Kidney disease with no clear cause in heat workers

A twenty-nine-year-old man has a blood test for a new job on a plantation. He feels well, has no diabetes, his blood pressure is normal and he takes no ongoing medications. His creatinine, however, comes back high. In conversation, he says he has cut sugarcane since adolescence, works under strong sun for many hours and that two cousins are on dialysis. The scene is fictional and was written for teaching. This text uses that picture as a setting for clinical reasoning: why a chronic kidney disease without the usual causes calls for a detailed occupational history, which test pattern usually appears and why the cause is still debated.

NEXO is a daily medical diagnosis game: one clinical case a day, up to six progressive clues, and ICD-10 proximity feedback across five levels.

This text is not a nephrology guide. Investigation, biopsy and treatment follow their own guidelines and depend on each service. The interest here is the reasoning: how work and heat enter the history, why an abnormal test in a young person without symptoms deserves attention and how to handle a disease whose cause has not yet been settled. If you play the case of the day in NEXO, you will recognize the move: the missing clue is often in the question about the patient's daily life.

Key points

• In several hot agricultural regions of the world, there is a chronic kidney disease in young adults without diabetes, hypertension or another known cause.
• The picture is usually silent, with creatinine rising gradually and little protein in the urine.
• Heavy manual work in the heat, with little water and few breaks, is the most studied hypothesis, but the cause is still debated.
• The occupational history and the family history help to recognize the pattern.
• Water, rest and shade at work are prevention measures that have been studied.

Why this disease is a setting for reasoning

Johnson, Wesseling and Newman describe a chronic kidney disease of unknown cause in agricultural communities in various parts of the world (Johnson et al., 2019). The name changes from place to place: Mesoamerican nephropathy, chronic kidney disease of nontraditional origin, chronic interstitial nephritis in agricultural communities. The common point is a loss of kidney function in people who do not have the usual risk factors.

For the clinician, this disease is a good setting because it shows the limit of routine questions. Faced with a high creatinine, the list usually starts with diabetes, hypertension, glomerular diseases and medications. When none of that appears, the missing question is about work, heat, water and family.

What the scene teaches

In the opening scene, the age, the type of work, the heat and the relatives on dialysis form a pattern. No clue, on its own, defines the diagnosis. The post on signs, symptoms and history shows how context changes the weight of each finding. Here, the occupational history is part of the examination.

A diagnosis of exclusion

Claudel et al. recall that this disease is a diagnosis of exclusion, made in people from endemic regions, and that the phenotype is not yet fully defined (Claudel et al., 2024). In practice, this means that investigation of known causes remains mandatory. The occupational clue does not end the search: it adds a hypothesis.

Investigate before labeling

Before thinking of a work-related disease, the investigation follows the path of any high creatinine: confirm the result with another measurement, estimate filtration, examine the urine, measure protein, review medications and supplements, do a kidney ultrasound and look for signs of systemic diseases. Claudel et al. recall that the diagnosis is only made after other causes have been excluded (Claudel et al., 2024). An early label can hide a treatable glomerulopathy, an obstruction or a medication effect. The order matters: first what has specific treatment, then the occupational hypothesis.

Where and in whom the disease appears

Wesseling and colleagues describe an epidemic of chronic kidney disease unrelated to diabetes, hypertension or other known causes on the Pacific coast of Central America, with many deaths among young men who work in agriculture, especially sugarcane cutters (Wesseling and colleagues, 2020). The authors report the disease also in other industrial crops and in heavy manual labor in hot environments outside agriculture, but not among subsistence farmers.

A pattern on several continents

Rutter and colleagues gathered population surveys from several countries to estimate the frequency of reduced kidney function in adults aged 18 to 60 without the known causes of kidney disease (Rutter and colleagues, 2025). The highest frequencies appeared in men from rural areas of a region of India and of northwestern Nicaragua, at about 14 in every 100. Outside Central America and South Asia, the frequency stayed below 2 in every 100. The authors note that there may be clusters not yet identified elsewhere.

Young men, but not only them

Gonzalez-Quiroz and colleagues followed young adults from rural communities of northwestern Nicaragua for several years (Gonzalez-Quiroz and colleagues, 2024). New chronic kidney disease appeared only in the men. Wesseling and colleagues, however, note that women in the affected regions also have frequency and mortality from kidney disease above what is expected (Wesseling and colleagues, 2020). The post about baseline rate in diagnosis explains why the local frequency of a disease changes how a test is read.

