High Altitude Renal Syndrome - What Are the Risks?

Introduction

High-altitude regions are natural environments that are hypobaric or hypoxic with low-temperature conditions. The atmospheric pressure and the partial pressure of oxygen are decreased in high-altitude areas. It can cause mountain sickness and other effects on the respiratory, cardiovascular, and nervous systems due to changes in metabolism and physiological functions. High altitude also influences renal structure and functions. Mountain climbers, trekkers, tourists, and high-altitude dwellers experience various physiological and pathological changes due to high-altitude exposure.

What Is High Altitude Renal Syndrome?

The high-altitude renal syndrome refers to a chronic asymptomatic condition of high-altitude dwellers, which is defined as polycythemia due to high-altitude, microalbuminuria, systemic hypertension, and hyperuricemia with glomerular filtration rate that is relatively preserved. High-altitude causes changes in kidneys like changes in volume status, renal plasma flow rate and clearance, and changes in acid-base and electrolyte balance. It also causes glomerular hypertrophy.

How Does High Altitude Renal Syndrome Occur?

Hypoxic conditions in high-altitude regions cause changes in the kidneys due to multiple compensatory mechanisms like changes in ventilation, sympathetic nervous activity, cardiac output, and erythropoiesis.

How Do Kidneys Respond in High-Altitude Regions?

At high altitudes, the kidneys play a vital role in acclimatization and high-altitude syndromes like mountain sickness, high-altitude cerebral edema, and pulmonary edema (swelling caused by fluid in the lungs) by regulating the body fluids and electrolyte and acid-base balance. The normal response of kidneys in a high-altitude condition is increased urinary output. The kidneys sense the decrease in oxygen levels and release erythropoietin hormone to improve the oxygen levels. This hormone stimulates the bone marrow to produce a high amount of red blood cells to cause an increase in the oxygen-carrying capacity of the blood. To provide space for the increased red blood cells, the body extracts fluid from the blood, which leads to an increase in urine output.

What Are the Effects of Acute High-Altitude Exposure on Kidneys?

• As a response to acute exposure, the body’s tissue oxygenation increases by increasing pulmonary ventilation. This causes respiratory alkalosis. The kidneys excrete excess bicarbonate and retain the hydrogen ions as a compensatory mechanism, to reduce respiratory alkalosis, but the increased oxygenation is maintained.

• Renal excretion of sodium and water is also increased. This reduces the circulating levels of sodium and water and increases the hematocrit levels.

• High altitudes increase the pH (potential of hydrogen) and cause a diuretic effect. This is the reason for increased urine output at high altitudes. The diuretic effect increases the concentrations of red blood cells, thereby increasing the hematocrit values. The diuretic effect induced by the hypoxic and hypobaric conditions is associated with a decrease in the levels of antidiuretic hormone, renin, and aldosterone and an increase in the levels of the natriuretic hormone, plasma, and urinary adrenaline.

What Are the Effects of Chronic High-Altitude Exposure on Kidneys?

• Long-term exposure to high altitudes causes an increase in hematocrit levels which is accompanied by an increase in hemoglobin levels and blood viscosity.

• Changes are observed in the glomerular filtration rate (GFR) due to an increase in renal blood flow. An increase in renal blood flow is due to increased hemoglobin levels.

• Long-term high altitude exposure worsens kidney function. It causes a reduction in the glomerular filtration rate, which reduces reabsorption and oxygen consumption. Long-term exposure is associated with a high prevalence of proteinuria and a low prevalence rate of metabolic syndrome.

What Are the Pathological Changes in Kidneys Due to High-Altitude Exposure?

High-altitude exposure causes various pathological changes, including polycythemia, hyperuricemia, microalbuminuria (moderate elevation in the level of urine albumin), and systemic hypertension. The prevalence of proteinuria is high, and it is due to the hypoxic effect in the renal parenchyma, glomerular hypertension, and high blood viscosity. Hyperuricemia (increased uric acid level in the blood), hypertension, and polycythemia (abnormal increase in red blood cells) cause albuminuria. High-altitude polycythemia causes kidney damage. High-altitude polycythemia-induced kidney damage presents histological features like basement membrane thickening, glomerular hypertrophy, and segmental or complete glomerulosclerosis.

Increased blood pressure due to chronic hypoxia, increased cell proliferation, endothelial cell dysfunction, increased collagen production, and increased uric acid production due to hypoxia, genetic factors, and dietary structure contribute to chronic kidney disease at high altitudes. Individuals with chronic kidney disease at high altitudes experience rapid progression to end-stage renal disease.

High-altitude pulmonary edema and arterial hypoxemia may occur in hemodialysis patients due to the increased risk of volume overload. High-altitude exposure is also associated with acute kidney injury.

What Are the Endocrine Changes Associated With High Altitude Renal Syndrome?

• High altitude causes an increase in sympathetic activity, which is characterized by an increase in urinary norepinephrine concentration. Hypoxia stimulates the release of adrenaline from the adrenal medulla. This causes an increase in heart rate, stroke volume, and tissue vasodilation to improve oxygen delivery to the tissues.

• High altitude activates the renin-angiotensin-aldosterone system and causes glomerular hyperfiltration through efferent arteriolar vasoconstriction.

• Erythropoietin production is increased to increase the oxygen-carrying capacity of the blood.

How Is High-Altitude Renal Syndrome Managed?

• The treatment measure for the effects of high altitude on the kidneys is to reduce the altitude. Continuous oxygen inhalation at the plains improves oxygen saturation and reverses the hypoxic effects on kidneys.

• Drugs like Acetazolamide can treat proteinuria by increasing the levels of arterial oxygen. It can also treat focal segmental glomerulosclerosis that occurs secondary to high-altitude polycythemia. Acetazolamide also improves pulmonary gas exchange and relieves symptoms of acute mountain sickness.

• Angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers, are given to treat microalbuminuria and reverse ventricular remodeling. It is beneficial for treating pathological changes in the kidneys and heart.

• For patients with chronic kidney disease or diabetic nephropathy, high altitudes are usually not recommended; if such patients enter high-altitude regions, their blood pressure, blood glucose, and urine volume should be closely monitored.

Conclusion

Acute and chronic exposure to high altitudes causes various effects on the kidneys. Pathological changes like systemic hypertension, polycythemia, hyperuricemia, and microalbuminuria are strongly associated with high-altitude exposure. It also promotes the progression of chronic kidney disease and end-stage kidney disease. The kidneys adapt to high altitudes by regulating the systemic fluid balance and electrolyte and acid-base homeostasis. Pharmacological interventions and reducing exposure to high altitude help in reversing the adverse effects.