Renal stone formation and passage during space flight can potentially pose a severe risk to crew member health and safety and could affect mission outcome. Although renal stones are routinely and successfully treated on Earth, the occurrence of these during space flight can prove to be problematic. [1]
Several factors contribute to the formation of renal stones in space. Dietary changes, bone metabolism, dehydration, increased salt intake as well as decreased urine volumes and increased urine saturation are all possible causes of renal stone formation. [2] It has been noted that spaceflight-induced changes in urine biochemistry are conducive for stone formation. [1]
Other possible causes include:
The most common renal stone is calcium oxalate and is usually caused by treatable metabolic disorders of hypercalcuria (increased calcium levels in the urine). These stones cause pain with passage and blockage and have been known to recur. [2]
Uric acid stones have similar characteristics as the calcium oxalate stones, but occur much more rarely (approximately 5% of all renal stones). Since they are translucent, they cannot be seen by radiographs. [2]
Struvite stones are generated by infections of urease-containing microorganisms that are capable of hydrolyzing the urea in the urine to carbon dioxide and ammonia. Struvite stones can form when urinary pH rises above 7.2, can fill the renal collection system, and can erode into the renal tissue. [2]
Cystine stones, caused by hereditary cystinuria, begin forming in childhood and can grow large enough to fill the renal collection system. [2]
Calcium phosphate stones, or otherwise called brushite, are caused by high urine pH and a supersaturation of calcium phosphate salt in the urine. [2]
It is more cost effective to prevent stone formation during a mission than is it to treat it. Increased fluid intake will increase urine volume and dilute the stone-forming salts to below the upper risk levels. [5] Avoiding foods that are high in fat and high in oxalate (nuts, pepper, chocolate, rhubarb, spinach, dark green vegetables, fruits) can help reduce hyperoxaluria (excessive urinary excretion of oxalate). Reducing the amount of meats and other purine-containing foods suppresses hyperuricosuria (increased amounts of uric acid in the urine). [6]
Oral alkali (such as potassium citrate) raises the urine's pH and helps suppress calcium oxalate crystal formation. This also works by binding the calcium to form calcium citrate (a crystal growth and aggregation inhibitor). Studies have also shown an additive effect of potassium citrate. [6] The ingestion of potassium citrate has been associated with increased bone density [7] as well as the prevention of bone loss by providing an alkali load averting the bone resorbing effect of sodium chloride excess. [8] Potassium citrate has also been shown to reduce bone loss in postmenopausal women [9] and also improves calcium balance in patients with distal renal tubular acidosis [10]
Bed rest studies [11] are used as ground-based analogs to space flight environments. During these studies, the rate of bone loss and subsequent urine composition are similar to those observed in space. A recent ground-based study tested the effectiveness of potassium-magnesium citrate (similar to the currently used potassium citrate) as a countermeasure for renal stones. [12]
The Integrated Medical Model (IMM) [13] group at Glenn Research Center in Ohio has been analyzing and optimizing data gathered on renal stone formation since late 2008.
Since the risk of renal stone formation could, as has,[ clarification needed ] result in the loss of a crew member to a mission, [1] regular testing is conducted. To date, there has been only one inflight instance of renal stone formation (described in detail in Valentin Lebedev's book, Diary of a Cosmonaut: Two hundred eleven days in space). [1]
The Skylab missions were the first missions that extended past several days in duration. Testing during these missions showed that calcium excretion increased early in flight and almost exceeded the upper threshold for normal excretion. [15]
Investigations of environmental and biochemical renal stone formation risk factors on short and long duration Shuttle missions showed that an increased risk of calcium oxalate and uric acid stone formation was evident immediately post-flight. [16] Nutrition, urinary pH and volume output were found to be the largest contributing factors for these formations. [17] During longer Shuttle missions, the risk for stone formation rapidly increases throughout the mission and persists after landing. [18]
Figures 4-2a and 4-2b show the relative risks of stone formation in a representative crewmember of a space shuttle flight. A retrospective medical chart review for stone formation in U.S. astronauts reported that 12 different astronauts reported 14 cases of renal stone formations with 9 of those instances occurring in the postflight period. [15]
Data gathered during 129- to 208-day Shuttle-Mir missions suggest that the spaceflight environment and subsequent return to Earth change the composition of the astronauts' urine and promoted the formation of renal stones. [19] This data shows that there was an increased risk for calcium oxalate and calcium phosphate stones during flight, and an increased risk for calcium oxalate and uric acid stones immediately after flight. This post-flight stone development could be attributed to low urine volumes and higher urinary pH. [15]
Flight experiment 96-E057, Renal stone risk during spaceflight: Assessment and countermeasure evaluation, [20] was conducted on Expeditions 3, 4, 5, 6, 8, 11, 12, 13, and 14. The aim of this experiment was to evaluate the in-flight effectiveness of potassium citrate as a countermeasure against the formation of renal stones during long duration space flight. The results of this experiment described the renal stone forming potential in crewmembers as a function of time in space as well as the stone forming potential during the postflight period. [15] [21]
Exploration missions pose an extra threat to mission outcome and crewmember health and safety due to the longer duration of the mission as well as the greater distances traveled. Since acute illness caused by the formation and passage of renal stones could cause the loss of a crewmember to a mission, it is critical that valid countermeasures are put in place before exploration missions begin. [15]
Table 4-4 outlines specific scenarios and time considerations for exploration missions.
