Earlier nephrology consultation may not be associated with improved short-term survival of acute kidney injury in very elderly men
Clinical Interventions in Aging
earlier nephrology consultation may not be associated with improved short-term survival of acute kidney injury in very elderly men
Qinglin li 1
Meng Zhao 0
Jing Du 1
Xiaodan Wang 1
0 Department of Clinical Data repository , Chinese People's liberation Army general hospital, Beijing , China
1 Department of geriatric n ephrology
PowerdbyTCPDF(ww.tcpdf.org) Objectives: A delayed nephrology consultation (NC) may be associated with a poor prognosis in acute kidney injury (AKI) patients. The aims of this study were to compare the clinical and laboratory characteristics of elderly AKI patients evaluated and not evaluated by nephrologists and to generate a hypothesis regarding the relationship between the timing of the NC and 90-day outcomes. Methods: From 2007 to 2015, this study explored associations among the presence and timing of NC with the non-intensive care unit stay and 90-day mortality in elderly AKI patients at the Geriatric Department of the Chinese People's Liberation Army General Hospital. Early NC and delayed NC were defined as NCs performed before and 2 days after the day of AKI diagnosis, respectively. Multivariable logistic regression was used to adjust for confounding and selection bias. Results: In total, 623 patients were included for the final analysis, of whom 162 (26%) were evaluated by nephrologists. The 90-day mortality rate was 33.2%, and dialysis was required in 1.4% of patients (9/623). Multivariable analysis showed that a higher prevalence of preexisting chronic obstructive pulmonary disease, AKI diagnosis time, peak serum creatinine level, blood urea nitrogen level, AKI stage, and mortality was associated with the NC. The NC was delayed (.48 h) in 59 patients (36.4%) (median time to consultation, 4 days). The median AKI diagnosis time, presence of oliguria, uric acid level, and a more severe AKI stage were associated with delayed consultation. Moreover, delayed consultation presented a similar 90-day mortality rate to that of an early NC (50.8% vs 44.7%, respectively, P=0.448). Conclusion: In very elderly AKI patients, those evaluated by nephrologists have more severe AKI and a higher mortality rate than those not evaluated by nephrologists. An earlier NC may not be associated with improved 90-day survival.
phenomenon is that the SCr level alone is a relatively late
and imprecise biomarker of kidney dysfunction, which may
also lead to a delayed diagnosis, especially in the elderly
Clinical studies have shown that a timely nephrology
consultation (NC) could potentially have many benefits such
as allowing earlier identification and modification of AKI
patients’ outcomes. For example, Mehta et al concluded
that a delayed NC was associated with increased mortality
among dialyzed and nondialyzed patients in the intensive
care unit (ICU).12 Recent studies have also indicated that an
early NC may improve hospital-acquired AKI prognosis,12–16
although few studies have examined the effect of an early
NC on outcomes in very elderly patients ($75 years) or
diagnosing AKI using KDIGO criteria.
The aims of this study were to compare the clinical and
laboratory characteristics of elderly AKI patients
evaluated and not evaluated by nephrologists and to generate a
.rvdoepww ll.syeuon ahnydpo9t0h-edsaisyoofutthceomreelast.ionship between the timing of the NC
tt:/sphw rsopea Study population and methods
from roF This was a retrospective cohort study. All elderly patients
ed ($75 years) who were admitted to the Geriatric Department
lado of the Chinese People’s Liberation Army (PLA) General
onw Hospital between January 2007 and December 2015 were
gnd evaluated for AKI during their hospital stay. The study
igA design was approved by the Clinical Ethics Committee of the
isn Chinese PLA General Hospital, and each participant provided
itonn written informed consent. All AKI patients were followed
ltIrveen up fCorli9n0icdalaydsaataftewreAreKnIodtieadg,n oinsicsluodriunngtitlhdeeadtehm.ographic
(phroisftiolery(aogfeh,ygpenerdteern,sainodn,bcoodryonmaarsysdinisdeeaxs)ea,nchdrcoonmicoorbbisdtrituicestive pulmonary disease [COPD], and diabetes mellitus), time
of AKI diagnosis, etiology of AKI (induced by infection,
hypovolemia, cardiovascular events, nephrotoxic drugs,
surgery, or uncertain causes), need for dialysis, need for
mechanical ventilation (MV), urine output, and mean aortic
pressure. Other laboratory data evaluated included baseline
levels of SCr, SCr at AKI diagnosis, peak SCr, blood urea
nitrogen (BUN), uric acid, serum prealbumin, albumin,
kalemia, serum calcium, serum magnesium, serum
phosphate, and hemoglobin.
