Risk Factors for Hospital Death of Patients with End-Stage Renal Disease Without Previous Diagnosis of Severe Chronic Renal Failure Arriving in an Emergency Situation at the Hospital

Abstract

Objectives. Many end stage renal disease (ESRD) patients get their first nephrologic care under critical clinical conditions and without previous diagnosis of chronic renal failure (CRF), a situation even worse than the late referral of CRF patients for nephrologic treatment. Data on these “nonreferred” patients are scarce. The objectives of this study were to assess clinical and laboratory features, the reasons for coming to the hospital and the factors associated with death in nonreferred ESRD patients first seen by a nephrologist in an emergency situation. Methods. Retrospective study (04 1996–03 2000) using the medical records of patients diagnosed with ESRD at the nephrologic emergency visit in a university tertiary hospital. Clinical and laboratory parameters were reviewed. Patients were divided into two groups according to hospital outcome: survivors or nonsurvivors. Results. There were 414 patients (12% of all nephrologic emergency visits), aged 49 ± 17 years, 266 males (64%) and 208 (55%) hypertensive. Mortality rate was 13.7% (54/393). When compared to survivors, nonsurvivors were older, used mechanical ventilation and vasoactive drugs more frequently, presented higher infection rate, and showed lower plasma creatinine. Multivariate logistic regression showed as factors independently associated with death: first nephrologic visit at intensive care unit, infection as cause for seeking medical care, and increasing age. Plasma creatinine above 10 mg/dL was a protective factor for death. Conclusions. ESRD patients reaching dialysis in a nephrologic emergency situation presented high hospital mortality, which was mostly associated with their poor clinical condition at admission.

• Dialysis
• End stage renal disease
• Late referral
• Mortality rate
• Multivariate logistic regression
• Retrospective study

Introduction

Late referral to the nephrologist has been shown to be an important factor for early death in chronic dialysis.[[1]], [[2]], [[3]] In Brazil, Sesso and Belasco analyzing 205 chronic renal failure (CRF) patients found that 52% had the diagnosis of end stage renal disease (ESRD) made less than one month before starting dialysis.[[4]] Among these patients the survival rate in the first six months of dialysis was lower than in patients with earlier diagnosis: 69% vs. 87%. In addition, the Brazilian Register of Dialysis showed that over 25% of all patients admitted in 1997 in 86 dialysis centers in Brazil had had no predialysis nephrologic care (Brazilian Society of Nephrology Bulletin).

Many ESRD patients have their first nephrologic care under critical clinical conditions and without previous diagnosis of CRF, a situation even more inadequate than the late nephrologic referral, which could be called “nonreferral”. Although data about these patients are scarce, this condition seems to be relatively frequent.[[1]], [[5]], [[6]] The objectives of the present study were to assess clinical and laboratory features, the reasons for seeking hospital care, the mortality rate, and factors associated with death in these nonreferred ESRD patients.

Subjects and Methods

From April 1996 to March 2000 the Acute Renal Failure Unit (Acute Renal Failure Unit attends all intrahospital nephrologic consultations except for renal biopsies) performed 3,456 nephrologic visits at Hospital das Clínicas, a tertiary university hospital with 2,700 beds. This population included 414 ESRD patients (12% of the total visits), who did not have the diagnosis of CRF made before hospital admission and had not been previously referred to nephrologic care. ESRD was defined on clinical basis (chronic complains compatible with uremia: sickness, loss of appetite, weakness, nycturia, progressive decrease in insulin need for diabetic patients, etc.) and mandatory finding of a plasma creatinine value ≥3.0 mg/dL. Some of the patients mentioned having “renal problems” already for a long time and/or they brought previous laboratory tests showing abnormal urinalysis or plasma creatinine. However all of them informed that they had not been seen by a nephrologist before. ESRD was confirmed by renal ultrasonography in 192 cases. In cases of patients informing to have diabetes but with no diabetic retinopathy, the cause of ESRD was considered other than diabetic nephropathy.

