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Role of osmolality in blood pressure stability after dialysis and ultrafiltration.

To clarify the mechanisms involved in the stability of blood pressure during ultrafiltration (UF) alone versus regular dialysis, this study systematically examined the importance of changes in serum potassium, osmolality, and plasma norepinephrine during several dialysis maneuvers. Six stable, normotensive chronic dialysis patients were subjected to a uniform 2 to 3% decrease in body weight during the 2 hours of each dialysis maneuver. Supine to upright mean blood pressure (MBP) decreased (90 to 75 mm Hg, P less than 0.05), and three patients became symptomatic after weight loss during regular dialysis, but orthostatic blood pressure was stable (89 to 86 mm Hg, NS) and the patients were asymptomatic after UF and weight loss. Isokalemic regular dialysis did not afford hemodynamic stability, as orthostatic MBP declined (85 to 56 mm Hg, P less than 0.02), and four of the patients were again asymptomatic after standing. A continuous hypertonic mannitol (25%) infusion during the 2-hour dialysis, however, kept osmolality from decreasing and was associated with a stable orthostatic MBP (89 to 83 mm Hg, NS). A continuous infusion of isotonic mannitol (5%) given in a volume of five times that of the hypertonic mannitol failed to prevent orthostatic hypotension (80 to 60 mm Hg, P less than 0.005). Plasma norepinephrine concentrations were high in these patients and increased only modestly after weight loss. These results implicate constant plasma osmolality as a critical protective factor of blood pressure during UF and further demonstrate that changes in blood pressure may be associated from changes in both serum potassium and plasma norepinephrine concentration.

Blood↗

Plasma volume recovery after ultrafiltration in patients with chronic renal failure.

We studied the effect of standardized ultrafiltration (UF, 2 liters in 60 min) on plasma volume (PV, 131I-albumin space) and its recovery, with special reference to the tissue hydration before UF. Twenty-one UF sessions were performed in 15 patients with endstage renal failure. The PV reduction, which varied considerably, was maximal at the end of UF (range, -0.7 to -21.9%); after that PV recovered reaching a plateau in the second hour after UF. A highly significant negative correlation was found between the interstitial fluid volume (IVF, calculated from 82Br space-PV) and the PV reduction at this stage (r = -0.89, P less than 0.0001). Despite avoidance of major changes in total extracellular fluid in the next 24 hr, a further restoration of PV took place which was partial in subjects with normal tissue hydration, but complete or even excessive in grossly overfilled subjects. This PV repletion was accompanied by an increase in the intravascular mass of albumin (P less than 0.02). The negative correlation between initial IFV and PV change persisted after 24 hr (r = -0.83, P less than 0.0005). In most occasions the blood pressure fell, but only in eight occasions frank hypotension followed. Heart rate remained remarkably unaltered, even during hypotensive episodes. Changes in plasma renin activity followed no uniform pattern. Our findings indicate that the tissue hydration state has a strong influence on changes in PV during fluid removal and the subsequent repletion of PV.

Adult↗

Ultrafiltration coefficients of glomeruli from human biopsies.

Ultrafiltration coefficient (Kf) was measured in vitro using glomeruli isolated from 28 human renal biopsies in order to asses both the relationship between glomerular structure and filtration characteristics and the relationship between Kf and patients' clinical state. The patients, ages 1 to 72 years, had a wide variety of renal diseases and serum creatinines of 1 to 16 mg/dl. Glomeruli were examined by light, immunofluorescence and electron microscopy, and glomerular alterations were measured. Filtration was induced in isolated glomeruli by an oncotic gradient and Kf calculated. Glomerular diameter (D), averaged for each patient, varied from 131 to 315 microns, and Kf varied from 5.7 to 51 nl/min mm Hg. Hydraulic conductivity (Lp) in 15 biopsies averaged 1.45 mu.min-1.mm Hg-1.cm-2. In order to identify the significant predictors of Kf and delineate their relationships, stepwise multiple regression analysis was performed. Kf increased with increasing glomerular size and with increasing degree of glomerular hypercellularity. D, in turn, increased with body surface area, urinary protein, and degree of capillary damage, and decreased with percent senescent glomeruli and degree of epithelial foot process broadening. Kf did not significantly correlate with clinical measures of renal function.

