Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN. METHODS: Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as "non-progressors" (IgAN237 ≤0.38) and "progressors" (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio slopes were calculated. RESULTS: Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71-531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P < .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = -0.278, P = .02 for score-1; rho = -0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = -0.31, P = .009 and rho = -0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median -5.98 versus -1.22 mL/min/1.73 m2 per year for IgAN237-1, P < .001; -3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P = .001). CONCLUSION: The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.

Haemodialysis with Tinzaparin Versus Dialysate Citrate as Anticoagulation.

Anticoagulation with citrate-containing haemodialysate (cHD) is an alternative to tinzaparin haemodialysate (tHD). The study investigated whether cHD would differ when changed from tHD. The same 18 patients were their own controls followed up with cHD for 5 months. LDL-cholesterol decreased at the end of a cHD session (p = 0.01). Neutrophils (p = 0.013) and monocytes (p = 0.007) dropped more during a cHD session. During the follow-up period of cHD, approximately 50% needed additional tinzaparin. Before the cHD session could start, there was a lower total cholesterol at 2 weeks (p = 0.014) and LDL-cholesterol at 1 month (p = 0.011) versus an increase of LDL at 5 months (p = 0.02). Only patients without additional tinzaparin had a reduction of -C-reactive protein (CRP) at 2 months of cHD (p < 0.05) but not later. Solely cHD seems possible only in half of the patients. A greater reduction in granulocytes and monocytes during cHD indicates a more extensive blood membrane interaction, while CRP may be lower.

Response of angiopoietin-like proteins 3 and 4 to hemodialysis.

BACKGROUND/AIM: Patients on chronic hemodialysis (cHD) have decreased activity of lipoprotein lipase (LPL). Angiopoietin-like proteins (ANGPTL) 3 and 4 have been shown to inactivate LPL. The aim of this study was to investigate the levels of the ANGPTLs in plasma of cHD-patients and to evaluate if cHD may alter these levels. MATERIAL AND METHODS: Baseline data were collected from cHD patients (n = 23), and controls (n = 23) and samples were analyzed from 17 patients during low-flux or high-flux HD, and from ultrafiltrate (n = 5). The levels of ANGPTL3 and 4, LPL and triglycerides were studied in a cross-over design on cHD with local citrate compared to tinzaparin as anticoagulant. RESULTS: The level of ANGPTL3 was higher than ANGPTL4 in patients and controls (p<0.01); the ANGPTL3 was 2.0 and ANGPTL4 was 3.3-fold higher in cHD versus controls. The levels of ANGPTL4 increased during cHD. After 180 min of HD the values had decreased again. When the dialysis was performed with high-flux filter, the mean level of ANGPTL4 at 180 min was below the value observed before cHD (p = 0.003). There was immunoreaction for ANGPTL4 in UFs when using high-flux, but not with low-flux, filter. ANGPTL3 was not detectable in UF. On cHD with citrate, no LPL activity was released into the blood. CONCLUSIONS: ANGPTL3 and ANGPTL4 were increased in HD patients. Anticoagulation with tinzaparin during cHD causes release of ANGPTL4 from tissues into blood. cHD using high-flux filters, to some extent, removed ANGPTL4. With citrate the levels of ANGPTL4 decreased.

Lipoprotein lipase activity is favoured by peritoneal dialysis compared to hemodialysis.

