Figures
Abstract
Background
Previous studies have analyzed factors associated with renal infarction so that patients can be provided with earlier diagnosis and treatment. However, the factors associated with development of chronic kidney disease (CKD) following renal infarction are unknown.
Methods
We retrospectively reviewed the records of patients with a diagnosis of renal infarction based on enhanced computed tomography. All patients were admitted to a single emergency department in Taiwan from 1999 to 2008. Univariate and multivariate analysis were used to assess the effect of different factors on development of CKD based on estimates of the glomerular filtration rate (eGFR) at admission and at 3–12 months after discharge.
Results
Univariate analysis indicated significantly increased risk of CKD in patients older than 50 years, with symptoms for 24 h or less before admission, lower eGFR at admission, APACHE II score greater than 7, SOFA score greater than 1, ASA score greater than 2, and SAPS II score greater than 15. Multivariate analysis indicated that only SOFA score greater than 1 was significantly and independently associated with CKD at follow-up (p<0.001).
Citation: Lin W-L, Seak C-J, Wu J-Y, Weng Y-M, Chen H-C (2014) Risk Factors for Development of Chronic Kidney Disease following Renal Infarction: Retrospective Evaluation of Emergency Room Patients from a Single Center. PLoS ONE 9(6): e98880. https://doi.org/10.1371/journal.pone.0098880
Editor: Giuseppe Remuzzi, Mario Negri Institute for Pharmacological Research and Azienda Ospedaliera Ospedali Riuniti di Bergamo, Italy
Received: November 25, 2013; Accepted: May 8, 2014; Published: June 9, 2014
Copyright: © 2014 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Renal infarction is a rare but potentially serious condition that is typically characterized by unilateral flank or abdominal pain, hematuria, and proteinuria. Diagnosis can be difficult because these and other signs and symptoms are non-specific and are often consistent with pyelonephritis, tumor, urolithiasis, and other conditions [1]. Diagnosis is best made by contrast-enhanced computed tomography (CT) and/or renal angiography. CT results typically indicate the presence of a wedge-shaped hypodense area in the peripheral region [2], [3]. Thrombosis, embolism, and arterial lesion are the main causes of renal infarction [4].
Prompt initiation of therapy with an anti-coagulant and/or a thrombolytic agent is often the preferred treatment for renal infarction. Catheter-directed intra-arterial thrombolysis may also be effective [5]. However, such treatments are not effective in all patients, possibly due to delays in diagnosis [2]. Patients can recover from renal infarction, but some patients develop irreversible chronic kidney disease (CKD). Many previous case studies and case series have investigated factors associated with renal infarction in order to allow earlier diagnosis [3]–[8]. However, the factors associated with development of CKD following renal infarction are not yet well-established.
In the present study, we identified factors associated with development of CKD following renal infarction by analysis of patients from a single institution in Taiwan who experienced renal infarction from 1999 to 2008.
Methods
Patient selection
All patients were admitted to the Emergency Department (ED) of Chang Gung Memorial Hospital (Taoyuan, Taiwan) from 1999 to 2008 due to a diagnosis of renal infarction based on enhanced computed tomography (CT). All patients received out-patient follow-up and had serum creatinine measured at admission. Variables were excluded if they were missing in more than 50% of patients, if all subjects had the same value, and if they were not numerically coded. Ultimately, 40 patients were enrolled. The Institutional Review Board of Chang Gung Memorial Hospital approved this retrospective study and the patients provided written informed consent.
Clinical and demographic data
Clinical and demographic data were obtained by retrospective chart review. Serum creatinine was measured by the Jaffe reaction with alkaline picrate. Prognostic scores were calculated upon ED admission (before treatment) based on APACHE II criteria [9], SOFA criteria [10], ASA criteria [11], and SAPS II criteria [12]. These scores were readily available, and although they were not designed to predict the risk of CKD after RI, we investigated their potential use in this new context. CKD was diagnosed based on K/DOQI guidelines [13] and an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 at ER admission and 3 months after discharge. The eGFR was calculated by the Cockcroft and Gault formula, which was developed in 1976 [14].
Data Analysis
Continuous variables are expressed as means ± SDs if the distribution was normal and as medians with interquartile ranges (IQRs) if the distribution was non-normal. Categorical variables are expressed as frequencies and percentages. The difference in eGFR at two time points was assessed by a paired t-test. The differences in the presence of CKD in patients with different characteristics were assessed by a Chi-square test or Fisher's exact test, as appropriate. For identification of risk factors associated with CKD, the point estimates and 95% confidence intervals (CIs) of odds ratios (ORs) were calculated by univariate and multivariate logistic regression models. All significant variables in the univariate analysis were used for backward selection in the multivariate logistic regression model; variables that did not improve model fit for a p-value less than 0.1 were discarded, but potential confounding variables (age and gender) were forced into the model. All statistical analyses were performed with SAS software version 9.2 (SAS Institute Inc., Cary, NC). A two-tailed p-value less than 0.05 was considered statistically significant.
