Abstract

Objectives: Acute Kidney Injury (AKI) may be prevalent among patients with urinary tract infection, in the presence of certain risk factors. We aim to identify the prevalence, risk factors and outcomes of AKI among that patient population.

Methods: A retrospective cross-sectional study was conducted. Hospitalized patients with urinary tract infection who had at least two serum creatinine measurements were selected. The KDIGO definition of AKI was applied. The outcomes were baseline and discharge serum creatinine changes, renal recovery, and requirement of dialysis and in-hospital mortality. Analysis was performed using the unpaired t-test, two sample t-test, Pearson’s Chi square and binary logistic regression, as indicated.

Results: Sixty-four percent developed AKI in which 47% were found to have Stage I, 24.2% Stage II, 28.8% Stage 3 AKI and 64.6% regained serum creatinine around their baseline. Younger age < 40 years had lower risk of AKI (ORs 0.36; 95% CI 0.190.67; p=0.001). Mean ± SD baseline serum creatinine and discharge serum creatinine were significantly higher in UTI-AKI patients (63.2 ± 21.2 vs 97.1 ± 67.8 µmol/L (p=<0.001) and 62.5 ± 23.1 vs 130.9 ± 151.2 µmol/L (p=<0.001), respectively, with wider variance ratio (p=<0.001). A higher risk of AKI was observed in patients with CKD and ICU admission. (ORs 11.4; 95% CI 1.46, 88.97; p=0.020, ORs 9.6; 95% CI 1.15,80.25; p=0.036, respectively). Usage of antihypertensives and PPIs increased the risk of AKI (95% CI 1.08, 3.31; p=0.024 and 95% CI 1.138, 3.167; p=0.014). Three percent required dialysis. Mortality was 0.6% in patients with AKI.

Conclusion: Acute Kidney Injury was highly prevalent among patients with urinary tract infections, with the majority being classified as stage 1 AKI. Higer baseline and discharge serum creatinine changes were found in UTI-AKI patients. Patients with underlying CKD, ICU admission, and on antihypertensives or Proton Pump Inhibitors (PPIs) were at significantly higher risk of AKI.

Keywords

Urinary Tract Infection; Urosepsis; Acute Kidney Injury; Pyelonephritis; Antihypertensives; Ppis

Introduction

Sepsis is the leading cause of hospital-acquired Acute Kidney Injury (AKI) [1], and Urinary Tract Infection (UTI) is notoriously the commonest bacterial infection [2]. AKI is associated with high morbidity, mortality, prolonged hospital stays and the subsequent development of Chronic Kidney Disease (CKD) [3-5]. The prevalence of AKI is alarming, up to 7% of hospital admissions and 30% of Intensive Care Unit (ICU) admissions. It carried higher morbidity and mortality to the certain population such as post-cardiac arrest patients who required dialysis, surgical patients received general anaesthesia or non-general anaesthesia and neonates with encephalopathy [6-8]. Thyagarajan, et al. (2021) reported that despite the increasing cost, 62% per year reduction of mortality among all-cause AKI-hospitalisation [9]. A meta-analysis by Melo, et al. concluded that AKI outcomes were worse in developing countries compared to developed countries [10]. Singh, et al. (2013) found that sepsis was the most frequent cause of hospital-acquired AKI in the ICU and surgical wards [11]. Regarding AKI in the ICU, Magboul, et al. (2020) concluded that diabetes mellitus, hypertension, and sepsis were among the risk factors [12].

Pathophysiology of AKI

Although not fully understood, the pathophysiology of AKI is typically divided into pre-renal, intrinsic renal and post-renal categories. Pre-renal AKI involves a reduction in Renal Blood Flow (RBF), causing decreased glomerular Filtration Rate (GFR) [13]. Intrinsic renal causes of AKI typically involve injury to the tubules, glomeruli, intra-renal blood vessels, or the interstitium [14]. AKI due to tubular injury is referred to as Acute Tubular Necrosis (ATN), the most common cause of hospital-acquired AKI [15]. Other intrinsic causes include acute Glomerulonephritis (GN), injury to intrarenal arteries, and acute interstitial nephritis, which is commonly associated with infections or drugs [16]. In post-renal or obstructive uropathy, the driving force of filtration diminishes due to rising tubular pressure. Vasoconstriction of arterioles and inflammatory processes also contribute to decreased GFR after obstruction [17].

Defining AKI

Acute Kidney Injury is diagnosed when absolute serum creatinine (SCr) rises ≥ 26.5 µmol/L (0.3 mg/dL) in past 48 hours or with a rise of SCr more than twice from the baseline in past seven days or urine output <0.5 ml/Kg/hour in past 6 hours [18].

