Renal Function Markers

Proper renal function is important in normal homeostasis as they excrete waste products and remove excess fluid through steps of excretion and reabsorption. The kidneys regulate the bodies electrolytes as well as produce hormones such as EPO that stimulates the bone marrow to produce erythrocytes. The kidneys produce a second hormone called renin from the juxtaglomerular cells located in the renal arteries. When renin is secreted it acts on angiotensinogen and converts it to angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme. Angiotensin II acts on blood vessels and causes vasoconstriction that raises blood pressure.

The kidneys play such an important role in normal physiology that its imperative that they are kept functioning properly. It is common to have screening tests done annually to evaluate renal function. It is not uncommon for a physician to order a renal function test to role out chronic kidney disease (CKD). There are few tests that are important and can paint a picture as to how well the kidneys are functioning. Blood urea nitrogen (BUN) provides a rough measurement of the GFR. Urea is formed in the liver as an end product to protein metabolism. It is a breakdown product from use of amino acids. In impaired renal function, the kidneys will inadequately excrete urea, which elevates blood BUN levels. Serum creatinine is another important indicator of renal health because it is solely excreted by the kidneys. Creatinine is a waste product created by muscle metabolism. Creatinine is synthesized via creatine, phosphocreatine, and adenosine triphosphate (ATP). Creatine is synthesized in the liver and is transported through blood to the other major organs where through phosphorylation is converted to phosphocreatine. Creatine becomes phosphocreatine through a catalytic reaction by creatine kinase. The by-product produced by that reaction is creatinine. Little to no tubular reabsorption of creatinine occurs so if there are elevated levels detected in the blood, it is an indicator of renal impairment. The creatinine levels in the blood and urine can be used to calculate the creatinine clearance which correlates to the GFR.

It is important to note that a creatinine concentration in urine may also be tested during a drug of abuse screen. Normal creatinine levels indicate a test sample is undiluted, therefore if there are decreased levels of creatinine it indicates a manipulated test and the test must be repeated.

The GFR describes the flow rate of filtered fluid through the glomerular capillaries into the Bowman’s capsule per unit time. Its important to note that a normal GFR level decreases with age so that must be taken into account when screening patients with suspected CKD, for example the reference range for GFR in adults age 20-29 is 116, in adults 60-69, the GFR should be around 85. A physician can also properly stage CKD based on ones GFR. A progressively decreasing GFR indicates disease progression and more aggressive treatment needs to be considered. GFR is measured typically using a patients creatinine level in accordance with there age, sex, and body size. There are multiple equations that can be used that have all been validated, but are slightly different. Certain physicians or hospitals may have standardized ways of calculating the GFR. There is the Bedside Schwartz equation which should be used for patients 18 years of age and younger. The Modification of Diet and Renal Disease (MDRD study equation and the Chronic Kidney Disease Epidemiology Collabortion (CKD-EPI) equation are the most commonly used for adults 18 and older.

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Physicians may order microalbumin testing to screen individuals who are at high risk for developing CKD, especially diabetics. A urine microalbumin test detects minute levels of albumin in the urine. Albumin is one of the first proteins that be detected in the urine when renal function becomes impaired. Albumin is part of the globular protein family whose main function is to regulate the colloid osmotic pressure. Albumin also serves as a protein carrier for hydrophobic molecules such as lipid-soluble hormones, unconjugated bilirubin, free fatty acids, as well as some types of particular drugs like warfarin and phenytoin.

The kidneys are arguably one of the most important organs in homeostasis and its important that they are functioning properly. There are number of tests that can be performed to test renal function with each one giving a little piece of the puzzle. Physicians can use these tests to rule out CKD, or stage a patients disease progression.

-Caleb

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Urinalysis

A urinalysis is exactly what the name entails. An analysis of a patients urine. A urinalysis is a fairly common test that may be ordered as part of an annual physical or part of diagnostic testing. It can be used as an evaluation of UTIs, Diabetes Mellitus, kidney disease, kidney stones, proteinuria, rhabdomyolysis, liver disease, or if a patient presents with particular symptoms such as abdominal pain, flank pain, painful urination, blood upon urination, and fever. Pregnancy testing is also part of a routine urinalysis if ordered.