Biopsy↗

Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity.

During a 10 year period, 14 out of 227 patients (6.2%) undergoing continuous ambulatory peritoneal dialysis (CAPD) developed permanent loss of ultrafiltration capacity (UFC). The risk of UFC loss increased from 2.6% after one year to 30.9% after six years of treatment. A six hour, single dwell study with glucose 3.86% dialysis fluid was carried out in nine of the UFC loss patients and in 18 CAPD patients with normal UFC. Intraperitoneal dialysate volumes were calculated using 131I-tagged albumin (RISA) as volume marker with a correction applied for its elimination from the peritoneal cavity. The RISA elimination coefficient (KE), which can serve as an estimation of the upper limit of the lymphatic flow, was also calculated. Diffusive mass transport coefficients (KBD) for investigated solutes (glucose, creatinine, urea, potassium, total protein, albumin and beta 2-microglobulin) were calculated during a period of dialysate isovolemia. Two patterns of UFC loss were observed: (a) seven patients had high KBD values for small solutes resulting in rapid uptake of glucose, whereas KBD values for proteins were normal; (b) two patients had normal KBD values but a threefold increase both in the fluid reabsorption rate and KE. We conclude that loss of the osmotic driving force (due to increased diffusive mass transport for small solutes) and increased fluid reabsorption (possibly due to increased lymphatic reabsorption) are the two major causes of permanent loss of UFC in CAPD patients.

Biological Transport↗

Uptake of dextran sulphate by glomerular intracellular vesicles during kidney ultrafiltration.

Dextran sulphate is often used as a model for albumin in understanding capillary-tissue exchange and the charge selective nature of the capillary wall, particularly in kidney ultrafiltration. In investigating the mechanism of transport in the kidney, autoradiographic analysis of the distribution of iodinated dextran sulphate in perfused rat kidneys demonstrates the preferential accumulation of the probe in the glomerular capillary wall. Tritium-labeled dextran sulphate is found to be specifically taken up by intracellular 20 to 40 nm vesicles that can be isolated post-perfusion. The molecular weight profile of vesicular dextran sulphate demonstrates that the dextran sulphate containing vesicles are from vascular glomerular cells. Dextran is not taken up by the vesicles. These results suggest that the apparent charge selectivity associated with the transglomerular transport of the dextran sulphate is associated, in part, with cell-mediated processes at the glomerular level.

Animals↗

Ultrafiltration and solute kinetics using low sodium peritoneal dialysate.

Low sodium peritoneal dialysate has been reported to enhance sodium loss and alleviate signs of fluid overload in continuous ambulatory peritoneal dialysis patients. To elucidate the mechanisms involved, we compared ultrafiltration and solute kinetics using low sodium dialysate (LNaD; 105 mEq/liter sodium, 2.5% glucose, 348 mOsm/liter), conventional dialysate with equal osmolality (CD1.5; 132 mEq/liter sodium, 1.5% glucose, 348 mOsm/liter) and conventional dialysate with equal glucose concentration (CD2.5; 132 mEq/liter sodium, 2.5% glucose, 403 mOsm/liter). A 2 liter, six hour exchange of each dialysate was performed on separate days in 10 chronic peritoneal dialysis patients. Transperitoneal solute diffusion was assessed by calculating the permeability-area product (PA) of the peritoneal membrane from the dependence of plasma and dialysate solute concentrations on tie. Net fluid removed using LNaD of 190 +/- 90 (SEM) ml was similar to that using CD2.5 (250 +/- 90 ml) but higher (P < 0.01) than that using CD1.5 (-200 +/- 60 ml). Sodium loss was higher using LNaD (72 +/- 11 mEq, P < 0.01) and CD2.5 (41 +/- 12 mEq, P < 0.05) than using CD1.5 (-18 +/- 8 mEq). Changes in plasma sodium concentration were small during each dwell and were not different among the study dialysates. PA values for urea (23.4 +/- 1.6 ml/min), creatinine (10.0 +/- 1.0 ml/min), and glucose (10.3 +/- 1.3 ml/min) were similar when determined in each dialysate. The PA value for sodium (7.6 +/- 1.5 ml/min) could only be accurately determined in LNaD. We conclude that: (1) net fluid removed is greater using LNaD than CD1.5 despite similar osmolalities because LNaD has a higher glucose concentration and glucose is a more effective osmotic solute than sodium; (2) sodium loss when using LNaD is enhanced by both diffusion and convection; and (3) sodium diffuses across the peritoneum slower than urea, creatinine and glucose. These data suggest that LNaD alleviates signs of fluid overload by increasing net fluid removal and enhancing sodium loss.