UTI and AKI

Systemic vasodilation in sepsis contributes to a reduction in renal blood flow, which may lead to an initial ischemic insult. This triggers the release of inflammatory mediators such as free oxygen radicals, proteolytic enzymes, and cytokines, resulting in damage to the glycocalyx in the peritubular capillaries and the tight junctions, particularly in the kidney’s outer medulla. Interstitial inflammation and edema further exacerbate ischemia. Even after renal blood flow is restored, cellular damage continues [19-20]. Urinary tract infections can also directly or intrinsically damage the kidneys. Damage to tubular cells disrupts the tight junctions between them, reducing the effective Glomerular Filtration Rate (GFR) via a leak-back mechanism. When the damaged tubular epithelial cells are shed into the tubules, they may form obstructive casts, blocking urine flow and leading to oliguria [21-22].

Materials and Methods

Ethical issues

The research followed the tenets of the Declaration of Helsinki. Ethical approval for the study was granted by the Ethics Committee of the Faculty of Medical Sciences, University of the West Indies Mona, Jamaica with approval number CREC-MN.014, 2022/2023.

Study design

This study was a retrospective cross-sectional study to evaluate the prevalence, risk factors and adverse renal outcomes of UTI patients with AKI. The patients included were either diagnosed with symptomatic UTI or pyelonephritis or urosepsis during their admission from January 1, 2019, to December 31, 2021.

Data collection

Data were obtained between 2^nd January 2023 to 30^th April 2023 from the electronic data system of the University Hospital of the West Indies, Jamaica for the research purpose. Data extraction included the patients’ age, gender, pre-existing comorbidities, baseline serum creatinine, peak serum creatinine, serum creatinine at discharge, hourly urine output, need for dialysis, mortality during admission, microorganisms identified in urine culture, ICU admission, potential nephrotoxic medications administered during admission, and laboratory values at presentation. Data were de-identified. Data entry was done into a password-protected Microsoft excel file. The authors have no access to information that could identify the individual participants during or after data collection. According to the calculation, the minimum size of the sample required was 292.

Statistical analysis

Data from Microsoft excel was transferred to the IBM SPSS as well as Stata software for statistical analysis. Patients were divided into UTIAKI and UTI without AKI. Categorical and numerical variables were appropriately classified. Two-sample t-test was applied to compare the mean and unpaired t-test variance ratio was applied to check the significance of variance ratio between two groups. In the presence of outliers in baseline, peak and discharge serum creatinine of both groups, two-sample Wilcoxon Rank-Sum (Mann-Whitney) test was also applied to compare the sum of median (P50). Dichotomous categorical data of AKI, UTI, gender, requirement of dialysis and mortality were analyzed using the Pearson Chi-square test. Differences were expressed as Odds Ratios (ORs) with 95% Confidence Intervals (CIs). Binary logistic regression was conducted on comorbidities and medications in association with the development of UTI. The data were analyzed with the aim of accepting (H0) or rejecting the null hypothesis (Ha). Statistical significance was defined as a p-value <0.05. All statistical analyses were conducted using IBM SPSS version 29 as well as Stata 18.

Primary and Secondary Outcomes

Primary Outcomes:

• Prevalence of AKI

The proportion of hospitalized patients with Urinary Tract Infections (UTIs) who develop acute kidney injury (AKI).

• Renal Recovery

Categorization of renal recovery among AKI patients from the time of diagnosis to discharge or death:

• Complete Recovery: Serum creatinine (SCr) returns to baseline levels.

• Partial Recovery: SCr improves but does not return to baseline.

• No Recovery: No improvement in SCr, indicating permanent kidney damage.

The comparison of serum creatinine was made between baseline and peaked and/or last serum creatinine before discharge or death, with a variation of ± 26.5 μmol/L.

Secondary outcomes: Requirement of dialysis and in-hospital Mortality.

Inclusion and exclusion criteria

Key inclusion criteria were hospitalised patients between January 1, 2019 to December 31, 2021, age ≥ 18 years old who were diagnosed with symptomatic urinary tract infection or pyelonephritis or urosepsis in their record summaries with at least two serum creatinine measurements within seven days. Persons were excluded if they were asymptomatic for urinary tract infections or no urine culture done or culture report with indeterminate/contaminated findings or having concomitant other infections or creatinine measurement < 2 times within seven days or has been on dialysis prior to the admission (Figure 1).

Figure 1: Flow diagram of screening and inclusion.

