Exercise and Kidney Health: Core Curriculum 2026

Abstract

Exercise triggers complex effects on kidney physiology that vary with intensity, duration, and environmental conditions. While moderate physical activity improves cardiovascular and renal outcomes, intense or prolonged exertion, particularly in endurance sports, can lead to acute kidney injury. Adaptations in kidney physiology during exercise include reduced plasma flow, altered glomerular filtration, and hormone-mediated fluid retention. These changes are protective but may become maladaptive with dehydration, heat stress, or excessive fluid intake. High-intensity exercise increases oxidative stress and proteinuria, while ultramarathon participation may cause transient creatinine elevation from muscle breakdown, complicating AKI diagnosis. Prevention strategies include individualized hydration plans, electrolyte replacement, and avoidance of NSAIDs. In special populations, such as children with CKD or patients on dialysis, structured exercise enhances quality of life and physical function when implemented safely. Clinicians must balance the benefits of exercise with kidney-related risks, promote safe training practices, and recognize early signs of exertional complications to optimize renal and overall health in physically active individuals. This curriculum reviews the physiology of exercise on kidney function and provides evidence-based strategies for patient counseling and risk reduction.

Physiology of Exercise and the Kidney

Exercise has profound effects on systemic and kidney physiology, influencing hemodynamics, vascular function, and metabolic regulation. Routine physical activity is associated with improved cardiovascular outcomes and reduced progression of chronic kidney disease (CKD), whereas extreme or unregulated exertion may precipitate acute kidney injury (AKI). At least 150 minutes per week of moderate-intensity aerobic activity, combined with muscle-strengthening exercises on two or more days per week, as a foundational goal for adults is recommended by both the American Heart Association and Kidney Disease: Improving Global Outcomes (KDIGO). In developed countries, where CKD is often driven by metabolic disease, the benefits of exercise extend beyond fitness, as it improves insulin sensitivity and lipid metabolism. By modulating inflammation, oxidative stress, and intraglomerular pressure, exercise provides nephroprotective effects that complement its systemic benefits. This Core Curriculum highlights the complex relationship between exercise and kidney health, outlining physiologic adaptations, strategies to safely harness its therapeutic potential with emphasis in endurance athletes, sports supplements, and considerations in specific populations.

Table 1 summarizes key learning points and practical considerations on exercise-induced kidney changes to take away from this article.

Kidney Response to Exercise

Case 1: A 38-year-old male ultra-marathon runner presents to the clinic for routine evaluation two days after completing a 56-km race. He reports mild fatigue but no overt symptoms. Vitals signs are normal. Urinalysis showed no RBCs. Laboratory studies reveal the following:

Laboratory	Result	Reference range
Serum creatinine, mg/dL	2.0 (baseline 1.0)	0.7–1.3
Urine output, L/day	2.0	2 or more
Serum CK, U/L	12,000	<200
Serum LDH, UI/L	430	100–215
Serum CRP, mg/dL	15.6	0–5
Uric acid, mg/dL	6.8	3.0–7.0

Question 1: Which of the following is the most likely explanation for the laboratory findings?

1. Acute tubular necrosis due to myoglobin-induced nephropathy

2. Prerenal acute kidney injury due to volume depletion and decreased renal perfusion

3. Increased creatinine production from skeletal muscle breakdown

4. Chronic kidney disease from long-term endurance exercise exposure

For the answer to this question, see the following text.

A 2011 large-cohort study found that just 15 minutes of moderate activity daily reduces all-cause mortality by 14% and prolongs life. Exercise increases energy demand, prompting sympathetic nervous system (SNS) activation to redistribute blood flow toward the musculoskeletal system and away from the gastrointestinal and renal systems. SNS-driven vasoconstriction, especially in afferent arterioles, lowers renal plasma flow (RPF) and glomerular filtration rate (GFR). Norepinephrine activates the renin-angiotensin-aldosterone system (RAAS), increasing kidney sodium, chloride, and bicarbonate reabsorption.

During exercise, reduced GFR is a compensatory mechanism to conserve circulating volume by lowering sodium filtration and enhancing proximal reabsorption contributing to decreased urine output. Due to RAAS activation and sympathetic stimulation, both RPF and GFR decline, with the fall in RPF exceeding that of GFR. Therefore, the filtration fraction and glomerular permeability rise, promoting macromolecule diffusion across the glomerulus, which plays a role in exercise-induced albuminuria.

Exercise-induced heat triggers vasodilation and sweating to allow heat dissipation. Hypotonic fluid loss via sweating can lead to lower plasma volume. To compensate, vasopressin (ADH) is released, promoting renal water reabsorption to maintain perfusion and osmolality. After exercise, persistent muscle vasodilation may cause orthostatic intolerance which may be mitigated by plasma volume expansion via renal sodium and water retention, highlighting the kidneys’ vital role in restoring blood pressure via renal vasoregulation.

Exercise increases oxygen demand, potentially generating reactive oxygen and nitrogen species (ROS/RNS). While low ROS levels support muscle function and growth, excessive ROS can cause muscle fatigue and cellular injury, especially in kidneys due to their high metabolic demands. Regular exercise may enhance antioxidant defenses and reduce oxidative stress, offering potential renal protection.

Kidney Response to High Intensity Exercise

Exercise intensity can be measured using absolute metrics (e.g., METs, calories burned) or relative to an individual’s capacity (e.g. percent of maximal oxygen consumption (%VO₂max), maximal heart rate, perceived exertion). Intensity categories include low (<45% VO₂max), moderate (45–59% VO₂max), high (60–99%), and maximal (100%). High-intensity interval training is time-efficient but may elevate muscle (CK, myoglobin) and kidney injury markers (neutrophil gelatinase associated lipocalin (NGAL), albuminuria). Creatinine clearance stays stable with low-intensity exercise but drops significantly at ≥83% VO₂max. During high-intensity exercise, in addition to increased glomerular permeability due to changes in GFR and RPF as discussed before, accumulated metabolic byproducts alter tubular electrochemical gradient and impair reabsorption of low-molecular weight proteins. This results in mixed tubular-glomerular proteinuria as observed after 100Km inclined walk, in healthy adults.