Adult↗

Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the DOPPS.

Longer treatment time (TT) and slower ultrafiltration rate (UFR) are considered advantageous for hemodialysis (HD) patients. The study included 22,000 HD patients from seven countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Logistic regression was used to study predictors of TT > 240 min and UFR > 10 ml/h/kg bodyweight. Cox regression was used for survival analyses. Statistical adjustments were made for patient demographics, comorbidities, dose of dialysis (Kt/V), and body size. Europe and Japan had significantly longer (P < 0.0001) average TT than the US (232 and 244 min vs 211 in DOPPS I; 235 and 240 min vs 221 in DOPPS II). Kt/V increased concomitantly with TT in all three regions with the largest absolute difference observed in Japan. TT > 240 min was independently associated with significantly lower relative risk (RR) of mortality (RR = 0.81; P = 0.0005). Every 30 min longer on HD was associated with a 7% lower RR of mortality (RR = 0.93; P < 0.0001). The RR reduction with longer TT was greatest in Japan. A synergistic interaction occurred between Kt/V and TT (P = 0.007) toward mortality reduction. UFR > 10 ml/h/kg was associated with higher odds of intradialytic hypotension (odds ratio = 1.30; P = 0.045) and a higher risk of mortality (RR = 1.09; P = 0.02). Longer TT and higher Kt/V were independently as well as synergistically associated with lower mortality. Rapid UFR during HD was also associated with higher mortality risk. These results warrant a randomized clinical trial of longer dialysis sessions in thrice-weekly HD.

Adult↗

Effects of bovine colostral ultrafiltrates on growth and differentiation of 3T3-L1 preadipocytes.

This study was designed to compare the effects of whole and size-fractionated bovine colostrum with bovine calf serum (BCS) on the growth and differentiation of 3T3-L1 fibroblasts. High (HMW) and low (LMW)-molecular-mass ultrafiltrate fractions of colostrum were prepared from defatted colostrum (COL) by diafiltration through membranes with a molecular-mass cut-off of 30 kDa. Incorporation of [(3)H]thymidine into the cells was used as a reflection of DNA synthesis/cell proliferation. The growth-promoting activity of LMW was 2.3- and 2.5-fold higher than COL and HMW, respectively (P <0.05), and 185 microg/ml LMW stimulated cell proliferation equivalent to 10% BCS. Although insulin-like growth factor (IGF)-I, IGF-II and platelet-derived growth factor AB stimulated 3T3-L1 cells, antibodies to these factors did not inhibit the LMW effects. The LMW fraction was about twice as effective as COL and HMW in stimulating differentiation of the cells into adipocytes, but maximal differentiation was only 60% of that seen with 10% fetal bovine serum (FBS). Treatment with COL, HMW, IGF-I and insulin induced peroxisome-proliferator-activated receptor gamma RNA, but levels were about half of that with 10% FBS treatment and LMW induction was 80% of FBS. Low amounts of leptin mRNA were detected in adipocytes and abundance did not differ between treatments with BCS, hormones or COL fractions. This study showed that bovine colostral LMW stimulated the growth and differentiation of 3T3-L1 preadipocytes and may be a useful serum substitute to support the growth of these cells.

3T3 Cells↗

Ultrafiltration of renin in the mouse kidney studied by inhibition of tubular protein reabsorption with lysine.

