Factors Affecting Kidney Function
Adults lose kidney function and capacity with normal aging. A number of factors, including drug reactions and degenerative disease not endemic to the kidneys, may bring added stress.
An analgesic is any medicine intended to kill pain. Analgesics that contain narcotics are for more severe pain and require a prescription from a physician. However, many analgesics can be purchased over-the-counter (OTC) (aspirin, ibuprofen, acetaminophen, and naproxen). OTC analgesics rarely present a problem for most people if the recommended dosage is taken. However, some conditions (eg, chronic kidney disease), long-term use, or taking them in combination with other analgesics make OTC analgesics dangerous. Analgesics such as aspirin, ibuprofen, acetaminophen, and naproxen have been attributed to incidence of acute kidney failure in persons with lupus erythematosus or chronic renal conditions, persons of advanced age, or persons who have had a recent binge of alcohol consumption (NIDDK 1998).
Painkillers that combine two or more analgesics (eg, aspirin and acetaminophen together) with caffeine or codeine are more likely to cause kidney damage. These mixtures are often sold in powder form. Single analgesics (eg, aspirin) are less likely to cause kidney damage (NIDDK 1998). More research is required to determine whether aspirin or acetaminophen contributes to kidney failure, or whether people with ailments that predispose them to kidney failure are more likely to use painkillers. It is recommended that each patient be considered individually with respect to their risk of kidney failure, length of time painkiller will be taken, and other existing illnesses, particularly in the elderly and persons with chronic conditions (Fored 2001). If possible, avoid acetaminophen-based analgesics, as these may be most toxic to the kidneys.
Glomeruli, tiny blood vessels in nephrons where blood is filtered in the kidneys, can become inflamed by autoimmune disorders (eg, Goodpasture syndrome and lupus erythematosus). When an autoimmune disorder occurs, the body attacks itself with its own immune system. In the kidneys, this type of inflammation is called glomerulonephritis (Glanze 1996; NIDDK 1999). While glomerulonephritis is usually caused by an autoimmune disorder, it can also be caused by infection (eg, streptococcal bacterial).
Congenital and Genetic
Congenital abnormalities of the kidneys are not uncommon. Sometimes the two kidneys are joined together at their base. Some people are born with only one kidney, both kidneys on the same side of the body, or underdeveloped kidneys that barely function. Polycystic kidney disease is a genetic condition that may manifest at birth, but often appears in young adulthood or middle age.
Acute kidney damage can result from an allergic reaction to a drug, taking large quantities of a drug (eg, pain killers) for a long period of time, taking out-dated tetracyclines, taking potent antibiotics, accidental ingestion of poisons, toluene inhalation (eg, industrial exposure and glue sniffing), or combining prescription drugs, OTC drugs (aspirin, acetaminophen, ibuprofen, naproxen sodium), and alcohol (NIDDK 1998). Regular blood tests to assess kidney function are recommended for anyone taking medicine known to damage the kidneys or with a condition that puts them at risk for developing kidney disease.
Discovered in 1932, homocysteine is a sulfur-containing amino acid normally found in small amounts in the blood of healthy persons. Homocysteine is derived from dietary protein (meat, milk, eggs) and is metabolized in the liver using vitamins B6 and B12. High levels of homocysteine can result from genetic disease (homocystinuria), kidney disease, hyperthyroidism, psoriasis, systemic lupus erythemotosus, drug treatment for chronic diseases, and dietary vitamin deficiencies (folic acid, B6, B12) (Welch 1998).
Homocysteine levels tend to increase with age and are higher in men than women. High homocysteine levels can be very damaging to kidneys and the vascular system (Dierkes 1999; Marangon 1999; Levin 2002). Accumulation of toxic homocysteine has been associated with the development of cardiovascular disease (artherosclerosis, stroke, heart attack), pulmonary embolism and deep venous thrombosis, dementia (Alzheimer's disease, multi-infarct dementia), and ESRD (Joosten 1997; McCaddon 1998; Welch 1998; Dierkes 1999; Levin 2002; Seshadri 2002). Cardiovascular disease (CVD), common in patients with chronic kidney disease (CKD), is responsible for the majority of morbidity and mortality in patients (Levin 2002).