How the disease presents

Correa-Rotter and colleagues describe a typical clinical picture: normal or slightly high blood pressure, a silent and progressive fall in the filtration of the kidneys, little protein in the urine and, often, high uric acid or low potassium (Correa-Rotter and colleagues, 2014). Diabetes is absent. Biopsies show chronic disease of the tubules and of the interstitial tissue of the kidney, with secondary signs in the glomeruli.

A test that misleads

The same authors note that proteinuria, when present, is usually low and that the urine sediment often shows neither blood nor casts (Correa-Rotter and colleagues, 2014). A nearly normal urine strip, in a patient without symptoms, can let the problem go unnoticed. That is why creatinine and the estimate of kidney filtration weigh more than the strip.

Potassium and uric acid as clues

Correa-Rotter and colleagues suggest that low potassium and high uric acid may be a response to repeated dehydration, with activation of hormones that regulate salt and water (Correa-Rotter and colleagues, 2014). The authors also note that chronic low potassium, by itself, can damage the tubules. For reasoning, these findings are clues that fit the history of heat and sweat, not proof of the cause.

The symptoms of the workday

In the follow-up by Gonzalez-Quiroz and colleagues, accumulated time working with sugarcane and symptoms of excessive sun exposure at work were associated with new kidney disease (Gonzalez-Quiroz and colleagues, 2024). Weight loss, nausea, vomiting, cramps and use of anti-inflammatory drugs were associated with the time when kidney function began to fall. Asking about these complaints during the harvest can help date the onset of the problem.

Heat as the main hypothesis

Glaser and colleagues propose the term heat stress nephropathy to describe chronic kidney disease linked to repeated exposure to heat with physical exertion and little hydration (Glaser and colleagues, 2016). The authors link the emergence of these epidemics to rising temperatures and argue that the disease may be one of the first epidemics linked to global warming.

Small and repeated injuries

Glaser and colleagues describe that exposure to heat with dehydration and volume loss causes, immediately, worsening of chronic diseases, heat exhaustion and heat stroke (Glaser and colleagues, 2016). Chronic kidney disease, according to the authors, would come from repetition: hot shifts, intense exertion and little water, day after day, harvest after harvest. For reasoning, this changes the question. It is not enough to know whether the patient has already had heat stroke. What matters is knowing what a typical work week looks like and whether they drink enough water during the shift, whether they urinate little and dark at the end of the day and whether they have access to breaks.

Work dose, risk dose

Wesseling and colleagues describe a dose-response relationship: in certain regions, every ten years of work on coastal plantations tripled the risk in men and more than doubled it in women (Wesseling and colleagues, 2020). The authors also report that sugarcane cutters with better general health than other workers had worse kidney health markers, linked to years of work in sugarcane. This type of finding reinforces the question about how long and under what conditions the person worked.

The worker as sentinel

Wesseling and colleagues describe sugarcane cutters with extreme heat stress as a sentinel population (Wesseling and colleagues, 2020). In a hotter world, other occupations with heavy exertion in the sun, such as construction and mining, also enter the conversation. The WHO gathers the effects of heat on health on its page on climate change, heat and health.

A cause still under debate

Caplin and colleagues recall that, despite two decades of research, the main cause is still debated and that it is not clear which spectrum of kidney diseases the term includes nor what its geographic extent is (Caplin and colleagues, 2026). The authors review the evidence for and against the role of heat and discuss what can already be done with what is known.

The toxic hypothesis

Vervaet and colleagues studied biopsies from patients with chronic interstitial nephritis in agricultural communities and found a lesion in the proximal tubules similar to that caused by certain drugs toxic to the kidneys (Vervaet and colleagues, 2020). In rats, the lesion appeared with the drug and did not appear in a group that was only dehydrated. The authors argue that the disease is a nephropathy caused by toxin. This view competes with the heat hypothesis, and the two are not mutually exclusive.

Other exposures studied

Wesseling and colleagues review other hypotheses studied, such as pesticides, metals, infections and use of anti-inflammatory drugs, and conclude that none of them explains the epidemic as well as occupational heat stress (Wesseling and colleagues, 2020). Gonzalez-Quiroz and colleagues, on the other hand, describe an onset syndrome that suggests a triggering factor still unknown (Gonzalez-Quiroz and colleagues, 2024). The post on diagnostic uncertainty helps to think about how to act when the cause is still open.