Results

There were 309 patients with UTI selected for final data analysis in which 182 patients had symptomatic UTI, 64 patients had pyelonephritis, and 63 patients had urosepsis. Of these patients, 199 (64.4%) were found to have AKI. The mean age of the patients with AKI was 69 ± 17.3 years and the mean age of non-AKI patients was 62.6 ± 21.5 years. Among the patients with AKI, 97 were males, and 102 were females. The UTI patients without AKI had mean ± SD baseline SCr 63.2 ± 21.2 µmol/L (95% CI 59.2,67.2) whilst UTI-AKI patients had Mean ± SD baseline SCr 97.1 ± 67.8 µmol/L (95% CI 87.6, 106.6). Regarding peak SCr, the UTI without AKI patients had mean ± SD of 70.9 ± 28.5 (95% CI 65.6, 76.3) and UTI-AKI patients had Mean ± SD of 261.6 ± 243.9 µmol/L (95% CI 227.5, 295.7). On discharge, Mean ± SD for UTI without AKI group and UTI-AKI groups were 62.5 ± 23.1 µmol/L (95%CI 58.1,66.9) and 130.9 ± 151.2 µmol/L (95% CI 109.7,151.9), respectively with a significant variance ratio (p= <0.001). The unpaired variance ratio t-test of baseline and discharge serum creatinine revealed that UTI-AKI group had significantly higher baseline and discharge SCr with wider variance compared to non-AKI group (p= <0.001 for both). Comparison of baseline, peak and discharged serum creatinine levels are shown in the figure (Figure 2). In the presence of outliers, especially in UTI-AKI group, further analysis with two-sample Wilcoxon Rank-Sum (Mann-Whitney) test was applied which revealed the p value of <0.001 (p=<0.001 < 0.05=α) for baseline, peak and discharge serum creatinine. It indicated that at the 5% level of significance that median baseline, peak and discharge serum creatinine in UTI without AKI patients were not the same as that for UTI-AKI patients.

Figure 2: Box plot comparison of baseline, peak and discharged serum creatinine of UTI without AKI and UTI-AKI.

The demographics/characteristics of participants are shown in (Table 1).

Characteristics	Population with UTI n=309	UTI with AKI n=199	UTI without AKI n=110	ORs	95% CI	p value
Age (mean ± SD)	66.7 ± 19.1	69.0 ± 17.3	62.6 ± 21.5	NA	NA	NA
< 40 years	48 (15.5)	21 (10.5)	27 (26.3)	0.36	0.194,0.679	0.001
40-65 years	71 (22.9)	49 (24.6)	22 (20.0)	1.3	0.74,2.305	0.355
> 65 years	188 (60.8)	129 (64.8)	59 (53.6)	1.6	0.991,2.56	0.055
Gender
Male	140 (45.3)	97 (31.4)	43 (13.9)	1.18	0.97,1.45	0.093
Female	169 (54.7)	102 (33.0)	67 (21.7)	0.82	0.61,1.054	0.103
Co-morbidities
DM	116 (37.5)	77 (24.9)	39 (12.6)	1.15	0.708,1.864	0.573
HTN	185 (59.8)	130 (42.0)	55 (17.8)	1.32	0.578,2.327	0.322
Cardiac Failure	26 (8.4)	20 (6.4)	6 (1.9)	1.94	0.754,4.977	0.164
CKD	21 (6.8)	20 (6.4)	1 (0.3)	11.4	1.46,88.97	0.02
Acute stroke	54 (17.4)	34 (11.0)	20 (6.4)	17	0.504,1.705	0.808
BPH	41 (13.2)	30 (9.7)	11 (3.5)	0.92	0.767,3.328	0.208
CAD	15 (4.9)	11 (3.6)	4 (1.3)	1.6	0.482,4.99	0.459
Indwelling U-Cath	28 (9.0)	23 (7.4)	5 (1.6)	2.62	0.990,6.962	0.052
Renal calculi	14 (4.5)	10 (3.2)	4 (1.3)	2.9	0.429,4.58	0.574
ICU admission	15 (4.9)	14 (4.5)	1 (0.3)	9.6	1.15,80.25	0.036
Requirement of Dialysis in AKI group	6 (1.9)	6 (3.0)	NA	NA	1.006,1.057	0.066
Overall mortality	2 (0.6)	2 (0.6)	0 (0)	NA	0.996,1.024	0.291
Length of hospital stay (days)	13.5 ± 16.7	15.7 ± 19.6	9.6 ± 8.5	NA	8.0,11.3	0.002

Table 1: Characteristics of UTI with AKI patients admitted between 2019 and 2021 n (%).
DM = Diabetes Mellitus; HTN = Hypertension; CKD = Chronic Kidney Disease; BPH = Benign Prostatic Hyperplasia; CAD = Coronary Artery Disease; HIV = Human Immunodeficiency Virus; SCD = Sickle Cell Disease

Age vs AKI among cases and controls

Only 10.5% developed AKI in the <40 years age category, 24.6% in the 40-65 years old and 64.8% in >65 years old age categories. In non-AKI group, 26.3% were age < 40 years, 20% were age between 40- 56 and 53.7% were age > 65 years. Patients < 40 years old were found to have a lesser rate of AKI (OR 0.3, 95%. CI 0.194, 0.679, p= 0.001) (Figure 3).

