S. Uchino

BACKGROUND: There are no suitably powered epidemiological studies of 'transient azotaemia' (TA). The objective of this study was to describe the epidemiology of TA and its independent association with hospital mortality. We hypothesized that TA would be associated with an independent increase in the risk of death. METHODS: We retrospectively studied all patients admitted to a university-affiliated hospital in Australia between January 2000 and December 2002. Patients were excluded if they were <15 years old, were on chronic dialysis, had kidney transplant or if their length of hospital stay was <24 hours. We defined TA as rapidly recovering acute kidney injury (AKI) (return to no-AKI risk, injury, failure, loss, end stage (RIFLE) class within 72 hours of onset). We performed descriptive and comparative statistical analysis of data. The primary outcome of the study was the association between TA and hospital mortality in multivariate logistic regression analysis. RESULTS: Among 20 126 study patients, 3641 (18.1%) had AKI according to the RIFLE criteria and 1600 had AKI, which recovered during their hospital stay. Recovery of AKI occurred most commonly within 1 day after diagnosis (37.7%, n = 603). Furthermore, 1172 patients (73.3%) who recovered from AKI did so within 3 days (TA). After correcting for confounding factors, compared with patients without AKI, patients with TA had a significantly higher odds ratio for hospital mortality (2.26; 95% confidence interval: 1.85-2.76). CONCLUSIONS: Transient azotaemia is common in hospital patients, represents close to a third of all cases of AKI and is independently associated with a significantly higher risk of death.

BACKGROUND: The RIFLE classification scheme for acute kidney injury (AKI) is based on relative changes in serum creatinine (SCr) and on urine output. The SCr criteria, therefore, require a pre-morbid baseline value. When unknown, current recommendations are to estimate a baseline SCr by the MDRD equation. However, the MDRD approach assumes a glomerular filtration rate of approximately 75 mL/min/1.73 m(2). This method has not been validated. METHODS: Data from the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study, a prospective observational study from 54 ICUs in 23 countries of critically ill patients with severe AKI, were analysed. The RIFLE class was determined by using observed (o) pre-morbid and estimated (e) baseline SCr values. Agreement was evaluated by correlation coefficients and Bland-Altman plots. Sensitivity analysis by chronic kidney disease (CKD) status was performed. RESULTS: Seventy-six percent of patients (n = 1327) had a pre-morbid baseline SCr, and 1314 had complete data for evaluation. Forty-six percent had CKD. The median (IQR) values were 97 micromol/L (79-150) for oSCr and 88 micromol/L (71-97) for eSCr. The oSCr and eSCr determined at ICU admission and at study enrolment showed only a modest correlation (r = 0.49, r = 0.39). At ICU admission and study enrolment, eSCr misclassified 18.8% and 11.7% of patients as having AKI compared with oSCr. Exclusion of CKD patients improved the correlation between oSCr and eSCr at ICU admission and study enrolment (r = 0.90, r = 0.84) resulting in 6.6% and 4.0% being misclassified, respectively. CONCLUSIONS: While limited, estimating baseline SCr by the MDRD equation when pre-morbid SCr is unavailable would appear to perform reasonably well for determining the RIFLE categories only if and when pre-morbid GFR was near normal. However, in patients with suspected CKD, the use of MDRD to estimate baseline SCr overestimates the incidence of AKI and should not likely be used. Improved methods to estimate baseline SCr are needed.

