ORIGINAL ARTICLE

Outcome of End-Stage Renal Disease Patients

with Advanced Uremia and Acidemia
ABSTRACT

Iqbal Ur Rehman, Muhammad Khalid Idrees and Shoukat

Objective: To determine the outcome of End-Stage Renal Disease (ESRD) patients presenting with advanced uremia and
acidemia requiring hemodialysis and adverse events seen within 72 hours of admission.
Study Design: Cross-sectional study.
Place and Duration of Study: Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from October 2010 to
March 2011.
Methodology: ESRD patients with advanced uremia and acidemia were included in the study. History, physical
examination, complete blood count, serum urea, creatinine, electrolytes, arterial blood gases analysis, and ultrasound of
kidneys were done in each patient. Adverse events and outcome were recorded for the next 72 hours. Data was analyzed
by SPSS version (10). Mean value and standard deviation of quantitative measurements were calculated and statistical
significance computed by t-test. A p-value 0.05 was taken as significant. Statistical significance of categorical variables
was determined by chi-square test.
Results: Out of the 194 ESRD patients (mean age 46.54 14.07 years), 28 (14%) expired and 166 (86%) survived within
72 hours of admission. Hypotension requiring inotropic support was the commonest adverse event observed in 40 (20.6%)
cases followed by fits in 31 (16%); and 25 (12.9%) patients required ventilatory support. Mortality was high in patients
above 50 years of age. There was no statistically significant difference between two genders regarding adverse events
and mortality.
Conclusion: The morbidity and mortality of patients with ESRD are serious concerns. Early referral of patients with ESRD,
before they develop severe acidosis, can prevent significant morbidity and mortality.
Key Words: Uremia. Acidosis. Dialysis. Inotropic. Mortality. Renal failure.

INTRODUCTION

The global burden of End-Stage Renal Disease (ESRD)

is rapidly rising and increasing number of patients is
entering in the pool of those on renal replacement
therapy (dialysis or transplant). Approximately 1.9 million
ESRD patients are undergoing hemodialysis worldwide.
Access to the facility of Renal Replacement Therapy
(RRT) correlates directly with socioeconomic development and regional income.1 The initiation of RRT in
developing world is restricted to fewer than a quarter of
ESRD patients.1 In 2010, only 58.9% of ESRD patients
received dialysis or had kidney transplantation. There
was disparity among different parts of the world
regarding access to renal replacement therapy, ranging
from less than 2% in most of sub-Saharan Africa to over
70% in high-income North America, high-income Asia
Pacific, and East Asia.2 The annual incidence of EndStage Renal Disease (ESRD) in Pakistan is estimated at
about 100 per million populations,3 and it is increasing
Department of Nephrology, Sindh Institute of Urology and
Transplantation (SIUT), Karachi.
Correspondence: Dr. Iqbal Ur Rehman, Department of
Nephrology, SIUT, Dewan Farooq Medical Complex,
Off M.A. Jinnah Road, Karachi.
E-mail: siutpakistan@gmail.com
Received: July 18, 2014; Accepted: October 16, 2015.

with each passing year. Only 10% of renal failure patients

receive renal replacement therapy.4

ESRD patients have a high mortality rate during the first

year of initiation of dialysis and at least 6% patients die
within first 90 days.5 Late nephrology referral has been
associated with adverse outcomes among ESRD
patients. In Pakistan, till few years ago, almost 100%
patients presented in emergency department with
uremia and required urgent dialysis.6 A recent survey
from Karachi (the largest metropolis of Pakistan) found
that 41% of family physicians did not know when to refer
a renal failure patient to nephrologist.7