Results
Baseline characteristics of study subjects
A total of 40 patients (29 males [72.5%] and 11 females [27.5%]) who were admitted to our ED for renal infarction, all of whom had eGFR measurements at admission and at 3–12 months after discharge, were included in the analysis (Table 1). The mean patient age was 53.18±15.10 years and the age range was 20 to 78 years. One patient (2.5%) had a previous renal infarction. The most common medications were aspirin (35%) and warfarin (15%). The median (IQR) duration of symptoms/signs before admission was 24.0 h (12.0–84.0). The most common symptoms were abdominal pain (85%) and flank pain (42.5%). Eighteen patients (45%) had an embolism in the heart or other region. The median (IQR) of the APACHE II, SOFA, ASA, and SAPS II scores were 7.0 (4.0–10.0), 1.0 (0.0–2.0), 2.0 (1.0–3.0), and 15.0 (13.0–19.0), respectively. Based on a Kruskal-Wallis test, the distributions of ICU prognostic scores (APACHE II, SOFA, ASA, and SAPS II) did not differ significantly among patients with different etiologies (cardiac or other embolism, n = 18; thrombosis or coagulation dysfunction, n = 16; renal artery dissection, n = 1; idiopathic disease, n = 5).
eGFR at admission and 3 to 12 months after discharge
The eGFRs of all enrolled patients were measured at admission and 3 to 12 months after discharge (Table 2). Eleven patients were evaluated at month-3, 2 at month-6, 6 at month-9, and 21 at month-12 (mean duration: 8.8±3.9 months after discharge) (Figure 1). The results indicate slightly higher mean eGFR after discharge than at admission (66.7±31.0 vs. 70.5±28.5 mL/min/1.73 m2, p = 0.035), but no significant change in Cr.
Factors associated with development of chronic kidney disease
A total of 13 patients (32.5%) developed CKD at the last follow-up. Table 3 shows a univariate analysis of risk factors associated with development of CKD. These results indicate significantly increased risk of CKD in patients with the following characteristics: older than 50 years (50.0% vs. 11.1%, p = 0.009), symptoms for 24 h or less before admission (45.8% vs. 12.5%, p = 0.027), lower eGFR at admission (per 1 mL/min/1.73 m2, OR = 0.74, 95% CI: 0.56–0.98, p = 0.034), APACHE II score greater than 7 (50.0% vs. 18.2%, p = 0.033), SOFA score greater than 1 (90.9% vs. 10.3%, p<0.001), ASA score greater than 2 (71.4% vs. 11.5%, p<0.001), and SAPS II score greater than 15 (57.9% vs. 9.5%, p = 0.001).
The final multivariate model was chosen with backward selection for variables that were significant in the univariate analysis. Variables that did not improve model fit (p<0.1) were discarded, except for age and gender, which were forced in the model for adjustment (Table 4). The results of this analysis indicated that only SOFA score greater than 1 was significantly and independently associated with CKD at follow-up (adjusted OR = 75.60, 95% CI: 5.62–1016.99, p = 0.001). In addition, previous hypertension and diabetes mellitus were not significantly associated with CKD (data not shown).
Discussion
We examined the records of 40 patients who were admitted to the ED of Chang Gung Memorial Hospital from 1999 to 2008 with a diagnosis of renal infarction based on enhanced contrast CT. Measurements indicate slightly higher eGFR after discharge than at admission, suggesting a slight improvement in renal function after discharge. A total of 13 patients (32.5%) with renal infarction were diagnosed with CKD after discharge. Univariate analysis indicated that numerous factors were significantly associated with CKD (age >50 years, symptoms for 24 h or less before admission, low eGFR at admission, APACHE II score greater than 7, SOFA score greater than 1, ASA score greater than 2, and SAPS II score greater than 15. However, multivariate analysis indicated that only SOFA score greater than 1 was significantly and independently associated with a diagnosis of CKD. Although the SOFA score was not designed to predict the risk of CKD after RI, our results suggest a potential new use for this parameter.
