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Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are heterogeneous disorders. The aim of this study was to identify and characterize subgroups of patients based on sex, ANCA, age at diagnosis, and organ involvement.

Methods: In total, 1,167 patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were retrospectively recruited to the study. Data including cumulative involvement of 10 different organ systems, end-stage kidney disease (ESKD), sex, proteinase (PR) 3–ANCA, myeloperoxidase (MPO)-ANCA, age at diagnosis, disease duration, and relapse were obtained from medical records. Clinical variables were analyzed for associations with sex, age at diagnosis, and relapse using logistic regression analysis. Thirteen clinical variables were included in hierarchical cluster analyses using the Ward method.

Results: In patients with GPA, PR3-ANCA, renal and pulmonary involvement, and ESKD were significantly associated with male sex, whereas MPO-ANCA was associated with female sex. Patients with GPA who were younger than 32 years of age at diagnosis were significantly more often females and had more ear–nose–throat involvement than patients older than 32 years. In patients with MPA, female patients were significantly younger at diagnosis than male patients. Relapse was significantly associated with young age at diagnosis and pulmonary involvement in GPA and with musculoskeletal involvement in MPA. Hierarchical cluster analyses identified five and seven patient clusters among individuals with GPA and MPA, respectively. PR3-/MPO-ANCA defined the largest clusters, whereas heart, gastrointestinal, and central nervous system involvement were hallmarks for three clusters for both patients with GPA and MPA.

Conclusion: Sex, age at diagnosis, and specific organ involvements define clinically relevant subgroups among patients with ANCA-associated vasculitides.

Background: Macrophages are involved in kidney transplants. The aim of the study was to investigate if changes exist in the levels of glomerular macrophage index (GMI) between two consecutive kidney transplant biopsies, and if so to determine their potential impact on graft survival.

Methods: Two consecutive biopsies were performed on the same renal graft in 623 patients. GMI was categorized into three GMI classes: ≤1.8 Low, 1.9–4.5 Medium, and ≥4.6 High. This division yielded nine possible switches between the first and second biopsies (Low-Low, Low-Medium, etc.). Cox-regressions were used and hazard ratios (HR) with 95% confidence interval (CI) are presented.

Results: The worst graft survival was observed in the High-High group, and the best graft survival was observed in the Low-Low and High-Low groups. Compared to the High-High group, a reduction of risk was observed in nearly all other decreasing groups (reductions between 65% and 80% of graft loss). After adjustment for covariates, the risk for graft-loss was lower in the Low-Low (HR = 0.24, CI 0.13–0.46), Low-Medium (HR = 0.25, CI 0.11–0.55), Medium-Low (HR = 0.29, CI 0.11–0.77), and the High-Low GMI (HR = 0.31, CI 0.10–0.98) groups compared to the High-High group as the reference.

Conclusions: GMI may change dynamically, and the latest finding is of most prognostic importance. GMI should be considered in all evaluations of biopsy findings since high or increasing GMI levels are associated with shorter graft survival. Future studies need to consider therapeutic strategies to lower or maintain a low GMI. A high GMI besides a vague histological finding should be considered as a warning sign requiring more frequent clinical follow up.

Background: Cardiovascular diseases are the dominant cause of morbidity in hemodialysis (HD) patients. Unless sufficient anticoagulation is used during HD, clotting may appear. The objective was to investigate if levels of fibrin degradation products (D-dimer) were increased before and during HD.

Methods: The combined observational study included 20 patients performing a total of 60 hemodialysis divided into three sessions of low-flux dialysis. None of the patients suffered from any clinically evident thromboembolic event before or during the study. Median bolus anticoagulation (mainly tinzaparin) doses were 84 Units/kg bow. Blood samples were drawn before HD (predialysis), and at 30min and 180min during HD with focus on analyzing D-dimer levels and its relation to interdialytic weight gain (IDWG) and speed of fluid elimination by HD (UF-rate).

Results: Predialysis, D-dimer levels (mean 0.767 ±0.821, min 0.136mg/L) were above the upper reference value in 95% of the sessions. D-dimer levels were lowered at 30min (p<0.001) and returned to predialysis levels at 180min. Predialysis D-dimer correlated with NT-pro-BNP, Troponin T, IDWG and UF-rate. Multiple regression analysis revealed that the D-dimer levels were significantly related to IDWG and the UF-rate.