In late referral patients with ESRD, metabolic acidosis is

present which is in most cases mild and partially or fully
compensated with pH > 7.2 and may not be life
threatening. However, more severe acidosis i.e. pH
< 7.2 can cause hemodynamic instability (hypotension,
cardiac arrhythmias),8 especially in patients with
advanced uremia. Metabolic acidosis, however, is not
the sole culprit for early mortality and morbidity whereas
other factors may also contribute.9 During the first year
of dialysis, mortality is lowest during the first month and
at peak during the second and third month.10 Analysis of
patients record from the authors institution revealed that
patients were received with advanced uremia and
metabolic acidosis requiring urgent hemodialysis via
temporary vascular access and frequently need

Journal of the College of Physicians and Surgeons Pakistan 2016, Vol. 26 (1): 31-35

31

Iqbal Ur Rehman, Muhammad Khalid Idrees and Shoukat

ventilatory and inotropic support with high (very early,

within 72 hours) mortality. As this type of presentation is
now rare in developed and Western countries, this
phenomenon is not reported in the literature and its
prognostic factors are not well studied.
There is lack of data regarding the outcome of patients
with advanced uremia and acidemia in our population.
This study was conducted to study the patients
demographics, occurrence of adverse events (fits,
hypotension requiring inotropic support and requirement
of ventilatory support) and their impact on outcome
(survival/expiry) of the patients who presented with
advanced uremia and acidemia.

METHODOLOGY

This cross-sectional study was conducted at Sindh

Institute of Urology and Transplantation (SIUT), Karachi,
Pakistan, from October 2010 to March 2011. Patients
between 15 - 60 years of age, presenting first time to
emergency department of SIUT having advanced
uremia (arbitrarily defined as serum urea level 250
mg/dl at first presentation at SIUT) and diagnosed ESRD
on the basis of clinical features, serum biochemistry and
ultrasound kidneys, were included in the study by
convenience sampling technique. Patients with acute or
chronic renal failure and those already on dialysis were
excluded from the study. The study was approved by the
Ethical Review Committee (ERC) of the institution.
Informed consent was obtained.

History was taken and physical examination done. Blood

samples for Complete Blood Count (CBC) and serum
biochemistry (serum urea, creatinine, electrolytes) sent
along with a separate heparinized sample of arterial
blood for pH, PO2, PCO2, O2 saturation and bicarbonate
measurement. Ultrasound of kidneys was done to see
the size of the kidneys and exclude obstruction.
Outcome of patients (whether the patient expired or
survived) was observed for the next 72 hours after
admission. Additionally, adverse events (fits, need of
mechanical ventilation and hypotension) were observed.
During this period, hemodialysis was done in supervision
of trained physician. The dialysis was of short duration
(90 - 120 minutes), with low flux hollow fibre
(polysulphone) dialyzer, without any anticoagulation
(saline flushes to prevent clotting of dialyzer),
bicarbonate dialysate, blood flow of 250 ml/minute and
dialysate flow of 500 ml/minute. Ultrafiltration was done
in patients having fluid overload. All the relevant
information (survival, death and adverse outcome) were
recorded on the proforma.
Data was entered and analyzed in statistical software
(SPSS version 10). Frequency and percentage were
computed for categorical (qualitative) variables like age
group, gender, outcome of end stage of renal disease
patients and adverse event. Mean and standard
deviation were computed for quantitative measurement
like age, temperature, hemoglobin, TLC, platelet,
32

potassium, sodium and pH. Statistical significance of

these variables was determined by t-test and value of p
equal or less than 0.05 was taken as statistically
significant. Similarly, the statistical significance of
categorical data was determined by chi-square test.
Stratification was done with regard to age, gender and
number of dialysis to observe the effect on outcomes.