As early as 1969, researchers began to make clinical observations linking elevated homocysteine to vascular diseases (McCully 1969). Subsequent investigations confirmed these observations (Clarke 1991; Ueland 1992; Stampfer 1992; 1995; Selhub 1995; Welch 1998). In CVD, there is evidence that elevated homocysteine levels are related to arterial wall damage, but the mechanism is unclear (Welch 1998). It may be that homocysteine has a toxic effect on the endothelial (cellular) lining of blood vessels. Data from a study on 14 916 healthy United States physicians with no prior history of heart disease demonstrated that highly elevated homocysteine levels are associated with a more than three-fold increase in the risk of heart attack over a 5-year period (Stampfer 1992). The Framingham Heart Study (1041 elderly subjects) and other studies have also confirmed that elevated homocysteine is an independent risk factor for heart disease (Selhub 1995; Chauveau 1993; van Guldener 2000; Hoffer 2001; Suliman 2001).
Kkidneys do not filter homocysteine properly; therefore, blood homocysteine levels increase in kidney disease patients (sometimes 3-4 times higher than normal) (van Guldener 2000; Friedman 2001; Herrmann 2001; Suliman 2001). Homocysteine is consistently elevated to very high levels in patients who require dialysis (Levin 2002). Plasma homocysteine concentrations often decrease after dialysis (Welch 1998). To further help lower homocysteine levels, dialysis patients often require high levels of nutrients, including folic acid, vitamin B12, TMG (also known as betaine or trimethylglycine), and vitamin B6 (Bostom 1996; Chauveau 1996; Robinson 1996; Sadava 1996; Tucker 1996; Welch 1998; van Guldener 2000; Herrmann 2001; Levin 2002).
Folic acid was used in a study conducted in 82 patients undergoing dialysis 3 times weekly for 4 weeks (hemodialysis, 70 patients; peritoneal dialysis, 12 patients) (Dierkes 1999). Results demonstrated that in both groups, homocysteine concentration was reduced by 35% after taking 2.5-5 mg of folic acid after each dialysis treatment.
As noted earlier, although dialysis has the effect of lowering homocysteine levels, folic acid further reduced homocysteine levels and, more importantly, had long-term effects even after supplementation was withdrawn (Dierkes 1999).
Although the relationship between CVD and CKD is convincing, therapeutic strategies appear to be underused in the care of patients with kidney disease. CVD and CKD have similar traditional (diabetes, hypertension, dyslipidemia, obesity) and nontraditional risk factors (hyperhomocysteinemia, anemia, disturbed mineral metabolism, parathyroid excess). Because these risk factors are also specific to kidney disease and are modifiable, they should be identified and treated in persons with CKD (Levin 2002). Patients with mild hyperhomocysteinemia have no clinical signs and are typically asymptomatic until the third or fourth decade of life (Welch 1998).
For some time, physicians have recognized the danger(s) of homocysteine, and have recommended use of vitamin supplements to lower homocysteine levels (Tucker 1996; Welch 1998). The "normal range" used by commercial laboratories is 5-15 micromoles per liter (μmol/L) of blood. However, epidemiological data reveal that homocysteine levels above 6.3 μmol/L result in a steep, progressive risk of heart attack, with each three-unit increase equaling a 35% increase in risk for heart attack (Verhoef 1996; Robinson 1996). There may be no safe "normal range" for homocysteine. A survey in Cardiologia reported that the average American's homocysteine level is 10 μmol/L (Andreotti 1999).
For many persons, daily intake of TMG (500 mg), folic acid (800 mcg), vitamin B12 (1000 mcg), vitamin B6 (100 mg), choline (250 mg), inositol (250 mg), and zinc (30 mg) will keep homocysteine levels in a safe range. Unfortunately, without a homocysteine blood test, it is impossible to know if the proper amounts of nutrients are being taken. Therefore, the only way to ascertain that your homocysteine level is below 7 is to have a blood test. Sometimes treatment must be individualized for complicated conditions. High levels of homocysteine can require up to 6 grams of TMG or vitamin B6 (in cystathione-B synthase deficiencies).