Figure 3: Age categories of patients with UTI with AKI vs UTI without AKI.

Relationship between co-morbidities, ICU admission and AKI

Hypertension was the most found co-morbidity among the groups though no significant difference between two groups was observed (p=0.322). However, a significantly higher risk of AKI was found in patients with underlying CKD (OR 11.4; 95% CI 1.46, 88.97; p=0.020). No other statistical significances were observed between two groups in other co-morbidities (Figure 4). In terms of ICU admission, patients who needed ICU admission had a 9 folds higher risk of AKI in presence of UTI (OR 9.6; 95% CI 1.15, 80.25; p=0.036).

Figure 4: Relationship between underlying co-morbidities and AKI-UTI.

Medications and UTI-AKI

Patients who received or continued to receive antihypertensives and proton pump inhibitors were found to have a higher chance for the development of AKI (OR 1.89; 95% CI 1.08, 3.31, p=0.024 and OR 1.89, 95% CI 1.138, 3.167; p=0.014). Use of other medications did not show statistical significance between cases and controls (Table 2).

Medications	Population with UTI	UTI with AKI n =199	UTI without AKI	Ors	95% CI	p value
Use of anti-hypertensive	155 (50.1)	114 (36.8)	41 (13.2)	1.89	1.08,3.31	0.024
ACEIs/ARBs	80 (25.9)	62 (20.1)	18 (5.8)	2.31	1.285,4.162	0.004
Β-blockers	56 (18.1)	44 (14.2)	12 (3.9)	2.32	1.167,4.606	0.014
CCB	84 (27.2)	64 (20.7)	20 (6.5)	2.13	1.208,3.767	0.008
Diuretics	60 (19.4)	47 (15.2)	13 (4.2)	2.3	1.187,4.486	0.012
NSAIDS	76 (24.6)	47 (15.2)	29 (9.4)	0.8	0.506,1.476	0.592
Inotropes	11 (3.6)	10 (3.2)	1 (0.3)	1.3	0.728,45.66	0.062
PPI	193 (62.5)	134 (43.4)	59 (19.1)	1.89	1.138,3.167	0.014
Statins	66 (21.4)	47 (15.2)	19 (6.1)	1.48	0.819,2.679	0.193
Anti-platelet	57 (18.4)	40 (12.9)	17 (5.5)	1.37	0.739,2.565	0.313

Table 2: Medications in relation to the development of UTI-AKI.
ACEIs = Angiotensin Converting Enzyme Inhibitors; ARBs = Angiotensin Receptor Blockers; β-blockers = Beta Blockers; CCBs = Calcium Channel Blockers; NSAIDs = Non-Steroidal Anti-Inflammatory Drugs; PPI = Proton-Pump Inhibitor

Severity and outcomes of UTI-AKI

Of the 199 UTI-AKI patients, 47% were found to have Stage I, 24.2% Stage II and 28.8% Stage 3 AKI according to KDIGO staging (Table 3). In terms of renal outcomes, 64.6% had complete recovery of renal function, 21.7% had incomplete recovery and 13.6% of patients had no improvement in renal function (Figure 5). Six patients with AKI required dialysis. The length of hospital stay is significantly longer in the AKI group with 16 ± 20 days compared to 9.6 ± 8.5 days of controls (95% CI 8.0,11.3, p=0.002). Mortality was observed only in the AKI group (n=6) (Figure 6).

Figure 5: Severity of UTI-AKI patients.

Figure 6: Renal outcomes of AKI patients with UTI.

Parameters	Total sample population with UTI n (%)	UTI with AKI (Cases)	UTI without AKI (controls)	95% CI for mean of total sample population	p value base on mean
Systolic BP (mean ± SD)	126 ± 31	123 ± 32	131 ± 28	118,137	0.21
Diastolic BP (mean ± SD)	71 ± 19	70 ± 20	74 ± 16	73,79	0.073
Laboratory parameters
Hb (g/dL)	11.8 ± 2.7	11.7 ± 2.8	12.0 ± 2.5	11.5,12.5	0.124
WBC (x109/L)	13.8 ± 7.9	14.7 ± 8.3	12.3 ± 6.8	10.9,15.9	0.009
Neutrophil %	74.4 ± 16.2	76.3 ± 16.9	71.0 ± 15.2	67.9,78.5	0.006
Platelet count (x109/L)	261 ± 122	250 ± 121	281 ± 123	233.2,305.1	0.543
Baseline Scr (µmol/L)	85 ± 58	97 ± 67	63 ± 21	59.2,106.5	0.012
Peaked SCr (µmol/L)	193 ± 296	261 ± 243	70 ± 28	65.5,295.7	<0.001
Discharged SCr (µmol/L)	106 ± 126	130 ± 151	62 ± 23	58.1,152.0	<0.001

