A Comparative Study of Community-acquired Acute Kidney Injury and Hospital-acquired Acute Kidney Injury from a Tertiary Care Hospital in North India

Abstract

Background:

In this observational study, clinical characteristics, etiologies, and outcomes of patients admitted to the hospital with community-acquired acute kidney injury (CAAKI) have been compared in contrast to those who hospital-acquired Acute Kidney Injury (HAAKI).

Methods:

This was a prospective study of adults aged 18 years or above diagnosed with acute kidney injury (AKI) over a period of 17 months at a tertiary care hospital.

Results:

230 patients had AKI with the mean age of the study population being 45.33 ± 12.68 years. 178 (77.4%) patients were enrolled from medical unit, 25 (10.7%) from surgical unit, and 27 (11.7%) from obstetrical unit. The observed incidence of AKI was 15/1000 admissions. About 58.2% had CAAKI and 96 (43.7%) had HAAKI. Out of 230 patients, 170 (73.9%) patients were male and 60 (26.1%) were female. Sepsis was the most common (52.1%) etiology of AKI among the medical cases. Urosepsis, scrub typhus, and pneumonia were the most common causes of AKI. Sixty percent of AKI was Kidney Disease Improving Global Outcomes Stage 1 or 2 and 40% was in Stage 3. Oliguria was seen in 56.5%, hyperkalemia in 34.7%, fluid overload in 6.1%, and metabolic acidosis in 22.6%. The majority of patients had multiple organ involvement (52.1%) at the time of enrollment. About 116 (50.4%) had lung injury requiring mechanical ventilation and 95 (41.3%) were on inotropes. Mortality occurred in 19.5%. Anemia, the use of vasopressor drugs, and the need for intensive care support were independent predictive factors for mortality.

Conclusion:

AKI was common in hospitalized patients and leads to significant inhospital mortality. AKI is largely a CAAKI, and the lesser extent is due to HAAKI. Many causes are potentially preventable. Early fluid resuscitation, effective antibiotics, appropriate antidotes, and timely referral of established AKI patients to centers with dialysis facilities can improve AKI outcomes.

INTRODUCTION

Acute kidney injury (AKI) is a major public health concern, associated with high mortality, morbidity, and long-term risk of chronic kidney disease (CKD). Significant differences exist in the epidemiology and outcomes of AKI from the developed and developing world. The global burden of AKI is estimated at 13.3 million cases per year, with 85% from low- and middle-income countries (LMICs) like India. Limited data on the incidence are available worldwide, and the data vary widely across studies depending on the setting and the populations investigated.[1]

Due to the lack of a central registry, there are limited data on the overall epidemiology of AKI from India. This often originates from single-center studies from urban locations[2,3] and describes AKI due to a single disease without reference to the underlying population.[4,5] The etiology of AKI depends on the cultural, economic, and geographical location and many are preventable. It is found that the epidemiology of AKI differs from country to country and it also varies from place to place within the same country.[6,7,8]

In developed countries, hospital-acquired AKI (HAAKI) is the most frequent form with an incidence of 7%–18%.[9] Hospital-acquired AKI (HAAKI) is a commonly found disease that has a substantially high risk of mortality for a number of hospitalized patients. On the basis of several studies, it has been found that causes of HAAKI often include sepsis, critical illness, surgery, and sometimes even the use of contrast media and aminoglycosides during hospitalization.[10,11] Community-acquired AKI (CAAKI) occurs in LMICs, affecting mostly young adults and children.[9,10] A number of studies have reported that the incidence of CAAKI was 2–3 times higher than HAAKI, but it is found to have the same prognostic significance as HAAKI on mortality, longer length of stay, and higher health-care costs.[12,13]

The majority of AKI cases are preventable or can be managed by simple measures. Despite advances in medical technique, AKI remains an underdiagnosed problem. When diagnosed late, AKI has adverse effects for the individual in general. It is associated with increased length of hospital stay and higher health-care costs.[12] The duration and severity of AKI is a risk factor for the development of complications such as a 10-fold increase in the risk of CKD and a 3-fold risk of end-stage kidney disease.[13,14,15]

In this observational study, clinical characteristics, etiologies, and outcomes of patients admitted to the hospital with CAAKI have been compared in contrast to those who acquired AKI during their hospitalization (HAAKI).

