Proteinuria as an important marker in the evaluation of the efficacy and safety of systemic thrombolysis in patients with acute ischaemic stroke

Chronic kidney disease (CKD) is highly prevalent in the general population [1]. In the National Health and Nutrition Examination Survey (NHANES) III, a study using American population based data, kidney impairment occurred in 11% of adults [2]. A large group of these patients will suffer from ischaemic stroke, because incidence of stroke is elevated amongst individuals with kidney disease. Normal persons usually excrete very small amounts of protein in the urine. Increased excretion of albumin is a sensitive marker for CKD due to diabetes, glomerular disease and hypertension. Strokes are not a group of diseases in which the level of protein in urine is routinely evaluated as the implication for treatment. However, common risk factors leading to kidney and brain damage indicate that the assessment of proteinuria may also be a significant parameter in the assessment of the safety and efficacy in treatment of patients with concomitant renal and cerebrovascular disease. Numerous publications emphasize the role of the association of lower estimated glomerular filtration rate (eGFR) and higher albuminuria with all-cause and cardiovascular mortality [3,4]. Most of the studies that evaluated the impact of CKD on the long-term outcome and mortality in patients with acute ischaemic stroke mainly took into account the level of eGFR [5]. Proteinuria was not a factor that drew the attention of researchers dealing with cerebrovascular diseases. Measurement in the first morning urine is preferred because its protein concentration correlates well with 24-h protein excretion and has relatively low intraindividual variability. The guideline recommends urinary albumin creatinine ratio in spot urine samples as the preferred measure rather than urine protein or albumin [6]. The rationale for this recommendation is that the albumin creatinine ratio is a more sensitive and specific measure of kidney damage, whereas urine protein is more difficult to standardize [6]. However, in stroke units this test is not routinely performed. Cerebral systemic thrombolysis (intravenous thrombolysis) with recombinant tissue plasminogen activator, initiated within 4.5 h after the onset of symptoms, is an effective medical therapy for acute ischaemic stroke but is associated with a number of haemorrhagic complications. Diagnosis of CKD, mainly based on the assessment of eGFR and clinical signs, was in most studies a significant factor affecting symptomatic haemorrhagic complications and poor clinical outcomes following administration of intravenous tissue plasminogen activator [7]. However, other studies did not show a significant impact of CKD on systemic thrombolysis. Also, these studies used eGFR in their assessment as a basic parameter [8]. Therefore, the use of other markers in the assessment of the impact of renal insufficiency on the safety and efficacy of intravenous thrombolysis can bring additional benefit. Gensicke et al. [9] carried out an evaluation of the impact of two important, measurable parameters on the long-term outcome of systemic cerebral thrombolysis, eGFR and proteinuria, and confirmed that proteinuria and reduced eGFR were each independently associated with poor outcome and death, but the statistically strongest association appeared for proteinuria. This is a very important point in any discussion about the impact of renal dysfunction on the outcome of systemic cerebral thrombolysis.