BACKGROUND: The lipoprotein lipase (LPL) pool is reduced by 50% in patients on hemodialysis (HD). LPL release by tinzaparin has not been investigated for peritoneal dialysis (PD). Therefore, the aim of this study was to investigate if tinzaparin differently alters the pool of LPL and triglyceride levels of patients on HD versus PD. MATERIALS AND METHODS: Thirty-two patients on chronic PD or HD were matched to nearest age and gender. In order to release and thereby estimate the endothelial pool of LPL, all patients received a bolus of tinzaparin (75 units/kg). Blood samples were drawn for analysis of LPL activity and triglycerides (TG) between the groups. RESULTS: The peak level of LPL released at 40 min after tinzaparin was similar in PD and HD patients. At 180 min, a slightly higher median level of LPL activity was noted in the PD patients (6.1 mU/mL (n = 6) versus 3.4 mU/mL (n = 16), p = 0.005). The TG concentration in plasma at 40 min was reduced relatively more in the PD patients than in the HD patients (p < 0.05). At 180 min, TG had returned to start levels in HD patients while they were still lowered in PD patients. CONCLUSIONS: The negative effect of uraemia on the LPL pool in HD patients, known from other studies, here is shown to be similar in PD patients. Tinzaparin administration releases the LPL pool during each HD but does not cause an exhaustion of the LPL system over time. In contrast to HD, the LPL pool is not altered during PD.

A significant proportion of patients treated with citrate containing dialysate need additional anticoagulation.

BACKGROUND: The blood membrane interaction induced during hemodialysis (HD) activates the coagulation system. To prevent clotting and to maintain dialyzer patency, an anticoagulant such as tinzaparin is used. To increase patency of the dialyzers and to reduce the risk of bleeding related to anticoagulation, citrate-containing dialysate has been introduced in Europe. 
 PURPOSE: The aim of this randomized, cross-over study was to investigate if citrate-containing dialysate was safe and efficient enough as the sole anticoagulation agent in chronic HD patients. 
 MATERIAL AND METHODS: In this clinical setting, 23 patients on chronic hemodialysis were randomized in a cross-over design using anticoagulation either by LMWH-tinzaparin or citrate (Cit) as dialysate (22 completed the study). The study included paired analyses of subjective patency, ionized calcium (iCa), urea reduction rate. 
During Cit-HD, the iCa was significantly more reduced with prolonged time. The lowest iCa measured was 0.96 mmol/l. The median iCa after 210 min of HD was 1.02 for Cit-Hd and 1.16 for standard tinzaparin-HD (p = 0.001). Patency of dialyzers was estimated as clear in 14%, stripes of clotted fibers in 36%, and a red filter in 32% of HD session. The addition of approximately 40% of the patients' usual dose of tinzaparin was given to 7 of the patients as a bolus. Four Cit-HD sessions had to be interrupted prematurely due to clotting. 
 CONCLUSION: A significant proportion of patients treated with citrate-containing dialysate need additional anticoagulation.

Lipoprotein lipase responds similarly to tinzaparin as to conventional heparin during hemodialysis.

BACKGROUND: Low molecular weight (LMW) heparins are used for anticoagulation during hemodialysis (HD). Studies in animals have shown that LMW-heparins release lipoprotein lipase (LPL) as efficiently as unfractionated (UF) heparin, but are less able to retard hepatic uptake of the lipase. This raises a concern that the LPL system may become exhausted by LMW-heparin in patients on HD. We have explored this in the setting of clinical HD. METHODS: Twenty patients on chronic hemodialysis were switched from a primed infusion of UF-heparin to a single bolus of tinzaparin. There were long term follow up of variables for the estimation of dialysis efficacy as well as of the LPL release during dialysis and the subsequent impact on the triglycerides. RESULTS: The LPL activity in blood was higher on tinzaparin at 40 but lower at 180 minutes during HD. These values did not change during the 6 month study period. There were significant correlations between the LPL activities in individual patients at the beginning and end of the 6 month study period and between the activities on UF-heparin and on tinzaparin, indicating that tissue LPL was not being exhausted. Triglycerides were higher during the HD-session with tinzaparin than UF-heparin. The plasma lipid/lipoprotein levels did not change during the 6 month study period, nor during a 2-year follow up after the switch from UF-heparin to tinzaparin. Urea reduction rate and Kt/V were reduced by 4 and 7% after 6 months with tinzaparin. CONCLUSION: Our data demonstrate that repeated HD with UF-heparin or tinzaparin does not exhaust the LPL-system.