MATERIALS AND METHODS

This was a prospective study carried out in the Department of Medicine in the Nephrology Unit, K. G. Medical University, Lucknow, Uttar Pradesh, India, from June 2019 to October 2020. After written and informed consent and ethical clearance from the institutional ethics committee, King George’s Medical University, Lucknow (reference code: 97^th ECM II B-thesis/P85), a total of 230 patients of HAAKI and CAAKI were enrolled for this study who were admitted in the Department of Medicine, Surgery, and Obstetric units, respectively. The sample size was calculated on the basis of the formula to estimate a single proportion. With an expected mortality of 22% at 90% confidence level and relative precision of 5%, the required sample size was 186 [Figure 1].

Figure 1.

Flow diagram of patients as per the Strengthening the Reporting of Observational Studies in Epidemiology. KDIGO = Kidney Disease Improving Global Outcomes, CAAKI = Community-acquired AKI, HAAKI = Hospital acquired acute Kidney Injury

The inclusion and exclusion criteria were classified as follows:

Inclusion criteria

1. The presence of uremic symptoms or oliguria or anuria of recent origin

2. AKI was diagnosed in accordance with AKIN guidelines,[5] and the results were as follows: (1) increased serum creatinine ≥0.3 mg/dL within 48 h, (2) serum creatinine increased by ≥1.5-fold relative to baseline values within 7 days, and (3) urine volume <0.5 mL/kg/h for 6 continuous hours [Table 1].

Table 1.

Acute kidney injury network criteria

Stage	Serum creatinine criteria	Urine output criteria
1	↑ to ≥1.5 x baseline or ↑ 0.3 mg/dL from baseline	<0.5 mL/kg/h ≥6 h
2	↑ to ≥2 x baseline	<0.5 mL/kg/h ≥12 h
3	↑ to ≥3 x from baseline or 4 mg/dL with acute ↑ ≥0.5 mg/dL or initiate of RRT irrespective of age at the time of initiation	<0.30 mL/kg/h ≥24 h anuria ≥12 h

Only one criterion (serum creatinine or urine output) should be fulfilled to qualify for a stage. RRT=Renal replacement therapy, ↑=Increased, x=Times

Exclusion criteria

1. Preexisting kidney disease (serum creatinine >1.5 mg/dL or ultrasonography of the abdomen suggestive of bilateral small kidneys/loss of corticomedullary differentiation/obstructive nephropathy/other renal pathologies)

2. Patients presenting with acute-on CKD or renal failure attributed to CKD.

Study protocol

All patients admitted in Department of Medicine, Surgery and Obstetrics & Gynaecology high dependency unit (HDU) were recruited for this study. After detailed history taking and physical examination, laboratory investigations were sent at the time of admission. Records were checked to confirm the presence of comorbid conditions, namely diabetes, hypertension, HIV, or HBsAg or HCV positivity, among others. Serum creatinine at admission, baseline serum sodium, serum potassium, liver functions, hemoglobin (Hb), total leukocyte count, and platelet count were done. An automated blood cell analyzer (Abbott Cell Dyn Ruby Hematology Analyzer, Abbott Park, Illinois, USA) was used for routine hematology testing, and an automated clinical biochemistry analyzer (ELITech Selectra ProM, ELITech Group, Puteaux, France) was used for kidney function test, liver function test, serum electrolytes, spot urinary albumin, serum protein, and albumin estimation.

Daily follow-up and daily clinical examinations of the patients were conducted during the hospital stay. For patients in the intensive care unit (ICU), urine output was recorded every 6 h and every 24 h later on for the patients in the HDU wards. The patients were monitored for any development of hypotension, oliguria, acute lung injury, acute respiratory distress syndrome (ARDS), encephalopathy, sepsis, thrombocytopenia, any requirement for mechanical ventilation, and the duration of ventilation required.

Tests for serum creatinine were repeated and performed serially from day 2 to 7 for each patient. The maximum stage of AKI and maximum serum creatinine for each patient were recorded. Individual patient requirements were considered while managing the patients as per antibiotic use, enteral nutrition protocol, fluid administration, vasopressors, management of hypoglycemia, decision on dialysis, and administration of blood products. The requirement of renal replacement therapy (RRT) was initiated in consultation with a nephrologist. The type of dialysis (hemodialysis and slow low-efficiency dialysis) and the total number of dialysis sessions required were considered as per individual patient requirements.

