kidney function tests and its interpretation

assessment of kidney function by kidney function tests

1. Assessment of Kidney Function Dr.G.VENKATA RAMANA MBBS DNB FAMILY MEDICINE

2. Assessment of Kidney Function Kidney function is most commonly approximated by the glomerular filtration rate ( GFR) This provides a quantitative measurement of the kidney’s ability to filter and clear solute from the body Equally important is the quality of the filtrate that is produced by the kidneys This can be assessed by examining the content of the urinary filtrate , which reflects renal tubular function and the integrity of the filtration barrier The amount of fluid that is processed by the kidney is reflected by the GFR GFR is defined as the sum of the filtration rates of all functional nephrons.

3. The normal GFR is ∼125 mL/min/1.73 m2 in men and 100 mL/min/1.73 m2 in women Changes in the overall filtering capacity of the kidney will result in parallel changes in GFR For example, diseased kidneys with significantly impaired filtering capacity will have a reduced GFR Estimating GFR Serum markers, such as creatinine and blood urea nitrogen, are commonly used to track changes in GFR They are inexpensive and convenient tools, but their limitations and shortcomings must be understood It is also important to recognize that the relationship between the change in creatinine and the change in renal function is nonlinear For example, a change in creatinine from 1.0 to 1.4 mg/ dL represents a greater decline in kidney function than a change from 3.0 to 3.4 mg/ dL , even though there is a 0.4 mg/ dL difference in both examples

4. Serum Markers of renal function Creatinine Accumulation of a muscle-derived metabolite that is predominantly cleared by glomerular filtration Use and Limitations A reduction in GFR results in a rise in serum creatinine However : 1. Creatinine is highly dependent on muscle mass Individuals at the extremes of muscle mass may have physiologic values that are lower or higher than the reference ranges 2. Dietary intake and drugs that inhibit tubular secretion ( notably cimetidine and trimethoprim) may falsely elevate creatinine levels

5. Factors affecting serum creatinine Trimethoprim and cimetidine block proximal tubular secretion of creatinine They can increase plasma creatinine level up to as much as 0.5 mg/Dl This effect is more pronounced in CKD when baseline creatinine is already elevated Cefoxitin and flucytosine interfere with the creatinine assay, giving a false elevation of plasma creatinine levels Acetoacetate in diabetic ketoacidosis can be falsely recognized by the colorimetric assay as creatinine and may elevate creatinine by as much as 0.5 to 2 mg/ dL Hypothyroidism increases plasma creatinine levels and hyperthyroidism decreases plasma creatinine levels

6. Blood urea nitrogen(BUN) Accumulation of urea, a product of protein metabolism Although BUN may rise in renal disease , an elevated BUN is not specific for renal impairment BUN can be increased by a number of nonrenal etiologies, including gastrointestinal bleeding , steroid use, and parenteral nutrition For practical purposes, BUN is most informative when the ratio of BUN: Cr exceeds 20:1 , which is suggestive of a prerenal state BUN can be reduced by malnutrition and liver disease, which reduce urea generation rates

7. Cystatin C Cystatin C is generated at a steady rate by nucleated cells It is filtered at the glomerulus and metabolized (but not reabsorbed ) in the tubules Equations that utilize cystatin C in combination with creatinine may be more accurate in estimating GFR than those that utilize creatinine alone

8. EQUATIONS TO ESTIMATE RENAL FUNCTION Cockcroft– Gault Estimates CrCl using age , weight, gender, and creatinine Easy to calculate, but loses accuracy when weight does not correlate to muscle mass. MDRD Estimates GFR using age , race, gender, and creatinine Less accurate in obese individuals and those with nearnormal GFR CKD-EPI Estimates GFR using age , race, gender, creatinine and/or cystatin May perform better than other equations in patients with higher GFR (particularly when both creatinine and cystatin are used in the equation )

9. MDRD Study Equation eGFR = 175 x ( S Cr ) -1.154  x (age) -0.203  x 0.742 [if female] x 1.212 [if Black] Abbreviations / Units eGFR (estimated glomerular filtration rate) = mL/min/1.73 m 2 S cr  (standardized serum creatinine ) = mg/ dL age = years

10. CKD-EPI Creatinine Equation (2021) Expressed as a single equation: eGFR cr  = 142 x min( S cr /κ, 1) α  x max( S cr /κ, 1) -1.200  x 0.9938 Age  x 1.012 [if female] where: S cr  = standardized serum creatinine in mg/ dL κ = 0.7 (females) or 0.9 (males) α = -0.241 (female) or -0.302 (male) min( S cr /κ, 1) is the minimum of S cr /κ or 1.0 max( S cr /κ, 1) is the maximum of S cr /κ or 1.0 Age (years)