Table 3: Clinical and Laboratory parameters of UTI with AKI and UTI without AKI patients (2019 to 2021).
Hb = Haemoglobin; WBC = White Blood Count; SCr = Serum Creatinine

Micro-organisms associated with UTI

The most common causative agent for UTI gathered from this study was Escherichia coli (32.6%) which is followed in prevalence by ESBL (17.8%), Klebsiella (16.2%), Enterococcus (8.7%), Proteus (5.2%), Pseudomonas (4.9%) and Enterobacter (3.9%). Infrequent causes of UTI include Providencia spp (1.3%), Acinetobacter (0.6%), Yeast/Fungi, Streptococcus and Staphylococcus species (1.9% each), Morganella morganii (1%) and non-fermenting GNB (0.3%). Remarkably Salmonella was seen in only 1 patient of the study population (0.3%) which was that of a patient with SCD (Table 4).

Organism Grown on culture	Total population with UTI n (%)	UTI with AKI n (%)	UTI without AKI n (%)	ORs	95% CI	p value
E. coli	101 (32.7)	62 (20.1)	39 (12.6)	0.82	0.503,1.348	0.44
ESBL	55 (17.8)	39 (12.6)	16 (5.2)	1.43	0.759,2.703	0.266
Klebsiella	50 (16.2)	34 (11.0)	16 (5.2)	1.21	0.635,2.31	0.562
Proteus	16 (5.2)	11 (3.6)	5 (1.6)	1.22	0.416,3.632	0.709
Enterobacter	12 (3.9)	9 (2.9)	3 (1.0)	1.69	0.448,6.375	0.434
Acinetobacter	2 (0.6)	2 (0.6)	0 (0)	NA	NA	NA
Pseudomonas	15 (4.9)	9 (2.9)	6 (1.9)	0.82	0.284,2.371	0.715
Enterococcus	27 (8.7)	20 (6.5)	7 (2.3)	1.64	0.672,4.02	0.272
Providencia	4 (1.3)	1 (0.3)	3 (1.0)	0.18	0.019,1.753	0.098
Staphylococcus	6 (1.9)	5 (1.6)	1 (0.3)	2.78	0.321,24.133	0.333
Streptococcus	6 (1.9)	5 (1.6)	1 (0.3)	2.78	0.321,24.133	0.333
Salmonella	1 (0.3)	1 (0.3)	0 (0)	NA	NA	NA
Morganella morganii	3 (1.0)	2 (0.6)	1 (0.3)	1.1	0.099,12.343	0.934
Non-Fermenting GNB	1 (0.3)	1 (0.3)	0 (0)	NA	NA	NA
Yeast/Fungi	6 (1.9)	5 (1.6)	1 (0.3)	2.78	0.321,24.133	0.333

Table 4: Organisms grown on blood/urine culture among patients with UTI and its’ association with AKI n=309.

Sensitivity to antimicrobial agents on urine culture

Based on the selected anti-microbial plates used for the sensitivity tests on urine culture, Gentamycin was the most sensitive antibiotic for E Coli (66.3%). In terms of other micro-organisms grown on culture, ESBL (90.9%), Klebsiella (56%) and Acinetobacter (100%) were most sensitive to Meropenem. proteus was most sensitive to Cefuroxime (68.8%), Pseudomonas most sensitive to Ceftazidime (73.3), Enterococcus most sensitive to Ampicillin (74.1%), Providencia spp most sensitive to Gentamycin (75%) and Enterobacter spp most sensitive to both Meropenem and Co-amoxiclav (83.3% respectively) (Table 5).

Table 5: Microorganisms and minimum rate of sensitivity to tested antibiotics on the samples taken for blood and urine culture from the patients with UTI.
E. coli = Escherichia coli; ESBL = Extended Spectrum Beta-Lactam; Kleb = Klebsiella; Staph = Staphylococcal sp; Abs = antibiotics; Amik = Amikacin; Ampi = Ampicillin; Cefta = Cefazidime; Ceftr = Ceftriaxone; Cefur = Cefuroxime; Cipro + Ci8profloxacin; Clind = Clindamycin; Co-amox = Co-amoxiclav; Co-tri = Co-trimoxazole; Genta = Gentamycin; Imi = Imipenem; Levo = Levofloxacin; Mero = Meropenem; Metro = Metronidazole; Mino = Minocycline; Nitro = Nitrofurantoin; Norfl = Norfloxacin; Oxa = Oxacillin; Polym = Polymyxin; Tiga = Tigacycline; Vanco = Vancomycin; Zosyn = Piparcillin/Tazobactam

