Monitoring Kidney Health
Kidney disease patients may have few symptoms, or even none at all, early in the course of the condition. Laboratory evaluation may be the only way that poor kidney function and disease can be discovered in their initial phases. Detecting disease before it progresses may allow intervention to have the greatest effect (Rosner 2006). There are many tests that give important insight into kidney function.
Glomerular filtration rate. Glomerular filtration rate (GFR) is the most important measure of kidney function. GFR is the volume of blood plasma that the kidney clears of a given substance each minute. In practice, it is indirectly measured by comparing blood and urine levels of the metabolite creatinine (Baynes 2014).
GFR decreases with age and renal disease, and is higher in men, pregnant women, and some disease states (eg, diabetes, obesity) (Rosner 2006; Baynes 2014). Average GFR is 120 mL/min in men and 100 mL/min in women (Baynes 2014), though lab reports usually do not provide exact values when GFR is above 60 mL/min (NKDEP 2012). Direct measurement of GFR requires both a urine and blood sample; an estimation based on serum creatinine, and incorporating adjustments for age, sex, and body size, is often used and referred to as estimated GFR (eGFR). eGFR can also be calculated using other metabolites (Rosner 2006; Levey 1999).
Creatinine and blood urea nitrogen. Creatinine is a breakdown product of phosphocreatine from muscle (Baynes 2014). It is released by muscle cells into the blood at a fairly constant rate and filtered from the blood by the kidneys and nearly completely excreted (Rosner 2006; Baynes 2014). Because its level in the blood is almost entirely dependent on the kidneys, it is a sensitive marker of renal function and is used to estimate GFR (Levey 1999).
Blood urea nitrogen (BUN) is a measure of the amount of urea in the blood (A.D.A.M. 2013b). Since excess nitrogen (a breakdown product of amino acid degradation) is removed from the body via the kidneys as urea, increases in BUN can indicate decreased kidney function (Gowda 2010). It is not as specific an indicator of kidney function as creatinine and GFR, so these values are often considered together when assessing kidney function (Lyman 1986; Qin 2013).
Cystatin C. Cystatin C is a newer blood marker of kidney function and has numerous advantages over standard tests. Unfortunately, it is not currently part of the standard blood chemistry panel, but it is available upon request from several labs. While mainstream medicine is just beginning to incorporate cystatin C testing into the clinic, Life Extension reported on the value of this novel blood test back in 2006 (Wagner 2006), and Foundation members can purchase a cystatin C blood test through the Life Extension website.
Compared with creatinine, cystatin C is less influenced by age, gender, body composition, diet, or preexisting infection or cancer, so its blood levels are more consistent across different patient populations (Lassus 2012; Shlipak, Matsushita 2013). This may make it a more sensitive indicator of GFR, and thus of kidney disease (Newman 1995; Mussap 2002). Indeed, a large analysis of pooled data from 11 general population studies involving 90 750 subjects and five additional studies of CKD patients involving 2960 subjects found that cystatin C is a better predictor of declining kidney function than creatinine. Whereas creatinine-based estimates of GFR are able to predict risks associated with declining kidney function when eGFR levels fall to 60 mL/min/1.73m2 or less, GFR estimates based on cystatin C level are predictive at approximately 85 mL/min/1.73m2. In other words, cystatin C-based estimates of GFR are able to predict risk when the magnitude of the decline in kidney function is less pronounced than that necessary for creatinine-based GFR estimates to be predictive. Although chronic kidney disease is not diagnosed until the eGFR reaches 60 mL/min, being able to detect earlier, less-significant decrements in kidney function is important, as the period of subclinical kidney dysfunction before overt kidney disease can be diagnosed based on creatinine may last one to two decades (Rush-Monroe 2013; Shlipak, Matsushita 2013).
Another advantage of cystatin C over creatinine is that while creatinine production is highly variable across populations, cystatin C production is more uniform. Since creatinine is a byproduct of muscle metabolism, individuals with greater muscle mass, those who engage in more physical activity, or those generally in better health produce more creatinine than people with lower muscle mass, physical activity levels, and poorer overall health. Thus, determining GFR based on creatinine levels requires that doctors approximate the rate of creatinine generation, which may not take all variables into account (Shlipak, Mattes 2013).
Current recommendations suggest that cystatin C measurement be used in combination with creatinine testing to confirm kidney disease diagnosis in patients with reduced GFR (45–59 mL/min) but no other signs of kidney damage (Shlipak, Mattes 2013).
Cystatin C is a better indicator of kidney function in elderly patients and predicts outcomes more accurately than creatinine (Hojs 2004; Fliser 2001). Compared with GFR, cystatin C has a stronger association with death from cardiovascular or any other cause in those with advanced CKD (Menon 2007; Ferri 2014c).
Cystatin C appears to offer novel applications beyond kidney function. In patients with normal kidney function, it was strongly and significantly associated with the risk of venous thromboembolism (Brodin 2012). Moreover, cystatin C has recently emerged as a promising predictor of cardiovascular risk (Salgado 2013; Angelidis 2013; Lassus 2012). Although more research is needed before cystatin C can be widely used to assess cardiovascular risk, studies so far suggest cystatin C testing may be a reliable measure of risk of incident or recurrent cardiovascular events and adverse outcomes. Also, cystatin C has been shown to be predictive of heart failure development, and increased levels have been associated with increased mortality in both acute and chronic heart failure (Lassus 2012).