11. Urinary Assessment Examining the chemical and microscopic composition of the urine is extremely useful in determining whether glomerular and tubular function is intact Evidence of renal disease may be present in the urinary assessment even before there are changes in the GFR Urinalysis : . Microscopic examination: Cells , crystals, and casts are common findings on urine microscopy Red blood cells (RBCs) suggest bleeding into the upper or lower genitourinary tract Microscopic hematuria has traditionally been defined as more than two RBCs per high-power field on microscopy

12. RBCs are typically 4 to 7 μm in diameter and have a characteristic red pigment with central opacity and smooth borders In glomerular diseases, the RBCs often taken on a dysmorphic appearance (blebs or outpouchings along the cellular contour) which suggest physical deformation as it squeezes through defects in the glomerular filtration barrier White blood cells (WBCs) suggest inflammation or infection WBCs can be distinguished from RBCs by their larger size , lack of pigment, and cytoplasmic granulation. WBCs in a clean urine sample are most commonly due to an infectious pathogen, allergic response, or inflammatory condition

13. Epithelial cells Squamous epithelial cells: Present in the urine because of shedding from the distal genital tract and essentially are contaminants Transitional epithelial cells: Seen intermittently with bladder catheterization or irrigation Occasionally , they may be associated with malignancy, especially if irregular nuclei are noted Renal tubular epithelial cells: May be seen in significant numbers with tubular injury Tubular epithelial cells from the proximal tubule tend to be very granulated

14. Organisms Bacteria are frequently seen in urine specimens, given the fact that urine is typically collected under nonsterile conditions Identification and susceptibilities of these organisms typically require high-powered magnification , staining, culture, and in vitro testing against antibiotics Fungi: Presence of Candida in urine is typically thought to be a contaminant from genital secretions or, in the presence of a long, indwelling bladder catheter, colonization Candida UTIs can cause similar symptoms to that seen with a bacterial infection

15. Other infectious fungal agents, including Aspergillus , Cryptococcus, and Histoplasmosis , can be seen in the chronically ill or immunocompromised patients Parasites: Presence of Trichomonas vaginalis and Enterobius vermicularis in urine are typically thought of as contaminants stemming from genital secretions Urinary crystals are often an incidental finding However , they can be used to identify the composition of kidney stones Casts are formed when the contents of the renal filtrate are trapped by proteins secreted into the tubular lumen (typically the Tamm– Horsfall protein ) Thus , a cast provides a snapshot of the tubular milieu at the time of its formation

16. COMMON URINARY CRYSTALS Calcium oxalate While these commonly appear as octahedral “envelopes ,” they can also take a rectangular, dumbbell , and ovoid shape Triple phosphate These are usually 3–6-sided prisms that resemble “coffin lids” Calcium phosphate These crystals usually have the appearance of a small rosette Uric acid Uric acid can have a variety of appearances, including rhomboids, rosettes, and four-sided “ whetstones”

17. Casts Hyaline casts Acellular amalgam of Tamm– Horsfall protein , formed in concentrated , Hyaline casts acidic urine Granular casts Encased tubular debris ( resembles a tube of sand) consistent with tubular damage Granular casts WBC casts Encased WBCs suggest interstitial inflammation such as pyelonephritis WBC casts

18. RBC casts Encased RBCs suggest glomerular hematuria, an important finding in glomerulonephritis RBC casts

19. URINALYSIS Specific gravity Assesses the relative density of urine Values less than 1.010 indicate a dilute urine (e.g., water ingestion, diabetes insipidus ) Values greater than 1.020 indicate a more concentrated urine (e.g ., dehydration , volume contraction ). Urine pH Assesses urine acidification Ranges between 4.5 and 7.8 Low urine pH can be observed in large protein consumption, metabolic acidosis, and volume depletion High urine pH may be seen in distal RTA

20. Ketones Detects acetoacetic acid (but not beta hydroxybutyrate ) Ketones are mainly seen in diabetic and alcoholic ketoacidosis , but can also be observed in starvation, vomiting, and strenuous exercise Glucose Assess glucose reabsorption at the proximal tubule If plasma glucose > 180–200 mg/ dL , positive results indicate overflow of glucose into the urine If plasma glucose < 180 mg/ dL , positive results suggest proximal tubular defect Hemoglobin Detects presence of heme pigment in the urine A positive result suggests hematuria However , if microscopy shows no urinary RBCs , assess for free hemoglobin/myoglobin (e.g ., rhabdomyolysis )

21. Protein Detects anionic proteins (albumin) Significant proteinuria suggests renal parenchymal disease affecting the glomerular filtration barrier Leukocyte esterase Detects WBC activity in the urine Can be used in conjunction with nitrite test to identify urinary tract infections A positive test may also suggest renal inflammation (e.g., interstitial nephritis ) Nitrites Detects bacterial conversion of nitrates to nitrites In conjunction with positive leukocyte esterase, can be used to identify UTI Note : Not all bacteria convert nitrates to nitrites

