BACKGROUND
Acute pyelonephritis (APN) is the most common bacterial infection involving the upper urinary tract system, including the renal parenchyma and pelvis. APN accounts for nearly 200,000 hospital admissions each year in the United States.[ 1 ] Complications include renal abscess, septic shock, and renal impairment (acute kidney injury [AKI]/acute on chronic kidney disease [CKD]). The association between APN and AKI is reported predominantly as only sporadic case series.[ 2–5 ] In this study, we intend to determine the incidence and risk factors for AKI in patients hospitalized with AKI and their clinical outcomes.
MATERIALS AND METHODS
This is a single-center prospective longitudinal study conducted at Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, Uttar Pradesh, India. All patients admitted with APN from December 2018 to May 2020 were included. The study was approved by the hospital ethics committee. Since this is an observational study, the patient participation consent was waived off by the institutional ethics committee. The demographic data, clinical details, and laboratory data of patients admitted with APN were noted. APN was defined as the presence of two of the following: (a) axillary temperature ≥38.3°C or chills; (b) flank pain or costovertebral angle tenderness; and (c) two or more of the following: dysuria, frequency, suprapubic pain, or urgency together with the presence of leukocyturia with more than ten leukocytes/mL of urine or more than five leukocytes per high-power field in centrifuged sediment or positive urine culture. Urine colony-forming units >105 were considered significant. Imaging in the form of an ultrasound abdomen and/or computed tomography (CT) scan was done based on the clinical situation. Findings suggestive of APN included unilateral or bilateral bulky, focal/diffuse hypoechoic or hyperechoic kidneys with or without perinephric fat stranding, gas in the renal parenchyma, perinephric collection, and/or renal abscess. Acute kidney injury was defined arbitrarily as serum creatinine >1.5 mg/dl, and anemia was defined as hemoglobin levels of <11.5 g/dl. Patients were treated with antibiotics as per culture sensitivity reports. All patients were given parenteral antibiotics for a minimum of 1 week, followed by oral antibiotics for a minimum total antibiotic duration of 2 weeks. Double J (DJ) ureteral stenting was done as indicated after an opinion from an urologist. Pigtail drainage of the perinephric or renal abscess was done as per the opinion from an urologist. A Foley’s catheter was introduced in patients with features of subvesical obstruction such as benign hyperplasia of prostate, urethral structure, uterovesical prolapse, and neurogenic bladder. Outcomes were divided into death, recovery of renal function, and persistent renal dysfunction at 3 months (CKD). Dialysis was initiated in patients with intractable hyperkalemia, intractable metabolic acidosis, advanced uremia, and signs of volume overload. Patients with hydroureteronephrosis were attached to urology and/or gynecology services as required.
Statistical analysis
Continuous data are presented as mean ± standard deviation (SD). Non-parametric data are expressed as median and range. The Chi-square test and Fisher’s exact test were used to compare categorical variables. Mann–Whitney U -test was used to compare nonparametric continuous variables for two groups. Wilcoxon signed-rank sum test was used for nonparametric continuous dependent variables. Statistical package for social sciences for windows version 25.