| Duration Length | Mission Location | Transit Time To Location (in days) | Length Of Stay (in days) | Transit Time Back To Earth (in days) |
|---|---|---|---|---|
| Short | Moon | 3 | 8 | 3 |
| Long | Moon | 5 | 170 | 5 |
| Short | Mars | 162 | 40 | 162 |
| Long | Mars | 189 | 540 | 189 |
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.
Kidney stone disease, also known as renal calculus disease, nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material develops in the urinary tract. Renal calculi typically form in the kidney and leave the body in the urine stream. A small calculus may pass without causing symptoms. If a stone grows to more than 5 millimeters, it can cause blockage of the ureter, resulting in sharp and severe pain in the lower back or abdomen. A calculus may also result in blood in the urine, vomiting, or painful urination. About half of people who have had a renal calculus are likely to have another within ten years.
Calcium oxalate (in archaic terminology, oxalate of lime) is a calcium salt of oxalic acid with the chemical formula CaC2O4 or Ca(COO)2. It forms hydrates CaC2O4·nH2O, where n varies from 1 to 3. Anhydrous and all hydrated forms are colorless or white. The monohydrate CaC2O4·H2O occurs naturally as the mineral whewellite, forming envelope-shaped crystals, known in plants as raphides. The two rarer hydrates are dihydrate CaC2O4·2H2O, which occurs naturally as the mineral weddellite, and trihydrate CaC2O4·3H2O, which occurs naturally as the mineral caoxite, are also recognized. Some foods have high quantities of calcium oxalates and can produce sores and numbing on ingestion and may even be fatal. Cultural groups with diets that depend highly on fruits and vegetables high in calcium oxalate, such as those in Micronesia, reduce the level of it by boiling and cooking them. They are a constituent in 76% of human kidney stones. Calcium oxalate is also found in beerstone, a scale that forms on containers used in breweries.
A bladder stone is a stone found in the urinary bladder.
Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling, diabetes insipidus, and renal tubular acidosis. Because chlortalidone is effective in most patients with high blood pressure, it is considered a preferred initial treatment. It is also used to prevent calcium-based kidney stones. It is taken by mouth. Effects generally begin within three hours and last for up to three days. Long-term treatment with chlortalidone is more effective than hydrochlorothiazide for prevention of heart attack or stroke.
Thiazide refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. In most countries, thiazides are the least expensive antihypertensive drugs available.
Potassium citrate (also known as tripotassium citrate) is a potassium salt of citric acid with the molecular formula K3C6H5O7. It is a white, hygroscopic crystalline powder. It is odorless with a saline taste. It contains 38.28% potassium by mass. In the monohydrate form, it is highly hygroscopic and deliquescent.
A calculus, often called a stone, is a concretion of material, usually mineral salts, that forms in an organ or duct of the body. Formation of calculi is known as lithiasis. Stones can cause a number of medical conditions.
Anuria is nonpassage of urine, in practice is defined as passage of less than 100 milliliters of urine in a day. Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It may occur with end stage kidney disease. It is a more extreme reduction than oliguria (hypouresis), with 100 mL/day being the conventional cutoff point between the two.
Feline lower urinary tract disease (FLUTD) is a generic category term to describe any disorder affecting the bladder or urethra of cats.
