete remission in 13 patients, partial remission in 6 patients) (p<0.01). The main limitation of our study is its small size and the use of a historical control group. We show that treatment with intramuscular injections of synthetic ACTH is feasible. Our data suggest that synthetic ACTH is less effective than cyclophosphamide in inducing a remission in high risk patients with idiopathic membranous nephropathy. The use of synthetic ACTH was also associated with many adverse events. Therefore, we advise against synthetic ACTH as standard treatment in membranous nephropathy.

[AL amyloidosis-associated factor X deficiency]. / Factor X-deficiëntie bij AL-amyloïdose.

BACKGROUND: An acquired bleeding tendency is a specific symptom that can indicate an underlying disease. CASE DESCRIPTION: Here we describe a 69-year-old patient with an acquired bleeding tendency resulting from a factor X deficiency due to an underlying amyloid light-chain (AL) amyloidosis. Factor X deficiency in AL amyloidosis arises from a quantitative and qualitative deficiency of factor X because it binds to amyloid fibrils exposed to circulating blood. CONCLUSION: Bleeding tendency is a rare complication of AL amyloidosis, often resulting from a factor X deficiency.

Variations in predialytic plasma conductivity in dialysis patients: effect on ionic mass balance and blood pressure.

In this study, variations in plasma conductivity (PC), as a surrogate marker of plasma sodium, as well as its relation with intradialytic ionic mass balance (IMB) and blood pressure were assessed in 73 patients. Plasma conductivity and IMB were retrieved on a treatment to treatment basis during a 6-month period. Dialysate sodium concentration was 140 mmol/L. A total of 4070 treatments were analyzed. Mean coefficient of variation for predialytic PC was 1.3%, and mean intraindividual range in predialytic PC measurements during the 6-month follow-up period was 0.9 mS/cm (plasma sodium ∼ 9 mmol/L). Predialytic PC was related to both diffusive and total IMB (r = 0.91, p < 0.001; and r = 0.35, p < 0.01). The average diffusive IMB over a 6-month period was negative in 33% of patients, and the average PC increased during dialysis in 14% of patients. Averaged predialytic PC was significantly related to systolic blood pressure (r = 0.35; p < 0.01), whereas within patients, predialytic systolic blood pressure was significantly different between treatments with the lowest and highest predialytic PC (139 ± 24 vs. 147 ± 21 mm Hg; p < 0.05). In conclusion, depending on PC, diffusive ionic transfer from dialysate to patient may occur in a significant percentage of patients using a dialysate sodium concentration of 140 mmol/L. Variations in PC are related to blood pressure, which might suggest a volume-independent effect of sodium.

The influence of bicarbonate/lactate-buffered PD fluids on N{ε}-(carboxyethyl)lysine and N{ε}-(carboxymethyl)lysine in peritoneal effluent.

OBJECTIVE: Accumulation of advanced glycation end products (AGEs) may be involved in the pathogenesis of peritoneal membrane dysfunction. As glycoxidation may play an important role in AGE formation, peritoneal dialysis fluids with low levels of glucose degradation products (GDPs) might result in a reduction in AGE concentration in the peritoneal effluent. The aim of this study was to compare the effects of conventional glucose-containing dialysis solutions and low GDP level fluids on the concentration of the AGEs N(ε)-(carboxymethyl)lysine (CML) and N(ε)-(carboxyethyl)lysine (CEL) in peritoneal effluent. DESIGN: Prospective randomized control study. METHODS: 23 patients were treated with either conventional glucose-containing fluid (n = 11, group A) or low level GDP fluid (n = 12, group B) during a period of 12 weeks. Before and after this period, CML and CEL were measured in peritoneal effluent. RESULTS: In groups A and B there were changes in CML concentrations [respectively 13.7 ± 17.0 and -16.0 ± 46.0 nmol/L (NS)] and CEL concentrations (respectively 20.3 ± 26.6 and -8.8 ± 18.9 nmol/L, p = 0.015). Residual renal function (RRF) in groups A and B was, respectively, 6.8 and 6.1 mL/min (NS). CML, but not CEL, in the peritoneal effluent was inversely related to RRF (r = -0.67, p < 0.05). CONCLUSION: CEL, but not CML, in the peritoneal effluent appears to be influenced by the prescription of low GDP level fluid, probably due to the highly reduced concentration of methylglyoxal, which is needed for formation of CEL. CML is primarily influenced by RRF.

