Acute Kidney Injury Due to Rickettsial Infection - Data from a Tertiary Care Center in Southern India

Introduction

Tropical countries account for nearly 50% of the world’s population, a figure projected to rise to 60% in the coming decade.¹ Many of these nations, especially in Southern Asia and Sub-Saharan Africa, grapple with high burdens of infectious diseases, inadequate sanitation, climate change, limited access to primary care, and poorly regulated traditional medicine. This confluence creates a distinct epidemiological landscape, contributing to a unique AKI burden associated with significant morbidity and mortality. Common tropical infections leading to AKI include diarrheal illnesses, malaria, leptospirosis, scrub typhus, dengue, and hantavirus infections.^1,2

Among these, scrub typhus, caused by Orientia tsutsugamushi^3,4 and transmitted by the bite of an infected mite larva (chigger or Leptotrombidium deliense), poses a substantial public health threat. An estimated 1 billion people are at risk globally,⁵ with ∼1 million annual case reports. Endemic regions include South and Southeast Asia, and parts of Latin America.⁶ Severe disease may involve life-threatening complications such as myocarditis, meningoencephalitis, coagulopathy, Acute Respiratory distress syndrome (ARDS), AKI, and septic shock. Rickettsial-associated AKI occurs in 10-60% of patients.^7-12

Rickettsial-associated AKI often goes unrecognized due to non-specific presentation, which frequently mimics other tropical diseases, making timely diagnosis challenging. This diagnostic dilemma further exacerbates morbidity and complicates patient outcomes. Underdiagnosis can lead to progression toward CKD.^13,14 Reported case fatality rates range from 3% to 50%.¹⁵

Despite increasing recognition of renal involvement in scrub typhus, regional data on prevalence, clinical course, and risk factors remain limited. In this retrospective, single-center study from a tertiary hospital in Southern India, we describe the prevalence of AKI in scrub typhus patients, along with clinical features, laboratory abnormalities, complications, and outcomes.

Materials and Methods

This cross-sectional observational study was conducted on adult patients diagnosed with scrub typhus at R.L Jalappa Hospital, affiliated to Sri Devaraj Urs Medical College, a tertiary care hospital in Kolar, Karnataka, India, between January 2021 and December 2024. Rickettsial infection was diagnosed based on clinical assessment, positive serology using Weil-Felix test (OX antigen subtypes: K, 2, and 19), and indirect immunofluorescent antibody assay (IFA). The study was initiated after obtaining approval from the Institutional Ethics Committee. Informed written consent was obtained from the participants. Autonomy and confidentiality were maintained. Patients with co-infection with dengue, leptospira, and malaria were excluded. Based on the study by Jayaprakash et al.,¹⁶ in Chennai, India, the reported prevalence (p) of AKI in scrub typhus was 18.7% (36/193). Hence, with 5% margin of error (d) and a 95% confidence interval, the minimum required sample size was 106.¹⁶

Demographic details, laboratory parameters (hematological, biochemical, and coagulation profiles), treatment, and outcomes were collected from patient records. AKI was defined and staged according to the KDIGO criteria.¹⁷ AKI, acute hepatitis, ARDS, pneumonia, meningitis, sepsis, and multiorgan dysfunction syndrome (MODS) were considered systemic complications. The difference was compared between patients with and without AKI, focusing on continuous data for demographic characteristics (age) and laboratory parameters. The association of clinical presentations (symptoms and signs), treatment details, and outcomes of rickettsial infection between the patients with and without AKI was also checked.