AKI was diagnosed exclusively based on SCr levels,
that is, an SCr increase $0.3 mg/dL ($26.5 µmol/L)
within 48 h, or an increase to $1.5-fold above the baseline
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value within the prior 7 days.1 The KDIGO criteria were
used. AKI severity was scored according to the difference
between the SCr baseline and peak values, using the KDIGO
staging criteria: stage 1, an increase $26.5 µmol/L, or an
increase $1.5- to 1.9-fold above the baseline value; stage 2,
an increase to $2- to 2.9-fold above the baseline value; and
stage 3, an increase to $3-fold above the baseline value, an
increase to $353.6 µmol/L, or initiation of renal replacement
therapy. Urine output was not available in the cohort, and the
KDIGO urine output criteria could not be applied.
The baseline SCr level was the most recent stable measure
obtained 3 months prior to hospital admission for AKI.5 The
peak SCr was the highest SCr level reached in the episode.
Estimated glomerular filtration rates (eGFRs) were calculated
by the Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) method.17 Oliguria was defined as urinary
output ,400 mL/24 h.
The exclusion criteria were age ,75 years, patients with a
history of CKD of any stage,18 hospital stay of ,48 h, those who
had no SCr or only one SCr examination, those with missing or
incomplete medical history, and those with early death in ,48 h
after admission. Females were also excluded, because fewer
females were treated than males during the study period.
All elderly AKI patients were divided into two groups:
those evaluated and not evaluated by nephrologists.
Thereafter, AKI patients evaluated by nephrologists were further
divided into two subgroups (early and delayed consultation)
based on the time to consultation from the day of laboratory
diagnosis of AKI. An early NC was defined as #48 h and a
delayed NC was defined as .48 h.
The primary outcome was 90-day mortality. Clinical and
laboratory characteristics were also recorded.
Continuous variables are presented as the mean ± standard
deviations, or medians (25%–75% interquartile range),
depending on the variable distribution. Discrete variables
are presented as counts or percentages. Between-group
comparisons were performed using Student’s t-test or the
Mann–Whitney U-test. Correlations between potential factors
were assessed using Pearson’s chi-squared or Fisher’s exact
test. Multivariable logistic regression models were
constructed with forward variable selection, with the exit criterion
set at P,0.25. A P-value ,0.05 was considered to reflect
statistical significance. Statistical analyses were performed
using Statistical Package for the Social Sciences (SPSS)
Version 17.0 for Windows (SPSS Inc., Chicago, IL, USA).
Among 1,711 study patients, 668 (39%) developed AKI.
Only 45 patients were excluded, resulting in 623 AKI patients
suitable for analysis. The study flowchart is presented in
Figure 1. The median age of the cohort was 87 years. The
median baseline SCr level was 74 µmol/L, and baseline
eGFR was 78.4 mL/min/1.73 m2. Using the KDIGO criteria,
294 patients (47.2%) had stage 1 AKI, 157 (25.2%) had stage 2
AKI, and 172 (27.6%) had stage 3 AKI. Of the 623 patients,
78.2% had coronary disease, 73.8% had hypertension, 70.3%
had COPD, and 35.8% had diabetes mellitus. An NC was
performed in 26% (162/623) of AKI patients and occurred
) days after the day of AKI diagnosis. Most patients
referred to nephrologists were subjected to an early NC
(63.6%). The overall 90-day mortality was 33.2% (207/623),
and dialysis was required in only 1.4% (9/623) of patients.
As shown in Table 1, NC patients were older (median age:
88 vs 87 years, P=0.115), and the majority of these patients
had COPD (79% vs 67.2%, P=0.005). Of the 162 (26%)
patients referred to nephrologists, AKI diagnosis occurred
after 2 days (1–5 days), compared to 4 days (2–7 days) for
patients not evaluated by nephrologists (P=0.001). The
median SCr level (70 vs 75 µmol/L, P=0.010) and eGFR
(80.1 vs 78 mL/min/1.73 m2, P=0.032) at baseline were
significantly different between the two groups.
As shown in Table 1, patients evaluated by nephrologists
presented higher mortality rate (46.9% vs 28.4%, P,0.001),
with more patients in KDIGO stage 3, and fewer patients
in stage 1 (51.9% vs 19.1%, 22.8% vs 55.7%; P,0.001).