Each patient was followed up till discharge or death. The parameter for complete renal recovery was fixed to return of serum creatinine to <1.5 mg/dL and nonoliguric state. Partial renal recovery was defined when serum creatinine at discharge was declining but did not return to normal. When serum creatinine was persistently high at discharge or death, it was assumed that renal recovery did not occur.

Definitions

If AKI was present at admission or it developed within 48 h of hospital admission, we defined CAAKI. This arbitrary time of 48 h was used to allow subclinical CAAKI to manifest. Those who developed kidney injury after at least 24 h of admission were considered hospital-acquired AKI (HAAKI). Hypotension was defined as systolic blood pressure (BP) <90 mmHg or the requirement of inotropes to maintain a mean arterial pressure of 65 mmHg. Oliguria was defined as urine output <0.5 mL/kg/h for more than 6 h. Anuria was defined as urine output <100 mL for 12 h. ARDS was defined by the Berlin definition of ARDS.[16] Encephalopathy was defined as any decline in mental status, asterixis, or other neurologic symptoms in the concurrent presence of high urea and creatinine, provided that there was no intracranial pathology or liver cirrhosis. Thrombocytopenia and anemia were defined as platelet count <100,000/dL and Hb <9 g/dL, respectively. Sepsis was defined as per the Surviving Sepsis Campaign definition.[17] Hypertension was defined as systolic BP >150 mmHg and/or diastolic BP >90 mmHg. Hyponatremia and hypernatremia were defined as serum sodium levels <135 meq/L and >145 meq/L, respectively. Hypokalemia and hyperkalemia were defined as serum potassium levels <3.5 meq/L and >5.5 meq/L, respectively.

Statistical analysis

All statistical analyses were performed using the statistical software package. The continuous variables have been presented as mean ± standard deviation, and the categorical variables have been shown as percentage values. Student’s t-test, ANOVA and Chi-square test were used for comparison between different variables. Mann–Whitney U-test, Kruskal–Wallis test, and Spearman’s correlation coefficient tests were used for stratification of 30 days mortality. The criteria for significance to be used for the study were P < 0.05. All statistical analyses have been conducted using MedCalc^® Statistical Software version 19.8 (MedCalc Software Ltd., Ostend, Belgium; https://www.medcalc.org; 2021).

RESULTS

The total number of patients hospitalized during the period of the study was 15,150. Of them, 230 (1.51%) had AKI with an incidence of 15/1000 admissions. This constituted 1.51% of ICU admissions (n = 15,150). Serum creatinine-based criterion was used for diagnosing AKI in 230 patients. One hundred and thirty-four (58.2%) patients had CAAKI with an incidence of 8.84 per1000 admissions. Ninety-six (43.7%) had HAAKI with an incidence of 6.33/1000 admissions [Figure 1].

One hundred and seventy-eight (77.4%) patients were enrolled from medical unit, 25 (10.7%) from surgical unit, and 27 (11.7%) from the obstetrical unit. Out of 230 patients, 170 (73.9%) patients were male and 60 (26.1%) were female. The mean age of the study population was 45.33 ± 12.68 years. In about 60%, AKI was Kidney Disease Improving Global Outcomes Stage 1 or 2, and in the other 40%, it was Stage 3. Oliguria was seen in 56.5%, hyperkalemia in 34.7%, fluid overload in 6.1%, and metabolic acidosis in 22.6%. The majority of patients had multiple organ involvement (52.1%) at the time of enrollment itself. About 116 (50.4%) had lung injury requiring mechanical ventilation and 95 (41.3%) were on inotropes. Among the 95 (41.3%) patients who received vasopressors, 50 patients were on noradrenaline, 32 received noradrenaline + dopamine, 5 received dopamine alone, 4 received noradrenaline + dobutamine, and 4 received dobutamine alone. Of the 38 patients (16.1%) who developed infections during hospital stay, 17 patients had intra-abdominal infections, 5 had ventilator-associated pneumonia, and the rest had vascular and urinary catheter infections [Table 2].

Table 2.