1. In order to study the role of the kidney in the elimination of endogenous plasma renin, renin was measured in the plasma and urine of female mice. 2. The renin concentration was two orders of magnitude lower in urine than in plasma, but it increased after intraperitoneal injection of submandibular mouse renin. No correlation between the plasma renin concentration and the urinary renin concentration and renin excretion rate could be demonstrated. 3. Blockade of the tubular reabsorption of proteins by intraperitoneal injection of the basic amino acid lysine increased the urinary renin concentration, renin excretion rate and renin clearance two to three orders of magnitude, without affecting the plasma renin concentration. 4. This finding demonstrates that ultrafiltered renin is reabsorbed almost completely in the renal tubules and that the mechanism most likely is the same as for other filtered proteins. 5. The large renal renin clearance obtained after intraperitoneal lysine is in accordance with a major role of the kidneys in the elimination of renin from the circulation, by a glomerular ultrafiltration and tubular reabsorption and metabolization of renin.

Absorption↗

Peripheral donor leukocytes prolong survival of rat renal allografts.

BACKGROUND: The development of strategies to enhance the survival of transplanted organs and to potentially lower or even discontinue immunosuppressive therapy would represent a significant advancement in post-transplant patient care. METHODS: We studied the effect of pretransplant infusion of donor leukocytes alone or in combination with a short course of cyclosporine on the long-term outcome of a rat model of kidney allograft. RESULTS: A single intravenous infusion of donor peripheral blood leukocytes (100x10(6) cells) from Brown-Norway (BN) rats into major histocompatibility complex (MHC) incompatible Lewis recipients largely failed to prolong kidney allograft viability from the same donor transplanted 60, 40, or 30 days after cell infusion. A short course of cyclosporine (per se, unable to prolong graft survival) was started at the same day of donor leukocyte infusion, but instead was able to prolong the survival of the BN kidney transplant-performed 40 days later-but not of a Wistar Furth (WF) third party, with some animals even developing tolerance. A mixed lymphocyte reaction of host cells from long-term surviving rats to BN stimulator cells was significantly reduced as compared with controls. Donor BN DNA was detected in the peripheral blood of Lewis rats until day 40 after BN leukocyte infusion. Microchimerism persisted (60 to 70 days post-transplant) in most long-term graft recipients. Reducing the time interval between donor leukocyte infusion and subsequent kidney transplant to 10 days still prolonged graft survival. Donor peripheral blood mononuclear cells, but not polymorphonuclear cells, in the leukocyte preparation contributed to prolong kidney allograft survival. CONCLUSIONS: Pretransplant donor leukocyte infusion under the appropriate conditions can tip the immune balance toward improved graft acceptance. This result could be relevant to the achievement of donor-specific tolerance of the graft with the maintenance of an intact response to third-party antigens.

Animals↗

Glomerular ultrafiltration and apical tubular action of IGF-I, TGF-beta, and HGF in nephrotic syndrome.

In nephrotic glomerulopathies, there is ultrafiltration of high molecular weight forms of insulin-like growth factor-I (IGF-I), hepatocyte growth factor (HGF), and transforming growth factor-beta (TGF-beta), which are bioactive in tubular fluid and act through apical tubular receptors. Experimental evidence indicates that ultrafiltered IGF-I, HGF, and TGF-beta may contribute to increased tubular phosphate and sodium absorption, synthesis of extracellular matrix proteins, and secretion of chemokines such as monocyte chemoattractant protein-1 (MCP-1). Through these mechanisms, glomerular proteinuria may contribute to tubulointerstitial pathobiology in nephrotic syndrome.

Animals↗

Computer simulations of ultrafiltration profiles for an icodextrin-based peritoneal fluid in CAPD.

