PubMed · 5438475
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T Inou, N Akiyama. 1970-02-10. [Artificial dialysis].. https://pubmed.ncbi.nlm.nih.gov/5438475/
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Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a "hub" protein for graft injury irrespective of causation. Sixty-nine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection.
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OBJECTIVES: To determine the current pattern of use of angiotensin converting enzyme inhibitor and monitoring of renal function in general practice and to audit all admissions to a regional renal unit for uraemia related to use of these drugs. DESIGN: Postal questionnaire sent to 400 general practitioners; audit of clinical notes of all patients receiving these drugs in one large general practice; audit of all cases of uraemia (creatinine concentration >500 micromol/l) related to treatment presenting to hospital renal services over 12 months. SETTING: General practices in the North Wales health authority and one in central Manchester. Regional renal unit in Salford. MAIN OUTCOME MEASURES: Proportion of general practitioners who regularly monitored renal function before and after initiation of angiotensin converting enzyme inhibitors. Indications for treatment and details of monitoring of renal function in patients receiving these drugs. Incidence of related uraemia and evidence of comorbid disease, other aetiological factors, delayed detection, and patient outcome. RESULTS: 277 (69%) general practitioners replied; 235 (85%) checked renal function before but only 93 (34%) after the start of treatment, and 42 (15%) never checked renal function. Angiotensin converting enzyme inhibitors were prescribed for 162 patients from a total of 3625 aged >35 years (mean age 66.4 (SD 15.9) years). Monitoring of renal function occurred before treatment in 55 (45%) and after start of treatment in 35 (29%) of the 122 patients treated in general practice. Angiotensin converting enzyme inhibitors could be causally implicated in 9 (7%) of 135 admissions for uraemia (mean age 74.2 (7. 2) v 62.1 (2.1) years; P<0.01). 3 patients had renovascular disease and 6 had congestive cardiac failure with another intercurrent illness. Renal function had not been checked in any patient after the start of treatment; mean duration of illness before admission was 10.5 (3.2) days. Mean length of hospital stay was 20.9 (10.4) days; there were 8 survivors. CONCLUSION: Cases of uraemia related to treatment with angiotensin converting enzyme inhibitors are still encountered and are often detected late because of lack of judicious monitoring of renal function in vulnerable, often elderly, patients, especially at times of intercurrent illness. Guidelines for appropriate monitoring of renal function may help to minimise the problem.