Importantly, there are some populations in whom cystatin C may not provide accurate measurements of kidney function. These include people with uncontrolled thyroid disease and those using corticosteroids. These individuals should discuss the best kidney function testing options with their healthcare provider (Shlipak, Mattes 2013).
Electrolytes and albumin. For individuals with kidney disease, standard blood chemistry panels may reveal abnormalities in electrolytes. Kidney injury can cause increases in blood potassium and phosphate and decreases in bicarbonate, sodium, and calcium; blood pH may also become more acidic, a metabolic condition known as acidosis (Ferri 2014a).
Levels of the blood protein albumin, as it is lost in the urine, can also be reduced in certain types of kidney disease (Bolisetty 2011; Kaysen 1998).
Homocysteine. Homocysteine is a modified amino acid generated as a byproduct of protein metabolism. Elevated blood levels of homocysteine have been associated with cardiovascular risk; this link is attributable to the detrimental effect of homocysteine on the endothelial cells that line the inside of blood vessels (van Dijk 2013; Debreceni 2014; Cacciapuoti 2012; Pushpakumar 2014; Sipkens 2013; Lee 2013). Homocysteine is also highly correlated with eGFR and is elevated in 85–100% of patients with end-stage kidney disease. A large study in individuals with heart disease found that homocysteine was significantly and markedly predictive of risk of death from CKD. In this study, patients with CKD who were in the lower third of homocysteine levels had the same mortality rate as those with normal renal function, while those in the top third of homocysteine levels had a seven-fold mortality risk (van Guldener 2006; Shishehbor 2008).
Another study showed that homocysteine levels correlated with the stage of CKD in individuals with type II diabetes (Pastore 2014). Similarly, a study on children with CKD showed that increased plasma concentrations of homocysteine were associated with advanced stages of CKD (Fadel 2014). Yet another study demonstrated a strong association between high homocysteine levels and CKD. In fact, the likelihood of having CKD increased over five-fold among subjects whose homocysteine levels were high compared with subjects whose levels were normal. Moreover, higher serum homocysteine levels were associated with lower eGFR in this study (Chao 2014).
More information about homocysteine is available in Life Extension’s Homocysteine Reduction protocol.
Complete blood count. A count of blood cells in a patient with kidney disease may reveal reduced numbers of red blood cells (anemia) due to decreases in production of the hormone erythropoietin or may show blood concentration/dehydration due to the kidney’s inability to prevent water loss (Ferri 2014a).
Urine output, osmolality, specific gravity. Urine output can be decreased in acute kidney injury. For instance, a 24-hour urine output of < 20.5 mL in a 150-lb adult meets the criteria for “Failure” according to the RIFLE (Risk, Injury, Failure, Loss of Kidney Function, and End-stage kidney disease) classification system (Bellomo 2004).
Urine specific gravity and osmolality measure the ability of the kidneys to concentrate urine (A.D.A.M. 2013c). When water intake is low, healthy kidneys produce concentrated urine by excreting less water, thus keeping the body hydrated. In kidney diseases such as renal tubular disease or diabetes insipidus, urine remains dilute, which results in low urine specific gravity or osmolality, as the kidney loses its ability to concentrate urine (Hamilton 2000; Rosner 2006).
Urine protein. The presence of elevated amounts of protein in the urine (proteinuria; > 150 mg/day) represents a loss in the ability of the glomeruli in the kidney to selectively retain blood proteins, which ultimately leads to difficulties maintaining blood volume and is a powerful predictor of kidney failure (Cravedi 2013; Johnson 2012). Urine protein measurements can be either total protein or, specifically, the blood protein albumin. Urine protein measurements can be standardized to the amount of creatinine in the urine (to compensate for differences in urine concentration) and are expressed as urine protein to creatinine ratio or urine albumin to creatinine ratio (UACR). Slightly high UACR (2.5–25 mg/mmol in men or 3.5–35 mg/mmol in women) is called microalbuminuria; a level above these values is called macroalbuminuria (Johnson 2012). Changes in UACR may be used to track disease progression or response to therapy (Marre 2003; Younes 2010).
Abdominal X-rays or CT scans may be taken if kidney, ureter, or bladder stones are suspected. Ultrasound can evaluate kidney size; acutely injured kidneys may be enlarged on ultrasound whereas chronically diseased kidneys are usually smaller than normal. Ultrasound can also detect urinary tract obstruction, and can be used to detect abnormalities in renal blood flow (Meola 2012; Ferri 2014a; Cohen 2010).
Blood pressure is usually monitored in patients with kidney disease, as it both contributes to and results from diminished kidney function. Electrolyte changes, especially increased blood potassium levels, may affect heart rhythm, so electrocardiogram (ECG or EKG) is sometimes used to monitor for arrhythmia (Ferri 2014a).