RESULTS

This study included 194 ESRD patients (130 males and

64 females) having advanced uremia and acidemia. The
average age of the patients was 46.54 14.07 years and
most of the patients were above 50 years of age.
Patients who expired were older as compared to those
who survived (52.29 12.77 vs. 45.57 14.09 years) and
this difference was statistically significant (p= 0.019). All
the patients had fairly advanced uremia with a mean
serum urea of 349.04 77.6 mg/dl and mean serum
creatinine of 14.44 4.41 mg/dl respectively. About 40%
patients had hyperkalemia. The patients who expired
had lower pH (7.01 0.11) as compared to those who
survived (7.14 0.09) and this difference was statistically
significant (p=0.0005). Table I shows the descriptive
statistics of study variables.
Table I: Descriptive statistics of study variables (n=194).
Variables

Mean SD

Max - Min

98.59 0.96

103 - 98

88.06 20.51

122 - 47

Platelet

246.78 139.95

716 - 5

Sodium

134.66 8.48

168 - 107

H.ion (nmol/L)

79.15 21.94

Creatinine mg/dL

14.44 4.41

Age (years)

Temperature*
Hemoglobin

Mean arterial pressure

TLC

Potassium**
pH

Urea mg/dl

46.54 14.07
7.87 1.82

15.48 8.23
5.41 1.35

65 - 15
11 - 3

56 - 1
9-2

7.12 0.13

7.29 - 6.84

349.04 77.6

594 - 251

*Out of 194 patients, 66 (34%) had temperature more than 100F

** Out of 194 patients, 78 (40.2%) had hyperkalemia

144 - 52

36.9 - 8.0

Hypotension requiring inotropic (vasopressor) support

was the commonest adverse event that was observed in
40 (20.6%) patients followed by fits (seizures) in 31
(16%) patients while 25 (12.9%) patients required
ventilatory support. Fits and ventilatory support were
more common in patients below 30 years of age while
hypotension was observed in patients above 50 years of
age. Frequency of fits and ventilatory support was nearly
same in male and female (p=0.46 and p=0.90,
respectively) while hypotension was more common in
females than males (28.1% vs. 16.9%); but this
difference did not reach statistical significance (p=0.07).
Frequency of hypotension and ventilatory support was
high in those cases who had only one session of dialysis
as compared to those who required 2 and 3 dialysis
sessions during the period of 72 hours (p=0.001 and
0.0001 respectively) while there was no statistically

Journal of the College of Physicians and Surgeons Pakistan 2016, Vol. 26 (1): 31-35

Outcome of ESRD with advanced uremia and acidemia

significant difference in case of fits (p=0.172). These

patients had more severe metabolic acidosis and
consequent highest mortality as shown in Table II.
Dialysis prescription varied very little from patient to
patient as all the patients had short duration dialysis and
dialysate flow (500 ml/minute) whereas dialysate
compositions (prepared in the institution in bulk) were
fixed and dialyzer used was of the same size (1.4 m2) for
all the patients.

Fourteen percent (28/194) patients expired and 86%

(166/194) survived within 72 hours after admission.
Mortality/expiry rate was highest (20.8%) among those
above 50 years of age while it was about 8% (8 out of
98) in those below 50 years of age. Mortality was
statistically significantly higher in those above 50 years
of age as compared to those below 50 years (p=0.029).
There was no difference in both genders regarding
mortality (p=0.918). Similarly, mortality/expiry rate was
100% in those cases who had only one dialysis session.
Frequencies of adverse events and mortality are
summarized in Table III.
Table II: Comparison of characteristics between survived and expired
patients.
Variables

Survive group

Expired group

p-value

111 (66.9%)

19 (67.9%)

0.918

45.57 14.09

52.29 12.77
99.16 1.60

0.001*

(mmHg)

91.62 18.25

66.94 20.71

0.0005*

TLC (1000/mm3)

14.63 7.39

20.46 11

0.0005*

376.64 92.67

0.042

5.89 2.03

0.002*

Gender
Male

Female

Age (years)

Temperature (F)

Mean arterial pressure

Hemoglobin (gm/dl)
Platelets (100,000/mm3)
Urea (mg/dl)

Creatinine (mg/dl)

Bicarbonate (mmol/L)
PCO2

(n=166)

55 (33.1%)

98.49 0.78

7.88 1.83

(n=28)

09 (32.1%)

7.76 1.79

247.21 136.7

244.25 147.68

14.45 4.51

14.04 4.07

344.39 74.09
7.62 2.85

14.86 5.31

0.0005*

H ion (nmol/L)

75.32 19.15

101.82 23.98

Fits

Hypotension

Ventilatory support

* Significant

21 (12.7%)

21 (12.7%)
10 (6%)

Table III: Adverse events and mortality.

