1 Departments of Nephrology and 2 Biostatistics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Correspondence and offprint requests to: Professor V. Sakhuja, Department of Nephrology, Post Graduate Institute of Medical Education and Reseach, Chandigarh 160 012, India.
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods. All elderly patients (>60 years) admitted over a 12-month period were screened prospectively throughout their hospital stay for the development of ARF.
Results. Of 31860 patients admitted, 4176 (13%) were elderly. Of these 59 (1.4%) developed ARF in the hospital. Nephrotoxic drugs contributed towards development of ARF in 39 (66%), sepsis and hypoperfusion in 27 (45.7%) each, contrast medium in 10 (16.9%) and postoperative ARF occurred in 15 (25.4%) patients. These pathogenetic factors were responsible for ARF in different combinations. Amongst these combination of pathogenetic factors, radiocontrast administration (partial 2 28.1, P<0.0001), surgery (partial
2 14.89, P=0.001), and drugs (partial
2 6.22, P=0.0126) predicted ARF on their own. Nine patients (15.23%) needed dialytic support. Of 59 patients, 15 (25.4%) died, of those who survived, 38 (86.3%) recovered renal function completely and six (13.6%) partially. Mortality in the elderly with ARF was significantly higher than in those without ARF (25.4 vs 12.5%;
2 8.3, P=0.03). Sepsis (odds ratio 43), oliguria (odds ratio 64), and hypotension (odds ratio 15) were independent predictors of poor patient outcome on logistic regression analysis.
Conclusion. Incidence of treatment-related ARF in the elderly was 1.4%, with more than one pathogenetic factor playing a role in the development of ARF in the majority. Sepsis, hypotension, and oliguria were the independent predictors of poor patient outcome.
Keywords: geriatric; hospital acquired; nephrotoxic drugs; radiocontrast; sepsis
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
ARF in the elderly per se is not an uncommon illness in the developed world because of sizeable geriatric population. In fact, ARF has been considered a typical geriatric disease. Good studies on the epidemiology of ARF in community are available [3,4]. However, the important point is to distinguish the elderly who present with well-established ARF from those who develop ARF when they are being treated for a non-nephrological illness. Not only are the causes different in these two situations but the incidence of the latter can also be minimized if not prevented altogether. Studies on the elderly with ARF have included patients with established ARF at presentation as well as those where some form of therapy resulted in ARF [58]. Some have looked only at one aspect of treatment-related ARF such as postoperative [9], radiocontrast nephropathy [10] and NSAIDs-induced renal failure [11]. In some studies, elderly patients admitted to the medical unit alone [12] or to the intensive care unit [13] have been studied. Those studies that have looked at hospital-acquired ARF in general have not studied the elderly as a separate group [1416].
This prospective study was therefore carried out to determine the magnitude of treatment-related ARF in the elderly in a hospital setting, to examine various pathogenetic factors, and to study factors that could predict an adverse outcome.
![]() |
Subjects and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The first serum creatinine obtained after admission to the hospital was taken as the baseline value. ARF for the purpose of this study was defined as elevation of serum creatinine to over 176.8 µmol/l in the patients with normal baseline serum creatinine, and increase of more than 132.6 µmol/l when baseline serum creatinine was over 176.8 µmol/l despite correction of any clinically obvious haemodynamic or mechanical factors. After identification, a detailed record of the patient's history, physical examination, and laboratory investigations was made to document the demographic characteristics and the pathogenetic factors causing ARF. The underlying original disease for which patients were admitted were broadly categorized as surgical (those who needed surgery), cardiac (admitted for evaluating cardiac disease), infectious (presented with infection involving different organ systems), and a miscellaneous group comprising all other illnesses. These patients were then followed daily until their discharge, death, or the return of their renal functions to baseline. A serial record of urine output and serum creatinine was maintained. Various complications of renal failure that were specifically looked for and recorded were hyperkalaemia, neurological abnormalities, metabolic acidosis, gastrointestinal bleeding, pericarditis and congestive cardiac failure. Dialytic support was instituted according to standard clinical indications. Patients were classified as oliguric or non-oliguric based on the lowest daily urinary output during the azotaemic phase. Oliguria was defined as urine volume of less than 400 ml/day.
In order to assign a possible cause for ARF, a number of clinical criteria were applied. Nephrotoxic drugs were considered the cause of renal failure if a patient had received a drug with known nephrotoxic potential for a minimum of 3 days prior to the defined increase in serum creatinine concentration [14]. Sepsis was considered to be present when two or more of the following were present as a result of systemic infection: (i) temperature >38°C or <36°C; (ii) heart rate >90/min; (iii) respiratory rate >20/min or pCO2 <32 mm, and (iv) white blood count >12000/mm3, <4000/mm3 or >10% band forms [17]. Surgery was assumed to be responsible for ARF where serum creatinine concentration showed a significant increase within 72 h of surgery. Radiographic contrast agents were considered to be the cause of renal failure when serum creatinine rose within 72 h following a radiological procedure employing such agents [14]. Decreased renal perfusion or hypoperfusion was identified as a causative factor if there was overt/orthostatic hypotension, loss of skin turgor with decrease of more than 5% of body weight or clinically apparent congestive cardiac failure [16]. Hypotension was defined as systolic BP less than 80 mmHg. Those patients in whom the renal function improved with correction of haemodynamic factors were not included.