BACKGROUND: The three-pore model of peritoneal transport has the ability to predict ultrafiltration (UF) profiles rather accurately, even when high molecular weight (MW) solutes are employed as osmotic agents in continuous ambulatory peritoneal dialysis (CAPD). In the present simulations, we wanted to assess, for various theoretical perturbations, the UF properties of a peritoneal dialysis (PD) solution with an osmotic agent having an average MW of 20 kD and a "number average MW" of 6.2 kD, which is similar to that of icodextrin (ICO). METHODS: For a PD solution containing a completely monodispersed 20 kD MW osmotic agent, the degree of UF modeled is much higher than that reported for ICO. Hence, to model the behavior of ICO, we subdivided the ICO molecules into eight or more different MW size fractions. For simulations using six or eight subfractions, we obtained an excellent fit of simulated to reported UF data. More dispersed solutions produced UF profiles similar to that with eight fractions. RESULTS: A 2.05 L 7.5% ICO PD solution, despite being slightly hypotonic, yielded a UF volume of nearly 600 mL in 12 hours, modeled for patients not previously exposed for ICO. After nine hours, the UF volume exceeded that produced by 3.86% glucose. The UF rate and volumes increased in proportion to (1) the ICO concentration, (2) the peritoneal surface area, and (3) the peritoneal UF coefficient, but was almost insensitive to increases in the instilled fluid volume. Simulated for patients previously exposed to ICO, having steady-state plasma concentrations of ICO degradation products, the predicted UF volume at 12 hours was reduced to approximately 400 mL. CONCLUSION: Employing the three-pore model of peritoneal transport and taking into account the polydispersed nature of ICO, it was possible to accurately computer simulate the UF profiles of ICO in accordance with reported data. The simulations suggest an advantage of using ICO in patients with type I UF failure, where UF with a high-MW osmotic agent will exceed that seen in patients not showing UF failure who are on glucose-based PD solutions.

Absorption↗

Effects of uremic ultrafiltrate on the regulation of the parathyroid cell cycle by calcitriol.

BACKGROUND: Calcitriol (CTR) is used in the treatment of hyperparathyroidism secondary to renal failure because it decreases parathyroid hormone (PTH) synthesis and parathyroid cell proliferation. Previous studies in tissues other than parathyroids have demonstrated that uremic factors affect the action of CTR on the target cells. We questioned whether the uremic milieu interferes with the inhibition of parathyroid cell proliferation by CTR. METHODS: Studies were performed in vitro using freshly excised normal dog parathyroid tissue incubated for 24 hours with and without CTR and in the presence of either total uremic ultrafiltrate (UUF) from uremic patients or high-pressure liquid chromatography (HPLC)-derived fractions (hydrophilic compounds eluting early and hydrophobic compounds eluting late) of this UUF (F1 to F4). Parathyroid cell proliferation was assessed by flow cytometry. RESULTS: The addition of CTR 10-8 and 10-7 mol/L to parathyroid tissue produced an inhibition of the proliferation that was prevented in the presence of UUF. In a medium containing CTR 10-8 mol/L, the addition of F1, F2 and F3, but not F4, prevented the CTR-induced inhibition of parathyroid cell proliferation. With CTR 10-7 mol/L, the inhibition of proliferation was observed even in the presence of F1, F2 and also F4, but was prevented by F3. Uric acid (7 mg/dL), indoxyl sulfate (5 mg/dL) and p-cresol (1.4 mg/dL), which coeluted with F1, F2 and F4, respectively, did not interfere with the inhibitory action of CTR 10-7 mol/L; however, the addition of phenol (0.14 mg/dL), which coeluted with F3, prevented the CTR-induced inhibition of parathyroid cell proliferation. CONCLUSIONS: The presence of uremic toxins prevents the inhibition of parathyroid cell proliferation induced by calcitriol.

Animals↗

Ultrafiltrable adenosine triphosphate and 2,3-diphosphoglycerate concentrations in cold-stored human erythrocytes.

Free ATP and DPG concentrations in ACD-preserved human erythrocytes (rbc) were estimated by measuring these organic phosphates in ultrafiltrates of cell lysates prepared at 0 to 2 C. The free ATP concentration in hypotonic hemolysates decreased from 0.59 to 0.08 mumol/ml rbc during four weeks of cold storage. In French Pressure Cell lysates, free ATP increased from 0.23 to 0.47 mumol/ml rbc in the first week and then declined to 0.12 mumol/rbc during the following three weeks. In two weeks, the free DPG level decreased from 0.64 to 0.41 mumol/ml rbc in hypotonic lysates and from 1.08 to 0.15 mumol/ml rbc in French Pressure Cell lysates. It is proposed that, as total DPG concentration decreases during cold storage, free ATP concentration also decreases due to increased ATP binding to hemoglobin sites vacated by DPG. It is suggested that it is the change in the free rather than the total ATP which may be more relevant to the metabolism of the cold-stored erythrocyte.