Demographic and clinical characteristics of the study patients (n=230)

Parameters	n (%)
Gender
Male	120 (52.2)
Female	110 (47.8)
Age, mean±SD	45.33±12.68
Types of AKI
Community-acquired AKI	125 (54.3)
Hospital-acquired AKI	105 (45.7)
Setting of AKI
Medical	178 (77.4)
Surgical	25 (10.7)
Obstetrical	27 (11.7)
KDIGO stage
Stage I	60 (26.0)
Stage II	75 (32.6)
Stage III	95 (41.3)
Blood urea (mg/dL)	136.24±83.04
Serum creatinine (mg/dL)	4.29±3.6
Oliguria	130 (56.5)
Hyperkalemia	80 (34.7)
Metabolic acidosis	52 (22.6)
Multiorgan failure	120 (52.1)
Vasopressor supportive	95 (41.3)
Mechanical ventilation	116 (50.4)
Dialysis	52 (22.6)
Outcome
Survived	185 (80.4)
Expired	45 (19.5)

AKI=Acute kidney injury, KDIGO=Kidney Disease Improving Global Outcomes, SD=Standard deviation

In 80 (64.0%) of the patients, the underlying cause for AKI was infective, whereas 54 (43.2%) had noninfective primary clinical conditions. Among the patients with infective etiology, the most common infection was observed as urinary tract infection (UTI) 27 (21.6), followed by scrub typhus 20 (16.0) and pneumonia 12 (9.6). Other infections reported were leptospirosis 9 (7.2), infected diabetic foot 10 (8.0), and bacterial peritonitis 2 (1.6). Hypovolemia 13 (10.4%) due to diarrheal illness 10(8.0%) and acute pancreatitis 3(2.4%). Obstructive uropathy 10(8.0%) and postoperative AKI 5(4.0%) were noticed as the main surgical causes of AKI. Puerperal sepsis 6(4.8%), severe preeclampsia 3(2.4%), and postpartum hemorrhage (PPH) 1(0.8%) were found to be the obstetrical causes of AKI.

The most common causes of noninfective etiological factors of AKI were biological toxins 13(10.4%) and cardiac causes 3(2.4%). The most common comorbidity reported was, chronic liver disease (13%), followed by hypotension (10.4%), hypertension (preeclampsia) 3(2.4%), and chronic obstructive pulmonary disease (COPD) (4%) [Table 3].

Table 3.

Etiological risk factors for acute kidney injury in the study population

Condition	Total 230, n (%)	CAAKI (n=125), n (%)	HAAKI (n=105) n (%)	P
Sepsis	120 (52.1)	80 (64.0)	40 (38.1)	<0.001
UTI	40 (17.4)	27 (21.6)	13 (12.4)	<0.05
Scrub typhus	30 (13.0)	20 (16.0)	10 (9.50)	<0.03
Pneumonia	20 (8.7)	12 (9.6)	8 (7.6)	<0.05
Leptospirosis	10 (4.3)	9 (7.2)	1 (0.95)	0.51
Infected diabetic foot	12 (5.2)	10 (8.0)	2 (1.9)	<0.01
Bacterial peritonitis	8 (3.4)	2 (1.6)	6 (5.7)	0.51
Hypovolemia	25 (10.86)	13 (10.4)	12 (11.4)	<0.05
Diarrheal illness	17 (7.4)	10 (8.0)	7 (6.7)	0.51
Acute pancreatitis	8 (3.5)	3 (2.4)	5 (4.7)	<0.01
Surgical causes	25 (10.86)	13 (10.4)	12 (11.4)	<0.01
Obstructive uropathy	16 (6.9)	10 (8.0)	6 (5.7)	<0.06
Postoperative	9 (3.9)	5 (4.0)	4 (3.8)	<0.03
Obstetrical causes	27 (11.7)	10 (8.0)	17 (16.1)	0.51
Puerperal sepsis	10 (4.3)	6 (4.8)	4 (3.8)	0.51
Severe preeclampsia	7 (3.0)	3 (2.4)	4 (3.8)	<0.01
Postpartum hemorrhage	10 (4.3)	1 (0.8)	9 (9.3)	<0.03
Nephrotoxic agents	10 (4.3)	2 (1.6)	8 (7.6)	<0.01
Biological toxins	13 (5.6)	13 (10.4)	0	<0.01
Cardiac causes	10 (4.3)	3 (2.4)	7 (6.7)	<0.05