Oliguria (9.9% vs 4.1%, P=0.006), dialysis (5.6% vs 0%,
P,0.001), requiring MV (51.9% vs 31.9%, P,0.001),
anemia (109±23 vs 113±22 g/L, P=0.013), a lower
prealbumin level (168 vs 186 g/L, P=0.011), and hypoalbuminemia
(33±5.2 vs 34.8±5.5 g/L, P=0.001) were more frequent
among patients referred to nephrologists. NC patients had
significantly higher uric acid (399.2 vs 360 µmol/L, P=0.005),
kalemia (4.3 vs 4.1 mmol/L, P=0.035), and phosphate levels
(1.3 vs 1.2 mmol/L, P=0.031). As expected, patients
evaluated by nephrologists had higher SCr, BUN, and peak SCr
levels at the time of AKI diagnosis (all P,0.001), and the
presence or absence of an NC was associated with 90-day
mortality (Figure 2).
Multivariate logistic regression analysis revealed that an
NC was significantly associated with a higher prevalence of
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Notes: Values are n (%), mean ± sD or median (interquartile range). 1 mmhg =0.133 kPa.
Abbreviations: AKI, acute kidney injury; nC, nephrology consultation; BMI, body mass index; COPD, chronic obstructive pulmonary disease; sCr, serum creatinine; egFr,
estimated glomerular filtration rate; MAP, mean aortic pressure (1 mmHg =0.133 kPa); MV, mechanical ventilation; BUn, blood urea nitrogen; sD, standard deviation.
preexisting COPD (odds ratio [OR] =1.794; 95% confidence
interval [CI]: 1.118–2.879; P=0.015), AKI diagnosis time
(OR =0.888; 95% CI: 0.812–0.972; P=0.010), peak SCr
level (OR =1.006; 95% CI: 1.003–1.008; P,0.001), BUN
level (OR =1.022; 95% CI: 1.002–1.043; P=0.033), AKI stage
(OR =1.472; 95% CI: 1.021–2.122; P=0.038), and mortality
(OR =0.531; 95% CI: 0.303–0.931; P=0.027) (Table 2).
nC timing – factors associated with
a delayed nC
Several baseline differences were noted between the early
and delayed consultation groups (Table 3). Of the 59 (35.6%)
patients with delayed consultation, AKI diagnosis occurred
after 2 days (2–7 days), while the median time to
consultation was 4 days (3–8 days). Delayed NC patients were more
likely to be older (median age: 89 vs 88 years, P=0.207) and
to have a lower median eGFR (78.6 vs 81.4 mL/min/1.73 m2,
P=0.233) than the early NC group. They had higher peak SCr
(227 vs 183 µmol/L, P=0.180), lower uric acid (361.7 vs
419 µmol/L, P=0.004), lower kalemia (4.1 vs 4.4 mmol/L,
P=0.140), and lower phosphate (1.2 vs 1.3 mmol/L, P=0.031)
levels at the time of AKI diagnosis. Accordingly, the
prevalence of oliguria was significantly lower in the delayed NC
group (1.7% vs 14.6%, P=0.008).
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Multivariate logistic regression analysis revealed that a
delayed NC was significantly associated with AKI diagnosis
time (OR =1.269; 95% CI: 1.078–1.495; P=0.004), oliguria
(OR =0.116; 95% CI: 0.014–0.952; P=0.045), uric acid
level (OR =0.996; 95% CI: 0.994–0.999; P=0.009), and a
more severe AKI stage (OR =3.365; 95% CI: 1.297–8.733;
P=0.013) (Table 4).
Influence of a delayed NC on patient
As shown in Table 3, more patients were classified as
KDIGO stage 3 and fewer patients were classified as stage 1
and stage 2 (57.6% vs 48.5%, 18.6% vs 25.2%, 23.7%
vs 26.2%; P=0.238). Dialysis was necessary in 5.1% of
the delayed group, compared to 5.8% of the early group
(P=1.000). Surprisingly, delayed consultation was not
associated with increased mortality (50.8% vs 44.7%, P=0.448)
It is widely recognized that the timing of an NC is
associated with AKI patient outcomes. However, few studies
have specifically examined this important topic with regard
to the very elderly population. This analysis was restricted
to patients who developed AKI, compared to the clinical
and laboratory characteristics of patients evaluated and
not evaluated by nephrologists, and generated a hypothesis
regarding the relationship between the timing of the NC
and short-term outcomes. In this observational study, 39%
of patients developed AKI, and fewer patients (26%) were
evaluated by nephrologists. These patients presented higher
mortality than those not evaluated, most likely due to their
more severe illness characteristics (more patients with
oliguria, greater need for dialysis, higher SCr and BUN levels,
and more stage 3 patients).
