Defining the cause of death in hospitalised patients with acute kidney injury.

BACKGROUND: The high mortality rates that follow the onset of acute kidney injury (AKI) are well recognised. However, the mode of death in patients with AKI remains relatively under-studied, particularly in general hospitalised populations who represent the majority of those affected. We sought to describe the primary cause of death in a large group of prospectively identified patients with AKI. METHODS: All patients sustaining AKI at our centre between 1(st) October 2010 and 31(st) October 2011 were identified by real-time, hospital-wide, electronic AKI reporting based on the Acute Kidney Injury Network (AKIN) diagnostic criteria. Using this system we are able to generate a prospective database of all AKI cases that includes demographic, outcome and hospital coding data. For those patients that died during hospital admission, cause of death was derived from the Medical Certificate of Cause of Death. RESULTS: During the study period there were 3,930 patients who sustained AKI; 62.0% had AKI stage 1, 20.6% had stage 2 and 17.4% stage 3. In-hospital mortality rate was 21.9% (859 patients). Cause of death could be identified in 93.4% of cases. There were three main disease categories accounting for three quarters of all mortality; sepsis (41.1%), cardiovascular disease (19.2%) and malignancy (12.9%). The major diagnosis leading to sepsis was pneumonia, whilst cardiovascular death was largely a result of heart failure and ischaemic heart disease. AKI was the primary cause of death in only 3% of cases. CONCLUSIONS: Mortality associated with AKI remains high, although cause of death is usually concurrent illness. Specific strategies to improve outcomes may therefore need to target not just the management of AKI but also the most relevant co-existing conditions.

Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients.

BACKGROUND AND OBJECTIVES: Many patients with AKI are cared for by non-nephrologists. This can result in variable standards of care that contribute to poor outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To improve AKI recognition, a real-time, hospital-wide, electronic reporting system was designed based on current Acute Kidney Injury Network criteria. This system allowed prospective data collection on AKI incidence and outcomes such as mortality rate, length of hospital stay, and renal recovery. The setting was a 1139-bed teaching hospital with a tertiary referral nephrology unit. RESULTS: An electronic reporting system was successfully introduced into clinical practice (false positive rate, 1.7%; false negative rate, 0.2%). The results showed that there were 3202 AKI episodes in 2619 patients during the 9-month study period (5.4% of hospital admissions). The in-hospital mortality rate was 23.8% and increased with more severe AKI (16.1% for stage 1 AKI versus 36.1% for stage 3) (P<0.001). More severe AKI was associated with longer length of hospital stay for stage 1 (8 days; interquartile range, 13) versus 11 days for stage 3 (interquartile range, 16) (P<0.001) and reduced chance of renal recovery (80.0% in stage 1 AKI versus 58.8% in stage 3) (P<0.001). Utility of the Acute Kidney Injury Network criteria was reduced in those with pre-existing CKD. CONCLUSIONS: AKI is common in hospitalized patients and is associated with very poor outcomes. The successful implementation of electronic alert systems to aid early recognition of AKI across all acute specialties is one strategy that may help raise standards of care.

Complementing institutional with localised strategies for climate change adaptation: a South-North comparison.

Climate change and disasters pose a serious risk to sustainable development. In the South, local coping strategies are an important element of adaptation to climate and disaster risk. Such strategies have emerged because of the limited assistance provided by urban actors and associated social security and governance systems. In the North, in contrast, local coping strategies are comparatively poorly developed. However, the extent of the changing climatic conditions is also reducing the capacity of Northern institutions to deal with climatic extremes and variability, which emphasises the need for more local-level engagement in the North. This paper analyses the differences in local and institutional responses to climate change and disasters in a Southern and a Northern city (San Salvador, El Salvador, and Manchester, United Kingdom, respectively), and highlights how the lessons learned might be translated into an improved distributed governance system; that is, an 'integrated engagement model', where local and institutionalised responses support rather than hinder each other, as is currently the case.