Age groups
30 years

31 to 50 years
> 50 years

0.649

7.01 0.11

134.18 8.54

Adverse event

0.917

0.0005*

134.76 8.49
7.14 0.09

0.734

21.93 13.82

Sodium (mEq/L)
pH

0.019

10 (35.7%)

19 (67.9%)

15 (53.6%)

Number
36
62

0.74

0.0005*
0.002*

0.0001*

0.0001*

DISCUSSION

The authors specifically studied outcome of uremic

patients who were acidotic and in need of emergency
dialysis, which is a common scenario in Pakistan due to
late diagnosis or referral. Most of those patients, who
have an uneventful course within few days after starting
dialysis, usually do well subsequently. The total number
of patients with a span of 6 months, suggests that this is
still a frequent mode of presentation in Pakistan. The
average age of these patients (46.54 14.07 years) is
much less than that reported from USA11 but close to
that in other South Asian countries.12 The number of
males was almost twice that of females in this study.
This is contrary to the finding from community based
study from Karachi13 which did not find gender
difference in occurrence of kidney disease among
general population. The lesser number of females in this
study is probably due to gender bias and social
deprivation of females.

This study included patients with severe acidosis i.e.

pH < 7.3. The patients who eventfully expired had more
severe acidemia compared to those who survived.
Acidosis of such severity may lead to adverse
hemodynamic effects such as arteriolar dilatation and
depression of myocardial contractility.8 In an
experimental study, the effect of metabolic acidosis
induced by infusion of hydrochloric acid in pigs was
studied which showed that lowering of pH to 7.1 resulted
in diminished cardiac contractility and increased the
ventricular stroke work per minute.14 Numerous studies
on patients with lactic acidosis in critical care setting
have highlighted the adverse effects of profound
acidemia.15 The authors were unable to find any study
where effect of such profound metabolic acidosis in
uremic patients has been studied.

It is difficult to compare these patients (whose acidosis

is rapidly corrected by dialysis) with non-uremic patients
with lactic acidosis. More than 40% patients had
hyperkalemia but it had no effect on mortality. It is
probably because of the rapid removal of potassium in
process of hemodialysis. Patients who expired had
higher temperature and higher TLC as compared to
those who survived. This could be due to presence of
some unrecognized infection (such as UTI) or result
from systemic inflammation due to metabolic acidosis.
Patients with higher PCO2 (respiratory acidosis) had

Fits

7 (19.5%)

11 (17.8%)

Hypotension
6 (16.7%)
7 (11.3%)

Ventilatory support

Expired

5 (13.8%)

3 (8.3%)

7 (11.3%)

5 (8.1%)

96

13 (13.5%)

27 (28.1%)

13 (13.5%)

20 (20.8%)

Males

130

19 (14.6%)

22 (16.9%)

17 (13.1%)

19 (14.6%)

Total

31 (16%)

40 (20.6%)

25 (12.9%)

28 (14%)

Number of adverse events

Females

64

12 (18.8%)

Journal of the College of Physicians and Surgeons Pakistan 2016, Vol. 26 (1): 31-35

18 (28.1%)

8 (12.5%)

9 (14.1%)

33

Iqbal Ur Rehman, Muhammad Khalid Idrees and Shoukat

higher mortality. Patients with pure metabolic acidosis

have lower PCO2 due to respiratory compensation but
exhaustion of respiratory muscles leads to concomitant
respiratory acidosis (more pronounced among diabetic
CKD patients) and consequent higher morbidity and
mortality.16