The first step in an urinalysis is collection of the specimen from the patient. An optimal sample is an early morning sample, as it is the most concentrated produced during the day. There are no fasting requirements or medication schedule dosage changes unless otherwise directed by the patients ordering physician. 30-60 mL of urine is collected in a clean urine specimen cup through a clean catch method that should be explained to the patient upon request of sample.

There are different variants of urinalysis. One is the macroscopic observation of the urine. This is the direct visual observation which includes noting its quantity, clarity, and color. Urine is normally yellow and clear without any cloudiness. Abnormalities can mean different things and further analysis is needed.

Cloudy: Infection

Dark Yellow: Dehydration

Brown: Liver disease (caused by an accumulation of bilirubin)

Red: Blood (Indicates UTI, stones, tumors, renal trauma)

Orange/Tea Colored: Rhabdomyelitis (Breakdown of muscle)

Foamy: May suggest excess protein

It is important to note that certain medications taken for UTIs can change the color of the urine, Phenazopyridine in particular.

Macroscopic -Urinalysis

Dipstick chemical analysis is performed on a narrow plastic strip which has individual tests denoted with different colored squares. The entire strip is dipped into the urine sample and color changes of the squares are noted either by the technologist or by inserting it into an instrument to read it. Each square takes a specific amount of time to react so its important to allow the reaction to come to fruition before resulting. The color change of particular squares are compared to a reference guide and can point out abnormalities.

In no particular order the squares on the dipstick indicate;

Specific gravity (concentration of the urine)

pH

Protein concentration

Glucose concentration

Presence of Ketones

Hemoglobin

Leukocyte esterase (Suggestive of WBC in urine)

Nitrite (Suggestive of bacteria in urine)

Bilirubin

Urobilinogen

Multistix-Urinalysis-Color-Key

Dipsticks are convenient and are easy to interpret and cost-effective. Its important to keep in mind that dipsticks are qualitative and not quantitative in that they only suggest that there is an abnormality, they don’t quantify that abnormality. Further analysis is required for such results.

Microscopic analysis can detect cells, cellular debris, bacteria, crystals, and certain casts to confirm the dipstick results and further quantify analysis. Once the samples are received they must be centrifuged and discarding the supernatant. Epithelial cells may suggest inflammation or damage to the gallbladder and casts and cellular debris suggest inflammation of the kidneys and upper urinary tract. On very rare occasions tumor cells can be seen which are diagnostic for certain renal carcinomas and other urinary tract cancers.

If red cells are noted it could indicate either an infection, trauma, or stones. They can also indicate glomerulonephritis which is inflammation of the kidneys. Sometimes small amounts of red cells will be seen in healthy individuals.

Urine is considered a sterile body fluid therefore there should be no white blood cells or bacteria. Any amount of WBC or bacteria within the urine is considered abnormal and is suggestive of an UTI, cystitis, or pyelonephritis.

Identifying crystals if any is important and lend diagnostic information as to what is pathologically going on within the body.

Uric acid crystals can vary in size and shape, but usually resemble a rhomboid shape. These crystals are common in individuals with urate nephrolithiasis or acute urate nephropathy.

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Cystine crystals are usually colorless hexagonally shaped and look similar to benzene rings (bringing it back to organic chemistry days). These occur in patients with cystinuria which is a genetic defect in renal cystine transport and in acidic urine (pH <6.0).

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Struvite crystals are often described as having a coffin-lid appearance. These crystals are typically magnesium ammonium phosphate and are seen in alkaline urine (pH >7.0). Seen in patients with UTIs caused by urea-splitting bacteria (Proteus mirabilis) or in patients with infected calculi (struvite stones).

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Calcium oxalate crystals are typically found in acidic urine and can take on multiple shapes. Some may look like colorless ovoids, biconcave discs, or even rods. Usually seen in patients with high dietary oxalate ingestion, patients with nephrolithiasis or those in ethylene glycol toxicity with renal failure.

Triple-phosphate-crystal

These are some of the more common crystals that will be seen. Urinalysis isn’t flashy and isn’t always fun as it is someones urine, but it is an important part of routine testing to better deliver care to the patient.

-Caleb