Acute worsening of renal function in patients with ADHF is common and increasingly recognized as an independent risk factor for morbidity and mortality [19–23]. Renal impairment in ADHF develops as a consequence of new onset kidney injury (AKI) or of acute deterioration of pre-existed CKD (ACKI). This study is the first study, to the best of our knowledge, comparing the prognostic implications of AKI with ACKI. The results demonstrated that acute worsening of renal function in ADHF was more prevalent in patients with pre-existed CKD than those without. Patients with ACKI, as opposite to those with AKI, were at greater risk of adverse outcomes during hospitalization for ADHF.
The reported incidence of acute worsening of renal function in ADHF varies from 29% to 70% depending on the study entry criteria and the definition used to characterize renal dysfunction [3, 24]. In our study, despite exclusion of cardiogenic shock, contrast medium-induced nephropathy, and severe chronic renal failure, acute worsening of renal function was still very frequent (44.3%) during hospitalization for ADHF. The incidence was similar with the previous study which enrolled patients with similar characteristics . In contrast to the most previous studies [2–4, 23, 26] in which serum creatinine on admission or back-calculating creatinine was used as the baseline renal function, we applied preadmission eGFR as the underlying renal function and defined AKI and ACKI without bias . An important finding in our results was that ACKI was more frequent than AKI (56.6% vs. 39.8%) in ADHF. Compared with AKI, ACKI was associated with more severe renal injury (defined as RIFLE category) and more proportion of patients in this group required renal replacement therapy during hospitalization. Consistent with the previous report , worsening renal function occurred relatively early in the course of the hospitalization with the median time of 4 days of maximum RIFLE class reached.
Diuretic resistance is common in ADHF, while its prevalence and prognostic implications are less well defined. It is noteworthy that diuretic resistance in our cohort was more prevalent among those with worsening renal function (23.8% in ACKI and 17.7% in AKI) than those with ADHF alone (7.8% in those with pre-existed CKD and 4.7% in patients without CKD). In patients with worsening renal function, prevalence of diuretic resistance seemed to be higher in ACKI than that in AKI group. Although the mechanisms underlying diuretic resistance remain to be clarified, it has been suggested that hypoalbuminemia, commonly seen in CKD, may increase the volume distribution of loop diuretics and impair their delivery to the kidney . Moreover, accumulation of organic acids in CKD may act indirect competition with diuretics for secretion at the proximal tubule . Given the fact that diuretic resistance, particularly with worsening renal function, results in marked persistent volume over-load in ADHF , it may represents a subset of more advanced HF and contribute to the poor outcomes. In this study, we demonstrated that more patients with ACKI needed ultrafitration for diuretic resistance compared to those with AKI. The presence of diuretic resistance was identified as one of the strongest independent risk factors for all-cause and cardiac mortality in patients with ADHF, particularly those with pre-existed CKD (Table 4 & 5).
Renal dysfunction is one of the most important risk factors for poor outcomes in patients with ADHF [29, 30]. However, the difference in prognostic implications between AKI and ACKI has not been well established. Our results demonstrated that patients with ACKI were at higher risk of all-cause and cardiac mortality than those with AKI. Among survivors in the cohort, those with ACKI had longer hospital and CCU stay and higher re-hospitalization as compared with AKI patients. Consistent with the previous study , the severity of acute kidney injury predicted non-renal recovery, particularly in patients with AKI. The patients with pre-existed CKD were older, and had more co-morbid diseases such as diabetes, hypertension and ischemic heart disease. More proportion of those with background CKD had lower levels of serum albumin and hemoglobin. To verify the impact of ACKI and AKI on outcomes, logistic regression was used to adjust for the possible confounding factors. In addition to known risk factors, pre-existed CKD and acute worsening of renal function during hospitalization were still found to be significantly associated with all-cause and cardiac mortality. Supporting with our results, in a community-based cohort of patients with CKD, an episode of superimposed dialysis-requiring ARF was associated with very high risk for non-recovery of renal function . In the multivariate logistic regression analysis, we also found that pre-existed CKD was an independent risk factor for development of acute worsening of renal function during admission. When the patients who died in hospital were excluded, full recovery of renal function at discharge was 72.2% in those with AKI, which was much lower than that in the population–base studies (93%)  and also lower than that in patients with post-trauma AKI (77.5%) . It is noteworthy, creatinine values were restored to previous levels in only 30.7% of those who had pre-existed CKD and survived their acute illness, though we could not exclude the possibility that the relatively low rate of renal recovery might be related to the strict definition for full renal recovery used in the study.
RIFLE classification provides a well-stratification system for acute renal injury and has been used more commonly . In our study, the RIFLE was able to predict all-cause and cardiac mortality in both AKI and ACKI. The predictive effect was still significant after adjustment by the confounding factors, suggesting that RIFLE classification might be useful for stratification of patients with concomitant cardiac and renal dysfunction. Consistent with early report , the RIFLE criteria was suitable to evaluate the AKI, as well as to predict its association with adverse outcome in patients with ADHF.
Acute worsening of renal function in patients with ADHF has been described as cardiorenal syndrome type 1 . The previous reports studied the syndrome have not differentiated AKI and ACKI. Our results indicated that ACKI, as compared with AKI, was associated with higher risk of adverse outcomes, suggesting that type 1 cardiorenal syndrome should be classified in two subgroups based on the underlying renal function. Since the prevalence of CKD has been increasing, particularly in those with cardiovascular disease, it is important to identify CKD early. Estimated GFR should be included in the assessment of risk stratification for individual patients with cardiovascular disease, in addition to traditional cardiovascular risk factors. Since ACKI increased mortality and treatment cost, the need for adequate definition and early screening has never been greater.
We classified ACKI based on RIFLE criteria. This classification may have missed a significant number of patients because those with preexisted CKD would require a considerable increase in creatinine to enter this classification (e.g., a baseline creatinine of 200 μmol/L requires a rise to 300 μmol/L for entry into the R category). Appropriate criteria for ACKI therefore needs further study and definition.