biochemical markers play an important role in accurate diagnosis and also for assessing risk and adopting therapy that improves clinical outcome . over decades research and utilization of biomarkers has evolved substantially .
national institute of health ( nih ) 2001 defined a biomarker as " a characteristic that is objectively measured and evaluated as an indicator of normal biological , pathologic processes , or pharmacologic responses to a therapeutic intervention . as markers of renal function creatinine , urea , uric
acid and electrolytes are for routine analysis whereas several studies have confirmed and consolidated the usefulness of markers such as cystatin c , -trace protein .
creatinine is a breakdown product of creatine phosphate in muscle , and is usually produced at a fairly constant rate by the body depending on muscle mass .
creatinine is a commonly used as measure of kidney function.the normal creatinine clearence test valve is 110 - 150ml / min in male and in female it is 100 - 130ml / min.the national kidney disease education program recommends calculating glomerular filtration rate from serum creatinine concentration .
the diagnosis of renal failure is usually suspected when serum creatinine is greater than the upper limit of the  normal  interval . in chronic renal failure and uremia ,
an eventual reduction occurs in the excretion of creatinine by both the glomeruli and the tubules .
creatinine values may alter as its generation may not be simply a product of muscle mass but influenced by muscle function , muscle composition , activity , diet and health status .
the increased tubular secretion of creatinine in some patients with kidney dysfunction could give false negative value .
the elevated values are also seen in muscular dystrophy paralysis , anemia , leukemia and hyperthyroidism .
the decreased values are noticed with glomerulonephritis , congestive heart failure , acute tubular necrosis , shock , polycystic kidney disease , and dehydration .
urea is major nitrogenous end product of protein and amino acid catabolism , produced by liver and distributed throughout intracellular and extracellular fluid . in kidneys urea is filtered out of blood by glomerulli and is partially being reabsorbed with water .
the most frequently determined clinical indices for estimating renal function depends upon concentration of urea in the serum .
it is useful in differential diagnosis of acute renal failure and pre renal condition where blood urea nitrogen 
urea clearance is a poor indicator of glomerular filtration rate as its overproduction rate depends on several non renal factors , including diet and urea cycle enzymes .
increased blood urea nitrogen ( bun ) is seen associated with kidney disease or failure , blockage of the urinary tract by a kidney stone , congestive heart failure , dehydration , fever , shock and bleeding in the digestive tract .
the high bun levels can sometimes occur during late pregnancy or result from eating large amounts of protein - rich foods . if the bun level is higher than 100 mg / dl it points to severe kidney damage whereas decreased bun is observed in fluid excess .
low levels are also seen in trauma , surgery , opioids , malnutrition , and anabolic steroid use .
cystatin c has been proposed to be a marker as it is produced by all nucleated cells at a constant rate and is freely filtrated by the glomeruli and completely catabolized in the proximal tubules .
the concentration of serum cystatin c is mainly determined by glomerular filtration , which makes cystatin c an endogenous marker of glomerular filtration rate . in a meta analysis study by dharnidharka et
al found cystatin c was superior to serum creatinine as a marker of glomerular filtration rate .
other studies have shown similar results when compared with other markers such as a 1-microglobulin and  2-microglobulin .
cystatin c was found to be an effective marker for glomerular filtration rate in patients with cirrhosis following liver transplantation .
cystatin c has been found more useful for detecting early renal impairment in both type 1 and type 2 diabetic patients .
moreover cystatin c was also found to be associated with mild kidney dysfunction with increased risk for cardiovascular events , peripheral arterial disease and heart failure .
this protein is filtered at glomerulus and then reabsorbed in proximal tubule or excreted in urine and hence have potential to meet the criteria for use as a marker of glomerular filtration rate .
-trace protein is a low - molecular weight glycoprotein belonging to the lipocalin protein family with 168 amino acids and a molecular weight of 2300029000 , depending on the degree of glycosylation .
it has been reported to be a better indicator of reduced glomerular filtration rate than serum creatinine .
serum  -trace protein has been found to be elevated in patients with renal diseases . however , when compared , cystatin c is still a better indicator than serum -trace protein .
fructose polymer inulin ( mw 5kda ) satisfies the criteria as an ideal marker of glomerular filtration rate .
rapid measurement of glomerular filtration rate by an inulin single - bolus technique would be practically useful .
a new technique of measuring iohexol clearance using timed dried capillary blood spots was shown by mafham m et al .
blood spot iohexol clearance showed potential in estimating glomerular filtration rate accurately in large - scale epidemiological studies especially among individuals without established chronic kidney disease .
