Does urinary tract infection cause proteinuria or microalbuminuria? A systematic review.

Proteinuria, the presence of increased quantities of protein in the urine [1,2] can be detected by a variety of methods [3] including reagent-strip tests (e.g. Albustix), which can be used in a point-ofcare testing environment, and chemical tests available in the laboratory. Highly specific immunoassays for specific proteins including albumin are also used. Screening for proteinuria has diagnostic value in the initial detection and confirmation of proteinuric renal disease. Proteinuria is also an important predictor of progressive kidney damage [4] and a potent independent cardiovascular risk marker and predictor [5]. Among patients with suspected or proven chronic kidney disease (CKD), including diabetic nephropathy, reflux nephropathy and early glomerulonephritis, urinalysis for proteinuria is accepted as a useful way of identifying patients at risk of progressive kidney disease. Urinalysis for proteinuria is recommended as part of the initial assessment of patients with hypertension [6–8]. In people with diabetes mellitus the identification of increased urinary albumin excretion allows the diagnosis of diabetic nephropathy. Microalbuminuria also serves as a risk marker for progressive kidney disease and increased cardiovascular risk [9], even among non-diabetic individuals [10–13]. Urinary tract infections (UTIs) are commonly said to be associated with positive results in reagentstrip urinalysis for proteinuria, with some reviews suggesting between 63 and 83% of cases of cultureconfirmed UTI having reagent-strip positive tests for protein [14]. Symptomatic UTIs account for 2–3% of all consultations in general practice and around 6% in the case of women. Asymptomatic UTI is found in approximately 4–7% of pregnant women, 10% of elderly men and 20% of elderly women. Uropathogenic strains of Escherichia coli account for the majority of UTIs that occur in the community [15,16]. Because of the reported association between UTI and proteinuria and the high prevalence of asymptomatic UTI, many published guidelines and expert consensus opinions recommend the exclusion of a UTI if a test result for urinary total protein is positive [1,17–19] or, prior to the diagnosis of microalbumunuria, in patients with diabetes [20,21]. Thus, common current clinical practice requires physicians to submit a second mid-stream urine sample to the microbiology department for a urine culture to either exclude UTI as a potential cause of proteinuria or consider it as a confounding factor. If there is a UTI, the patient is treated, and 2 weeks post-treatment a further biochemical investigation is required to confirm whether proteinuria/albuminuria is present. Further tests are also necessary when a UTI has been excluded. Our experience is that the yield of positive culture and sensitivity in this situation is very low. We have attempted to identify the origins of these recommendations for proteinuria screening with respect to UTI by conducting a systematic review to determine if there is quality evidence underpinning the common clinical practice of excluding UTI in patients with positive tests for protein. We researched the literature to answer the series of questions detailed in the following text: