Prognosis and Serum Creatinine Levels In Acute Renal Failure at the Time of Nephrology Consultation: An Observational Cohort Study

Jose Ramon Perez-Valdivieso; Maira Bes-Rastrollo; Pablo Monedero; Jokin de Irala; Francisco Javier Lavilla

Disclosures

BMC Nephrology 

In This Article

Discussion

This longitudinal study shows that a relative increase in baseline serum creatinine by ≥ 101% compared with the levels measured at the time of nephrology consultation is an independent predictor of mortality. Such an increase was also associated with worse functional renal recovery irrespective of the degree of ARF severity or presence of comorbid illnesses.

Due to the heterogeneous nature of ARF,[11] it was important to adjust for the severity of illness with Liano score, and for the acute kidney injury with the RIFLE criteria. We have chosen the Liano score because of its ability to discriminate mortality from survival and its ability to calibrate the observed mortality rate with the expected mortality in ARF.[11,14,27] The RIFLE consensus criteria gives a standard definition and a level of classification of severity in ARF,[20] a request often made by the experts.[6,18,19] Working in this manner may allow continuing further investigation in ARF, and is one of the main strengths of this study. Patients did not do worse because they had more severe ARF or comorbid illnesses. Instead, patients presenting the same RIFLE criteria and Liano scores, but with higher serum creatinine increments prior to the nephrology consultation, showed higher mortality rates.

Using multivariate logistic regression analysis, we found that an increment in creatinine with respect to baseline level of 101% at the time of nephrology consultation started is a factor independently and strongly predictive of death in this cohort. Doubling the basal creatinine level presented an odds ratio of 1.81 for mortality among general population. This increased to a threefold (OR = 2.66) mortality in patients who needed continuous renal replacement therapy. These results might suggest that the increase of serum creatinine level at the moment when the ARF began to be treated by an expert was related to the outcome. However, we should concede the possibility that the more abrupt increase in serum creatinine was, the worse the prognosis. Because of the observational nature of the present study, our findings need to be interpreted with caution. We cannot determine with certainty that finding a higher increase in the percentage of creatinine was a consequence of a delayed nephrology consultation. It could be that among patients who received the nephrology intervention at the same time, some of them presented a higher increase in the percentage of creatinine because of an abrupt deterioration of renal function. Nevertheless, after adjusting for severity of ARF and comorbid illnesses, patients who had had higher increments in percentage of creatinine prior to being treated by a nephrologist did present higher mortality rates. We might stand for prompt expert consultation because these ARF patients at risk would benefit from an intensive and specialized treatment, and further kidney damage could be minimized.

The cohort included a heterogeneous distribution of patients, in terms of unit, nature, or source of admission; but with an important number of oncology patients (35.4%) since our institution is a well-known center in Spain for the treatment of oncologic diseases. For this reason, we adjusted adding the oncology factor to the logistic regression in an extra analysis. However, because of its longitudinal design, we could obviate the Berkson bias (to take a falsely typical population of patients since the group of people being studied has no form of control over whether to participate).[28] Also, it could be argued that this was a single center study, with its limits to apply to other hospitals. We have tried to minimize any bias using objetive data collected by a single investigator following strict criteria, and reviewing the data. Urine output data were not available; therefore it was not possible to estimate the RIFLE criteria according to this value. We started to collect the data before the RIFLE criteria was formulated, and most of the ward patients had no urine output measured on a six hourly basis. We assume that we might underestimate some cases according to the RIFLE criteria; but only 21 and 62 patients from groups R and I respectively had oliguria. Although we cannot rule out the possibility of residual confounding, it is unlikely that it can fully explain the observed strong associations. Moreover, when we adjusted for RIFLE criteria, an increase of our estimations occurred in the multivariate model; so misclassification of this covariate would most likely bias the odds ratios toward the null value.

We calculated the MDRD equation to obtain a baseline serum creatinine in patients with no previous history of renal failure because a true baseline is often unknown. We solved the equation assuming a GFR of 75 ml/minute/1,73 m2, which has been reported to estimate a lower limit of a normal GFR.[4,13,20] Because GFR was assumed to be 75 ml/min, using MDRD for patients with unknown pre-morbid renal dysfunction may underestimate severity of ARF according to the RIFLE criteria.[29,30] This lack of reliability is one of the controversial issues regarding the RIFLE criteria, but it is still unresolved.[31] Although the MDRD formula may be less accurate at normal GFR, resulting in overdiagnosis of ARF, it should not be a disadvantage in a clinical setting where ARF is taken seriously, and the MDRD also has the advantage of not requiring body weight data [32] that could be wrongly estimated in fluid retention settings.

We chose to calculate the percentage change in creatinine respect to its baseline because serum creatinine is modulated by muscle bulk. Therefore, smaller changes as 0.3 or 0.5 mg/dL will have distinct significance for patients with different genders and/or ages, whose normal baseline levels are different.[18] For this reason, we found that a relative increase in creatinine was more accurate than an absolute increase one.

The higher presence of chronic renal failure in the < 101% increment group might be explained because concern about it could have induced earlier nephrology consultation, even if the patient did not present signs of ARF in that time. However, we must admit that 74 chronic renal failure patients (48.68%) might have presented an unstable serum creatinine value at hospital admission, thus underestimating the severity of ARF for them. Chronic renal failure was included in this study to represent the common clinical practice, and thereafter it was adjusted for in the analysis because of expecting different outcomes than the general population.

On the other hand, the higher proportion of cases of ARF developed in the community in the ≥ 101% increase group might suggest that nephrology consultation may have been delayed because of time spent before hospital admittance, giving serum creatinine an extra time to reach a higher value.

Our results about mortality in the Renal Replacement Therapy sub-group are consistent with previously reported,[9,33,34] and it is of interest the higher mortality rate in patients in the ≥ 101% increase group. What we may learn here is that this group of patients is most likely to benefit from a more intensive treatment.

The degree of renal injury is likely to affect renal recovery. Patients where consultation was started with ≥ 101% creatinine increase had significant higher creatinine levels at discharge compared to their baseline levels, and many of them would be expected to develop chronic renal malfunction. Adjustment for confounding factors in the analysis was done, too.

We analyzed 6-months mortality separately, since the time when patients are discharged from hospital might vary between admission units. Although it could be argued that all-cause mortality at six months is non specific, we found that a high number of deaths (175) occurred in the first 60 days. These findings agree with previous reports and recommendations about optimal follow-up time in patients with established ARF.[20,26,35]

It is of interest to note that 306 patients from the original population of 1008 would not have been diagnosed of ARF had the RIFLE criteria been used then. They did not present oliguria nor enough creatinine increment, but were diagnosed of ARF according to another criteria at that time. Some experts might prefer to use more inclusive criteria because of concern about under-recognizing ARF.[6]

Finally, had our patients presented other mortality rates, if they would have been treated by a nephrologist before reaching serum creatinine levels more than twice their baseline levels, is a question beyond this study and needs further research.

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