Conclusions: D-dimer levels were elevated in a high proportion predialysis and during HD and related to the IDWG and the UF-rate. Awareness of D-dimer levels and future studies will help clarify if optimization of those variables, besides anticoagulation and biocompatibility measures, will eradicate the repeated subclinical thromboembolic events related to each HD; one reason that may explain organ damage and shortened life span of these patients.

Introduction: The impact of therapeutic plasma exchange (TPE) on short-term mortality in adult patients with sepsis-induced organ dysfunction remains uncertain. The objective of the study is to assess the effect of adjunct TPE in this setting through a comprehensive literature review.

Methods: The National Library of Medicine’s Medline, Ovid (Embase), the Cochrane Library database and clinicaltrial.gov from January 01, 1966, until October 01, 2022, were searched for terms: therapeutic plasma exchange, plasmapheresis, sepsis, and septic shock. We reviewed, selected and extracted data from relevant randomized clinical trials (RCTs) and matched cohort studies (MCSs) comparing short-term mortality in critically ill adult septic patients treated with standard therapy versus those receiving adjunct TPE. Risk of bias was assessed in the RCTs using Cochrane Collaboration tool and in MCSs using ROBINS-I tool. Summary statistics, risk ratios (RRs), and confidence intervals (CIs) were calculated using random effects model.

Results: This systematic review included 937 adult critically ill septic patients from five RCTs (n = 367) and fifteen MCSs (n = 570). Of these total, 543 received treatment with TPE in addition to standard care. The meta-analysis includes all five RCTs and only six MCSs (n = 627). The adjunct TPE treatment (n = 300) showed a significant reduction in short-term mortality (RR 0.59, 95% CI 0.47–0.74, I2 3%) compared to standard therapy alone (n = 327). The systematic review of all 20 trials revealed that adding TPE to the standard therapy of critically ill septic patients resulted in faster clinical and/or laboratory recovery.

Conclusions: Our comprehensive and up-to-date review demonstrates that adjunct TPE may provide potential survival benefits when compared to standard care for critically ill adult patients with sepsis-induced organ dysfunction. While results of this meta-analysis are encouraging, large well-designed randomized trials are required to identify the optimal patient population and TPE procedure characteristics prior to widespread adoption into practice.

Introduction: Although hemodialysis is lifesaving in patients with kidney failure extensive interdialytic weight gain (IDWG) between dialyses worsens the prognosis. We recently showed a strong correlation between IDWG and predialytic values of cardiac markers. The aim of the present study was to evaluate if the cardiac markers N-terminal pro-B-type natriuretic peptide (proBNP) and troponin T were influenced by IDWG and speed of fluid removal (ultrafiltration-rate).

Methods: Twenty hemodialysis patients performed in total 60 hemodialysis (three each). Predialytic values of proBNP and troponin T and changes from predialysis to 180 min hemodialysis (180–0 min) were compared with the IDWG calculated in percent of body weight. The ultrafiltration-rate was adjusted (UF-rateadj) to IDWG: (100 × weight gain between dialysis [kg])/(estimated body dry weight [kg] × length of hemodialysis session [hours]).

Results: UF-rateadj correlated (Spearman) with (1) predialytic values of IDWG (r = 0.983, p < 0.001), proBNP (r = 0.443, p < 0.001), and troponin T (r = 0.296, p = 0.025); and (2) differences in proBNP180–0min (r = 0.572, p < 0.001) and troponin T180–0min (r = 0.400, p = 0.002). UF-ratesadj above a breakpoint of 0.60 caused more release of proBNP180–0min (p = 0.027). Remaining variables in multiple regression analysis with ProBNP180–0min as dependent factor were predialytic proBNP (p < 0.001) and the ultrafiltration-rate (p < 0.001).

Conclusion: Higher UF-rateadj during dialysis was correlated to increased levels of cardiac markers. Data support a UF-rateadj lower than 0.6 to limit such increase. Further studies may confirm if limited fluid intake and a lower UF-rateadj should be recommended to prevent cardiac injury during dialysis.