These 414 patients were studied using information from the specific Acute Renal Failure Unit medical records. The following parameters were analyzed: 1. Age; 2. Gender; 3. Hospital division where patients were at the time of the first Acute Renal Failure Unit visit: Emergency Room, Intensive Care Unit (ICU) or ward; 4. Reason for hospital admission: infection, hypervolemia, neurological event, coronary event, hypertension, uremia, or others; 5. Probable cause of renal disease: glomerulonephritis, diabetes mellitus, hypertension, malignant hypertension, obstructive nephropathy, systemic lupus erythematous or others; 6. Report of previous diseases: diabetes mellitus, hypertension, cancer, acquired immunodeficiency syndrome (AIDS), or positive test for HIV (AIDS/HIV), liver disease or others. The use of vasoactive drugs, mechanical ventilation, need for dialysis, and number of dialysis performed during hospitalization were also analyzed. The number of hospitalization days until death or hospital discharge was recorded. Laboratory parameters at the first Acute Renal Failure Unit visit were reviewed: blood urea, plasma creatinine, plasma sodium, plasma potassium, blood pH and bicarbonate, and hemoglobin. Patients were divided into two groups according to their outcome: death (nonsurvivors) or hospital discharge (survivors). At hospital discharge, all survivors were referred to maintenance dialysis outside Hospital das Clínicas. Outcome was recorded for 393 patients and these patients were used for the mortality study.

This study was approved by the Ethics Committee of Hospital das Clínicas.

Statistical Analysis

A BMDP package software was used (version PC-90). For comparison between the two groups Student's “t” test or Mann-Whitney test were used for continuos variables, and Chi square test with Yates correction or Fischer's exact test were used for categorical variables. Multivariate logistic regression was performed with those variables significant at univariate analysis and those considered clinically important. The tested model included: age (continuous, estimated for each increase in 10 years of age), gender (reference: male), patient at ICU in the first Acute Renal Failure Unit visit (reference: no ICU), cause of hospital admission (reference: no infection nor cardiovascular events), number of dialysis (reference: no dialysis), plasma creatinine at first Acute Renal Failure Unit visit (reference: ≤10 mg/dL) and previous knowledge of having hypertension or diabetes (reference: absence, for both variables). The P-value <0.05 was considered significant. Data are presented as mean ± SD or percentage.

Results

There were 266 men (64%), age was 49 ± 17 years (11 to 95 years) and mortality rate was 13.7% (54 patients out of 393). At first Acute Renal Failure Unit visit 294 patients (71%) were in the emergency room, 81 in the ward (20%) and 39 (9%) in the ICU. Patients were followed for 13 ± 15 days (median 8, range 1–88 days). Previous diseases were reported by 377 (91%) patients: 208 (55%) had hypertension, 71 (19%) diabetes, 15 (4%) cancer, 6 (2%) AIDS/HIV, 6 (2%) liver disease, and 71 (19%) other diseases. The main cause for hospital admission was uremia in 150 patients (36.7%), hypervolemia in 90 (22%), hypertension in 35 (8.6%), infection in 26 patients (6.4%), coronary event in 24 (5.9%), neurologic event in 8 (2.0%), and other causes in 76 (18.5%). Probable cause of the renal disease was hypertension in 103 patients (33.4%), diabetes in 70 (22.7%), glomerulonephritis in 47 (15.3%), obstructive nephropathy in 41 (13.3%), systemic lupus erythematous in 8 (2.6%) and other causes in 39 (12.7%). Mechanical ventilation was used by 39 patients (10%) and vasoactive drugs by 38 (9%). Dialysis was performed in 293 patients (71%), with a mean number of dialysis per patient of 3.9 ± 4.1 (median 2, range 1–26). Among the 111 patients without dialysis, 10 (9%) died in hospital and the other 101 were rapidly transferred to Dialysis Units outside Hospital das Clínicas to start chronic dialysis treatment as outpatients. Patients without dialysis were in better clinical condition than those who needed dialysis in the hospital as they had lower values of urea, plasma creatinine, plasma potassium, and higher value of hemoglobin than those who needed dialysis. (Data not shown).

At first Acute Renal Failure Unit visit, blood urea was 253 ± 88 mg/dL (72–600 mg/dL), plasma creatinine was 13.1 ± 6.9 mg/dL (2.7–39 mg/dL), plasma sodium 137 ± 6 mEq/L (105–188 mEq/L), plasma potassium 5.3 ± 1.2 mEq/L (2.8–9.2 mEq/L), blood pH 7.27 ± 0.11 (6.74–7.53), blood bicarbonate 15.3 ± 5.4 mEq/L × (2.1–37.6 mEq/L) and hemoglobin 8.6 ± 2.1 g/dL (3.0–15.7 g/dL).