Antibiotics used to treat the sampled population with UTI

Beta Lactams were the most commonly selected antibiotics to treat UTI and among them, ceftriaxone (57.3%) was used most frequently followed by Co-amoxiclav (28.2%), Meropenem (21.7%) and Piperacillin-Tazobactam (15.9%). We found that the agents who are known as potential nephrotoxic agents such as Vancomycin, Amikacin and Gentamicin were the least commonly used drugs to treat UTI (3.6%, 2.9% and 1% respectively) (Figure 7).

Figure 7: Antibiotics selected to treat UTI patients at UHWI between 2019-2021.

Discussion

Data on the prevalence and incidence of AKI related to UTI were scarce. Królicki T, et al. (2022) who focussed on post-renal transplant patients found that the incidence of AKI in UTI with sepsis was 75.2% and in UTI only was 41% [22]. In our study, the prevalence of patients with overall UTI was 64.4%. These indicate that the prevalence of AKI is significantly high and close monitoring of renal function is required for early detection of AKI among hospitalised patients with UTI. We found out that there were significant differences in mean, standard deviation and variance ratio of baseline and discharge serum creatinine among the hospitalized patients with UTI. It indicates that UTI was associated with higher fluctuation of serum creatinine and probable incident CKD.

In terms of potential risk factors which contribute AKI in this population, Fünfstück, R et al. (2006) stated that the rate of UTI is typically higher in the older population. In our study, the mean age of the sample population was 67 years ± 19 years with 40.1% of the cases over 65 years old belonging to the AKI group? Significantly lower risk of AKI was observed in the younger patients <40 years old which supported the role of defence mechanism in the process of renal insufficiency [23]. Other studies indicated that patients at risk for AKI with UTI are those with hypotension, hypovolemia, sepsis, urinary obstruction, contrast media and the concomitated use of nephrotoxic agents [24,25]. Use of anti-hypertensive was a concern according to our findings. The continuation or prescribing antihypertensives significantly increased a substantial risk of AKI in the setting of UTI. It raises a concern that adjustment of anti-hypertensives may be necessary when hypertensive patients engage with UTI. The use of PPIs is also a probable risk factor of AKI. Avoidance of potential nephrotoxic agents should be warranted in patients whose renal function are abnormal at baseline and hemodynamically unstable or at risk for developing AKI.

Hsu, et al. (2008) made a comparison between patients with CKD and patients known to have hospital-acquired AKI and it was revealed that there was an increased risk of AKI once the eGFR less than 60 mL/min/1.73 m2 [26]. In addition to low GFR, Hsiao C, et al. (2015) further broadened the risks associated with AKI among UTI patients. These included older age (OR 1.02, 95% CI 1.00-1.04, P=0.04), Diabetes Mellitus (DM) (OR 2.23, 95% CI 1.35-3.68, P=0002), upper UTI (OR 2.63, 95% CI 1.53-4.56, P=0001) and febrile during hospitalization (OR 1.71, 95% CI 1.04-2.83, P=0036) [27]. Although eGFR was not calculated in this study, we found that the patients with impaired renal function at baseline are more likely to develop AKI in the setting of an associated UTI (OR 11.4; 95% CI 1.46, 88.97; p=0.020). However, there were no statistically higher risks of AKI was found among hypertensive and diabetic patients. Catheter-Associated UTI (CA-UTI) is one of the commonest causes of healthcare acquired infections. The indwelling urethral catheter account for 70-80% of these infections [28]. In this study, the patients with indwelling catheters had a higher rate of AKI (OR 2.62, p=0.052). Hence, prolonged use of indwelling catheters should be limited to reduce the rate of AKI.

In sepsis, the release of Nitric Oxide (NO) is believed to be the culprit of widespread vasodilatation, hypotension and septic shock as NO synthase incubates within the vascular endothelium and releases endotoxins within smooth muscle [29-30]. Unsurprisingly, this study depicted that the mean systolic and diastolic blood pressure were lower in AKI group with symptomatic UTI, pyelonephritis or urosepsis.

Although the risk of CKD after UTI is low, the severity of renal insufficiency can be varied with the virulence of micro-organism and the host’s homeostasis [31]. However, a considerable number of UTI-AKI patients (13.6%) had no improvement in renal functions, indicating the likelihood of CKD and the need for continuous follow in renal outpatient clinics. Unfortunately, we could not get enough follow up data of this sampled population as most patients did not follow up at our institution.

