Plasma Exchange in Clinical Practice

Plasma exchange (PEX) is a treatment method with increasing range of indications. However, due to the small number of randomized trials, its effectiveness is still under debate in certain conditions. The aim of our chapter is to present the major principles of PEX, discuss safety issues and reveal current data for treatment effectiveness of the method. Novel indications for PEX will also be discussed

Vitamin D and Renal Disease

The metabolism of vitamin D (VD) is severely impaired in chronic kidney disease (CKD). Uremia is not only associated with the reduction of its active form 1,25-dihydroxyvitamin D but also in the reduction of all VD metabolites. CKD-associated abnormalities in VD are part of the CKD-related mineral-bone disease. However, VD has beneficial effect on the kidneys due to its pleiotropic effects, namely, antiproteinuric effect and renin-angiotensin-aldosterone system suppression, thus making the relationship between VD and the kidney even more complicated. The aim of our chapter is to reveal the changes in vitamin D axis in CKD, to outline the possible beneficial effects of vitamin D in renal patients, including end-stage renal patients and kidney transplant recipients, and to address the current opinions concerning treatment with cholecalciferol, calcitriol, and vitamin D analogs

Vitamin D After Kidney Transplantation: Metabolism and Clinical Importance

Vitamin D (VD) is a key factor in calcium-phosphorus metabolism. In addition, it has increasing popularity due to its pleiotropic effects: renal protection, antineoplastic properties, and diabetes mellitus and hypertension control. The VD axis is severely impaired in chronic kidney disease. The changes are present even in the earliest stages and progress as kidney function worsens. Significant changes in VD occur after successful kidney transplantation, as different factors interplay, leading to widespread VD insufficiency in kidney transplant recipients. The aim of our review is to demonstrate the changes in VD metabolism after kidney transplantation and to reveal their full impact on graft and patient survival in the post-transplant setting. Furthermore, current strategies for VD supplementation and their efficacy will be discussed

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I 2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None