Beyond Traditional Risk Factors: Heat Stress–Induced Kidney Injury and the Emerging Spectrum of Chronic Kidney Disease of Unknown Origin (CKDu)

Chronic Kidney Disease of Unknown Origin (CKDu) is an emerging global health concern characterized by a tubulointerstitial pattern of nephropathy predominantly affecting young, otherwise healthy adults without traditional risk factors such as diabetes, hypertension, or exposure to known nephrotoxins. It is increasingly recognized among outdoor laborers in tropical and subtropical regions, where chronic heat exposure, recurrent dehydration, and occupational stress contribute to renal injury. Repeated episodes of heat-stress–related acute kidney injury (AKI) are thought to play a pivotal role in the initiation and progression of CKDu.

Case Presentations:
We present two South Asian males working in outdoor environments who developed kidney injury in the absence of systemic comorbidities.

Case 1: A 29-year-old South Asian male, a farmer by occupation with a history of alcohol use disorder, presented with altered mental status and loss of consciousness following prolonged sun exposure while working outdoors. On admission, he was normotensive with serum creatinine 365 µmol/L and potassium 5.8 mmol/L. Urinalysis showed mild proteinuria and no hematuria, with normal renal ultrasound. Kidney biopsy revealed acute tubular necrosis with mild interstitial edema and variable interstitial fibrosis, consistent with acute tubulointerstitial nephritis. Immunologic causes were excluded. He improved with hydration and supportive therapy, suggesting heat-stress–related AKI representing an early manifestation of CKDu.

Case 2: A 36-year-old South Asian farmer without prior medical illness presented with progressive fatigue, poor appetite, and weight loss after years of prolonged outdoor work in a hot climate. Initial evaluation revealed severe renal dysfunction (serum creatinine 865 µmol/L) with metabolic acidosis and mild anemia. Urinalysis showed low-grade proteinuria without hematuria; autoimmune and serological tests were negative. Renal ultrasound demonstrated bilaterally small echogenic kidneys. He required three sessions of hemodialysis and was discharged with partial renal recovery (serum creatinine 269 µmol/L), consistent with CKDu secondary to environmental heat stress and dehydration.

These two patients illustrate the clinical spectrum of CKDu—from heat-stress–induced AKI to established CKD. The common thread is recurrent exposure to high ambient temperatures and dehydration, leading to subclinical tubular injury, incomplete recovery, and eventual interstitial fibrosis.

CKDu primarily affects young adults engaged in agricultural or outdoor work in hot climates where prolonged heat exposure and dehydration cause progressive tubulointerstitial damage. The disease is characterized by tubular atrophy, interstitial fibrosis, and ischemic glomerular changes, leading to progressive kidney dysfunction. Laboratory findings may include electrolyte disturbances such as hypokalemia and hyperuricemia. Despite its high mortality and frequent progression to end-stage kidney disease, the precise cause of CKDu remains unclear, with several risk factors proposed, including exposure to agrochemicals, heavy metals, metalloids, intense physical labor, and recurrent dehydration. The disease’s scope remains uncertain due to limited epidemiological data. Nevertheless, early diagnosis and timely management—including rehydration, electrolyte correction, and anti-inflammatory therapy—are crucial to slow progression and improve long-term outcomes.