Hypercalciuria is the condition of elevated calcium in the urine. Chronic hypercalciuria may lead to impairment of renal function, nephrocalcinosis, and chronic kidney disease. Patients with hypercalciuria have kidneys that excrete higher levels of calcium than normal, for which there are many possible causes. Calcium may come from one of two paths: through the gut where higher than normal levels of calcium are absorbed by the body or mobilized from stores in the bones. After initial 24 hour urine calcium testing and additional lab testing, a bone density scan (DSX) may be performed to determine if the calcium is being obtained from the bones.
Bladder stones or uroliths are a common occurrence in animals, especially in domestic animals such as dogs and cats. Occurrence in other species, including tortoises, has been reported as well. The stones form in the urinary bladder in varying size and numbers secondary to infection, dietary influences, and genetics. Stones can form in any part of the urinary tract in dogs and cats, but unlike in humans, stones of the kidney are less common and do not often cause significant disease, although they can contribute to pyelonephritis and chronic kidney disease. Types of stones include struvite, calcium oxalate, urate, cystine, calcium phosphate, and silicate. Struvite and calcium oxalate stones are by far the most common. Bladder stones are not the same as bladder crystals but if the crystals coalesce unchecked in the bladder they can become stones.
Dent's disease is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, excess calcium in the urine, formation of calcium kidney stones, nephrocalcinosis, and chronic kidney failure.
Nephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe the deposition of poorly soluble calcium salts in the renal parenchyma due to hyperparathyroidism. The term nephrocalcinosis is used to describe the deposition of both calcium oxalate and calcium phosphate. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification in radiology. It is caused by multiple different conditions and is determined by progressive kidney dysfunction. These outlines eventually come together to form a dense mass. During its early stages, nephrocalcinosis is visible on x-ray, and appears as a fine granular mottling over the renal outlines. It is most commonly seen as an incidental finding with medullary sponge kidney on an abdominal x-ray. It may be severe enough to cause renal tubular acidosis or even end stage kidney disease, due to disruption of the kidney tissue by the deposited calcium salts.
Medullary sponge kidney is a congenital disorder of the kidneys characterized by cystic dilatation of the collecting tubules in one or both kidneys. Individuals with medullary sponge kidney are at increased risk for kidney stones and urinary tract infection (UTI). Patients with MSK typically pass twice as many stones per year as do other stone formers without MSK. While having a low morbidity rate, as many as 10% of patients with MSK have an increased risk of morbidity associated with frequent stones and UTIs. While many patients report increased chronic kidney pain, the source of the pain, when a UTI or blockage is not present, is unclear at this time. Renal colic is present in 55% of patients. Women with MSK experience more stones, UTIs, and complications than men. MSK was previously believed not to be hereditary but there is more evidence coming forth that may indicate otherwise.
Sodium cellulose phosphate is a drug used to treat hypercalcemia and hypercalciuria. It has been used to prevent kidney stones.
Distal renal tubular acidosis (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the distal tubule and cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes. It leads to relatively alkaline urine, due to the kidney's inability to acidify the urine to a pH of less than 5.3.
Equil 2 is a computer program used to estimate the risk of nephrolithiasis. The input data includes excretion, concentration, and the saturation of trace elements or other substances, which are involved in the creation of kidney stones and the output will be provided in terms of PSF score or other equivalent formats. In some studies SUPERSAT, another program, provided more accurate measurements in some of the parameters such as relative supersaturation (RSS).
Idiopathic hypercalcinuria (IH) is a condition including an excessive urinary calcium level with a normal blood calcium level resulting from no underlying cause. IH has become the most common cause of hypercalciuria and is the most serious metabolic risk factor for developing nephrolithiasis. IH can predispose individuals to osteopenia or osteoporosis, and affects the entire body. IH arises due to faulty calcium homeostasis, a closely monitored process, where slight deviations in calcium transport in the intestines, blood, and bone can lead to excessive calcium excretion, bone mineral density loss, or kidney stone formation. 50%-60% of nephrolithiasis patients suffer from IH and have 5%-15% lower bone density than those who do not.
Alkali citrate is an inhibitor of kidney stones. It is used to increase urine citrate levels - this prevents calcium oxalate stones by binding to calcium and inhibiting its binding to oxalate. It is also used to increase urine pH - this prevents uric acid stones and cystine stones.
This article incorporates public domain material from Human Health and Performance Risks of Space Exploration Missions (PDF). National Aeronautics and Space Administration. (NASA SP-2009-3405).