Severe Acute Kidney Injury Survivors in India and Southeast Asia Face Staggering Rates of Long-Term Adverse Events

Highlights of the InSEA-RRT Registry Findings

The India and Southeast Asia Renal Replacement Therapy (InSEA-RRT) registry study provides a sobering look at the long-term trajectory of critically ill patients who survive an episode of severe acute kidney injury (AKI). Key findings include:

1. Extremely high in-hospital mortality: 47% of patients with KDIGO Stage 3 AKI did not survive their initial hospitalization.
2. Significant long-term risk: Survivors faced an incidence rate of 46.6 major adverse kidney events (MAKE) per 100 person-years over the subsequent two years.
3. High rates of CKD development: New-onset chronic kidney disease occurred at a rate of 58.6 per 100 person-years among survivors.
4. Identifiable risk factors: Older age, male sex, preexisting CKD, malignancy, cardiac-associated AKI, and failure of initial renal recovery were independent predictors of poor outcomes.

Background: The Growing Crisis of Severe AKI in Resource-Limited Settings

Acute kidney injury (AKI) is no longer viewed as a transient clinical event but as a major gateway to chronic kidney disease (CKD) and end-stage renal disease (ESRD). While the short-term mortality associated with severe AKI (particularly Stage 3) is well-documented in high-income countries, there has been a critical lack of longitudinal data from India and Southeast Asia. This region faces unique challenges, including a high burden of infectious diseases, varying access to renal replacement therapy (RRT), and socioeconomic barriers to long-term follow-up.

Critically ill patients in these regions often present with severe complications, and the transition from AKI to CKD represents a significant public health threat. Understanding the epidemiology of Major Adverse Kidney Events (MAKE)—a composite of persistent kidney dysfunction, the need for long-term dialysis, and all-cause mortality—is essential for developing targeted intervention strategies and resource allocation in these diverse healthcare environments.

Methodological Framework: The InSEA-RRT Cohort

The India and Southeast Asia Renal Replacement Therapy (InSEA-RRT) registry is a landmark multicenter cohort study. Between April 2019 and December 2023, researchers enrolled 2,315 critically ill patients across 24 hospitals in Southeast Asia and India.

Patient Selection and Definitions

The study focused exclusively on patients with Stage 3 AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. This stage represents the most severe tier of AKI, often requiring intensive care and frequently necessitating renal replacement therapy.

Outcome Measures

The primary endpoint was the 2-year MAKE. This composite outcome is increasingly used in clinical trials and epidemiological studies because it captures the holistic burden of kidney-related morbidity and mortality. It includes:
1. Persistent kidney dysfunction (defined as a sustained increase in serum creatinine).
2. New requirement for long-term dialysis.
3. All-cause mortality.

Secondary endpoints included the incidence of new-onset CKD and the rate of CKD progression among those with preexisting kidney disease.

Results: Quantifying the Post-AKI Burden

The study results underscore a dual burden: a high immediate fatality rate followed by a precarious recovery for survivors.

In-Hospital Outcomes and Initial Mortality

Of the 2,315 patients enrolled, 1,033 (47%) died during the index hospitalization. This high mortality rate reflects the severity of illness in patients reaching KDIGO Stage 3 AKI in these regions and may also reflect late presentation to tertiary care centers.

Two-Year Major Adverse Kidney Events (MAKE)

Among the survivors who were followed post-discharge, the incidence of MAKE was remarkably high at 46.6 per 100 person-years (95% CI 42.7-50.6). When breaking down the composite endpoint, mortality remained a dominant factor, accounting for 32% of the events post-discharge. This suggests that the physiological insult of severe AKI has systemic consequences that extend far beyond the renal system, contributing to cardiovascular instability and overall frailty.

Renal Progression: The AKI-to-CKD Transition

The data on renal recovery were equally concerning. The incidence of new CKD was 58.6 per 100 person-years, while CKD progression in those with prior kidney issues was 35.4 per 100 person-years. These figures indicate that even if a patient survives the acute phase, their kidneys are often permanently altered, placing them on a trajectory toward ESRD.

Predictors of Poor Outcomes

Multivariable-adjusted models identified several independent risk factors associated with 2-year MAKE:
1. Demographic factors: Older age and male sex.
2. Comorbidities: Preexisting CKD and malignancy.
3. Etiology: Cardiac-associated AKI (often involving complex cardiorenal syndromes).
4. Recovery status: Non-recovery of kidney function at the time of discharge was one of the strongest predictors of future events.

Expert Commentary: Bridging the Gap in Post-AKI Care

The InSEA-RRT study highlights a critical “care gap” in the management of AKI in India and Southeast Asia. In many of these healthcare systems, the focus is predominantly on the acute management of the crisis—stabilizing the patient and providing RRT. However, the data show that the period after discharge is just as dangerous.

From a mechanistic perspective, the high rate of CKD development suggests that the initial inflammatory surge and subsequent fibrotic processes in the kidney are not being adequately mitigated. The finding that cardiac-associated AKI carries a higher risk emphasizes the need for multidisciplinary care involving both nephrologists and cardiologists.

Furthermore, the socioeconomic implications cannot be ignored. In resource-limited settings, the cost of long-term dialysis is often prohibitive, making the prevention of CKD progression a matter of survival rather than just quality of life. The study suggests that we need to move toward a “renal recovery clinic” model, where high-risk survivors are monitored closely for blood pressure control, proteinuria, and the avoidance of nephrotoxic agents.

Conclusion: A Call for Longitudinal Renal Surveillance

The findings from Tangchitthavorngul et al. serve as a clarion call for clinicians and policymakers in India and Southeast Asia. Severe AKI is not a self-limiting condition; it is a chronic disease catalyst.

To improve outcomes, the medical community must:
1. Implement standardized post-AKI follow-up protocols.
2. Focus on early identification of patients at high risk for non-recovery.
3. Invest in public health initiatives to manage CKD risk factors like diabetes and hypertension in AKI survivors.

As the burden of critical illness grows in these regions, the long-term health of the kidneys must become a priority in the continuum of intensive care.

References

1. Tangchitthavorngul S, Lumlertgul N, Peerapornratana S, et al. Epidemiology and long-term outcomes of critically ill patients with severe AKI in India and Southeast Asia. Intensive Care Med. 2025 Jul;51(7):1306-1319. doi: 10.1007/s00134-025-08008-7.
2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024.
3. Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411-1423.