Hypotension was the commonest adverse event

observed in 20.6% cases followed by fits (16%) and
12.9% patients required ventilator support. High
mortality rate (60%) observed in patients who were on
ventilator followed by hypotension (47.5%) and fits
(2.3%). Seizures are not uncommon in patients with
advanced uremia on presentation and are multi-factorial
in causation. Seizures in uremic patients can be a
manifestation of uremia, metabolic derangements or the
treatment of these derangements.17 Bergen and
colleagues reported the incidence of seizures (fits) of
approximately 10% in patients with chronic renal
failure.18 The lower frequency of seizures among our
study participants may be due to short period of
observation (72 hours).

Mechanical ventilation was required in 12.9% patients

which is less than 26% as reported by Rocha19 among
maintenance dialysis patients admitted in ICU. Patients
with advanced uremia often have pulmonary edema,
inability to clear upper airways and exhaustion due to
respiratory muscle fatigue. Similarly, 20.6% of our
patients had hypotension and required inotropic support
compared to 24% as reported by Rocha.19 The
difference in the two study populations is that there was
high proportion of patients with sepsis in the study of
Rocha while these patients had severe metabolic
acidosis.

The outcome of ESRD patients with advanced uremia

was quite dismal in this study. Fourteen percent patients
expired within 72 hours of admission. This is much
higher than the 6% mortality during first 90 days of start
of dialysis in USA.5 In Canada,20 early 90-day mortality
after initiation of dialysis was upto 34.7% of one year
mortality. However, there is wide variation in patient
mortality in different parts of the world. DOPPS found
that one-year mortality rates were 6.6% in Japan, 15.6%
in Europe and 21.7% in the USA and variability in
demographic and co-morbid conditions at inception of
dialysis could explain only part of the differences in
mortality rate between these countries.21 It has been
observed that both cardiovascular and noncardiovascular mortality risk factors are equally
increased among dialysis patients and should be
focused.22
In this study, frequency of expired patients was high in
above 50 years of age. This is well known phenomenon
that mortality increases with increasing age.20 Mortality
rate was similar in male and female patients in this study.
Gender difference has been reported in the survival of
34

new ESRD patients. Bloembergen et al. found that

males receiving chronic dialysis had a 22% higher
mortality than females, mostly because of excess risk of
acute myocardial infarction and malignancies.23
However, another study from European cohort showed
that young and diabetic women starting dialysis had
higher non-cardiovascular mortality risk than men while
females of 45 years old and above had lower
cardiovascular mortality than men.24 The authors did not
find such gender difference in this study. This may be
because of smaller number of females. Higher
frequency of hypotension, need of ventilatory support
and 100% mortality among patients, who survived to
have only one dialysis session, reflects that these
patients were more seriously sick. The dialysis
prescription was more or less the same among all the
patients and it is not possible to judge the effect of
dialysis on survival or mortality in this small single centre
study.
This study is, to the best of authors' knowledge, the first
of its kind from this part of the world which highlights the
high mortality rate among ESRD patients presenting
with advanced uremia and metabolic acidosis/acidemia
during first 72 hours of admission. It highlights the
importance of accurate reporting of events during initial
days of start of dialysis. Early referral to nephrologist
and attendance of pre-dialysis clinics may facilitate the
avoidance of central venous catheters, timely creation of
AV fistula, correction of anemia, mineral bone
metabolism and malnutrition, which ultimately improve
survival on dialysis.25

It is a single center study and observation period was

only 3 days, so co-morbid conditions other than ESRD
could affect the outcome and adverse events.

CONCLUSION

The morbidity and mortality of patients with ESRD are

serious concerns for patients presenting late with
advanced uremia and severe metabolic acidosis. Early
referral of patients, with ESRD before they develop
severe acidosis, will prevent significant morbidity and
mortality.

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