At rest, only 5–10% of RPF reaches the medulla. During exercise, medullary blood flow is preserved via local vasodilators (e.g., nitric oxide, prostaglandins), countering angiotensin-II’s vasoconstriction. NSAIDs impair this adaptation by inhibiting prostaglandins synthesis. At exercise intensity above 60% VO₂max, increased medullary flow disrupts the corticomedullary osmotic gradient limiting urine concentration due to impaired water reabsorption in the collecting duct despite lower urine output. Figure 1 summarizes exercise-induced changes in renal physiology.

Figure 1.

Changes in renal physiology with increasing exercise intensity based on the available data from studies of the effects of exercise in kidney function. Abbreviations: ROS/RNS, reactive oxygen species/reactive nitrogen species; LMWPs, low molecular weight proteins; SNS, sympathetic nervous system; GFR, glomerular filtration rate; RPF, renal plasma flow; RAAS, renin-angiotensin II-aldosterone system; Na+, sodium; Cl−, chloride; HCO3−, bicarbonate. Created with Canva.com

Acute Kidney Injury (AKI) in Endurance Athletes

Endurance events are typically defined as lasting up to 6 hours or covering distances ≤42.195 km (26.2 miles) at a high to maximal-intensity exercise, whereas ultra-endurance events exceed this duration or distance and may span multiple days and multiple exercise types (e.g., running, cycling, swimming) as defined by the Ultra Sports Science Foundation. Though regular physical activity reduces all-cause mortality, frequent ultra-endurance participation has been linked to adverse cardiovascular effects, including transient right ventricular dysfunction and increased prevalence of myocardial fibrosis and remodeling, particularly among athletes with high cumulative training loads.

During ultra-endurance events, plasma volume may increase up to 16.5% and stay elevated for 1–3 days post-race, normalizing by day 4–5. These changes are driven by sharp rises in plasma renin and vasopressin (up to nine-fold) and a 9.8% increase in intravascular protein, likely from lymph flow or tissue breakdown. Inflammatory and muscle injury markers— creatine kinase (CK), lactate dehydrogenase (LDH) and uric acid—also rise and may stay elevated for up to 6 days. Notably, serum creatinine increases despite higher urinary excretion, reflecting greater muscle-derived production rather than reduced filtration. This complicates AKI diagnosis, as creatinine elevations may indicate physiological adaptation rather than true kidney injury.

The KDIGO criteria define AKI as a ≥0.3 mg/dL rise in serum creatinine within 48 hours or a ≥1.5-fold increase from baseline in 7 days. However, serum creatinine is influenced by non-renal factors like muscle mass, protein intake, and creatine supplements—highly variable in endurance athletes. Exercise-induced augmented renal clearance further limits serum creatinine reliability in this group.

Returning to Question 1, the correct answer is increased creatinine production from skeletal muscle breakdown (c). While AKI is a concern in endurance athletes, this patient has normal urine output and elevated urine creatinine, suggesting intact renal filtration. The rise in serum creatinine in this setting is most likely due to increased production from skeletal muscle breakdown, not intrinsic or pre-renal AKI. This case highlights the limitations of serum creatinine-based definitions of AKI following ultra-endurance exercise.

Cystatin-C and urinary biomarkers [e.g., albumin, NGAL, kidney injury molecule-1 (KIM-1), and interleukin (IL)-6, -8, -18] provide greater sensitivity for detecting subclinical kidney injury post-exercise. However, their use remains limited to research settings, as cut-offs are not standardized and they are not routinely applied in clinical practice. Subclinical AKI, defined by elevations in biomarkers without concurrent creatinine rise, reflects structural injury that may not meet KDIGO criteria for clinical AKI. Increases in these biomarkers, along with tubular injury observed on urine microscopy, have been reported following marathons. In ultramarathoners, dipstick findings such as proteinuria, hematuria, and high specific gravity were associated with AKI (reported in up to 34% of athletes), but these abnormalities are usually transient and resolve within several days of recovery.

While long-term CKD risk in endurance athletes is uncertain, recurrent AKI episodes may drive progression via tubular injury, RAAS activation, and oxidative stress. Shorter, more intense races carry greater AKI risk, as do inadequate recovery between races, NSAID use, dehydration, and low protein intake. Other risk factors include female sex (due to lower muscle mass resulting in lower total body water and hormonal influences), supplement use, and training in hot environments.

Mechanisms of Exercise-Induced AKI

Heat Stress and Kidney Injury During Exercise

Case 2: A 28-year-old previously healthy man is brought to the emergency department after collapsing during a high-intensity outdoor boot camp workout on a hot and humid summer day. He had been participating in repetitive sprint and resistance circuits for the past 45 minutes. On arrival, he is confused, disoriented, and agitated.

Vital signs: Temperature 40.5°C (104.9°F), heart rate 122 bpm, blood pressure 98/60 mmHg, respiratory rate 26/min, and oxygen saturation 97% on room air. Physical exam reveals flushed, hot skin with no evidence of sweating. He is unable to follow commands but withdraws from pain. Initial labs show

Test	Result	Reference Range
Serum sodium, meq/L	137	135–145
Serum creatinine, mg/dL	2.1	0.6–1.2
CK, U/L	9,500	40–150
Serum potassium, mEq/L	5.6	3.5–5.0
ALT, U/L	225	10–40
AST, U/L	290	10–30
Urinalysis
Color	Dark yellow
Specific Gravity	>1.020
Casts	Hyaline

Question 2: What is the most appropriate next step in management?

1. Administer an infusion of D5W

2. Begin external cooling with ice packs or cold-water immersion

3. Administer dantrolene to reverse muscle breakdown

4. Initiate hemodiafiltration for clearance of myoglobin

For the answer to this question, see the following text.

Heat stress results from both ambient conditions and metabolic heat generation. Approximately 15% of individuals working in high-heat environments develop AKI or CKD, even without physical exertion. During exercise, rising core temperature leads to sweat-driven heat loss and blood flow redistribution away from the kidneys, reducing RPF by 15–30% with temperature increases of 0.5–2.0°C. Women have increased basal metabolic rate causing higher core temperatures by 0.3–0.6°C during luteal phase of the menstrual cycle. Exercising in extreme heat (50 °C vs. 21 °C) further decreases RPF, as seen in U.S. military personnel hospitalized with heat stroke—40% of whom developed AKI.