Results

During the study, fever profile evaluation was performed for over 7000 patients, among whom 176 patients with rickettsial infection fitting the inclusion criteria were considered. Among the 176 patients included in the study, 44 (25%) developed AKI. The clinical presentation, including symptoms and signs, baseline characteristics, and laboratory parameters of the study population have been summarized in Table 1. The mean age of patients was 37.46 ± 16.27 years. For the duration of hospitalization, it was 10.54 ± 5.68 days. Among the 44 patients who developed AKI, all were admitted to intensive care, representing 25% of the total study population. The duration of Medical Intensive care unit/Intensive care unit (MICU)/ICU stay was 5.71 ± 2.69 days. Among patients with AKI, 39 had subtype K (22.15%), five had subtype 2 (2.84%), and none had subtype 19. Among the patients with absent AKI, 113 patients had subtype K (64.2%), 8 had subtype 2 (4.54%), and 11 had subtype 19 (6.25%).

The prevalence of AKI was 25% (44/176), and the prevalence of overall complications was 81% (143/176). The distribution of AKI stages in this study, as per KDIGO guidelines, is as follows:132 (75%) patients had no AKI, 27 (15.3%) had stage 1 AKI, eight (4.5%) had stage 2 AKI, and nine (5.1%) had stage 3 AKI. The month-wise distribution of rickettsial infection and the occurrence of AKI have been presented in Figure 1.

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Figure 1:

Seasonal trends of rickettsial infection.

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Discussion

We present data from 176 patients who tested positive for typhus in our hospital over 4 years from 2021 to 2024. We did not have facilities for ELISA or PCR testing for Orientia tsusugamushi and hence relied on Weil-Felix and IFA for confirmation.

Fever was universal (100%), associated with chills in 95% of patients, cough in 50%, nausea and vomiting in 44%, and dysuria in 23%; however, a skin eschar was seen in only 1%. This could be because eschars are difficult to identify in dark-skinned individuals. Other studies have reported an increasing incidence coinciding with the rainy season, where warm, humid conditions facilitate the proliferation of the mite vectors. However, we found that more cases occurred in the winter months from November to January.

Various previous studies [Supplementary Table 4] have reported AKI incidence in the range of 6.6-45%.^{7,10,11,16-36} In our study, the incidence was 25%, with most patients in KDIGO stages 1 and 2. Dialysis was necessary only in 4% of patients. When patients with AKI were compared to those without, we found that older age, male sex, longer duration of hospitalization, leucocytosis, thrombocytopenia, hypotension, ARDS, and increased liver enzymes predicted a higher risk of AKI. These findings are similar to those of other published literature.^7,10,17,18 Thrombocytopenia and the need for intensive care (ICU) support are significant predictors of AKI in scrub typhus. In our AKI cohort, >50% of the study population proportion (61.5%) had thrombocytopenia, and a substantial number required ICU support (25%).

Furthermore, AKI was a risk factor for mortality. The mortality rate in our study was 2.8% as compared with that of 0.8-27.5% in other studies.^7-11 In our study, older age, longer duration of hospital stays, severity of leukocytosis, thrombocytopenia, AKI, hypoalbuminemia, and hepatic dysfunction were associated with mortality. Moreover, mortality was linked to the comorbidities (ARDS, encephalopathy, and multiorgan failure) and the requirement for intensive care unit support.

AKI associated with scrub typhus infection is not as rare as previously assumed. Our study from a semi-rural tertiary center adds to the evidence of published literature on AKI in scrub typhus, which is an emerging epidemic in India. Prompt intensive management is the mainstay for these cases of complicated scrub typhus to prevent severe morbidity or mortality. It is important to consider the possibility of scrub typhus when patients present with fever and varying degrees of AKI along with a history of environmental exposure in an area where scrub typhus is endemic. Prompt diagnosis and the use of appropriate antibiotics can alter the clinical course of the disease and prevent the development of serious or fatal complications. The limitation of our study was that this was a retrospective single-center study, and the results cannot be generalized to larger studies of scrub typhus-associated AKI.

We show that AKI associated with scrub typhus had serious disease with a high incidence of severe manifestations, complications, and mortality. Enhanced awareness of this entity is paramount, as early identification and treatment of risk factors have the potential to significantly reduce the prevalence of AKI and its associated morbidity and mortality.