Adenosine Triphosphate↗

Ultrafiltration profiling and measurement of relative blood volume as strategies to reduce hemodialysis-related side effects.

Hemodialysis (HD) side effects, such as hypotension and muscle cramps, may be related to excessive ultrafiltration (UF) in relation to refilling of fluids from the extravascular space, resulting in hemoconcentration and reduction of relative blood volume (RBV). This study examines the suitability of RBV measurements and UF modeling to reduce the incidence of dialysis side effects. We followed up 188 dialysis sessions in 53 patients. RBV and incidence of side effects were evaluated. Six treatment regimens were examined: UF profile 0, with a constant UF rate; UF profile 1, with a linear decreasing UF rate; UF profile 2, with a stepwise decreasing UF rate; and UF profiles 3 through 5, with intermittent high UF rates interrupted by UF pauses. During dialyses with a constant UF rate (UF profile 0), 10.6% of the treatments were associated with symptomatic hypotension. UF profiles 2 through 5, intermittently using high UF rates, caused a marked increase in hypotensive episodes (18.4%). In contrast, UF profile 1, providing a continuously decreasing UF rate, showed a reduced incidence of hypotension at only 5.7%. Symptomatic hypotension occurred in 13 of 53 patients during one or more dialysis sessions. With the help of RBV measurements, a subgroup of 8 patients with hypovolemia-induced hypotension could be identified. In these patients, an individual threshold of RBV could be defined, below which 92.3% of all hypotensive episodes occurred. In the remaining 5 hypotension-prone patients, there was no correlation between the occurrence of symptomatic hypotension and low RBV during HD treatments. In conclusion, UF profiles intermittently using high UF pulses cannot be recommended. RBV measurements help define a subgroup of patients at risk for hypovolemia-induced hypotension. Only these patients may benefit from blood volume-controlled UF. The incidence of symptomatic hypotension can likely be reduced if an individual threshold of RBV is avoided during HD treatments, eg, using lower UF rates in these patients.

Blood Volume↗

Linear decay of relative blood volume during ultrafiltration predicts hemodynamic instability.

BACKGROUND: Relative blood volume (RBV) changes during hemodialysis (HD) are poorly understood. We wish to define characteristics of RBV profiles at different hydration states predictive of hemodynamic instability. METHODS: Thirty patients underwent online RBV monitoring during an HD session with intermittent ultrafiltration (UF) pulses administered until the onset of hypotension. The RBV decay constant (tau) was derived from curve fitting. Linear divergence, the net deviation of the RBV curve during UF from predicted linear decay, was computed from initial 1-minute slopes. RESULTS: The best correlation with proximity to dry weight (PDW) was provided by linear divergence (r = 0.817; P < 0.001), its major determinant in multiple regression analysis. Other predictors were RBV at initiation of UF pulse, UF pulse volume, and UF decay constant (tau(UF)). These parameters were significantly different in UF pulses within 1 kg and 1 kg or greater of dry weight. There were no correlations with refill parameters. The occurrence of hypotension was not different at RBVs less than 90% (7.4%) or 90% or greater (5.3%). tau(UF), linear divergence, RBV at initiation of UF pulse (all P < 0.001), and UF decay amplitude (P < 0.01) were different between hypotensive and normotensive UF pulses. Hypotension was the only independent predictor of tau(UF) (R2 = 0.40; P < 0.001). The only independent predictor of linear divergence was PDW (R2 = 0.667; P < 0.001). CONCLUSION: Approaching dry weight, the RBV decline during UF switched from exponential to linear decay, probably indicating failing vascular refill. Monitoring deviation from linearity may allow improved hemodynamic stability and attainment of optimal post-HD weight.

Adult↗

Association between blood pressure, ultrafiltration, and hemodialysis graft thrombosis: a multivariable logistic regression analysis.