Access flow, venous saturation, and digital pressures in hemodialysis.

BACKGROUND: A hemodialysis arteriovenous fistula (AVF) requires surgical modification in patients with cardiac overload or dialysis access-associated steal syndrome (DASS). Creation of an artificial stenosis (banding) within the AVF may be used, but this technique lacks the guidance of objective parameters. The aim of this pilot study was to identify indicators that reflect AVF flow in dialysis patients with either access-related cardiac overload (CO) or DASS requiring corrective surgery. METHODS: Patients underwent serial measurements of subclavian venous saturation (Sat(ven)), access flow (Flow(us)), and index digital pressures (P(dig)) during a corrective banding procedure. RESULTS: Data were obtained in 14 individuals (9 men; mean age, 53 +/- 6 years) during 16 studies (CO, n = 8; DASS, n = 8). Before surgery, correlations between preoperative flow, Sat(ven) and P(dig) were not significant. Stepwise banding of the AVF altered Sat(ven) in both groups from a mean of 91% +/- 1% (open AVF) to 84% +/- 2% (closed AVF, P < .001). The CO patients demonstrated a larger drop (-13%) compared with the DASS patients (-4%). Values of P(dig) increased from 68 +/- 9 to 90 +/- 9 mm Hg (P < .001), and both groups demonstrated a similar +23 mm Hg increase. In concert, the digital brachial index also significantly improved in all patients from 0.60% +/- 0.09% to 0.74% +/- 0.10%. Linearity was present between alterations in Flow(us) and Sat(ven) in all patients, but mostly in the CO patients (r(2) = 0.96). CONCLUSIONS: Stepwise banding of hemodialysis fistulas leads to dose-dependent decreases in flow and ipsilateral subclavian venous saturation combined with augmented digital pressures in patients with cardiac overload and dialysis associated steal syndrome. Intraoperative measurements of venous saturation and digital pressures may have the potential of guiding surgical correction in these patients.

Ionic dialysance and the assessment of Kt/V: the influence of different estimates of V on method agreement.

BACKGROUND: Ionic dialysance was recently introduced as a means to assess Kt/V (K(ID)t/V). With this method, urea distribution volume (V) has to be estimated. The primary aim of the present study was to assess the agreement between equilibrated Kt/V assessed by urea kinetic modelling (eKt/V) with K(ID)t/V taking into account different estimates of V, and to assess the monthly variation in V. Secondly, the mechanisms behind the intra-treatment changes in ionic dialysance and inter-treatment variability of K(ID)t/V were assessed. METHODS: Sixty-six patients were included. eKt/V was estimated using 30 min post-treatment sampling in the second generation Daugirdas equation. V was assessed by the formulae of Watson and Chertow (V(Watson); V(Chertow)), double-pool urea kinetic modelling (V(UKM)) and by ionic dialysance (V(IOD)) [Diascan; Hospal(R)]. RESULTS: The use of V(UKM) or V(IOD) instead of V(Watson) or V(Chertow) improved the relation between eKt/V and K(ID)t/V (both r = 0.93; P < 0.001 vs r = 0.84 and r = 0.81; P < 0.001). Mean values of eKt/V (1.19 +/- 0.21), K(ID)t/V(UKM) (1.19 +/- 0.30) and K(ID)t/V(IOD) (1.21 +/- 0.25) were comparable. Intra-class correlation coefficient of V(IOD) was 0.87 with a 1-month interval and <0.75 after 2 and 3 months. Intra-class correlation coefficient of V(DP) was 0.79 with a 1-month interval and <0.75 after 2 and 3 months. Inter-treatment variation in K(ID)t/V during six consecutive dialysis sessions was 6.1% +/- 0.6%. Changes in blood flow were the main determinant of variations in K(ID)t/V (P < 0.05). During treatment, ionic dialysance decreased by 12 +/- 13 ml/min (P < 0.001). The decline in blood volume was the major determinant of the intra-dialytic change in ionic dialysance (P < 0.05). CONCLUSION: The use of V(IOD) and V(UKM) results in better agreement between eKt/V and K(ID)t/V compared with anthropometric formulae. K(ID)t/V was comparable with eKt/V and thus lower than expected for a single-pool method. V(IOD) and V(UKM), should be assessed at least monthly. K(ID)t/V varies widely between consecutive dialysis sessions, mainly due to differences in blood flow. During treatment, ionic dialysance decreases, which is related to the relative decline in blood volume.