High blood pressure (or hypertension) creates a significant risk factor for kidney failure. This risk factor is amplified for persons with ADPKD. After investigaing the 24-hour blood pressure profile of ambulatory patients, particularly to measure nocturnal fall of blood pressure, researchers found that in ADPKD patients, the reduction in nocturnal blood pressure was attenuated (lessened), indicating increased risk for kidney damage (Li Kam Wa 1997). Further studies are needed to evaluate the contribution of nocturnal hypertension on the overall progression of renal failure. However, in another related study of untreated children, it was found that nocturnal hypertension was a major risk factor for renal deterioration (Lingens 1997).
Impaired Blood Supply
Any condition that impairs blood flow to the kidneys (eg, diabetes mellitus, hemolytic uremic syndrome, physiological shock, lupus erythematosus) can damage or cause obstruction of small blood vessels in the kidneys.
A kidney may become infected when the flow of urine is restricted in the urinary tract (NIDDK 1998). An obstruction may lead to stagnation of urine in the kidney that allows infection to spread into the bladder. Possible causes of an obstruction are a congenital defect, kidney stone, bladder tumor, or enlargement of the prostate gland. Tuberculosis of the kidney occurs when infection is carried by the blood to the kidney from somewhere else in the body (usually the lungs).
Destructive cell-signaling chemicals called inflammatory cytokines contribute to degenerative, inflammatory, and autoimmune diseases (Van der Meide 1996; Licinio 1999). Degenerative diseases (congestive heart failure, anemia, rheumatoid arthritis, fibrinogen formation, fibrosis, diabetes, asthma, lupus, psoriasis) appear to be factors in or possible underlying causes of kidney failure and disease. People with multiple degenerative disorders often exhibit excess levels of pro-inflammatory markers in their blood. Therefore, seemingly unrelated inflammatory or autoimmune diseases can have a common link to kidney disease (ie, inflammatory cytokines). In kidney failure, inflammatory cytokines restrict circulation and damage nephrons (the filtering units of the kidneys).
For those with degenerative diseases, particularly multiple ones, cytokine profile and C-reactive protein blood tests are highly recommended (available through your own physician or Life Extension Foundation). If the cytokine test reveals excess levels of cytokines--tumor necrosis factor-alpha (TNF-α), interleukin-1b (IL-1b)--nutritional supplementation, dietary modifications, and low-cost prescription medications (pentoxifylline or PTX) are advised (see Life Extension’s Inflammation [Chronic] protocol for a discussion of systemic inflammation and recommendations for reducing inflammatory conditions).
Kidney stones are more common in middle age and usually caused by excessive concentrations of substances such as calcium, uric acid, or cystine in the urine (NIDDK 1998). Hyperparathyroidism, cystinuria, and hyperoxaluria are rare, inherited metabolic disorders that can cause kidney stones. In cystinuria, too much of the amino acid cystine can lead to the formation of stones made of cystine. In patients with hyperoxaluria, the body produces too much of the salt oxalate. Excessive oxalate in the urine cannot be dissolved, crystals settle out, and stones form. Absorptive hypercalciuria occurs when the body absorbs too much calcium from food. Extra calcium ends up in the urine, and the high levels cause calcium oxalate or calcium phosphate crystals to form in the kidneys or urinary tract. Other causes are hyperuricosuria (a disorder of uric acid metabolism), gout, excess vitamin D intake, and blockage of the urinary tract. Certain diuretics ("water" pills) or calcium-based antacids, by increasing the amount of calcium in the urine, can increase the risk of kidney stone formation (NIDDK 1998).
Tumors in the kidneys, either benign or malignant, are rare. When malignant, the most common type is renal cell carcinoma, particularly in adults over 40 years.
Urinary tract infections (UTIs) are frequently occurring health conditions caused by various urinary systemic infections, sexual contact, bacteria entering the kidneys via the bloodstream or urethra, kidney stone blockages, and kidney damage (Glanze 1996). Infection can lead to impaired kidney function. Therefore, a kidney infection should be treated immediately to prevent more serious disease. A direct blow to the kidneys can also cause extensive damage (eg, a car accident, industrial accident, sports injury, or accidental fall) (NORD 2002).