Statistical analysis
The pathogenetic factors causing ARF in different combinations were analysed. To study whether these pathogenetic factors were able to predict the cause of ARF, a hierarchical log linear model for the analysis of categorical data to explain the potentially complex relationships amongst various pathogenetic factors in a multiway cross tabulation was employed [18]. A number of variables including age, hypotension, sepsis, presence and duration of oliguria, need for dialysis, and surgery were compared in survivors and non-survivors. The predictive ability of these variables was examined using a logistic regression model by multivariate analysis using the SPSS version 6 computer software. All the values were expressed as mean±2 SD and P values of less than 0.05 were considered significant.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Sepsis was responsible in 27 patients (45.7%). Cultures yielded positive growth of bacteria in 15 and fungal organisms in two patients. Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were the common bacterial organisms and Candida and Aspergillus were the fungi most often isolated. Foci of infection were intravenous line in 13, lungs in seven, urinary tract in six, and bedsores in three patients. Sepsis alone contributed to ARF in three patients.
Hypoperfusion was the cause of ARF in 27 (45.7%) patients. Hypoperfusion resulted from hypotension due to volume contraction in 16 (27%) and cardiac dysfunction including cardiac arrhythmias and congestive cardiac failure in six (10.2%). Septic shock in five patients (8.5%) was the cause of hypoperfusion. Volume contraction was due to diuretics in two patients. Hypoperfusion alone contributed to ARF in five patients.
Surgery could be implicated as cause of ARF in 15 (25.4%). In the majority of these, ARF occurred following abdominal surgery (10), followed by cardiac surgery (three), neurosurgery (one) and vascular surgery (one). Post-operative ARF occurred only in presence of other pathogenetic factors such as nephrotoxic drugs (13), sepsis (nine) and hypoperfusion (five).
Contrast agents accounted for renal failure in 10 patients (16.9%). These agents were administered during contrast enhanced computerized tomographic scans in five, cardiac catheterization in three and during endoscopic retrograde cholecystopancreatography (ERCP) in two patients. Contrast alone contributed to ARF in two patients.
The above pathogenetic factors were responsible for ARF in different combinations. A total of 31 such combinations were seen. Frequently seen combinations are shown in Table 2. On applying the hierarchical log linear model, radiocontrast administration (partial
2 28.1, P<0.0001), surgery (partial
2 14.89, P=0.001), nephrotoxic drugs (partial
2 6.22, P=0.0126) on their own and the combination of radiocontrast, surgery, and sepsis (partial
24.08, P=0.0434) achieved statistical significance in predicting ARF.
|
Overall mortality in all elderly hospitalized patients was 12.7%, while in the elderly with ARF it was 25.4% (Table 1). Comparison of survivors and non-survivors is shown in Table 3
. Sepsis, oliguria and hypotension were independent predictors of poor patient outcome on multivariate analysis by logistic regression analysis (Table 3
). There was no significant difference in the effect of underlying original disease on the mortality. In the surgical group, four of 16 died, and in those with cardiac illness three of 12 died. In the infectious and miscellaneous four of the eight patients died in each group (
2 1.33, P=0.249). Of 44 patients who survived, 38 (86.3%) recovered renal functions completely, while 6 (13.6%) had deranged renal functions at the time of discharge.
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In a hospitalized patient, despite a wide variation in spectrum of disease in which ARF can occur, only a limited number of pathophysiological factors such as reduced renal perfusion, sepsis, surgery, nephrotoxic drugs, and radiocontrast agents are operative in the majority of the patients [1416]. The above pathogenetic factors generally seldom operate in isolation in this setting. Combinations of different factors are present in individual patients. In the studies carried out so far, a single factor has been incriminated arbitrarily as the cause of ARF despite the presence of other factors. This, we feel is not correct as it is extremely difficult to blame a single factor as a sole cause of ARF. In this study, in addition to individual factors, we also studied the combination of different causative pathogenetic factors and their predictive values. Drugs along with sepsis, hypoperfusion, or surgery were the common pathogenetic combinations observed. Amongst different combinations, radiocontrast administration (partial 2 28.1), surgery (partial
2 14.89), and nephrotoxic drugs (partial
2 6.22) on their own were statistically significant in predicting the ARF.