Hyperthermia contributes to kidney injury through:

• Reduced renal oxygen delivery leading to oxidative stress

• Systemic release of proinflammatory cytokines

• Elevated ATP demand to maintain fluid/electrolyte balance

• Increased uric acid from purine and ATP breakdown

These effects are intensified by dehydration and high-intensity exercise (>60% VO₂max), which impair urine concentration and promote sodium/volume loss, making hydration essential. In one study, treadmill walking at 40°C showed that unmonitored hydration, compared to hydration rate matching the amount of sweat loss,led to increases in urine NGAL, albuminuria, and reduced urine flow. Hydration alone, even when matching sweat loss, raised serum creatinine more than hydration plus cooling, highlighting that hydration helps but does not fully protect against heat-related AKI.

For case 2, the patient meets criteria for exertional heat stroke, characterized by CNS dysfunction and core temperature >40°C. Immediate aggressive cooling (ice packs or cold water immersion -option B.) is the cornerstone of treatment and should be initiated urgently. Rhabdomyolysis, AKI, and hepatic injury are common complications but are addressed after core temperature is controlled. Dantrolene is used in malignant hyperthermia, not exertional heat stroke. Effectiveness of extracorporeal therapies for clearance of myoglobin will be discussed in the next section.

Prevention strategies include:

• Hydration: The U.S. National Institute for Occupational Safety and Health (NIOSH) recommends 237 mL of cool fluids every 15–20 minutes to limit body weight loss to <1.5%.

• Heat acclimatization: Gradual exposure over 10 days improves performance, lowers core temperature, enhances skin blood flow, retains fluids/electrolytes, and may support renal perfusion. While heat acclimatization appears beneficial, its effect on AKI risk and eGFR remains inconclusive.

• Heat hygiene: use of light and breathable clothes, mid-exercise cooling using ice towels, exercise during cooler daytimes and in places with air circulation are measures that allow heat dissipation. Periods of rest during high-intensity exercise would help by decreasing heat generation.

Rhabdomyolysis

Case 3: A 40-year-old marathon runner presents to the emergency department after completing a race. He reports fatigue, muscle cramps, and dark, cola-colored urine. Dipstick urinalysis reveals 2+ blood but no RBCs in urine microscopy. Laboratory evaluation reveals

Test	Result	Reference range
Sodium, mEq/L	138	135–145
Potassium, mEq/L	5.0	3.5–5.0
Chloride, mEq/L	102	98–106
Bicarbonate, mEq/L	20	22–28
BUN, mg/dL	30	7–20
Creatinine, mg/dL	2.5	0.6–1.2
Calcium, mg/dL	9.0	8.5–10.5
Creatinine kinase, U/L	15,000	<200

Question 3: In addition to monitoring urine output, what is the most appropriate initial management for this patient?

1. Administer isotonic saline

2. Restrict fluids

3. Start diuretics

4. Begin bicarbonate therapy

For the answer to the question, see the following text.

Rhabdomyolysis often presents with muscle weakness, pain, and swelling; dark reddish-brown urine from myoglobinuria is a hallmark but not always present. Severity ranges from asymptomatic creatine phosphokinase (CK) elevations to life-threatening complications like compartment syndrome, hypovolemia, AKI, and arrhythmias. The most sensitive lab marker is elevated serum CK. Although no universal threshold exists, level ≥1000 U/L (3–5× upper normal limit) is commonly used to make a diagnosis. CK magnitude does not reliably predict kidney injury risk, however CK above 10,000 is more frequently observed associated with AKI.

AKI incidence varies. In one series of 30 military members with exertional rhabdomyolysis (ERM), 20% developed AKI—mostly mild. A 2009–2019 study found an 8.5% AKI incidence among ERM hospitalizations, with 65% of AKI cases using NSAIDs preadmission. Most had low comorbidity and no hereditary muscle disease. Additional ERM risk factors include NSAIDs, statins, and amphetamines. AKI in rhabdomyolysis (Fig. 2) is primarily caused by myoglobin release into the bloodstream, leading to myoglobinuria. At high concentrations (≥100–300 mg/dL), myoglobin forms casts causing tubular obstruction. Other important mechanisms are renal vasoconstriction as myoglobin avidly scavenges key vasodilators such as nitric oxide and stimulates potent vasoconstrictors like endothelin-1 and thromboxane. Direct cytotoxicity can also occur via oxidative stress as heme degradation produces ROS after filtered myoglobin is reabsorbed through megalin and cubulin in the proximal tubule. Free heme accumulates in mitochondria impairing respiration and triggering mitophagy. Beyond tubular injury, myoglobin can cross the glomerular barrier and be endocytosed by podocytes, inducing apoptosis, and proteinuria, which further aggravates tubulointerstitial injury. Hypovolemia from fluid sequestration in damaged muscle further exacerbates tubular injury. Intracellular release also leads to metabolic disturbances: acidosis, hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia. Aciduria worsens toxicity by promoting myoglobin breakdown into nephrotoxic compounds.

Figure 2.

Key considerations in exertional rhabdomyolysis. Created with BioRender.com

Considering Question 3, the patient presents with classic signs of exertional rhabdomyolysis, as indicated by fatigue, muscle cramps, dark urine (suggesting myoglobinuria), elevated serum creatinine, and markedly increased CK levels. The most appropriate initial management is aggressive IV hydration with isotonic saline (A) to preserve renal perfusion and promote urinary clearance of myoglobin. Prevention of AKI centers on early, aggressive IV saline to restore volume and target urine output (200–300 mL/h) with close monitoring of overall volume status. Urinary alkalinization with bicarbonate lacks strong evidence and carries risks (e.g., low ionized calcium). Diuretics like mannitol or furosemide offer no proven benefit and are generally discouraged. Renal replacement therapy should be used for standard indications; while CRRT removes more myoglobin than intermittent dialysis, it hasn’t been associated with improved outcomes.

A primary concern for both athletes and clinicians is the safe return to physical activity following ERM. Initial management should emphasize rest, limb elevation, ice, and hydration with an expected recovery time of 1–2 weeks before safe return to exercise. However, caution is advised when symptoms persist >1 week, CK remains ≥100,000 IU/L or >5000 IU/L beyond 2 weeks, or complications like AKI or compartment syndrome occur where prolonged recovery times with exercise avoidance may be recommended. A history of severe cramps, heat stroke, anesthesia-related events, or muscle symptoms with mild exertion warrants further evaluation for underlying disorders such as fatty acid oxidation defects (e.g., carnitine palmitoyl-transferase deficiency) or glycogen storage diseases (e.g., McArdle disease).