In terms of other outcomes, our study revealed only small numbers of patients with AKI required ICU admission (n=14) and dialysis (n=6). The length of stay in hospital was considerably longer in the patients with AKI 16 ± 20 days (95% CI 8.0, 11.3, p=0.002) with an overall low mortality rate of 0.6% in the AKI group. These adverse outcomes might be further decreased if AKI was detected earlier. New biomarkers, such as Kidney Injury Molecule-1 (KIM1), interleukin-18 (IL-18), cystatin C, and Neutrophil Gelatinase-Associated Lipocalin (NGAL), can detect AKI in vulnerable patients before functional loss occurs, helping to prevent irreversible damage [32]. Further studies on UTI-AKI with using biomarkers would be beneficial.

Conclusion

Patients with UTI had a high prevalence of AKI, with antihypertensives, PPIs, underlying CKD, and hypertension being key risk factors. Higher baseline and discharge serum creatinine among UTI-AKI patients was a concern. Despite low dialysis and mortality rates, renal recovery was poor, and the risk of incident CKD remains a significant concern. Longitudinal studies are needed to further investigate UTI-AKI.

Limitations of the Study

This study has some limitations. Firstly, it was conducted at a single center, predominantly involving Jamaican patients of Afro-Caribbean descent, a population known to be susceptible to AKI. Given that only hospitalized patients were included, the study may not reflect AKI prevalence in less severe cases treated in outpatient settings. These could introduce selection bias and limit the generalizability of the findings. While all eligible patients were included and their characteristics accounted for, the sample size was relatively small, which may have reduced the study’s statistical power and broader applicability to the region’s population.

Secondly, despite urine cultures being collected by qualified nurses, many samples were contaminated. By the time repeat cultures were taken, patients had often already started antibiotic treatment, leading to insignificant or no growth in cultures, which may have affected the study outcomes due to the performance bias.

Thirdly, although medications were administered according to standard patient care guidelines, the use of drugs such as antihypertensives (ACE inhibitors/ARBs, beta-blockers, calcium channel blockers, and diuretics), proton pump inhibitors (PPIs), NSAIDs, inotropes, and other nephrotoxic agents in patients with impaired renal function should have been adjusted or avoided. This may have contributed to selection bias, as medication effects were not fully controlled.

Fourthly, the inability to assess long-term outcomes due to difficulties in obtaining follow-up results after discharge represents a limitation related to incomplete follow-up data. This limits the study’s capacity to evaluate the prolonged impact of AKI on renal function and may underestimate the true burden of incident CKD and other long-term complications.

Finally, attempts to define AKI according to the KDIGO criteria were hampered by inadequate urine output monitoring, with a heavy reliance on serum creatinine changes. This limitation may have resulted in an underestimation of the true incidence of AKI in UTI patients.

Implication for Health Policy/Practice/Research/ Medical education

The high prevalence of AKI among hospitalized UTI patients requires maximum attention. The development of AKI secondary to serious urinary tract infections may be linked to certain modifiable risk factors. Further exploration of unknown risk factors could help reduce the prevalence of AKI and understanding the renal outcomes will be crucial for reducing long-term renal complications.

Ethical Considerations

Ethical issues (including plagiarism, data fabrication, double publication) have been completely observed by the authors.

Availability of Data and Materials

The datasets in this study from the corresponding authors can be available upon reasonable request.

Authors’ Contribution

KK Hoe was the principal investigator of the study. KK Hoe and T. Reid were responsible for conceptualizing the study, designing the protocol, and drafting the manuscript. KK Hoe revised the manuscript, critically evaluated its intellectual content, and prepared the final draft. T. Reid contributed to the final draft, reviewed the manuscript, and critically assessed its intellectual content. Both authors have reviewed and approved the manuscript and take responsibility for the accuracy and integrity of the work.