Radio contrast administration contributed to ARF in 17% of patients in the elderly in the present study as compared to 4% in the young [14]. In a prospective study in which elderly patients were subjected to cardiac catheterization, 10.5% developed ARF [10]. Though contrast-induced renal insufficiency is moderate and reversible, it increases the morbidity significantly. Drugs contributed to renal failure in 66% of patients in this study as compared to 39% in younger individuals [14]. Aminoglycoside antibiotics were the most frequent offending agents. This is quite expected as the erroneous estimation of glomerular filtration rate in the elderly based on serum creatinine concentration leads to inappropriate dosing with resultant renal toxicity. [20,21]. Haemodynamically mediated ARF is common in the elderly due to NSAIDs and ACE inhibitors [22,23]. In a prospective study, a significant rise of blood urea nitrogen and serum creatinine was seen in 13% of elderly patients receiving NSAIDs [11]. The syndrome of haemodynamic ARF caused by ACE inhibitors occurs in around 2.3% of all causes of drug induced ARF in elderly [23]. Bridoux et al. [24] found a high incidence of ARF caused by ACE inhibitors in older patients without renal artery stenosis.
Surgery was another independent predictor of ARF. Hypotension during and after surgery, postoperative fluid loss, cardiac arrhythmias, postoperative infections and the drugs used to treat these can be detrimental to renal function, with resultant higher incidence of ARF [21]. The incidence of postoperative ARF in the present study was similar to that in a previous study from this centre where predominantly younger patients were included (25.4 vs 24%). Acute tubular necrosis after elective or emergency surgery for abdominal aortic aneurysm is particularly frequent in aged people and is a common cause of ARF. At this centre, the number of vascular surgeries carried out is very small, this could account for the relatively lower incidence of postoperative ARF in this study.
Sepsis and hypoperfusion are two other important causative factors for ARF in the elderly. Infections particularly Gram-negative septicaemia accounted for 30% of ARF in the elderly in one study [7]. Hypovolaemia has been reported to cause ARF in 5060% of patients admitted in a geriatric unit [12]. In the present study sepsis and hypovolaemia contributed to renal failure in 45.7% of elderly patients each, as compared to 27% in young patients in a previous study [14]. However, if we look at different pathogenetic combinations, these two factors were not predictive of ARF on their own. Reduced renal water conserving capacity and thirst leads to dehydration and renal failure. Diminished renal perfusion has been thought to be a major cause of ARF in elderly [25]. However, in a hospitalized elderly patient where a number of pathogenetic factors are operating, our study suggests that factors other than hypoperfusion are more important.
Mortality in the elderly with ARF varies considerably in different series. It also depends on how aggressively they are subjected to interventions and high-risk surgeries [26]. It is as high as 63% where patients admitted to intensive care unit (ICU) alone have been studied [13]. Renal failure as a part of multiorgan failure has a grave prognosis. In the present study, the mortality in the elderly with ARF was twice the mortality of the elderly in-patients without ARF (25.4 vs 12.5%, P=0.03). Thus renal failure not only adds to the morbidity but also significantly increases mortality. In the elderly with ARF of various aetiologies admitted to ICUs, failure of more than two organs, high blood lactate, high catabolic rate associated with sepsis [13], coma, and the need for assisted ventilation [19] have been found to be markers of a poor prognosis. In developing countries with meagre resources, younger patients requiring ICU admissions are preferred over the elderly with similar comorbid conditions. Pascual et al. from Spain in their study of very old (>80 years) patients reported a low rate of ICU admissions in this age group. They have postulated that younger age could be criteria for preselection of patients for admissions to the ICU [27]. Hence, to evaluate accurately the prognosis and the prognostic factors it is necessary to include broader areas than ICU setting alone. Poor prognostic factors in a non-ICU setting include need for dialysis, oliguria, sepsis, shock [28], and hypoalbuminaemia [12]. In the present study, patients admitted all over the hospital have been studied, and on logistic regression analysis the independent predictors of poor patient outcome were sepsis, hypotension, and oliguria. The problem of sepsis and renal failure is a great challenge to the nephrologist. Endotoxins directly sensitize the renal tubular tissue to the effect of ischaemia even in the absence of detectable haemodynamic changes. Moreover, endotoxaemia also impairs tubular regeneration. [29] This phenomenon is much more marked in the elderly due to age-related changes in the kidneys. Ongoing sepsis results in multiorgan failure, which carries a grave prognosis.
To conclude, incidence of treatment-related ARF in the elderly is 14%, with more than one pathogenetic factor playing a role in the development of ARF in the majority. Sepsis, hypotension, and oliguria are the independent predictors of poor patient outcome. ARF in hospitalized elderly patients increases the mortality significantly. Precautions should be taken to minimize the development of ARF in this group of patients.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|