Assessment of Hydration Status

Maintaining euvolemia is essential for preserving kidney function, especially during exercise-induced physiological stress. Total body water (TBW) makes up 50–70% of body mass, varying by composition—fat-free mass contains ~70–80% water, while adipose tissue contains ~10%. A 70-kg person averages ~42 L of TBW. Two-thirds of TBW is intracellular fluid (ICF), vital for metabolism, while the remaining third is extracellular fluid (ECF), including interstitial fluid for nutrient exchange and plasma for circulation. The kidneys regulate dynamic fluid balance across these compartments via osmotic gradients driven by electrolytes and plasma proteins. Sweat is composed primarily of water, sodium (20–80mEq/L), and chloride (20–70mEql/L) and it also contains other solutes such as potassium, urea, and lactate. The concentration of these solutes varies according to exercise intensity, environmental conditions (ambient temperature, humidity), and individual factors (heat acclimation, hypovolemia, dehydration, age, genetics, body weight, metabolic efficiency). Hydration preserves renal perfusion and GFR during exercise, reducing tubular stress, rhabdomyolysis risk, and AKI. It also supports performance—one study in elite judo athletes found that a 3–4% reduction in TBW led to ~2% loss in grip strength, with intracellular water changes being the key predictor.

Measuring fluid and volume losses. Accurate assessment of fluid loss is essential for guiding individualized hydration strategies. Sweat rate has been observed to be directly proportional to sweat sodium concentrations and it is the primary determinant of fluid loss during exercise.

While sweat rate can be measured directly, it is more commonly estimated using changes in body mass:

$$\begin{gathered} \mathrm{S}\mathrm{w}\mathrm{e}\mathrm{a}\mathrm{t}\mathrm{R}\mathrm{a}\mathrm{t}\mathrm{e}(\mathrm{L}/\mathrm{h})=\left[\right(\mathrm{P}\mathrm{r}\mathrm{e}-\mathrm{e}\mathrm{x}\mathrm{e}\mathrm{r}\mathrm{c}\mathrm{i}\mathrm{s}\mathrm{e}\mathrm{w}\mathrm{e}\mathrm{i}\mathrm{g}\mathrm{h}\mathrm{t},\mathrm{k}\mathrm{g}-\mathrm{P}\mathrm{o}\mathrm{s}\mathrm{t}-\mathrm{e}\mathrm{x}\mathrm{e}\mathrm{r}\mathrm{c}\mathrm{i}\mathrm{s}\mathrm{e}\mathrm{w}\mathrm{e}\mathrm{i}\mathrm{g}\mathrm{h}\mathrm{t},\mathrm{k}\mathrm{g})+\mathrm{F}\mathrm{l}\mathrm{u}\mathrm{i}\mathrm{d}\mathrm{i}\mathrm{n}\mathrm{t}\mathrm{a}\mathrm{k}\mathrm{e},\mathrm{L}-\mathrm{U}\mathrm{r}\mathrm{i}\mathrm{n}\mathrm{e} \\ \mathrm{o}\mathrm{u}\mathrm{t}\mathrm{p}\mathrm{u}\mathrm{t},\mathrm{L}]/\mathrm{E}\mathrm{x}\mathrm{e}\mathrm{r}\mathrm{c}\mathrm{i}\mathrm{s}\mathrm{e}\mathrm{d}\mathrm{u}\mathrm{r}\mathrm{a}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n},\mathrm{h} \end{gathered}$$

This calculation provides an estimate of net fluid loss while fasting and without bowel movements during exercise, but it does not account for metabolic water production, respiratory water loss, or fluid shifts between compartments. The assessment of hydration status during exercise presents several challenges and each available tool has limitations.

Changes in Body Mass

While practical, changes in body mass reflect net fluid loss and do not differentiate between intracellular and extracellular fluid shifts. To accurately assess hydration status using body weight, it is important to consider that in well-hydrated individuals in energy balance, nude body weight (BW) measured upon waking after the first urination of the day will exhibit stability, with variations of less than 1%. It is recommended to obtain nude BW measurements on at least three consecutive mornings to establish a valid baseline for euhydration in active men who are not restricting fluid or food intake. In women, more frequent measurements may be needed due to cyclical hormonal variations affecting TBW and BW, especially during the luteal phase when fluctuations of more than 2 kg can occur.

Sweat Collection Techniques

Direct measurement of sweat rate and composition is feasible but technically demanding and may not be representative of whole-body sweat loss during dynamic exercise.

Urine markers

Urine specific gravity and osmolality are easily obtained but influenced by diet, renal function, and may not reflect acute hydration changes. After rapid intake of hypotonic fluids, urine may appear dilute despite persistent dehydration, as excretion precedes fluid equilibrium. For accurate assessment, use first-morning urine or samples after several hours of stable hydration.

Plasma Osmolality and/or Sodium Concentration

These are considered more accurate indicators of hydration status but require invasive blood sampling, limiting their practicality in real-time exercise settings.

Emerging Technologies

• Wearable Sensors: Noninvasive sensors that estimate hydration status through measurements of skin conductivity, bioimpedance, or other parameters are under development. However, their accuracy and reliability require further validation across diverse exercise intensities and environmental conditions.

• Hydration Monitoring Apps: These tools can assist athletes in tracking fluid intake but rely on estimations and do not provide direct measurements of fluid balance.

Practical patient recommendations

• Begin exercise in a euhydrated state by monitoring morning body weight and urine color.

• Replace fluid losses guided by body weight changes (1 kg ≈ 1 L fluid loss).

• Incorporate electrolyte-containing fluids during prolonged exercise.

• Avoid overconsumption of fluids to reduce risk of exercise associated hyponatremia (EAH).

• For patients with CKD or other renal vulnerabilities, hydration strategies should be individualized in consultation with a clinician.

No single “gold standard” method exists to assess fluid loss during exercise, but assessment of sweat rate and net fluid loss during exercise by measuring body weight before and after exercise is encouraged as a tool to guide hydration.