Pre-dilution on-line haemofiltration vs low-flux haemodialysis: a randomized prospective study.

BACKGROUND: Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology. Their clearance can be enhanced by the use of haemofiltration (HF). METHODS: The effects of low-flux haemodialysis (HD) (ultrapure dialysate; polyamide membranes) and pre-dilution on-line HF (1:1 blood/substitution ratio; target filtration volume: 1.2 times body weight) on cardiovascular and nutritional parameters, interdialytic levels of uraemic toxins and quality of life (QOL; Laupacis questionnaire) were assessed during 1 year follow-up. Forty patients were randomized. RESULTS: After 1 year, 27 patients were eligible for analysis (HF: 13 patients; HD: 14 patients). Left ventricular mass index did not change in the HF patients (127+/-33 --> 131+/-36 g/m(2) after 12 months) or in the HD group (135+/-34 --> 138+/-32 g/m(2)). Also, there were no changes in pulse wave velocity, and 48 h systolic and diastolic blood pressures. Lean body mass, assessed by dual-energy X-ray absorptiometry, increased in the HF group (44.8+/-8.9 --> 46.2+/-9.6 kg; P<0.05), but not in the HD group (49.4+/-9.2 --> 50.6+/-8.8 kg), although differences between groups were not significant. Insulin-like growth factor-1 levels remained stable in the HF patients, but decreased in the HD group (P<0.05 between groups). QOL for physical symptoms improved in the HF group (4.2+/-1.2 --> 5.0+/-1.1; P<0.05 within the HF group and P = 0.06 between groups), but not in the HD group (4.0+/-1.0 --> 4.4+/-1.4). beta2-microglobulin, complement factor D and homocysteine decreased significantly in the HF but not in the HD group, whereas l-ADMA, leptin and advanced glycation end-products-related fluorescence did not change. CONCLUSIONS: No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD. Treatment with on-line HF resulted in marked changes in the uraemic toxicity profile, an improvement in physical well-being and a small improvement in nutritional state.

Nitric oxide synthetic capacity in relation to dialysate temperature.

BACKGROUND: During hemodialysis, vascular reactivity is impaired, which can be corrected by lowering dialysate temperature. It has also been shown that nitric oxide (NO) is related to intradialytic hypotension. As NO synthesis may be temperature-dependent, this study addressed the influence of dialysate temperature on the NO synthetic capacity of plasma. METHODS: NO synthetic capacity was studied during hemodialysis with a dialysate temperature of 37.5 degrees C (dialysis-37.5 degrees C) and programmed extracorporeal blood cooling (cool dialysis; Blood Temperature Monitor; Fresenius C) in 12 stable patients. NO synthetic capacity was assessed ex vivo by [3H]L-citrulline formation from [3H]L-arginine in cultured endothelial cells after incubation with plasma samples obtained during the respective sessions. RESULTS: Core temperature decreased (-0.32 +/- 0.10 degrees C) and energy transfer rate was significantly lower (-27.5 +/- 2.8 W; p < 0.05) during cool dialysis compared to dialysis-37.5 degrees C (0.19 +/- 0.06 degrees C and -0.8 +/- 1.2 W respectively; p < 0.05). Systolic blood pressure decreased during dialysis-37.5 degrees C (-19 +/- 4 mm Hg; p < 0.05), but not during cool dialysis (-6 +/- 5 mm Hg). NO synthetic capacity increased during dialysis-37.5 degrees C (55.5 +/- 9.3 to 73.5 +/- 10.2 pmol/10(5) cells; p < 0.05), in contrast to cool dialysis (67.3 +/- 11.1 to 66.2 +/- 10.8 pmol/10(5) cells). CONCLUSION: The stimulatory effect of uremic plasma on endothelial NO synthesis was augmented during dialysis-37.5 degrees C but not during cool dialysis.