plasma clearance after single injection of iohexol gives a good estimate of glomerular filtration rate and is advantageous for the patients and clinicians .
some of them to mention are 125iodine ( i)-iothalamate , 51credta ethylenediamine tetra acetic acid , 99mtc - dtpa ( diethylene triamine penta acetic acid ) and 99mtc mercapto acetyl triglycine .
renal 125iodine ( i)-iothalamate clearance , is a simple and accurate test after a single subcutaneous injection , to measure glomerular filtration rate in adults . efficiency of 125 iodine ( i)-iothalamate was shown by geeta bajaj et al .
the same author found renal clearance of 125 iodine ( i)-iothalamate was reproducible , simple , and practical in healthy children and those with mild and advanced renal disease .
in one of the study the mean renal extraction of cystatin c was equal to the mean renal extraction of 125 iodine ( i)-iothalamate in hypertensive patients , suggesting tubular secretion of cystatin c. it was possible to get an accurate determination of 5lcr - edta clearance from a single - plasma sample in adults by applying the mean sojourn time - based approach previously shown to be very precise for determination of 99mtc - dtpa single - sample clearance . 5lcr edta- glomerular filtration rate is suggested for systemic lupus erythematosus patient with suspected renal involvement even when the serum creatinine concentration and creatinine clearance are normal .
the limitation of this marker is that glomerular filtration rate measured by 5lcr edta can be overestimated in patients with severe oedema .
clinically the appearance of significant amount of protein in urine is one of the earliest sign of almost all renal diseases .
estimation of proteinuria helps in differentiating between tubulointerstitial and glomerular diseases and also to follow the progress of renal disease and to assess the response to therapy .
normally excretion in most healthy adults is between 20 - 150 mg of protein in urine over 24 hrs .
proteinuria more than 3.5 gm / day is taken to be diagnostic of nephrotic syndrome .
panels of protein measurement including albumin ,  2-macroglobulin , igg and  2- microglobulin have been employed in differential diagnosis of prerenal and postrenal disease .
it has been recommended the use of the protein / creatinine ratio as an index of quantitative proteinuria in 24 hour urine collection .
the use of the clearance of haptoglobin , in particular provided valuable diagnostic information in cases in which the routine methods gave borderline values for the index of proteinuria . during pregnancy proteinuria assay in 24 hour urine sample
one of the investigations for proteinuria is semi - quantitative dipstick urinalysis as this method is relatively low cost and easily performed.in pregnancy automated dipstick urinalysis is a more accurate screening test for the detection of proteinuria than visual testing .
the finding of dipstick proteinuria should be confirmed by either a 24 hour urine collection or a protein - creatinine ratio .
tubular function tests involve evaluation of functions of the proximal tubule ( i.e. tubular handling of sodium , glucose , phosphate , calcium , bicarbonate and amino acids ) and distal tubule ( urinary acidification and concentration ) .
tsukahara h et al assessed the renal proximal tubular function in neonates by measuring urinary  2-microglobulin concentrations .
chen jy et al showed that in sick neonates the urinary  2-microglobulin and n - acetyl--d - glucosaminidase were the early markers of renal tubular dysfunction .
they concluded that the elevated levels of urinary  2-microglobulin and n - acetyl--d - glucosaminidase in neonates born with meconium - stained amniotic fluid indicated the existence of tubular dysfunction , probably due to prenatal distress .
serum osmolality was measured directly using osmometry , or estimated based on the direct measurement of the concentrations of the osmotically active substances ( i.e. sodium , glucose , blood urea nitrogen , and ethanol ) .
the difference between the measured osmolality and the calculated molarity is referred to as the osmole gap .
pa et al observed severe hyponatraemia in some of the patients by measuring urine osmolality and urine sodium . according to jeff ms
there are some genes which are involved in urine concentration which may encode solute - transport proteins and the vasopressin receptors .
these molecular mechanisms show the reduction in urine - concentrating ability with aging that predicts various changes in kidney function . while landon s et al showed that aquaporin-1 has a physiologic role in renal function and is also essential for maximal urinary concentrating ability . in a complete deficiency of aquaporin-1
electrolyte panel is frequently used to screen for an electrolyte or acid - base imbalance and to monitor the effect of treatment on a known imbalance that is affecting bodily organ function .
the test for electrolytes includes the measurement of sodium , potassium , chloride , and bicarbonate for both diagnosis and management of renal , endocrine , acid - base , water balance , and many other conditions .
the combination of decreased filtration and decreased secretion of potassium in distal tubule during renal failure cause increased plasma potassium .
creatinine is a breakdown product of creatine phosphate in muscle , and is usually produced at a fairly constant rate by the body depending on muscle mass .