Hydration Strategies

Case 4: A 33-year-old male recreational marathon runner with no known past medical history presents to your nephrology clinic for counseling on kidney health. He recently read an article about marathonassociated AKI and is concerned about staying well-hydrated during training and race day. He trains 5–6 days per week and plans to run a marathon in 4 weeks, which takes place in a hot, humid climate. He drinks a large volume of water (about 2 L) in the 1–2 hours before running but does not use any electrolyte supplements. He has noticed occasional dark urine after long runs. He denies NSAID use. On examination, he is well-appearing with normal vital signs and no peripheral edema. Baseline serum creatinine is 0.9 mg/dL. Urinalysis is normal.

Question 4: Which of the following represents the most appropriate counseling for this athlete regarding hydration and kidney protection?

1. He should continue pre-loading with >2 L of water immediately before running.

2. He should avoid electrolyte-containing drinks during the race.

3. He should replace fluid losses based on post-exercise body weight.

4. He should avoid sodium intake before and during exercise.

For the answer to this question, see the following text.

Effective fluid replacement is essential to optimize performance and minimize the risk of AKI during exercise. The American College of Sports Medicine (ACSM) and National Athletic Trainers’ Association (NATA) offer guidelines on fluid replacement before, during, and after exercise. Health care providers should help establish individualized hydration plans for physically active people that consider sweat rate, environment, acclimatization state, body size, exercise duration, exercise intensity, and individual fluid preferences and tolerance.

Pre-exercise hydration aims to start physical activity euhydrated with normal electrolyte levels. For most individuals, this can be achieved by consuming sufficient fluids with meals in the 24 hours prior to exercise, especially if there is adequate recovery time (8–12 hours) between exercise sessions. Some athletes with a pre-existing fluid deficit may need to drink 5–7 ml/kg of fluid at least 4 hours prior to exercise, and sometimes an additional 3–5 ml/kg 2 hours prior is recommended if changes in characteristics of urine that indicate dehydration, i.e. dark urine. Beverages with sodium (20–50 mEq/L) or sodium-containing snacks may be used to stimulate thirst and promote fluid retention. Overhydration should be avoided as it offers no clear performance advantage and can increase the risk of exercise-associated hyponatremia. During exercise, the goal is to prevent excessive dehydration and electrolyte imbalances. Fluid replacement needs will vary, but beverages containing electrolytes and carbohydrates can help to maintain fluid balance and exercise performance. For competitive athletes striving to maximize performance, using a “drink when thirsty” strategy may compromise performance. The NIOSH guidelines recommend drinking sport drinks with balanced electrolytes when working in the heat for more than 2 hours. Athletes should be encouraged to monitor their body weight changes during training to estimate sweat losses and guide individualized fluid replacement.

Rehydration post-exercise aims to fully replace any fluid and electrolyte deficits incurred during exercise. The urgency and specific strategy for rehydration depends on the magnitude of the deficit and the time available for recovery. If rest from exercise is planned for the next 24 hours, normal meals and snacks with adequate fluid intake can restore euhydration. Rapid rehydration is crucial when recovery time is short or another event follows soon, such as same-day tournaments, consecutive training sessions, or multi-stage endurance races. It is advised that athletes consume approximately 1.5 L of fluid for each kilogram of body weight lost during exercise, to compensate for increased urine production. Intravenous fluid replacement is generally not necessary unless there are signs of severe dehydration, or the individual cannot tolerate oral rehydration.

In Question 4, the athlete is at risk for exertional heat stress and dehydration-related acute kidney injury (AKI) due to high training intensity in a hot, humid environment. The most evidence-based hydration strategy is to replace fluid losses based on post-run weight, with the standard guideline of replacing 1.5 L for every 1 kg of weight lost (C). This accounts for both sweat and insensible losses, helping to restore plasma volume and protect renal perfusion.

Exercise-Associated hyponatremia (EAH)

Case 5: A 34-year-old female recreational runner collapses shortly after completing a marathon held in warm weather. She reports nausea, lightheadedness, and confusion. She did not take NSAIDs but reports drinking water frequently throughout the race, totaling approximately 3.5 liters. She did not consume any electrolyte supplements. On arrival to the medical tent, she is normotensive and physical exam reveals confusion but no focal neurological deficits. Labs reveal a serum sodium of 122 mEq/L, and her body weight is found to have increased by 2% compared to her pre-race weight.

Question 5: What is the most appropriate next step in management?

1. Administer isotonic saline

2. Restrict water intake and observe

3. Administer hypertonic saline

4. Encourage oral electrolyte solutions

For the answer to this question, see the following text.

EAH is defined as plasma sodium (PNa) concentration below 135 mEq/L that occurs during or within 24 hours after prolonged physical activity. The primary mechanism of EAH is a disturbance in the balance between total body water and total body sodium. While sodium loss through sweat and urine contributes, the predominant factor in EAH is often excessive fluid intake more than sweat loss, leading to a dilutional reduction in sodium concentration. Commercially available “electrolyte” beverages often contain a high glucose content to create an isotonic solution relative to plasma. However, glucose is rapidly absorbed, leading to a net consumption of free water. In athletes, including marathoners, EAH could be hypervolemic or hypovolemic. Hypovolemic hyponatremia is often triggered by prolonged exercise (>20 hours) in a hot environment and/or in individuals with higher sweat sodium losses. The most common form of EAH is hypervolemic in nature, resulting from two distinct processes: (1) non-osmotic stimulation of ADH, driven by exercise itself and by stimuli such as pain or nausea, and (2) overconsumption of hypotonic fluids during exercise. During exercise, ADH secretion can occur independent of plasma osmolality. This may be triggered by the physiological stress of exercise itself as well as associated stimuli such as pain, nausea, hypoglycemia, or hypovolemia. The inappropriate persistence of ADH activity promotes free water retention and limits renal excretion of excess fluid. Concurrently, athletes may ingest hypotonic fluids in amounts that exceed insensible and sweat losses, particularly during prolonged events. This fluid intake, when combined with impaired free water clearance due to ADH, contributes directly to hyponatremia. The risk of developing EAH has been reported at −6 to −2% body weight loss and as high as 85% in individuals with 4% weight gain.