CAAKI=Community-acquired acute kidney injury, HAAKI=Hospital-acquired acute kidney injury, UTI=Urinary tract infection

In the HAAKI group, 40 (38.1%) of the patients, the underlying cause of AKI was infective. Among the patients with infective etiology, the most common infection was observed to be pneumonia 8 (7.6%), followed by UTI 13(12.4%), scrub typhus 10(9.5%), and acute pancreatitis 5(4.7%). Obstructive uropathy 6(5.7%) and postoperative AKI 4(3.8%) were the surgical causes of AKI. Puerperal sepsis 4(3.8%), severe preeclampsia 4(3.8%), and PPH 9(9.3%) were reported to be the obstetrical causes of AKI.

In the case of noninfective etiology of AKI, the most prevalent cause was a nephrotoxic agent 8(7.6%) and cardiac reasons 7(6.7%). In the case of comorbid conditions in the patients with HAAKI, the most common comorbidity reported was hypertension (severe preeclampsia) 4(3.8%), COPD (8%), and chronic liver disease (8%), [Table 3].

The proportion of patients with oliguria (P = 0.001), fluid overload (P = 0.001), multiorgan failure (P = 0.001), metabolic acidosis (P = 0.001), requirement of vasopressors (P = 0.001, need for ICU support (P = 0.001), and dialysis (P = 0.015) was markedly higher in patients who died. As compared to the survival group, the Hb was significantly lower (P = 0.001) in patients who died. There were no major differences in other demographic and clinical characteristics between the groups. In multivariate binary logistic regression analysis, the presence of anemia, the use of vasopressor drugs, and requirement of ICU support were predictive factors for mortality [Table 4].

Table 4.

Characteristics of survivors versus nonsurvivors

Clinical characteristic	Survivor (n=219)	Nonsurvivor (n=11)	P
Age, mean±SD	45.94±16.722	51.54±8.092	0.409a
Male gender, n (%)	115 (52.5)	5 (45.4)	<0.05a
Medical ICU, n (%)	120 (64.86)	10 (90.9)	0.460a
24 h urine output (mL), mean±SD	1265.65±940.39	1064.51±695.24	0.877a
Oligoanuria, n (%)	90 (48.6)	8 (72.7)	<0.001a
Fluid overload (mL), median (IQR)	980 (600–1850)	1000 (600–1775)	<0.05a
Encephalopathy, n (%)	25 (13.5)	8 (72.7)	<0.05a
Multiorgan failure, n (%)	10 (45.7)	5 (45.4)	<0.05a
pH, mean±SD	7.27±0.12	7.24±0.55	0.56a
Serum potassium (mEq/L), mean±SD	4.56±0.84	4.63±0.10	0.55b
Creatinine (mg/dL), mean±SD	3.20±1.77	4.31±1.99	0.99c
Anemia, n (%)	105 (56.7)	10 (90.9)	<0.001b
Mechanical ventilation, n (%)	76 (41.1)	11 (100.0)	<0.001a
Vasopressor use, n (%)	50 (27.02)	11 (100.0)	<0.001a
RRT, n (%)	20 (10.8)	11 (100.0)	<0.05a

^aChi-square with Fisher's exact test exact significant (two-sided), ^bIndependent samples t-test, significant (two-tailed), ^cMann–Whitney U-test, significant (two-tailed) nonparametric independent samples test. RRT=Renal replacement therapy, IQR=Interquartile range, ICU=Intensive care unit, SD=Standard deviation

Total 134 patients with CAAKI, 70.9% (n = 95) showed complete recovery (CR) at the end of the 30 days, whereas 3.73% (n = 5) showed partial recovery (PR). Among 96 patients with HAAKI, 77% (n = 74) had CR and 3.1% (n = 3) had PR. Four patients continued to remain dialysis dependent at the end of the 1^st month in both the groups [Table 5].

Table 5.