References

1. Mori T, Shimizu T, Tani T (2010) Septic acute renal failure. Contrib Nephrol 166: 40-46.
2. Foxman B (2002) Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med Suppl 1A: 5S-13S.
3. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT (1983) Hospital-acquired renal insufficiency: a prospective study. Am J Med 74: 243-248.
4. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW (2005) Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16: 3365-3370.
5. Thakar CV, Christianson A, Freyberg R, Almenoff P, Render ML (2009) Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study. Crit Care Med 37: 2552- 2558.
6. Winther-Jensen M, Kjaergaard J, Lassen JF, Køber L, Torp-Pedersen C, et al. (2018) Use of renal replacement therapy after out-ofhospital cardiac arrest in Denmark 2005-2013. Scand Cardiovasc J 52: 238-243.
7. Park S, Lee S, Lee A, Paek JH, Chin HJ, et al. (2018) Awareness, incidence and clinical significance of acute kidney injury after non-general anesthesia: A retrospective cohort study. Medicine (Baltimore) 97: e12014.
8. Kirkley MJ, Boohaker L, Griffin R, Soranno DE, Gien J, et al. (2019) Acute kidney injury in neonatal encephalopathy: an evaluation of the AWAKEN database. Pediatr Nephrol 34: 169-176.
9. Thyagarajan B, Bowline I, Ma L, Saran A, Kumar M, et al. (2021) National Trends in Inpatient Diagnosis of Acute Kidney Injury and Associated Outcomes between 2000 and 2014. Wake Forest Journal of Science and Medicine.
10. Melo FAF, Macedo E, Fonseca Bezerra AC, Melo WAL, Mehta RL, et al. (2020) A systematic review and meta-analysis of acute kidney injury in the intensive care units of developed and developing countries. PLoS One. 15: e0226325.
11. Singh TB, Rathore SS, Choudhury TA, Shukla VK, Singh DK, et al. (2013) Hospital-acquired acute kidney injury in medical, surgical, and intensive care unit: A comparative study. Indian J Nephrol 23: 24-29.
12. Magboul SM, Osman B, Elnour AA (2020) The incidence, risk factors, and outcomes of acute kidney injury in the intensive care unit in Sudan. Int J Clin Pharm 42: 1447-1455.
13. Schrier RW, Wang W, Poole B, Mitra A (2004) Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest 114: 5-14.
14. Basile DP, Anderson MD, Sutton TA (2012) Pathophysiology of acute kidney injury. Compr Physiol 2: 1303-1353.
15. Sharfuddin AA, Molitoris BA (2011) Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol 7: 189-200.
16. Schetz M, Dasta J, Goldstein S, Golper T (2005) Drug-induced acute kidney injury. Curr Opin Crit Care 11: 555-565.
17. Schrier RW, Wang W (2004) Acute renal failure and sepsis. N Engl J Med 351: 159-169.
18. Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120: c179-84.
19. Li L, Bonventre JV (2016) Endothelial Glycocalyx: Not Just a Sugar Coat. Am J Respir Crit Care Med 194: 390-393.
20. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, et al. (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2: 431-439.
21. VA/NIH Acute Renal Failure Trial Network; Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, et al. (2008) Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 359: 7-20.
22. Królicki T, Bardowska K, Kudla T, Królicka A, Letachowicz K, et al. (2022) Acute kidney injury secondary to urinary tract infection in kidney transplant recipients. Sci Rep 12: 10858.
23. Fünfstück R, Ott U, Naber KG (2006) The interaction of urinary tract infection and renal insufficiency. Int J Antimicrob Agents 1: S72-S77.
24. Nahar A, Akom M, Hanes D, Briglia A, Drachenberg CB, et al. (2004) Pyelonephritis and acute renal failure. Am J Med Sci 328: 121-123.
25. Liu J, Yang Q, Lan J, Hong Y, Huang X, et al. (2021) Risk factors and prediction model of urosepsis in patients with diabetes after percutaneous nephrolithotomy. BMC Urol 21: 74.
26. Hsu CY, Ordoñez JD, Chertow GM, Fan D, McCulloch CE, et al. (2008) The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 74: 101-107.
27. Hsiao CY, Yang HY, Hsiao MC, Hung PH, Wang MC (2015) Risk Factors for Development of Acute Kidney Injury in Patients with Urinary Tract Infection. PLoS One 10: e0133835.
28. Stickler DJ (2008) Bacterial biofilms in patients with indwelling urinary catheters. Nat Clin Pract Urol 5: 598-608.
29. Fink MP, Payen D (1995) Role of Nitric Oxide in Sepsis and ARDS. Berlin, Springer.
30. Vincent JL, Zhang H, Szabo C, Preiser JC (2000) Effects of nitric oxide in septic shock. Am J Respir Crit Care Med 161: 1781-1785.
31. Smith JW (1989) Prognosis in pyelonephritis: promise or progress? Am J Med Sci 297: 53-62.
32. Yoon SY, Kim JS, Jeong KH, Kim SK (2022) Acute Kidney Injury: Biomarker-Guided Diagnosis and Management. Medicina (Kaunas) 58: 340.

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Article Information

Article Type: RESEARCH ARTICLE

Citation: Hoe KK, Reid T (2025) Prevalence, Risk Factors and Outcomes of Acute Kidney Injury among Hospitalized Patients with Urinary Tract Infection A Retrospective Cross-Sectional Study. Int J Nephrol Kidney Fail 11(2): dx.doi.org/10.16966/2380-5498.252

Copyright: ©2025 Ali MH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication history: 

Received date: 10 Mar, 2025

Accepted date: 18 Mar, 2025

Published date: 24 Mar, 2025