Why geography confuses

Rutter and colleagues recall that it is still not clear what explains the differences in frequency between regions (Rutter and colleagues, 2025). Hot places with intensive agriculture may also have contaminated water, pesticide use, poverty and little access to health care, and each of these conditions may weigh in. For the clinician, the lesson is practical: the region the patient comes from increases the probability of the disease, but does not say which exposure was the most important. Recording in detail the work, the water the person drinks and the products they handle helps research and the patient themselves.

Markers under study

Claudel and colleagues reviewed markers of kidney injury in urine and blood used in studies on the disease (Claudel and colleagues, 2024). The most measured were markers of tubular injury, but the variety of methods prevented pooling the results. The authors argue for markers that identify tubular disease early, which today is still a research goal.

Clinical pattern: a table for the consultation

The table below summarizes, in a didactic way, clues that help separate this disease from the usual causes of chronic kidney disease. It simplifies a complex topic and does not replace an evaluation by a nephrologist.

Clue	Kidney disease linked to work in the heat	Usual causes, such as diabetes and hypertension
Age	Young adults	More common in older people
Diabetes	Absent	Often present
Blood pressure	Normal or slightly high	Often high
Protein in the urine	Little or none	May be moderate or high
Potassium and uric acid	Low potassium and high uric acid are common	Vary according to the cause
Occupational history	Heavy work in the heat for years	No typical occupational pattern
Family history	Relatives and neighbors with kidney disease	Depends on the cause

What to ask in the consultation

Occupational history is usually short or absent in routine care. When faced with a high creatinine in a young adult with no evident cause, a few questions change how the case is read:

• What do you do for work, and for how long?
• How many hours a day do you work in the sun or in a very hot place?
• Do you have access to water, breaks and shade during the workday?
• Have you had cramps, nausea, vomiting or dizziness during work?
• Do you often use anti-inflammatory drugs for pain?
• Does anyone in your family or community have dialysis or kidney disease?

Why the family matters

In the opening scene, the cousins on dialysis do not prove a hereditary disease. In affected communities, several people in the same family may share the same work, the same heat and the same living conditions. The post about differential diagnosis shows how to keep open different hypotheses that explain the same clue.

Prevention in the workplace

Wesseling and colleagues report that an intervention with water, rest and shade applied during the harvest season appeared to halt the decline in kidney function in sugarcane cutters (Wesseling and colleagues, 2020). In another program, the same strategy appeared sufficient for workers with a light or moderate workload, but not for those with the heaviest workload. Glaser and colleagues advocate actions by governments, employers and health services to protect workers from the heat (Glaser and colleagues, 2016).

The clinician's role

The clinician does not control working conditions, but can record the exposure, advise on hydration and breaks, discourage frequent use of anti-inflammatory drugs and monitor kidney function in those who work at risk. Caplin and colleagues remind us that, even without a defined cause, there are already measures to take with what is known (Caplin and colleagues, 2026). The post about clinical decision-making shows how to choose tests and approaches when the evidence is still partial.

Monitoring across harvest seasons

Gonzalez-Quiroz and colleagues showed that it is possible to detect, in a young population, the moment when kidney function begins to drift from what is expected (Gonzalez-Quiroz and colleagues, 2024). For the clinician, this suggests a simple precaution: compare creatinine before and after the harvest or the hottest period, and not just look at a single value. A decline that appears each season tells a different story from a steady decline. This comparison also helps to talk with the patient about the relationship between work and the kidneys, and to decide when to refer to a specialist.

The biases that leave work out

Kidney disease linked to work in the heat is rarely missed for lack of tests. It usually slips by through predictable habits and biases:

1. Ending the investigation when diabetes and hypertension are ruled out.
2. Not asking about work, the workday and the heat.
3. Relying on a nearly normal urine dipstick to reassure the patient.
4. Attributing everything to a single cause, such as heat or a toxin, without considering the other.
5. Treating cases in the family as a coincidence.

Croskerry describes anchoring and premature closure among the most frequent cognitive errors in diagnosis (Croskerry, 2003). The post about diagnostic pause shows how a short moment of verification helps to notice what was left out.

Back to the scene

In the opening scene, the doctor who rules out the usual causes and asks about sugarcane, sun and water finds a known pattern. He completes the investigation of the other causes, refers the patient to the nephrologist, records the occupational exposure, talks about breaks, water and anti-inflammatories, and schedules follow-up. He does not close the cause, because science has not closed it yet, but he also does not leave the case without a name. At the next visit, he compares creatinine with the baseline value, asks again about the workday and reviews the medication list, because follow-up is part of the diagnosis.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues. You propose a diagnosis by searching for the ICD-10 code and receive proximity feedback at five levels, which shows whether the guess landed on the Exact ICD, Same category, Same group, Same chapter or Different chapter. This format connects with the theme of this text: a clue about work can change the hypothesis within the same chapter of kidney diseases.