Management and renal outcome of acute kidney injury patients in both groups

Variables	CAAKI 125, n (%)	HAAKI 105, n (%)	P
Use of vasoactive drugs	55 (44.0)	40 (38.0)	<0.05
Blood transfusion	24 (19.2)	10 (9.5)	<0.05
Dialysis	32 (25.6)	20 (19.0)	<0.001
Renal recovery at 3 months
Complete recovery	100 (80.0)	84 (80.0)	<0.001
Partial recovery	10 (8.0)	8 (7.6)	<0.001
Dialysis dependent	10 (8.0)	7 (6.7)	<0.05
Expired	5 (4.0)	6 (5.7)	<0.05

CAAKI=Community-acquired acute kidney injury, HAAKI=Hospital-acquired acute kidney injury

The 30-day mortality of the group was 19.5% (n = 45). Among these, about 6.5% of deaths (n = 15) occurred in the initial 48 h. Twenty (8.6%) patients expired between 48 h and 1 week and ten patients (4.3%) expired in the 2^nd week. The mortality was not different between CAAKI and HAAKI (22.4% [30/134] vs. 15.6% [15/96]; relative risk [RR] =0.94; confidence interval [CI]: 0.74–1.19). Compared to AKI 1, the RRs of death for AKI 2 and AKI 3 were 0.96 (CI: 0.66–1.40) and 1.02 (CI: 0.72–1.44), respectively. When compared to the stage of AKI, the mortality was similar to CAAKI and HAAKI [Table 6].

Table 6.

30-day mortality stratified for community-acquired acute kidney injury and hospital-acquired acute kidney injury and stage of acute kidney injury

AKI stage (n=230)	Entire cohort (n=11), n (%)	CAAKI (n=125), n (%)	HAAKI (n=105), n (%)	RR of death (95% CI)
Stage 1 (60)	2 (18.1)	1/35 (2.8)	1/25 (4.0)	0.64 (0.36–1.16)
Stage 2 (75)	3 (27.2)	1/40 (2.5)	2/35 (5.7)	0.96 (0.66–1.40)
Stage 3 (95)	6 (54.5)	3/50 (6.0)	3/45 (6.6)	1.02 (0.72–1.44)

CI=Confidence interval, RR=Relative risk, AKI=Acute kidney injury, CAAKI=Community-acquired AKI, HAAKI=Hospital-acquired AKI

DISCUSSION

In developed countries, AKI mainly occurs due to HAAKI, whereas it is mainly due to CAAKI in developing countries.[18] Our study result showed that AKI was mostly due to CAAKI and a lesser percentage was due to HAAKI. One explanation for this reason may be the underlying causes of AKI in our country such as sepsis, hypovolemia due to diarrhea, and nephrotoxic drugs. All these factors are prevalent in the community. The total incidence of AKI was 15/1000 admissions per year. Data on CAAKI from the developing world are not organized, different definitions of AKI are used in different regions, and it often originates in a single center of an urban location. The true incidence of CAAKI in developing countries is difficult to estimate because most patients do not go to urban hospitals, where they would have been included in a similar kind of study for incidence estimation.[5] Moreover, it is highly probable that gross underreporting results in the apparently lower incidence of AKI in the developing world due to insufficient monitoring of renal function in hospitalized patients which may be due to poor resources and lack of awareness among attending doctors.[18,19]

There are significant variations in the epidemiology and outcomes of AKI across different parts of the world. Compared to data from high-income countries, the current study had younger patients with few comorbidities.[1] In this study, the mean age was 45.33 ± 12.68 years. Most of the Indian studies had reported the mean age of patients varying from 40 to 60 years.[6,20,21] Sural et al. reported a considerably lower age of 28.6 years in a group of postsurgical patients.[22]

In this study, 77.4% of the patients developed AKI related to medical causes, and 10.7% and 11.7% of patients had surgical and obstetrical causes for AKI, respectively. Previous studies have shown that medical, surgical, and obstetrical causes accounted for 77.5%–87.6%, 8.3%–9.4%, and 3.4%–14.2% of cases, respectively.[2,23,24] Our observation thus stands comparable to the previous Indian data.

In the current study, sepsis was found to be the most common cause of AKI in critically ill patients,[25,26] accounting for 52.1% of the cases. UTI was the major contributor responsible for 17.4% of sepsis-associated AKI. A study from India reported UTI as the most common source of sepsis-related AKI in critically ill patients.[7] UTI may cause sudden deterioration in renal function. Further, hypovolemia, hypotension, sepsis, the use of nephrotoxic drugs, contrast media, and urinary obstruction are risk factors for AKI in UTI patients.