It may seem somewhat surprising that our multivariate analysis indicated that SOFA score was independently associated with development of CKD, but that the APACHE II, SAPS II, and ASA scores were not. The SOFA score is an indicator of organ dysfunction and morbidity that was originally developed to assess organ dysfunction in patients with sepsis, but has been validated for assessment of organ dysfunction in general. Although SOFA score is associated with mortality, the APACHE II, SAPS II, and ASA scores place greater emphasis on prediction of mortality. The authors designed the SOFA system with an emphasis on bedside applicability and simplicity based on commonly available variables. These prognostic metrics are widely used to predict outcomes of patients admitted to intensive care units (ICUs) [15]. Although a patient's individual prognostic score is not dispositive, it is often considered in guiding individual treatment decisions and in the distribution of limited medical resources [16]. Moreover, APACHE II, SAPS II, and ASA scores are often more suitable for characterization of patients with diseases that are imminently life-threatening, or the level of anaesthetic risk. Although renal infarction and CKD are serious conditions, appropriate clinical management allows patients to survive.
Our analysis indicated that the post-discharge eGFR was significantly higher than the eGFR at admission. However, it seems doubtful whether this small increase (3.8±11.1 mL/min/1.73 m2) was clinically significant. Nonetheless, these results indicate an improvement in kidney function, so this result is not surprising [17]. We find it encouraging that the SOFA score is the best predictor of CKD, because this score only requires measurement of 6 parameters (respiratory, cardiovascular, central nervous system, renal, coagulation, and liver). The APACHE II requires measurement of 34 variables and SAPS II requires measurement of 12 variables. We suggest that future studies of the development of CKD in patients admitted with RI consider use of the SOFA score to guide patient follow-up.
Our study had several limitations. First, our sample size was relatively small and all patients were from a single institution. Second, all patients were admitted to the ED and exclusion of out-patients with renal infarction may have provided a biased view of factors associated with development of CKD.
Conclusions
Our retrospective study of patients admitted to a single ED with renal infarction indicated that 32.5% of patients developed CKD within 3 months of discharge. Elevation of serum creatinine at admission and a SOFA score greater than 1? was the factor significantly and independently associated with development of CKD at follow-up.
Author Contributions
Conceived and designed the experiments: CJS. Analyzed the data: WLL HCC. Wrote the paper: WLL. Contributed analysis tools: JYW. Contributed materials: YMW.
References
- 1. Korzets Z, Plotkin E, Bernhein J, Zissin R (2002) The clinical spectrum of acute renal infarction. IMAJ 4: 781–784.
- 2. Huang CC, Lo HC, Huang HH, Kao WF, Yen DH, et al. (2007) ED presentations of acute renal infarction. Am J Emerg Med 25: 164–169.
- 3. Suzer O, Shirkhoda A, Zafar Jafri S, Madrazo BL, Bis KG, et al. (2002) CT features of renal infarction. Eur J Radiol 44: 59–64.
- 4. Tsai SH, Chu SJ, Chen SJ, Fan YM, Chang WC, et al. (2006) Acute renal infarction: a 10-year experience. Int J Clin Pract 61: 62–67.
- 5. Piffaretti G, Riva F, Tozzi M, Lomazzi C, Rivolta N, et al. (2008) Catheter-directed thrombolysis for acute renal artery thrombosis: report of 4 cases. Vasc Endovascular Surg 42: 375–379.
- 6. Bolderman R, Oyen R, Verrijcken A, Knockaert D, Vanderschueren S (2006) Idiopathic renal infarction. Am J Med 2006 119: 356.e9–12.
- 7. Domanovits H, Paulis M, Nikfardjam M, Meron G, Kürkciyan I, et al. (1999) Acute renal infarction. Clinical characteristics of 17 patients. Medicine (Baltimore) 78: 386–394.
- 8. Korzets Z, Plotkin E, Bernhein J, Zissin R (2002) The clinical spectrum of acute renal infarction. IMAJ 4: 781–784.
- 9. Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13: 818–829.
- 10. Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL (2001) Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 286: 1754–1758.
- 11. Keats AS (1978) The ASA classification of physical status—a recapitulation. Anesthesiology 49: 233–236.
- 12. Le Gall JR, Lemeshow S, Saulnier F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270: 2957–2963.
- 13.
NKF KDOQI Guidelines. Available: http://www.kidney.org/professionals/KDOQI/guidelines_ckd/toc.htm.
- 14. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41.
- 15. Minne L, Abu-Hanna A, de Jonge E (2008) Evaluation of SOFA-based models for predicting mortality in the ICU: A systematic review. Crit Care 12: R161.
- 16. Lemeshow S, Klar J, Teres D (1995) Outcome prediction for individual intensive care patients: useful, misused, or abused? Intensive Care Med 21: 770–776.
- 17. Ceriotti F, Boyd JC, Klein G, Henny J, Queraltó J, et al. (2008) Reference intervals for serum creatinine concentrations: assessment of available data for global application. Clin Chem 54: 559–566.