We examined 28 cases of surgically resected gastric cancer, excluding the diffuse type, for loss of heterozygosity (LOH) on 12 chromosomal arms using polymorphic DNA markers. LOH on chromosome 18q was detected in 61% (14 of 23) of the cases by the probes OLVIIA8, OLVIIE10, p15-65, SAM 1.1, and OS-4, and a putative common region showing LOH included the locus of the DCC tumor suppressor gene. LOH on chromosome 17p was also frequently found (8 of 19 or 42% of the cases) by the probes p10-3 and pHF12-1, and in 5 of these 6 cases the LOH on chromosome 17p was accompanied by LOH on chromosome 18q. On the other hand, the incidence of LOH was 30% or less using probes pHRnES, pHF12-65, p-c-mybE2.6, NJ3 3.2, pHF12-8, pHINS6.0, p9D11, hp2-alpha, pCMM6, and P1A5 on chromosomes 1q, 5, 6q, 7q, 9, 11p, 13q, 16q, 20, and 22q, respectively. LOH on chromosome 18q was frequent irrespective of the depth of tumor invasion, whereas the incidence of LOH on chromosome 17p was higher in the cases in which the tumor invaded beyond the muscularis propria than in those in which tumor invasion was limited to the submucosa and muscularis propria. These results suggest that LOH on chromosome 18q occurs at an earlier stage than LOH on chromosome 17p and that the inactivation of tumor suppressor genes located on chromosome 17p and 18q (e.g., the p53 and DCC genes) is critically involved in the development of the majority of gastric cancers. While alteration of the p53 gene is observed in various human cancers, that of the DCC gene is considered to occur more selectively in gastrointestinal cancers.

Using a large, international cohort, we sought to determine the effect of initial technique of renal replacement therapy (RRT) on the outcome of acute renal failure (ARF) in the intensive care unit (ICU). We enrolled 1218 patients treated with continuous RRT (CRRT) or intermittent RRT (IRRT) for ARF in 54 ICUs in 23 countries. We obtained demographic, biochemical and clinical data and followed patients to either death or hospital discharge. Information was analyzed to assess the independent impact of treatment choice on survival and renal recovery. Patients treated first with CRRT (N=1006, 82.6%) required vasopressor drugs and mechanical ventilation more frequently compared to those receiving IRRT (N=212, 17.4%), (p<0.0001). Unadjusted hospital survival was lower (35.8% vs. 51.9%, p<0.0001). However, unadjusted dialysis-independence at hospital discharge was higher after CRRT (85.5% vs. 66.2%, p<0.0001). Multivariable logistic regression showed that choice of CRRT was not an independent predictor of hospital survival or dialysis-free hospital survival. However, the choice of CRRT was a predictor of dialysis independence at hospital discharge among survivors (OR: 3.333, 95% CI: 1.845 - 6.024, p<0.0001). Further adjustment using a propensity score did not significantly change these results. We conclude that worldwide, the choice of CRRT as initial therapy is not a predictor of hospital survival or dialysis-free hospital survival but is an independent predictor of renal recovery among survivors.

BACKGROUND: A blood urea nitrogen (BUN)/creatinine ratio (BCR) >20 (0.081 in international unit) is used to distinguish pre-renal azotemia (PRA) and acute tubular necrosis (ATN). However, there is little evidence that BCR can distinguish between these two conditions and/or is clinically useful. METHODS: We conducted a retrospective study using a large hospital database. Patients were divided into three groups: 'low BCR' (if BCR when acute kidney injury (AKI) developed was ≤20), 'high BCR' (if BCR when AKI developed was >20) and 'no AKI' if patients did not satisfy any of the Risk, Injury, Failure, Loss and End-stage kidney disease criteria for AKI during hospitalization. RESULTS: Among 20 126 study patients, 3641 (18.1%) had AKI. Among these patients, 1704 (46.8%) had a BCR <20 at AKI diagnosis ('low BCR') and 1937 (53.2%) had a BCR >20 ('high BCR'). The average BCR for the two groups was 15.8 versus 26.1 (P < 0.001). Hospital mortality was significantly less in the 'low-BCR' group (18.4 versus 29.9%, P < 0.001). Multivariable logistic regression analysis for hospital mortality ('no AKI' as a reference) showed that the odds ratio of 'high BCR' (5.73) was higher than that of 'low BCR' (3.32). CONCLUSIONS: Approximately half of the patients with AKI have a BCR >20, the traditional threshold of diagnosing PRA. Unlike PRA patients who have a lower mortality than ATN patients, high BCR patients had higher hospital mortality compared with low BCR patients, which was confirmed with multivariable analysis. These findings do not support BCR as a marker of PRA.