Scrub typhus emerged as the second leading (13.0%) cause of sepsis-associated AKI in the current study. It is observed that scrub typhus is an important cause of acute undifferentiated febrile illnesses in the Indian subcontinent, and thus, it should be a part of the differential diagnosis of acute febrile illness with AKI. Although scrub typhus was the leading cause of AKI in a hilly region, due to changing scenario, it has been found to have become the second leading cause of AKI in the plane region. AKI is thought to be a consequence of multiorgan dysfunction secondary to sepsis.[7] Another study from India has reported that scrub typhus is a leading cause (53.1%) of AKI.

Leptospirosis, a spirochetal zoonosis, was responsible for AKI in 4.3% of patients. The incidence of AKI in leptospirosis varies from 10% to 60%, depending on the severity of the disease, age, and definition of AKI. AKI in leptospirosis is primarily nonoliguric. Several factors are involved including the direct nephrotoxic action of the Leptospira, hyperbilirubinemia, rhabdomyolysis, and hypovolemia.[24,27]

The third common source of sepsis in our study was pneumonia (8.7%). Murugan et al. reported AKI in 34% of patients with community-acquired pneumonia (CAP) and commonly in nonsevere CAP.[28] Another study reported 9.1% of AKI associated with sepsis secondary to pneumonia.

In this study, hypovolemia due to diarrheal illness caused AKI in 10.86% of patients in this study. This was less than the earlier reported research of 20.6%.[29] This decline is attributed to patient education regarding oral rehydration, improvements in hygiene and health infrastructure resulting inadequate management, and decreasing referrals to tertiary centers. A similar decline in diarrhea-related AKI has been reported in India by Prakash et al.[3]

A higher cumulative fluid balance is an independent risk factor for mortality in AKI. In the current study, the cumulative fluid balance was comparable among survivors and nonsurvivors. A positive balance exceeding 10% of total body weight or an absolute gain of 5.9 L is proposed as the defining limit for increased mortality in patients with AKI.[30,31] In the current study, the cumulative balance was much lower, with a median of 1 L, which might not have been sufficient enough to enhance the mortality risk. Our study result was compatible with Priyamvada et al.[32] where the cumulative balance was much lower, approximately 1 L.

Acute pancreatitis accounted for 3.5% of the cases in the present study. AKI is one of the most common complications in patients with severe acute pancreatitis. As per the study done by Patel et al incidence of AKI due to acute pancreatitis was 20%. This high incidence of AKI might be the result of hypoxemia, release of pancreatic amylase from the injured pancreas with impairment of renal microcirculation, decrease in renal perfusion pressure due to abdominal compartment syndrome, intra-abdominal hypertension, or hypovolemia.[33]

It was observed that toxins caused AKI in 10.0% of the cases. It included biological toxins (5.6%) and nephrotoxic medications (4.3%). AKI due to snake bites is an important cause of CAAKI in tropical countries. About 12%–30% of patients bitten by venomous snakes, primarily vipers, develop AKI. Hemorrhage, hypotension, disseminated intravascular coagulation (DIC), intravascular hemolysis, and rhabdomyolysis contribute to the development of AKI. Enzymatic activities of snake venoms account for direct nephrotoxicity. Immunologic mechanism plays a minor role. Mortality in snake bite-induced AKI is 1%–20%.[30,31] Early administration of anti-snake venom is a vital therapeutic measure. Treatment of established AKI is largely supportive in nature, RRT being the cornerstone.[34]

In the current study, 4.3% of patients developed AKI secondary to nephrotoxic drugs. The majority (8.3%) developed AKI during hospital stay. The drugs accounted for 66.7% of cases of HAAKI. Drug-induced AKI accounted for 20% of all AKI in an Indian study; aminoglycosides accounted for 40% of such cases.[35] The decreased incidence in our study which has been done 20 years later reflects the increasing awareness of nephrotoxic medications among the medical professionals and the general public. The etiology of drug-related AKI in our country has changed. Earlier, antibiotics were the most common cause followed by analgesics and contrast media. The variety of drugs associated with AKI in our study shows consistency with the changing epidemiology of drug-related AKI observed by Prakash J et al.[3]

