Infections and Acute Kidney Injury: A Global Perspective

Abstract

Globally, there are an estimated 13.3 million cases of acute kidney injury (AKI) annually. Although infections are a common cause of AKI globally, most infection-associated AKI occurs in low- and lower-middle-income countries. There are marked differences in the etiology of infection-associated AKI across age groups, populations at risk, and geographic location. This article provides a global overview of different infections that are associated commonly with AKI, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus, malaria, dengue, leptospirosis, tick-borne illnesses, and viral hemorrhagic fevers. Further discussion focuses on infectious conditions associated with AKI including sepsis, diarrheal diseases and pregnancy, peripartum and neonatal AKI. This article also discusses the future of infection-associated AKI in the framework of climate change. It explores how increased investment in achieving the sustainable development goals may contribute to the International Society of Nephrology's 0 by 25 objective to curtail avoidable AKI-related fatalities by 2025.

Keywords: Acute kidney injury; climate change; geography; global; infection; mortality.

Figure 1.. AKI definitions and considerations across the lifecourse.

AKI Kidney Disease: Improving Global Outcomes (KDIGO) definitions to define AKI are based on an acute increase in serum creatinine (SCr) within 48 hours or 7 days or a decrease in urine output (UOP). Differences in the AKI definition are found in neonates where a definition of AKI based on a fold-increase in SCr must be based on the lowest prior SCr as there are dynamic changes in creatinine over the first two weeks of life. Neonatal AKI based on the cumulative UOP over 24 hours instead of UOP recoded within 6–12-hour blocks in the standard KDIGO AKI definition. When applying the AKI definition over pediatric and adult populations, there must be patient or study-specific decisions on how to ascertain baseline creatinine based on the age of the population, availability of previous creatinine measurements, and the likelihood of having altered kidney function. As the definitions of AKI change over development, there are also differences in the etiology of infection that may impact AKI severity and likelihood of recovery that is also impacted by the developmental stage in which AKI occurs. Figure created with BioRender.com.

Figure 2.. The 5R approach to AKI.

The 5R approach to AKI includes AKI risk assessment, recognition, response, renal support, and rehabilitation. When assessing infection-associated AKI, prevention represents a critical opportunity to reduce the global burden of AKI as many infectious causes of AKI are amenable to public health interventions and addressing the social determinants of health. Improved health and nutrition during pregnancy and early childhood, reduction of infections through childhood vaccination, vector control programs, appropriate use of antimicrobials, expanded access to clean water, distribution and use of insecticide treated bednets, and AKI education can collectively reduce the burden of infectious illnesses and improve population health to reduce the impact of infection-associated AKI globally with the greatest potential benefit in LMICs. Figure created with BioRender.com.

Figure 3.. Approach to AKI recognition and clinical management in patients presenting with infections.

Among patients presenting to hospital with an infection, community-acquired AKI should be considered, and kidney function evaluated using serum creatinine and urine output with additional biomarkers, if available. AKI should be defined and staged. If a patient does not have AKI, they should receive routine care including antimicrobial agents and supportive care with additional monitoring of kidney function if needed or indicated. Patients with Stage 1 AKI should receive kidney protective care to prevent AKI progression including avoidance of nephrotoxic angtibiotics if possible and avoidance of non-steroidal anti-inflammatory drugs for fever.Patients should be counselled to discontinue any traditional remedies. Volume status and hemodynamics should be assessed, and appropriate resuscitation should be initiated. Patients with Stage 2 AKI or higher should receive kidney protective care and require additional clinical action to assess medication safety and interactions. Nephrotoxic antimicrobial agents should be replaced with appropriate alternatives, dose adjustments and medication interactions should be considered. Volume status and hemodynamics should be optimized. Patients should be referred early to higher level facilities if necessary, and nephrology team consulted. Patients with Stage 3 AKI have a considerable increase in mortality risk and should receive kidney protective care with action and the clinical team should evaluate whether additional kidney support is needed. Actions that may precipitate the need for dialysis should be avoided (especially volume overload, hyperkalemia), particularly in LMICs where dialysis may not be available, and additional clinical support should be considered. Figure created with BioRender.com.

Figure 4.. Map of infections in across geographic areas.

Map of infectious causes of AKI by geographic region. Infections listed by region represent regions most at risk of infections discussed in the article and may not be listed according to the relative contribution to AKI or incidence of AKI among people infected. Abbreviations: tick-borne illnesses (TBI). Figure created with BioRender.com.

Figure 5.. Sustainable Development Goals as they relate to kidney health, susceptibility to infection and kidney disease, and the ability of societies to respond.

The Sustainable Development Goals (SDGs) are categorized into goals that impact susceptibility to kidney disease (poverty, hunger, education, gender equality, inequities), relate to societal health (good health and well-being, affordable clean energy, economic growth, the presence of industry, innovation, and infrastructure, sustainable cities, responsible consumption and production), infection risk (clean water and sanitation, climate action, life below water and on land, good health and wellbring), and the resilience of society (peace, justice and strong institutions, partnerships to pursue SDGs). Figure created with BioRender.com.