22. Imaging Studies The appearance of the kidney, particularly on ultrasound, can provide a number of insights into the presence, cause, chronicity, and irreversibility of renal disease. However, it is generally not used to provide detailed quantitative data about renal function Anatomy Prior to a renal biopsy, an ultrasound is generally done to confirm the presence of two nonatrophic kidneys Ultrasound can also easily identify the presence of hydroureter or hydronephrosis caused by obstructive lesions Distortions of renal architecture by tumor or cystic infiltration (as seen in polycystic kidney disease) can also be easily appreciated on ultrasound

23. Size The average kidney is 10 to 13 cm in length Kidney size is proportional to body height A 13-cm kidney would be considered suspiciously large in an individual who is under 5 ft tall (despite being in the “normal” range ) A 10-cm kidney would be small for an individual greater than 6 ft tall Small kidneys suggest atrophy attributable to a chronic disease process or aberration in development Large kidneys (greater than 13 cm) can be seen with diabetic nephropathy , HIV-associated nephropathy , infiltrative disorders (amyloidosis, tumor infiltration), and inflammation (acute interstitial nephritis )

24. Echogenicity The renal parenchyma should be no more echogenic than the liver Increased echogenicity reflects an increase in tissue density, which is often associated with chronic parenchymal disease The combination of increased echogenicity and small kidney size is suggestive of chronic, irreversible damage

25. Renal Biopsy Obtaining and examining renal tissue through a renal biopsy is the most definitive, yet most invasive, technique for diagnosing renal disease Indications A cute renal failure of uncertain etiology N ephrotic syndrome N ephritic syndrome R apidly progressive glomerulonephritis A cute or chronic renal allograft dysfunction Depending on other clinical features, renal biopsy can be considered in asymptomatic hematuria or proteinuria Urine culture should be sterile before a biopsy attempt

26. Preprocedural evaluation Renal imaging to ensure that the patient has two kidneys of normal size and shape Native kidney biopsy is relatively contraindicated for atrophic kidneys <9 cm in size, as the risk of capsular hemorrhage increases in fibrotic kidneys (as does the risk of a low-yield biopsy result) Renal biopsy of a solitary native kidney should be undertaken only when absolutely necessary to preserve renal function, as there is a risk of marked bleeding leading to nephrectomy Blood pressure (BP) should be optimally controlled, with diastolic BP <95 mm Hg, to minimize bleeding complications

27. Blood coagulation parameters should be normalized as much as possible before renal biopsy Systemic anticoagulants, including antiplatelet therapy, aspirin, and nonsteroidal anti-inflammatory drugs, should be discontinued ≥5 days before renal biopsy Prothrombin time (PT) should be <1.2 times control Activated partial thromboplastin time ( aPTT ) should be <1.2 times control In a patient with renal insufficiency and elevated blood urea nitrogen levels with a prolonged bleeding time, DDAVP, 0.4 mcg/kg IV for 2 to 3 hours, is usually given before biopsy Intravenous or subcutaneous unfractionated heparin should be stopped at least 6 hours prior to the procedure and should not be resumed until at least 18 to 24 hours after the procedure

28. Complications After a biopsy, patients should be observed for about 24 hours The patient should remain supine for 6 hours and then remain at bed rest overnight Vital signs and CBC are closely monitored To minimize the risk of bleeding, BP should ideally be well controlled (goal <140/90 mm Hg ) Hematuria and the formation of a perinephric hematoma occur to some degree in all patients after renal biopsy A fall in hemoglobin of about 1 g/ dL is not unusual after an uncomplicated renal biopsy Blood loss requiring transfusion occurs in about 2.2% of renal biopsies

29. The most common site of significant blood loss is into the perinephric space, leading to a large perinephric hematoma Subcapsular bleeds usually tamponade themselves Rarely, a large subcapsular hematoma can compress the renal parenchyma and lead to pressure-induced ischemia and hypertension, a phenomenon referred to as a “Page Kidney” Significant bleeding into the urinary collecting system may also occur, which manifests as gross hematuria and may lead to ureteral obstruction

30. Intervention to control bleeding, such as embolization, is required in about 0.4% of cases Hypotension after renal biopsy can occur in 1% to 2% of patients and is usually fluid responsive Arteriovenous fistulas can be detected radiologically in up to 18 % of cases, but are rarely of clinical significance and usually resolve spontaneously Persistent pain at the biopsy site may result from a subcapsular or perinephric hematoma or from renal colic as blood clots pass through the collecting system