In the present study, 59 of the NCs (36.4%) were delayed
(.48 h), and a delayed consultation was not associated with
increased mortality. If this association is valid, it can be
inferred that consultation timing itself is not responsible for
the decreased mortality risk in elderly AKI patients.
Two recently published studies have evaluated the
association between the timing of the NC and patient outcomes.13,19
The retrospective observational study by Ponce et al enrolled
148 AKI patients (Acute Kidney Injury Network criteria)
treated in the ICU,13 of whom only 77 were evaluated by
nephrologists. Patients in the early NC group had a mean
SCr level of 6.6±1.8 mg/dL, compared to a mean SCr level
of 4.2±2.4 mg/dL in the delayed group. A delayed NC, using
a 48 h interval, was associated with increased mortality after
adjustment for multivariable analysis. In a study by Costa
e Silva et al,19 which was a prospective observational study
including 366 critically ill AKI patients (RIFLE [Risk, Injury,
Failure, Loss and End-stage Kidney Disease] criteria), 31.4%
(155/366) of patients underwent dialysis, and hospital
mortality occurred in 67.8% (248/366). The authors also reported
that delayed NC was associated with higher mortality and
increased dialysis dependence rates at hospital discharge.
There are several potential reasons why only 26% of the
AKI patients were evaluated by nephrologists. One
explanation may be the definition of AKI, which is neither uniformly
known nor accepted in the non-nephrologic community.15
Although the KDIGO criteria provide a unique basis for
epidemiologic and interventional outcome studies and
suggest increasing SCr and urine volume monitoring in patients
with a high risk for AKI, these criteria are not commonly
used in the clinical setting. Moreover, the SCr level has a
nonlinear relationship with the eGFR and requires time to
accumulate, thus contributing to delays in the detection
of important changes in kidney function. According to
the KDIGO criteria, the 48 h window for diagnosis does
enhance the sensitivity for earlier diagnosis relative to
the 7-day window because if the SCr level significantly
increases within 48 h, it is more likely to attract the attention
of clinicians. In contrast, if the patient’s SCr level increases
to 1.5 times the baseline value in 7 days, clinicians may not
be aware of AKI occurrence due to the “normal SCr” level,
especially among elder people with lower baseline SCr
levels. The results also confirmed that the AKI diagnosis
time was 2 days in the NC group, compared to 4 days in the
group without consultation. Finally, no universal definition
for NC timing exists for AKI patients. Elderly patients often
had many comorbidities, thus increasing the complexity of
medical care and possibly increasing the time required to
make treatment decisions.
Several other reasons may explain why early
consultation did not improve patient outcomes. First, the study
excluded patients with CKD. As CKD is a potent risk factor
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for mortality, excluding patients with CKD in this analysis
may have potentially underestimated the impact of an early
NC on survival. Second, although these elderly patients
were treated in non-ICU wards, they had close monitoring
and timely treatment by practitioners and had reduced the
short-term mortality to a certain extent. In addition, of the
163 stage 3 AKI patients, only nine patients required dialysis
during follow-up, and nine were evaluated by
nephrologists. Decisions about dialysis initiation in very elderly AKI
patients are influenced by several factors: AKI severity, blood
vessel volume, electrolyte and acid–base status, urine output,
hemodynamics, nutritional status, and attending physicians’
preferences. An important issue in the present study is that
dialysis cannot be initiated without an NC because in the
hospital, the nephrologist is the only professional who
initiates dialysis; so if the patient is not evaluated by a
nephrologist, they are not treated with dialysis.
The present study had some potential weaknesses. First, it
is a one-center retrospective study, and some potentially
important variables were not included, such as the Acute
Physiologic and Chronic Health Evaluation II score and
the sequential organ failure assessment score, which can
also predict AKI patient outcomes. Second, data from a
hospital catering to the elderly were analyzed, and because
most patients were male and fewer females were treated in
the hospital, females were excluded from the study. Thus,
biased results are unavoidable. Third, the definition of AKI
in this study was based on SCr levels. Urine output criteria
were not used because these data were incomplete. Fourth,
the follow-up duration was short. The study also did not
explore the effects of an NC on kidney outcome.
In summary, among very elderly patients with AKI, an NC
was associated with higher severity of disease (ie, higher peak
SCr levels, BUN levels, and AKI stage). As expected,
mortality significantly differed between patients who underwent a
consultation and those who did not receive a consultation.
Fewer AKI patients had a delayed NC (median of 4 days);
however, a delayed NC may not be associated with increased
This manuscript was edited for English language by
American Journal Experts. This study was funded by grants
from the National Natural Science Foundation of China
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