Comparisons between the two groups showed that nonsurvivors were older, were more frequently seen at first Acute Renal Failure Unit visit in the ICU, used more frequently mechanical ventilation and vasoactive drugs. Although the need for dialysis was similar in both groups, the number of performed dialysis was higher among nonsurvivors (see Table 1). Diabetes mellitus prevalence was similar in both groups (13.5% among nonsurvivors and 19.5% among survivors). The most usual reason for seeking medical care was uremia in both groups (26% among nonsurvivors and 39% among survivors). Nonsurvivors presented higher infection rate as reason for seeking medical care than survivors (14.8% vs. 4.8%, P-value = 0.001). The cause of ESRD was similar in the two groups. The most frequent cause of the renal disease in both groups was hypertension: 30.3% among nonsurvivors and 33.1% among survivors, followed by diabetes: 18.2% and 23.1% respectively.

Table 1. General characteristics of survivors and nonsurvivors

	Nonsurvivors (n = 54)	Survivors (n = 339)	P-value
Age (years)	58±17 (n = 53)	48±17 (n = 335)	<0.001
Gender (% of male)	59% (n = 54)	66% (n = 339)	0.410
ICU (%)	24% (n = 54)	7% (n = 339)	<0.001
Mechanical ventilation (%)	64% (n = 50)	2% (n = 338)	<0.001
Vasoactive drugs (%)	53% (n = 51)	3% (n = 337)	<0.001
Need for dialysis (%)	81% (n = 53)	70% (n = 338)	0.136
Number of dialysisa	6±6 (n = 39)	4±4 (n = 234)	0.008
Hospitalization time (days)	18±20 (n = 54)	13±14 (n = 337)	0.317

ICU: Intensive care unit.

^aOnly for those that needed it.

Laboratory results are presented in Table 2. Nonsurvivors showed lower values of plasma creatinine (9.8 ± 4.6 mg/dL vs. 13.6 ± 7.2 mg/dL, P-value <0.001). All other results were similar in both groups.

Table 2. Laboratory parameters of survivors and nonsurvivors at first nephrologist visit in the hospital

	Nonsurvivors (n = 54)	Survivors (n = 339)	P-value
Blood urea (mg/dL)	230±72 (n = 53)	256±92 (n = 338)	0.095
Plasma creatinine (mg/dL)	9.8±4.6 (n = 53)	13.6±7.2 (n = 337)	<0.001
Blood pH	7.27±0.13 (n = 46)	7.27±0.11 (n = 268)	0.678
Blood bicarbonate (mEq/L)	14.6±5.2 (n = 46)	15.4±5.5 (n = 274)	0.392
Plasma sodium (mEq/L)	137±7 (n = 53)	137±6 (n = 326)	0.452
Plasma potassium (mEq/L)	5.3±1.4 (n = 53)	5.4±1.2 (n = 332)	0.401
Hemoglobin (g/dL)	8.6±2.0 (n = 50)	8.5±2.1 (n = 322)	0.912

The final logistic regression model showed that the factors independently associated with death were: first Acute Renal Failure Unit visit in the ICU (OR: 3.0, 95% CI 1.3–7.2, P-value = 0.011), more than three dialysis sessions (OR: 3.9, 95% CI 1.5–9.8, P-value = 0.004), infection as cause for seeking medical care (OR: 3.2, 95% CI 1.1–9.9, P-value = 0.038) and each 10-year increase in age (OR: 1.3, 95% CI 1.1–1.6, P-value = 0.014). Plasma creatinine above 10 mg/dL was a protective factor for death (OR: 0.31, 95% CI 0.15–0.67, P-value = 0.002).

Discussion

It is well known that pre-dialysis nephrologic care is a critical issue for patients with CRF.[[7]] However, patients with ESRD may require emergency nephrologic care even without a previous CRF diagnosis. These nonreferred ESRD patients are part of a population that is seldom described, and in the present study constituted 12% of all emergency nephrologic visits carried out by an Acute Renal Failure Unit in a large university hospital. This group of patients arrived at the hospital in poor clinical condition, uremic and hypervolemic. The critical condition of these patients explains why 71% of them were first seen by the nephrologist in the Emergency Room, and the large number of emergency rescue dialysis required. The data of our nonreferred patients are similar to those reported in series analyzing late referral to dialysis.[[4]] Mortality rate was high (13.7%) but similar to that reported by Ratcliffe et al. among patients referred from 1 day to 3 weeks before starting dialysis.[[1]]

Most of the studies analyzing mortality in dialysis excluded deaths occurring in the first 90 days of treatment, which may have flawed their results.[[8]] In fact, Soucie and McClellan studying specifically this period showed that this exclusion makes 1-year mortality to be underestimated.[[9]] Even the authors who assessed mortality in the first 90 days of dialysis program did not consider patients like our nonsurvivor group.[[2]], [[10]] The fact that patients who died before starting regular dialysis are not included in usual dialysis mortality estimations may result in even higher underestimation of first year mortality of ESRD patients in dialysis. Reinforcing this possibility, a data analysis of death certificate by Sesso et al. found that 26% of end stage renal disease individuals died without receiving maintenance dialysis.[[11]]

To our knowledge, the important issue of risk factors for death in nonreferred ESRD patients has not been specifically assessed. In the present study risk factors for death were increasing age, first nephrologic visit occurring in the ICU, presence of infection and need for more than three dialyses. Plasma creatinine higher than 10 mg/dL was a protective factor for death.