Surgical causes accounted for AKI in 10.8% of patients which is comparable to the incidence reported in other studies.[2,24,29] Of these, 6.9% of patients had obstructive uropathy, and the other 3.9% were postoperative AKI. Whereas trauma, drugs, and cardiovascular surgery are the leading causes of surgical AKI in developed nations, obstructive uropathy constitutes a major cause of surgical AKI in developing countries like India. Obstructive uropathy was secondary to renal or ureteric calculi, carcinoma cervix, and prostatic enlargement. Postoperative AKI accounted for 4.1% of all cases of HAAKI in our study. Another study reported 21% of cases of HAAKI.

AKI is one of the most challenging complications of pregnancy in developing countries and is frequently related to suboptimal antenatal care, noninstitutional delivery, and unsafe abortion practices. Most cases occur during the third trimester and postpartum related to PE, eclampsia, placental abruption, PPH, DIC, and puerperal sepsis.[36]

In India, improvements in obstetric care have decreased obstetric AKI to 10%–12%.[3] However, medical care for pregnant women is still deficient, and hospital referral in pregnancy-related AKI (PRAKI) is generally delayed. Renal ischemia, caused by hemorrhagic shock or hypotension due to sepsis, is one of the dominant factors leading to AKI. In our study, obstetric AKI was 11.7%, and puerperal sepsis was the most common cause, followed by severe PE and PPH. In our previous reported study, PRAKI was 11.5%.[36]

Contrary to the high mortality in developed countries, AKI-associated mortality is lower (10%–40%) in developing countries because AKI affects younger people and is caused by a single disease, i.e. less commonly associated with multiorgan dysfunction syndrome (MODS).[3] Moreover, in developing countries, CAAKI is commonly due to volume-responsive azotemia, which is rapidly reversible on volume correction. In other words, mortality is high in AKI when associated with MODS.[3] The overall mortality rate in this study was 19.5%. Mortality associated with HAAKI was 13.0% compared to 6.5% with CAAKI patients. Another study reported 8.7% mortality.[24]

Only 22.6% of patients required RRT for AKI. RRT requirements in previous studies on CAAKI have been variable, ranging from 7.8% (UK) to 36% (Spain) to 53% (Himachal Pradesh) to 83% (Lucknow).[2,29,37] A study done by A. Kaul et al.[2] in CAAKI patients, showed requirements of RRT was 83%. In this study high percentage of RRT was most likely due to study conducted in a specialised Nephrology Department where more severe AKI cases was admitted. Complete renal recovery and partial renal recovery were seen in 169 (73.4%) and 8 (3.4%) patients, respectively. Our results are comparable to the study by Kaul et al.,[2] where 44% had CR, whereas 13% had PR. However, in the study by Kumar et al.,[29] CR was seen in almost 70%.

Our study demonstrated that AKI was largely a CAAKI and a lesser percentage was HAAKI. Sepsis, hypovolemia, envenomation, nephrotoxic drugs, and chemical were the main etiologies of AKI and were associated with significant mortality. Many causes are potentially preventable requiring the adoption of a public health approach, including the provision of safe water, infection control, vector management, better obstetric care, and campaigns to raise awareness about the safe use of drugs, pesticides, and chemicals. Early fluid resuscitation, effective anti-infective treatment, appropriate antidotes, and timely referral of patients with established AKI to centers with dialysis facilities will improve outcomes.

CONCLUSION

This study describes the clinical-etiological spectrum of AKI among hospitalized adults at a tertiary care hospital in India and describes the risk factors and in hospital outcomes of AKI. This unique spectrum represents CAAKI and HAAKI from urban and rural areas. Results from this study will elucidate the epidemiologic characteristics and burden of AKI in India.

Our study has certain limitations. First, because the study was carried out at a tertiary care hospital, it does not truly reflect the etiological spectrum of AKI prevalent throughout the country. Second, pediatric patients were excluded. Finally, the long-term outcome could not be studied in our patients due to lack of such follow-up. Nevertheless, our study describes very relevant information on the adult AKI spectrum encountered at a large tertiary care referral center in a developing country.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.