RESULTS
Ninety-five patients were included. Table 1 lists the baseline characteristics at hospital admission. Renal dysfunction at presentation was seen in 79/95 (83.2%) patients. 31/79 (39.2%) patients with AKI required dialysis during the hospital stay. The incidence of AKI was 2.4 times higher in men compared to women; P = 0.013. The mean age of patients with AKI was 56.87 ± 15.16 years versus 49.75 ± 15.42 years in non-AKI patients; P = 0.12. The mean duration of symptoms before hospitalization in patients with and without AKI was 8.30 ± 2.72 and 5.31 ± 0.91 days, respectively; P = 0.001. 73/79 (92.4%) patients with AKI had anemia as against 2/14 (14.2%) patients without AKI; P < 0.001. 38/67 (43.2%) patients with AKI had CT and/or ultrasonography (USG) documented bilateral pyelonephritis as against only 1/16 (6.25%) patients without AKI; P = 0.007. AKI developed in 100% of the patients with known CKD at baseline and 41.6% of the patients with normal baseline kidney function; P < 0.001. The mean creatinine at presentation in patients with baseline CKD and normal renal functions at baseline was 7.6 ± 3.4 mg/dl and 2.62 ± 2.7 mg/dl, respectively; P < 0. 001. Diabetes mellitus was present in 29/79 (36.7%) patients with AKI and 6/16 (37.5%) patients without AKI; P = 0.31. Hydroureteronephrosis was present in 29/79 (36.7%) patients with AKI as against 9/16 (52.9%) patients without AKI; P = 0.12. Leukocyturia was absent in 13.7% of the patients with the diagnosis of APN. There was no significant risk difference for AKI based on the presence of diabetes mellitus, degree of leukocytosis, culture positivity, and hydroureteronephrosis. DJ ureteric stenting was done in 29/95 (30.5%) patients. Pigtail drainage of the perinephric collection was done in one patient. CT images of a few of the patients in the study are shown in Figures 1 -4 .
Table 1: Baseline characteristics at hospital admission
Figure 1: Axial section of CECT shows left renal abscess along anterior cortex extending into perinephric space and left lateral abdominal wall with associated pyelonephritis and pyonephrosis. CECT: Contrast-enhanced computed tomography
Figure 2: Axial and coronal CECT images show enlarged right kidney with multiple intraparenchymal renal abscesses with small bubbly linear streaks of gas within the pelvicalyceal system with calculus at PUJ consistent with xanthogranulomatous pyelonephritis. CECT: Contrast-enhanced computed tomography
Figure 3: Axial and coronal noncontrast images show isodense polypoidal intraluminal mass lesion consistent with neoplastic etiology involving right lateral wall of urinary bladder extending into the bladder base and prostatic parenchyma. CECT: Contrast-enhanced computed tomography
Figure 4: Axial CECT image shows multiple peripherally enhancing renal abscess on both sides extending into perinephric space with associated pyelonephritis. CECT: Contrast-enhanced computed tomography
Outcome
Of the total of 95 patients, 6 (6.3%) patients died during the hospital stay. All these patients had renal dysfunction at presentation. 31/79 (39.2%) patients with AKI required dialysis during the hospital stay. At 3 months, renal functions normalized in 38/79 (48.1%) patients and 8/31 (25.8%) patients remained dialysis-dependent. 32/35 (91.4%) patients with persistent renal dysfunction and 7/8 dialysis-dependent patients had CKD at baseline. The baseline status was not known in the 8th patient. However, since her kidney functions did not improve after treatment of obstruction, she is believed to have had obstructive nephropathy in the context of long-standing obstruction. Patients with AKI had significantly increased duration of hospital stay 11.65 ± 5.9 versus 5.81 ± 0.91 days; P < 0.001. The results are summarized in Table 2 .