Although a low blood flow (Q(a)) is the most important cause of graft thrombosis, several studies have shown that Q(a) measurements do not accurately predict thrombosis. This suggests that additional variables may influence thrombosis. Identification of such variables may be essential to designing surveillance protocols that accurately predict thrombosis. In this nested case-control study, we prospectively followed 105 patients for up to 2.5 years in order to test the association of a number of variables with thrombosis. These included Q(a) (monthly by ultrasound dilution), percentage stenosis (quarterly by duplex ultrasound), mean arterial pressure (MAP), percentage ultrafiltration (%UF) during dialysis (%UF = 100[liters]/[kilogram of weight]), and other variables that defined patient and graft characteristics. Patients were divided into patent (n = 53) and thrombosed groups (n = 52), and MAP and %UF from seven consecutive dialysis sessions were analyzed. In the thrombosed group, the last session was the final session before thrombosis. A multivariable logistic regression model showed that Q(a), MAP (the predialysis average of seven sessions), and %UF (from the last session) were independently associated with thrombosis, whereas all other variables were not. The model yielded the following odds ratios for thrombosis: for a single Q(a) value (reduction of 1,000 mL/min), 12.0 (P < 0.01); for %UF (increase of 4%), 5.3 (P < 0.01); for MAP (reduction of 30 mm Hg), 4.1 (P = 0.02); and for percentage decrease in Q(a) (> or =20% versus <20%), 2.4 (P = 0.12). We conclude that in addition to Q(a), both %UF at the last session before thrombosis and average predialysis MAP from seven sessions are independently associated with thrombosis. These results help explain why Q(a) alone does not accurately predict thrombosis. A prospective study is needed to determine whether %UF at each session and a moving average MAP from seven sessions improve the prediction of thrombosis. However, it should be recognized that a large %UF is a preterminal event that likely provides too short a warning for intervention before thrombosis.

Blood Pressure↗

Determination of free insulin-like growth factor-I in human serum: comparison of ultrafiltration and direct immunoradiometric assay.

Two fundamentally different methods are currently used for the determination of free insulin-like growth factor-I (IGF-I): ultrafiltration by centrifugation (UF) and direct immunoradiometric assay (IRMA). The aim was to evaluate a commercial IRMA (DSL, Webster, TX, USA) and to compare it with UF. In the IRMA it is recommended that samples be incubated for 2 h at 5;C. When comparing samples (n = 8) incubated for 1 and 2 h, levels increased by 27 +/- 5% (P< 0.0001). When incubating samples at 22;C instead of 5;C, levels increased by 192 +/- 32% (P< 0.0001). Addition of IGF-binding protein-1 (IGFBP-1) to normal sera (n = 6) dose-dependently decreased ultrafiltered free IGF-I only (P< 0.0007). Similarly, UF was more sensitive than IRMA to addition of IGFBP-2 (P< 0.05). In healthy subjects (n = 35) IRMA yielded 20% higher levels than UF (1.09 +/- 0.09 vs 0.91 +/- 0.12 microg/L; P< 0.0001). IRMA and UF yielded similar results in healthy subjects treated with IGF-I (n = 5) or growth hormone (n = 7) and in acromegalic patients (n = 6) before and after somatostatin analogue treatment. However, marked differences were observed in conditions with elevated IGFBP-1 and -2. In type-1 diabetics (n = 23) ultrafiltered free IGF-I was more reduced than IRMA free IGF-I (38 +/- 9 vs 76 +/- 7% of matched controls (n = 13); P< 0.0001). In patients with chronic renal failure (n = 25), IRMA free IGF-I was identical to control levels (n = 13), whereas ultrafiltered free IGF-I was decreased by 51 +/- 7% (P< 0.0001). Similarly, women with anorexia nervosa (n = 9) studied before and after weight gain showed significant changes in ultrafiltered free IGF-I only (P< 0.03). In conclusion, IRMA was not very robust with respect to variations in sample incubation and this may bias results. IRMA generally yielded higher levels than UF, in accordance with the knowledge that IRMA measures free plus readily dissociable IGF-I. IRMA was less affected than UF by added IGFBP-1 and -2, and reductions in free IGF-I were better revealed by UF than IRMA.

Acromegaly↗