Most cases of mild EAH (PNa 130 to 135 mEq/L) are asymptomatic, and most of those patients are often hypovolemic. When symptoms are present, usually when PNa ≤ 129 mEq/L, they are usually nonspecific including nausea, headache, fatigue, malaise or more severe such as confusion, lethargy, seizures, and even coma. Symptomatic patients are commonly overhydrated (free water gain) as noted in multiple case series and meta-analysis. EAH related to excessive fluid intake does not reflect an inherent inability of normal kidneys to excrete free water. Rather, the disorder arises from the concurrence of excessive hypotonic fluid ingestion and impaired renal water clearance secondary to high ADH secretion.

Returning to Question 5, the patient has symptomatic hyponatremia ( PNa <125 mEq/L with confusion), and her weight gain during the race suggests hypervolemic EAH due to excessive fluid intake. In this setting, hypertonic (3%) saline (C) is indicated to reverse cerebral edema and prevent progression to seizures or coma. Isotonic fluids may worsen hyponatremia, and oral solutions are inappropriate due to her altered mental status.

Figure 3 presents a conceptual diagram for the approach and management of EAH, emphasizing the critical decision points based on the presence of neurologic symptoms and signs of hypovolemia. It is not intended as an exhaustive treatment algorithm. The diagram highlights the importance of prompt intervention, particularly with hypertonic saline (HTS) in symptomatic cases, to reverse or prevent worsening cerebral edema, the most life-threatening complication of EAH. Free water restriction helps treat hyponatremia regardless of the mechanism so athletes with EAH should be encouraged to limit free water intake to prevent further decline in PNa. For mild cases of asymptomatic hyponatremia fluid restriction alone might be sufficient. Crucially, the figure implicitly underscores the need for careful and frequent monitoring of PNa, urine osmolality, and urine output throughout treatment. This vigilant monitoring is essential to ensure effective correction of hyponatremia while avoiding overcorrection, which can lead to osmotic demyelination syndrome and other poor outcomes.

Figure 3.

Conceptual diagram for the approach and management of Exercise-Associated Hyponatremia (EAH). Abbreviations: SOsm, serum osmolarity; PNa, plasma sodium; HTS, hypertonic saline; UNa, urine sodium; NS, normal saline; ADH, anti-diuretic hormone; EAB, effective arterial volume; UOP, urine output. Created with Canva.com.

Populations at risk of EAH are:

• Low body weight

• Slow running pace leading to more time on the course increasing fluid intake opportunities

• Prolonged exercise under high temperature increasing sweat rates

• Female sex due to higher rates of fluid intake and less body weight loss during endurance events that could be related to higher fat percentage which has lower water content compared to lean tissue, as well as lower metabolic rate. Also, estrogen and progesterone can influence the diuretic effects of ADH potentially leading to increased water retention.

To prevent EAH, athletes—especially those participating in endurance events like marathons and ultramarathons—must carefully manage their hydration strategies. EAH commonly results from excessive consumption of low-sodium fluids, which, combined with the kidneys’ limited ability to excrete water during prolonged exercise, leads to dangerously low blood sodium levels. Prevention focuses on avoiding overdrinking and incorporate electrolyte replacement to match individual sodium losses in case of proven high sweat sodium losses. Early recognition and prompt management are crucial, as untreated EAH can cause severe complications such as cerebral edema, seizures, or coma.

Sports drinks and nutritional supplements

Case 6: A 29-year-old male amateur triathlete presents to clinic for sports counseling. He is training for an Ironman triathlon and has increased his workouts to 4–5 hours daily. He is healthy and takes no medications. He drinks water during workouts but has noticed early fatigue and occasional lightheadedness during long runs. He read about sports drinks and asks whether he should start using one to improve hydration and performance.

You review his training log and note that he loses ~2.8 kg after long runs, and laboratory testing from his prior annual physical was normal.

Question 6: Which of the following is the most appropriate recommendation regarding hydration and performance for this athlete?

1. Encourage water only during exercise.

2. Recommend a carbohydrate-containing sports drink with 6–8% carbohydrate concentration.

3. Suggest routine use of glycerol-based drinks for all endurance athletes.

4. Recommend a carbohydrate-containing drink with 3–5% carbohydrate concentration.

For the answer to the question, see the following text.

Sports drinks

In general, for activities lasting less than 1 hour, water alone is usually sufficient for hydration and in most cases, individuals who are physically active and maintain a well-balanced diet generally do not require electrolyte supplementation. Sports drinks containing sodium, carbs, glycerol, or caffeine (Table 2) may be helpful for activities lasting over 2 hours. The triathlete described in case 6 is engaging in prolonged, high-intensity endurance training and is experiencing early fatigue and lightheadedness, likely due to carbohydrate depletion and electrolyte loss. For activities lasting longer than 60–90 minutes, guidelines recommend using a sports drink that contains 3–5% carbohydrates (D), which optimizes energy delivery while maintaining adequate fluid absorption.

Nutritional supplements

In healthy individuals, high protein intake temporarily raises eGFR due to hyperfiltration, aiding nitrogen waste excretion. The recommended protein intake in healthy individuals is 0.8–1mg/kg of body weight per day. Athletes typically consume 1.4–2.0 g/kg/day, which is generally well tolerated. While long-term high-protein diets (>1.0 g/kg/day) have been linked to faster kidney function decline, confounding factors—such as NSAID use, AKI episodes, anabolic steroids, and comorbidities—may contribute. Common protein supplements (whey, casein, plant-based) are usually safe, but additives require case-by-case evaluation. Some studies suggest red meat may increase CKD risk due to acid load and inflammation, while plant proteins may be protective, though evidence is inconclusive. For CKD, recommended protein intake is:

• eGFR 60–90: ≥0.8 g/kg

• eGFR <60: 0.55–0.6 g/kg

• Dialysis: 1.0–1.2 g/kg (HD), up to 1.3 g/kg (PD).

Creatine supplementation, often paired with resistance training, enhances muscle strength, power, and hypertrophy. It also shows promise in reducing age-related muscle loss (sarcopenia) and may aid in recovery, neurological function, and certain diseases. Creatine supports ATP regeneration via the phosphagen system and may reduce oxidative stress by scavenging reactive oxygen species. A 10–20% increase in serum creatinine levels may occur as a byproduct of creatine metabolism, which can mimic impaired kidney function. Cystatin-c may provide accurate assessment of eGFR during creatine supplementation. However, studies have not shown adverse effects on renal function with creatine use.

Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—are involved in muscle metabolism and are often used (5–20 g/day) for recovery and to prevent muscle breakdown during intense exercise. However, adequate dietary protein generally suffices for muscle synthesis. BCAAs have not been linked to kidney harm. Emerging evidence suggests a potential role for BCAAs in supporting muscle maintenance and nitrogen balance in patients with CKD on low-protein diets, though findings remain inconclusive.

Nitric oxide boosters—including L-arginine, L-citrulline, and beetroot— enhance vasodilation and may improve muscle oxygen delivery. In general, evidence on effectiveness of NO boosters is mixed. Studies do not support L-arginine supplementation as an effective ergogenic aid for strength or power performance, likely due to poor bioavailability. L-citrulline (>3g), an endogenous precursor to L-arginine, may provide small but significant benefits for high-intensity strength and power performance. Beetroot juice (70–140 mL) has shown benefits in aerobic and anaerobic performance. L-arginine and beetroot may raise potassium levels, a concern in kidney disease. Beetroot also contains oxalates, potentially increasing kidney stone risk. Current evidence does not link NO boosters to kidney dysfunction.

Sodium bicarbonate enhances hydrogen ion efflux from muscle and delays fatigue during high-intensity exercise. Most studies show that it improves performance in short-term, high-intensity efforts lasting 30 seconds to 12 minutes and that it is less effective in endurance exercise but data supporting its efficacy is mixed. Dose is usually 0.2–0.3gr/kg of body weight. Side effects include nausea, bloating, cramping, diarrhea, and vomiting. Metabolic alkalosis, hypokalemia, high blood pressure, fluid retention may occur especially in patients with hypertension, CKD, or cardiovascular disease.

Anabolic-androgenic steroids (AAS) are synthetic testosterone derivatives used to enhance muscle mass and strength. Their kidney risks are multifactorial: rapid muscle growth leads to hyperfiltration, potentially causing glomerular damage. Case reports link AAS to focal segmental glomerulosclerosis, possibly due to androgen receptor activation in the kidneys. AAS also raises blood pressure and often causes proteinuria. While short-term, low-dose use under medical supervision is relatively safe, high doses and prolonged use significantly increase kidney risk.

Special Scenarios

Case 7: A 14-year-old girl with CKD stage 3 presents with her parents for follow-up. She has stable kidney function (eGFR 45 mL/min/1.73 m²), normal blood pressure, and no history of proteinuria or cardiovascular disease. She recently expressed a strong interest in joining her school’s soccer team. Her parents are concerned about whether participation in sports is safe, given her kidney disease. They ask: “Is it risky for her to play soccer, and should we be worried about hurting her kidneys or making her condition worse?“.

Question 7: What is the best advice for this family?

1. Discourage participation in contact sports

2. Encourage participation with hydration and regular monitoring

3. Limit activity to non-strenuous sports

4. Avoid all physical activity

For the answer to the question, see the following text.

Exercise and CKD

Exercise improves endothelial function, nitric oxide availability, insulin sensitivity, and reduces oxidative stress and inflammation. In CKD, it lowers intraglomerular pressure, improves renal perfusion, and reduces sympathetic activation. Benefits include improved VO₂max (~2.4 ml/kg/min), lower blood pressure, reduced arterial stiffness, and modest GFR and proteinuria improvements. It also decreases fatigue and enhances quality of life. Effective regimens include ≥30 min of moderate aerobic activity (40–60% VO₂max) 3–5x/week and/or resistance training 2–3x/week. Combined training offers additive benefits; results are typically seen after 8–12 weeks. Excessive exertion should be avoided in patients with uncontrolled hypertension or cardiovascular disease.

Exercise and Hypertension

Hypertension is common and can affect athletes and patients engaging in regular exercise. Careful consideration of blood pressure medications is warranted. Agents such as beta-blockers may blunt heart rate response and exercise tolerance, but studies have shown comparable cardiovascular benefits with or without beta-blockers in hypertensive patients. Additionally, diuretics can increase the risk of dehydration and electrolyte imbalance during prolonged activity. Athletes should work with their providers to tailor their antihypertensive therapy to their exercise regimen, and patients should be counseled on monitoring hydration and blood pressure during training.

Exercise and Dialysis

In patients on kidney replacement therapy, exercise has been shown to reduce sarcopenia, improve vascular compliance through increase of NO bioavailability, and reduce chronic systemic inflammation. In hemodialysis patients and transplant recipients, exercise has been shown to decrease fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH), increase klotho levels, raise bone alkaline phosphate and reduced sclerostin, resulting in improved bone mineral density and reduced bone loss. In patients with CKD, including those on hemodialysis, exercise reduces inflammatory markers, such as IL-6 and CRP, increases VO₂max by 2.0–2.5 mL/kg/min, increases 6-minute walk distance by 30 to 60 meters and increases muscle strength. Health-related quality of life also improves across CKD populations, while evidence for reduction in hospitalization and mortality risk is strongest in patients on hemodialysis. Intradialytic aerobic exercise has been shown to improve dialysis adequacy, ultrafiltration tolerance, and prevent deconditioning. Examples of exercises implemented in this population are interdialytic walking, strength training, tai chi, or yoga, 3 to 5 times per week. For intradialytic modality, the most frequently used is cycling at moderate intensity (RPE 12–14 or ~60–70% HRmax) during the first 2 hours of hemodialysis for 30 to 45 min with each dialysis session (3 times/week), light resistance exercise using elastic bands in upper body or ankle weights have also been used. Duration of studies has been from 8 weeks to 6 months, with an average of at least 12 weeks or more of consistent physical activity to observe sustainable benefits. In patients amenable to start an exercise routine, supervised programs yield better adherence and safety. If intradialytic programs are chosen, patients require close monitoring of symptoms and blood pressure with especial attention for patients with hypotension risk or if concerns for peritoneal leaks in case of peritoneal dialysis. Light upper body exercise has not been associated with harm to vascular access, including arteriovenous fistulas, but supervision is recommended.