Longitudinal changes of insulin-like growth factors and their binding proteins throughout normal pregnancy.

BACKGROUND: Insulin-like growth factors (IGFs) are anabolic proteins that are essential regulators of cell division, differentiation and growth. We describe the longitudinal changes in IGF-I, IGF-II and the binding proteins IGFBP-1, -2 and -3 before and during normal pregnancy. METHOD: Serum samples were taken before conception and then at 12, 24 and 36 weeks of gestation in 41 healthy women with uncomplicated pregnancies. We measured IGF-I using an automated chemiluminescent method, IGF-II and IGFBP-2 using in-house radioimmunoassays (RIAs), and IGFBP-1 and IGFBP-3 using commercial enzyme-linked immunosorbent assay (ELISA) and RIA kits, respectively. Because of the potential haemodilution effects during pregnancy, albumin was also measured in all samples. RESULTS: There was a significant fall in IGF-I during the first (36%) and second trimesters (21%) followed by an increase of 25% at 36 weeks. During pregnancy, the mean IGF-II concentrations fell by 12% at 12 weeks, 8% at 24 and 8% at 36 weeks compared with pre-conception values. When IGF-II results were adjusted for the haemodilution of pregnancy, its concentrations increased. During pregnancy, there was a rapid increase in mean IGFBP-1 levels by 17-fold (12 weeks), 24-fold (24 weeks) and 25-fold (36 weeks). IGFBP-2 concentrations fell after conception but started to increase towards term. This increase was more significant when adjusted for haemodilution. In contrast, IGFBP-3 concentrations increased significantly throughout pregnancy. CONCLUSION: Our data on the physiological changes of IGFs and their binding proteins add further evidence of the vital roles of these hormones throughout normal pregnancy.

Changes in serum markers of bone turnover during normal pregnancy.

BACKGROUND: Maternal calcium homeostasis adapts during pregnancy to provide for the needs of the growing fetal skeleton. Wide selections of bone turnover markers are currently available to assess the changes taking place; here, data are presented on two serum-based markers. METHODS: The use of serum-based biochemical bone turnover markers during pregnancy was assessed in a cohort of 41 women recruited prior to conception. Serum N-terminal extension peptide of procollagen (P1NP) was used to monitor bone formation and serum beta-crosslaps (S-CTX) used to assess resorption. Blood samples were measured at five time points from a pre-conceptual baseline, through pregnancy, to the final sample, which was taken within 1 week of delivery. RESULTS: An initial decrease from the baseline in both P1NP and S-CTX was observed at 12 weeks; however, it is suggested that this may be due to the haemodilutional effect of pregnancy rather than a true change in bone turnover. Significant increases from the baseline of both analytes were observed by 36 weeks (P1NP, P = 0.013; S-CTX, P = 0.002), when the calcium demands of the fetus are greatest. CONCLUSIONS: This study illustrates the use of serum-based bone turnover markers to assess turnover during normal pregnancy, a time when ionizing radiation cannot be used to assess bone turnover.

Plasma nitric oxide (nitrate/nitrite) levels in acute stroke and their relationship with severity and outcome.

Endothelium-derived nitric oxide is beneficial in experimental stroke. We assessed plasma NO levels in patients with acute stroke and their association with both severity and outcome. Plasma nitric oxide (NO), assessed as nitrate/nitrite (NOx), cyclic guanosine monophosphate (cGMP, second messenger to NO), L-arginine (substrate for NO) and L-citrulline (co-product with NO) levels were measured in 228 patients with acute ischemic stroke, 49 patients with acute hemorrhagic stroke, and 38 age and gender-matched normal volunteers. Stroke severity was assessed using the Glasgow Coma Scale, and the outcome was judged by discharge destination (home, institution, or dead). In our study, stroke patients had low levels of NOx (micromol/l): ischemic 49.9 (26.1); hemorrhage 41.7 (19.5); and control 64.0 (36.3) (P < .001); L-arginine (micromol/l): ischemic 85.1 (32.3); hemorrhage 69.9 (24.4); and control 104.0 (30.0) (P < .001); and L-citrulline (micromol/l): ischemic 30.5 (12.3); hemorrhage 26.7 (12.1); and control 39.4 (13.5) (P < .001). Cyclic GMP levels were elevated in stroke: ischemic 21.2 (16.1); hemorrhage 24.7 (17.5); and control 15.8 (9.2) (P = .024). Patients who died or became institutionalized had lower NOx, L-arginine, and L-citrulline levels, and higher cyclic GMP levels, than patients who were discharged home. NOx levels were not associated with feeding status in patients. Low levels of NOx are present in stroke and are associated with severity and outcome. Because endothelium-derived NO is beneficial in acute stroke, administering NO might be beneficial in acute stroke.