Background. When blood passes the extracorporeal circuit, air microbubbles (MBs) contaminate the blood. Some MBs will end up as microemboli in the lung, heart, and brain. MB exposure has no medical purpose and is considered to be bio-incompatible. Selecting venous chambers with a high removal rate of MBs is warranted to reduce the risks of air bio-incompatibility. The primary aim was to compare the Fresenius 5008 (F5008-VC) and the Emboless® (Emboless-VC) venous chambers regarding the elimination of MBs in the return bloodline during hemodialysis (HD).

Methods. Twenty patients underwent 80 sessions of cross-over HD using both the F5008-VC and the Emboless-VC randomized such that half started with the F5008-VC and half with the Emboless-VC. For 32 of the 80 sessions, measurements were also performed during hemodiafiltrations (HDF) after the initial HD. MBs were measured with an ultrasound device (within the size range of 20–500 μm) at the “inlet” and “outlet” bloodline of the venous chambers. The Wilcoxon pairwise test compared the percentage of MB elimination between venous chambers.

Results. During HD, the median reduction of MBs for the outlet was 39% with the F5008-VC and 76% with the Emboless-VC (P < .001). During HDF, the reduction was 28% with the F5008-VC and 70% with the Emboless-VC (P < .001).

Conclusion. Fewer MBs and subsequently fewer microemboli entered the bloodline of the patient using the Emboless-VC compared to the F5008-VC venous chamber during HD and during HDF. Venous chambers with a high removal rate of MBs will reduce the extent of air emboli.

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 eGFR_{180days-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.

Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are commonly prescribed anticoagulants for chronic hemodialysis (HD). The dialysis population comprises a unique group that receives heparin three times per week for a long period, with potential long-term cumulative metabolic effects such as osteoporosis and worsening lipid profile. HD patients have approximately half the number of lipases as healthy individuals, and their lipid metabolism is limited because of this decrease as well as partially inhibited function. Administration of UFH or LMWHs for anticoagulation can lead to metabolic starvation despite high triglyceride levels at the end of HD. In vitro studies indicate that UFH and LMWHs inhibit osteoblasts and promote osteoclasts. In patients on HD, long-term use of UFH or LMWHs did not worsen chronic kidney disease–mineral bone disease. Further investigation is needed to elucidate the underlining mechanisms of UFH and LMWHs and their possible influences on maintenance HD patients.

Background: Larger volumes of accidental air infused during medical care may end up as emboli while microbubbles of air are supposed to be absorbed and cause no harm. The aim of this autopsy study was to investigate if microbubbles of air accidently entering the bloodline may be detected as microemboli (ME) in tissue such as lungs, brain and heart. If so, do differences in prevalence exist between haemodialysis (HD) and amyotrophic lateral sclerosis (ALS) patients.

Methods: Included were data from 44 patients treated by medical healthcare before death. Twenty-five cases had been treated with chronic HD and 19 cases died from ALS. Since air in the bloodline activates coagulation, ME could appear. To discriminate between microbubbles caused by artificial contamination during autopsy versus microbubbles deposited in vivo, tissues were stained with a polyclonal fluorescent antibody against fibrinogen, fibrin and fragments E and D. Fluorescence staining was used to visualize ME counted within 25 microscopic fields (600x) of a tissue preparation. One tissue preparation was used if available from the lung, heart and frontal lobe of the brain and in five cases also the cerebellum.

Results: Microbubbles can be verified at autopsy as ME in the lung, heart and brain in tissue from patients exposed to more extensive medical care. There were significantly more ME in the lungs versus the heart or brain. Women had fewer ME than men. The HD group had a higher median of ME per section than the ALS group (lung: 6 versus 3, P = .007; heart: 2.5 versus 1, P = .013; brain: 7.5 versus 2, P = .001) and had more sections with ME findings than the ALS group (P = .002). A correlation existed between the time on HD (months) and ME in the lungs.

Conclusions: More ME were present in HD patients compared with those who suffered from ALS. Minimizing air contamination from syringes, infusions and bloodlines will decrease ME and subsequent tissue injury. Lay Summary Larger volumes of accidental air infused during medical care may end up as emboli while microbubbles of air are supposed to be absorbed and cause no harm. Microbubbles can be verified at autopsy as microemboli (ME) by air in lung, heart and brain in tissue from patients exposed to dialysis and more cannulation and infusions. Minimizing air exposure from syringes, infusions and bloodlines may decrease the risk of ME by air and subsequent tissue injury.