Our nonreferred patients were about 50 years old, an age similar to that reported for late referred patients in Brazil,[[5]] France,[[2]] and USA.[[12]] Age has been reported as a prognostic factor for early death in maintenance dialysis.[[10]] Sesso et al. showed that from 40 years of age on, the proportion of ESRD individuals who died without maintenance dialysis increases substantially. The chance of ESRD individuals older than 60 years of age not reaching maintenance dialysis is 12.4 times higher than individuals from 20 to 29 years of age.[[11]] Our data showed an increase of 30% in the risk for death per 10 years of age increment.

Being an ICU patient and the need of more than three dialyses were risk factors for death. The need for ICU admission is likely a consequence of the patients' critical condition. It is well known that acute renal failure patients in the ICU have very high mortality.[[13]] A recent study showed that ICU mortality for patients with ESRD on regular dialysis was intermediate (11%) between those with acute renal failure (23%) and those without renal failure (5%) at ICU admission.[[14]] However, these ESRD patients cannot be compared to those described in the present study, since they already were on regular dialysis treatment before ICU admission. To our knowledge no studies on the impact of late or nonnephrologic referral on ICU mortality of ESRD patients have been performed.

The prevalence of infection is higher among ESRD patients than in the general population and is considered to reflect diminished immunity and malnutrition.[[15]], [[16]] Sesso and Belasco, analyzing the role of chronic renal insufficiency late diagnosis on dialysis mortality showed that age, presence of pulmonary infection, and low serum albumin at start of dialysis were predictors of early death.[[4]] Anemia has also been associated with increased infection mortality, and almost all of our patients had severe anemia.[[17]] In maintenance dialysis, the early death caused by infection is commonly associated with temporary vascular access.[[3]] However, in our patients the presence of infection, even previously to dialysis catheter insertion, was a strong risk factor for death.

As in the present study, other authors have also reported that high values of plasma creatinine are protective against death in chronic dialysis.[[18]] de Lima et al. showed that patients dying within the first three months of dialysis had lower initial plasma creatinine than those who survived over 10 years.[[19]] Clermont et al. analyzing the ICU mortality of ESRD patients on regular dialysis showed that nonsurvivors tended to have lower plasma creatinine and peak creatinine values than survivors at the ICU admission (although not statistically significant).[[14]] Plasma creatinine levels have shown positive association with plasma albumin and so a low plasma creatinine suggests malnutrition.[[18]] Malnutrition can be due to spontaneous dietary protein intake decrease that occurs with the progression of chronic renal insufficiency.[[20]] Considering that our ESRD patients were not receiving appropriate medical care, the consequences of this natural decrease in protein intake were probably worse and not compensated for.

Despite the high prevalence of baseline disease related to renal injury (55% of hypertension and 19% of diabetes) almost all of the patients described in the present study did not even have ESRD diagnoses suspected. Late-referral of diabetic patients to a nephrologist is also a problem in Europe. Chantrel et al. found that more than 80% of the patients with type 2 diabetes enter maintenance dialysis under emergency conditions.[[6]] In addition, Lameire and Van Biesen reported that as much as 30% of physicians late-referring their ESRD patients were endocrinologists.[[5]] This observation shows that even endocrinologists may not be aware of the importance of pre-dialysis nephrologic care.

The lack of a prior referral to a nephrologist denied these patients the benefit of appropriate conservative treatment and to choose the modality of treatment, i.e., type of dialysis.[[21]] Losing this opportunity meant increased mortality and morbidity, that might have been prevented, and, for the Health System, important financial costs due to emergency hospitalization and dialysis, and need of ICU. Our findings reinforce the suggestion that a “think renal insufficiency” effort must be done towards internists and clinical specialists, so timely nephrologic care is more often provided to chronic renal patients. Improved information and timely nephrologic care of chronic renal insufficiency patients may avoid that these patients reach the nephrologist with infection and probably malnutrition, and requiring ICU and emergency dialysis, risk factors for death identified in the present study.