Table 2: Characteristics of patients of acute pyelonephritis with and without acute kidney injury
DISCUSSION
In our study, the incidence of AKI in patients with APN was 83.2%. In a similar study from Korea,[ 6 ] the incidence of AKI was 61.2%. Another Taiwanese cohort study of 790 patients reported a 2.63-fold (95% confidence interval: 1.53–4.56) increase in the odds of AKI in patients with pyelonephritis compared with patients admitted with lower urinary tract infection.[ 7 ] The reason for the higher incidence of AKI in our study might be due to the delayed presentation to the hospital, given poor socioeconomic status and less access to health-care facilities. The incidence of AKI was 2.4-fold high in men than women. Similar results of increased incidence of APN in men were reported in a study from South India by Umesha et al .[ 8 ] This is in contrast to Western studies.[ 9–11 ] The reason might be local gender differences in seeking medical care. CKD is considered an important risk factor for AKI in several infectious diseases.[ 7 , 12 , 13 ] Our study revealed that the incidence of AKI was higher in patients with baseline CKD. Patients with baseline CKD had more severe AKI compared to patients with normal renal functions. Similar results were shown by Jeon et al .[ 6 ] in a study from North Korea. According to some studies, rates of new onset of CKD after AKI range from 7% to 20% over a follow-up of 1–3 years.[ 14–16 ] However, in our study, all patients with AKI without baseline CKD had normal renal functions at the end of 3 months. In our study, USG/CT abdomen documented that bilateral pyelonephritis was associated with a higher incidence of AKI. Similar findings were noticed by Jeon et al .[ 6 ] AKI was significantly associated with anemia. This might be secondary to poor nutritional status with additional contribution from underlying CKD. Urine culture was positive in 54.7% of the cases in our study. Positivity rates of 48% were reported by Umesha et al .[ 8 ] Low rates of culture positivity might be due to prior use of antibiotics at home before presentation to the hospital. Escherichia coli was the most common organism grown in 31 cases accounting for 59.6% of all positive cultures, followed by Enterococcus faecalis in 10 patients. 7/31 (22.6%) E. coli isolates were extended-spectrum beta-lactamase. In a similar study including 800 patients, E. coli was responsible for 63% of the episodes.[ 17 ] This etiological spectrum and the increasing proportion of ESBL and multiresistant microorganisms demand a special effort in the etiological diagnosis of APN. There was no difference in the AKI incidence between culture-positive and culture-negative groups. Blood culture was done in 45 patients and turned out to be positive in only 6 patients. Four of six patients had the same growth in urine and blood culture. Urine culture was negative in two patients with Staphylococcus aureus septicemia. The discordance between the results of the urine and blood cultures in uncomplicated APN does not usually exceed 2%–3%, which explains why some suggest just a urine culture in these cases.[ 18 , 19 ] Patients with AKI had a significantly longer duration of symptoms before presentation to the hospital. The reason might be the use of inappropriate antibiotics and use of medications such as nonsteroidal anti-inflammatory drugs at home for pain flanks and fever. A recent study found that diabetes, upper urinary tract infection, and CKD were independent risk factors for developing AKI in patients with urinary tract infection.[ 7 ] Our cohort did not show any relation of development of AKI with diabetes mellitus. The possible explanation could be the fact that the glycemic control as assessed by HbA1C was not significantly different between the two groups in our cohort and the number of patients with diabetes mellitus was not large enough to draw firm conclusions. The patients with AKI had prolonged hospital stay as is expected for any form of AKI. Patients with even mild AKI are known to experience higher mortality than those without AKI,[ 20 ] and the role of AKI as an independent risk factor for mortality is well known.[ 21–23 ] Mortality associated with APN ranges between 3.2% and 9.8%.[ 24–26 ] Of the total of 95 patients, 6 (6.3%) patients died during the hospital stay. One of them had emphysematous pyelonephritis [Figure 2 ], two patients had underlying malignancies (one with bladder and the other with metastatic lung malignancy), one patient had severe sepsis with multiorgan dysfunction syndrome, and two patients had concomitant CKD and hepatitis C-related cirrhosis.
The study has certain limitations. It is a small study with a lesser number of patients. A larger study will be required to confirm the above findings. Baseline kidney functions were unknown in more than 50% of the patients. It is hard to predict if AKI was the consequence of pyelonephritis in all the cases or was secondary to antibiotic-induced acute interstitial nephritis and/or NSAID-induced acute tubular and/or interstitial injury.
CONCLUSIONS
AKI is a common complication of APN. It is usually reversible with early and appropriate management. Male gender, anemia, bilateral pyelonephritis, baseline CKD, and delayed presentation to hospital are associated with increased risk of AKI. It is associated with an increased risk of dialysis, hospitalization days, and mortality.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
Dr. Imtiyaz Wani, Professor of Nephrology for his guidance during the conduct of the study.
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