Children with CKD and Sports Participation

Children with CKD often have low physical activity, reduced exercise capacity, and muscle weakness, which worsen cardiovascular health and quality of life. The “pediatric inactivity triad” — exercise deficit disorder, dynapenia, and physical illiteracy — further limits activity. Structured exercise programs, especially those >25 sessions and >45 minutes long, improve strength, VO₂peak, and 6-minute walk distance, particularly in children under 12. Modalities like intradialytic cycling and resistance training are effective and safe. However, low adherence due to fatigue, symptoms, or logistics remains a major barrier, with up to 70% of ESKD patients unable to complete structured regimens.

Children with CKD should be encouraged to engage in daily age-appropriate physical activity, even at stage 3 or above, due to its benefits. While past guidance advised children with a solitary kidney to avoid contact sports, current AAP recommendations support individualized decisions based on kidney function and protective measures. Returning to case 7, encouraging physical activity such as soccer is both safe and beneficial with hydration and frequent monitoring (B). Temporary activity restrictions may be needed for uncontrolled hypertension, severe anemia, heart failure, orthostatic intolerance, or post-transplant recovery.

Hereditary renal hypouricemia (HRH)

Hereditary renal hypouricemia (HRH) is a rare autosomal recessive disorder caused by mutations in URAT1 or GLUT9, leading to hypouricemia and increased renal uric acid loss. Exercise-induced AKI in HRH may result from acute uric acid nephropathy, oxidative stress, or renal ischemia. It typically affects young males and presents with groin pain, nausea, and vomiting after intense activity. CK is often normal, and UA may appear normal despite underlying pathology. Though most recover in 2–3 weeks, unrecognized HRH can lead to recurrent AKI and permanent damage.

Table 1.

Teaching summary: exercise-induced kidney changes and practical considerations

Topic	Key Teaching Points
Renal Physiology and Exercise	- Exercise activates sympathetic nervous system and RAAS, reducing renal plasma flow and GFR to conserve sodium and water. - High-intensity/prolonged exercise increases glomerular permeability and tubular stress. - Moderate exercise benefits renal health; unregulated exertion in adverse conditions can impair function.
Acute Kidney Injury in Ultra-endurance Athletes	- Creatinine-based AKI definitions can be misleading due to muscle metabolism. - Use cystatin C, urine biomarkers (e.g., NGAL, KIM-1), and urinalysis. - Emphasize recovery, hydration, avoiding NSAIDs, and adequate protein intake.
Heat Stress and AKI	- Hot environments reduce renal perfusion and increase AKI risk. - Preventative measures include hydration and heat acclimatization. - Cooling strategies provide added protection beyond hydration.
Rhabdomyolysis	- Caused by myoglobin release; leads to tubular obstruction and injury. - Risk factors: intense exercise, heat, statins, NSAIDs, stimulants. - Symptoms: fatigue, dark urine, confusion; labs show high CK, creatinine. - Hydration is central to prevention and treatment.
Hydration Assessment	- Critical for preserving renal perfusion and GFR during exercise. - Use a multi-modal approach: body weight, urine color/volume, estimation of sweat rate. - Educate on pre/post-exercise weight tracking and urine assessment.
Hydration Strategies	- Pre-exercise: aim for euhydration, sodium may aid retention. - During exercise: use electrolyte + carbohydrate drinks to avoid dehydration and imbalances. - Post-exercise: rehydrate based on weight loss; oral intake usually sufficient.
Exercise-Associated Hyponatremia (EAH)	- Requires urgent recognition and care. - Linked to overhydration with low-sodium fluids and impaired renal water excretion. - Risk factors: long duration, slow pace, weight gain. - Prevention: match fluid intake with sodium losses. - EAH can cause cerebral edema, seizures, coma if untreated.
Nutritional Supplements	- Water is sufficient for <1 hour of activity. - Use electrolyte/carbohydrate drinks for >2 hours duration. - 3–5% carb concentration is ideal for absorption. - Sodium may help high-sweat athletes, but evidence is mixed. - Caffeine enhances performance; glycerol offers hyperhydration but may cause GI effects.
Special Scenarios -Pediatric CKD-	- Exercise benefits kids with CKD (strength, VO2 peak, quality of life). - Encourage daily activity - Contraindications: uncontrolled BP, severe anemia, recent transplant, etc. - Protective gear may be used in solitary kidney; contact sports not routinely contraindicated. - Monitor BP and kidney function regularly.

Table 2.

Sports drinks

Sport drink ingredient	Considerations	Dose
Sodium	Oral sodium-containing fluids may benefit individuals with high sweat sodium losses (>60 mEq/L) and sweat rates (>2.5 L/h). Routine supplementation is unnecessary without individualized sweat analysis. Studies show mixed results and no clear advantage in preventing EAH or altering serum sodium.	Most Western diets provide sufficient sodium (3–4 g/day). The Institute of Medicine recommends 1.5 g/day for young adults, even in hot conditions.
Carbohydrates	Muscle glycogen depletion reduces exercise capacity making pre- and post-exercise carbohydrate intake essential. Post-exercise intake of carbs with protein improves glycogen replenishment and recovery and enhances rehydration more effectively than fluids alone.	For activities lasting longer than 60–90 minutes, guidelines recommend using a sports drink that contains 3–5% carbohydrates. Carbohydrate-containing fluids (3–5% concentration) support hydration by enhancing water absorption, though higher concentrations may slow gastric emptying.
Glycerol	Glycerol is used as a sports supplement to promote hyperhydration and reduce hypohydration during exercise. It increases plasma osmolality without strongly triggering ADH, drawing water from intracellular to extracellular compartments. In the nephron, glycerol is filtered and reabsorbed via aquaporin-7, enhancing the medullary gradient and water reabsorption, thereby reducing urine output.	Typical doses are 1.2–1.4 g/kg body weight with 25–26 mL/kg fluid 90–180 minutes preexercise, or 1 g/kg in 1.5 L fluid post-exercise. It must be taken with fluids. Side effects include nausea, bloating, headache, dizziness, and laxative effects at high doses.
Caffeine	Small to moderate quantities of caffeine has been shown to improve exercise performance and endurance and it does not hinder rehydration or increase urine output during or after exercise.	Small to moderate quantities defined as 3–6 mg/kg taken 30–60minutes before exercise. The FDA considers up to 400 mg/day safe for healthy adults, but adverse effects may still occur depending on individual sensitivity and metabolism.