To use the case of the day as training, try three habits. Before each guess, ask what the patient does for work. When a test comes back abnormal with no evident cause, ask what story has not yet been told. After the result, note which clue would have anticipated the diagnosis.

Three exercises with cases

Ask about work. In each case, imagine the patient's workday and see what it adds.

Be suspicious of the normal test. Reread a case asking whether any near-normal test gave false reassurance.

Keep two hypotheses. When facing a debated cause, write down what favors and what weakens each explanation.

The post about learning based on clinical cases shows how cases help fix patterns that rarely appear in daily practice.

The limits on use of the game are described on the NEXO Economy page. If you research the teaching of clinical reasoning, the Researcher page explains how to get in touch. Professionals who write or review cases find information on the Curator and Creators pages, and institutions can learn about the proposal on the partnerships page.

Frequently asked questions

What is chronic kidney disease of unknown cause?

It is a progressive loss of kidney function in people without diabetes, hypertension or another known cause, described mainly in farming communities in hot regions.

Who is most affected?

Mainly young men who do heavy manual work in the heat, such as cutting sugarcane, but women and other occupations can also be affected.

Which tests are usually abnormal?

Creatinine rises and kidney filtration falls. Protein in the urine is usually low, and low potassium and high uric acid are common.

Is heat the cause?

Heat combined with exertion and little hydration is the most studied hypothesis, but other explanations, such as toxins, remain under debate.

Can it be prevented?

Water, rest and shade during work are measures that have been studied, with promising results for light and moderate workloads.

What can the clinician do?

Ask about work, investigate the other causes, monitor kidney function, advise on breaks, hydration and anti-inflammatories, and refer to the specialist.

Final checklist

• I investigated the usual causes of chronic kidney disease.
• I asked about work, the workday, heat and access to water and shade.
• I asked about cramps, nausea and vomiting during the harvest or the workday.
• I asked about anti-inflammatories and about cases in the family and the community.
• I was not reassured by a near-normal urine dipstick.
• I recorded the occupational exposure and planned follow-up.

Want to practice reasoning with progressive clues? Play the case of the day.

References

1. Caplin B, Kaur P, Ruwanpathirana T, et al. The 'known unknowns' of CKD of undetermined etiology in 2026. Am J Kidney Dis. 2026. PMID 42772347.
2. Claudel SE, Waikar SS, CURE Research Consortium. Systematic review of kidney injury biomarkers for the evaluation of CKD of uncertain etiology. Kidney Int Rep. 2024. PMID 38899184.
3. Correa-Rotter R, Wesseling C, Johnson RJ. CKD of unknown origin in Central America: the case for a Mesoamerican nephropathy. Am J Kidney Dis. 2014. PMID 24412050.
4. Croskerry P. The importance of cognitive errors in diagnosis and strategies to minimize them. Acad Med. 2003. PMID 12915363.
5. Glaser J, Lemery J, Rajagopalan B, et al. Climate change and the emergent epidemic of CKD from heat stress in rural communities: the case for heat stress nephropathy. Clin J Am Soc Nephrol. 2016. PMID 27151892.
6. Gonzalez-Quiroz M, Heggeseth B, Camacho A, et al. Population-level detection of early loss of kidney function: 7-year follow-up of a young adult cohort at risk. Int J Epidemiol. 2024. PMID 37930052.
7. Johnson RJ, Wesseling C, Newman LS. Chronic kidney disease of unknown cause in agricultural communities. N Engl J Med. 2019. PMID 31067373.
8. Rutter CE, Njoroge M, Cooper PJ, et al. International prevalence patterns of low eGFR in adults aged 18-60 without traditional risk factors. Kidney Int. 2025. PMID 39708999.
9. Vervaet BA, Nast CC, Jayasumana C, et al. Chronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathy. Kidney Int. 2020. PMID 31892415.
10. Wesseling C, Glaser J, Rodríguez-Guzmán J, et al. Chronic kidney disease of non-traditional origin in Mesoamerica: a disease primarily driven by occupational heat stress. Rev Panam Salud Publica. 2020. PMID 31998376.
11. World Health Organization. Climate change, heat and health. Information page.