Comparison of intact and 'whole molecule' parathyroid hormone assays in patients with histologically confirmed post-renal transplant osteodystrophy.

BACKGROUND: Fragments of parathyroid hormone (PTH) have been identified (amino acids 7-84) which may interfere with commercially available 'intact molecule' PTH assays. Novel assays which employ an antibody directed to the first seven amino acids of the N-terminus of PTH are thought to be free from cross-reactivity with the 7-84 fragments, and therefore measure true 'whole molecule' PTH. Transplant recipients (as well as those in end-stage renal failure) have been reported to have elevated levels of 'intact' in comparison with 'whole molecule' PTH. METHODS: PTH concentrations were assessed in serum samples obtained from female renal transplant recipients previously classified as either having hyperparathyroid (n = 14) or adynamic bone disease (n = 14) by transiliac crest bone biopsy. PTH was measured as 'whole molecule' (Scantibodies 'whole molecule' PTH) and 'intact' (DPC Immulite 2000 intact PTH and Scantibodies total PTH). RESULTS: Scantibodies 'whole molecule' PTH (all-subject mean 48.7 ng/L, +/- 53.0) were significantly lower than DPC intact (83.5 ng/L, +/- 88.1; P < or = 0.0001) and Scantibodies total PTH (80.5 ng/L, +/- 92.4; P < or = 0.0001). However, the differences between the 'whole molecule' and 'intact' measurements were similar across the two patient groups, and reflected the lower reference range employed by the 'whole molecule' assay. CONCLUSION: The 'whole molecule' PTH assay was unable to discriminate between the two patient populations and provided very little additional clinical information to that obtained from the intact PTH assays.

Creatinine assays: time for action?

BACKGROUND: Major differences in creatinine results between different laboratories and apparent inaccuracies when using commercial lyophilized standards were noted. In order to assess the variation and accuracy of the different methods we conducted a local audit. METHODS: To establish the variation between methods, plasma creatinine was measured on 47 human plasma samples by nine different laboratories using four different methods (Roche, Ortho, Olympus, modified Olympus). To establish the accuracy of the different methods, plasma creatinine was also determined on 16 of the plasma samples by tandem mass spectrometry (MS). In addition, all the laboratories measured the creatinine concentration on a commercial authenticated sample. RESULTS: All four methods gave significantly different (P<0.0001) plasma creatinine results when compared with each other. Generally, creatinine results produced by the Ortho method were considerably higher than those of the other methods, especially at higher creatinine concentrations (differences across methods between the lowest and highest result for the same sample ranged between 8% and 33%). All four methods generally gave higher results than those determined by tandem MS for samples with creatinine concentrations of < 250 micromol/L. Above this concentration the Olympus and Roche methods produced creatinine results that were lower then the tandem MS results, whereas results from the Ortho method were higher. Major matrix problems were found when a commercial lyophilized standard was used for creatnine estimation. CONCLUSION: No method gave good agreement with the tandem MS results, and there were major differences in measured plasma creatinine concentrations (up to 30% difference) between the various methods. We suggest that efforts should be made to standardize plasma creatinine measurement across all laboratories to minimize these problems.