creatinine is a commonly used as measure of kidney function.the normal creatinine clearence test valve is 110 - 150ml / min in male and in female it is 100 - 130ml / min.the national kidney disease education program recommends calculating glomerular filtration rate from serum creatinine concentration .
the diagnosis of renal failure is usually suspected when serum creatinine is greater than the upper limit of the  normal  interval . in chronic renal failure and uremia ,
an eventual reduction occurs in the excretion of creatinine by both the glomeruli and the tubules .
creatinine values may alter as its generation may not be simply a product of muscle mass but influenced by muscle function , muscle composition , activity , diet and health status .
the increased tubular secretion of creatinine in some patients with kidney dysfunction could give false negative value .
the elevated values are also seen in muscular dystrophy paralysis , anemia , leukemia and hyperthyroidism .
the decreased values are noticed with glomerulonephritis , congestive heart failure , acute tubular necrosis , shock , polycystic kidney disease , and dehydration .
urea is major nitrogenous end product of protein and amino acid catabolism , produced by liver and distributed throughout intracellular and extracellular fluid . in kidneys urea
the most frequently determined clinical indices for estimating renal function depends upon concentration of urea in the serum .
it is useful in differential diagnosis of acute renal failure and pre renal condition where blood urea nitrogen 
urea clearance is a poor indicator of glomerular filtration rate as its overproduction rate depends on several non renal factors , including diet and urea cycle enzymes .
increased blood urea nitrogen ( bun ) is seen associated with kidney disease or failure , blockage of the urinary tract by a kidney stone , congestive heart failure , dehydration , fever , shock and bleeding in the digestive tract .
the high bun levels can sometimes occur during late pregnancy or result from eating large amounts of protein - rich foods .
if the bun level is higher than 100 mg / dl it points to severe kidney damage whereas decreased bun is observed in fluid excess .
low levels are also seen in trauma , surgery , opioids , malnutrition , and anabolic steroid use .
cystatin c has been proposed to be a marker as it is produced by all nucleated cells at a constant rate and is freely filtrated by the glomeruli and completely catabolized in the proximal tubules .
the concentration of serum cystatin c is mainly determined by glomerular filtration , which makes cystatin c an endogenous marker of glomerular filtration rate . in a meta analysis study by dharnidharka et
al found cystatin c was superior to serum creatinine as a marker of glomerular filtration rate .
other studies have shown similar results when compared with other markers such as a 1-microglobulin and  2-microglobulin .
cystatin c was found to be an effective marker for glomerular filtration rate in patients with cirrhosis following liver transplantation .
cystatin c has been found more useful for detecting early renal impairment in both type 1 and type 2 diabetic patients .
moreover cystatin c was also found to be associated with mild kidney dysfunction with increased risk for cardiovascular events , peripheral arterial disease and heart failure .
this protein is filtered at glomerulus and then reabsorbed in proximal tubule or excreted in urine and hence have potential to meet the criteria for use as a marker of glomerular filtration rate .
-trace protein is a low - molecular weight glycoprotein belonging to the lipocalin protein family with 168 amino acids and a molecular weight of 2300029000 , depending on the degree of glycosylation .
it has been reported to be a better indicator of reduced glomerular filtration rate than serum creatinine .
serum  -trace protein has been found to be elevated in patients with renal diseases .
however , when compared , cystatin c is still a better indicator than serum -trace protein .
creatinine is a breakdown product of creatine phosphate in muscle , and is usually produced at a fairly constant rate by the body depending on muscle mass .
creatinine is a commonly used as measure of kidney function.the normal creatinine clearence test valve is 110 - 150ml / min in male and in female it is 100 - 130ml / min.the national kidney disease education program recommends calculating glomerular filtration rate from serum creatinine concentration .
the diagnosis of renal failure is usually suspected when serum creatinine is greater than the upper limit of the  normal  interval . in chronic renal failure and uremia ,
an eventual reduction occurs in the excretion of creatinine by both the glomeruli and the tubules .
creatinine values may alter as its generation may not be simply a product of muscle mass but influenced by muscle function , muscle composition , activity , diet and health status .
the increased tubular secretion of creatinine in some patients with kidney dysfunction could give false negative value .
the elevated values are also seen in muscular dystrophy paralysis , anemia , leukemia and hyperthyroidism .
the decreased values are noticed with glomerulonephritis , congestive heart failure , acute tubular necrosis , shock , polycystic kidney disease , and dehydration .
urea is major nitrogenous end product of protein and amino acid catabolism , produced by liver and distributed throughout intracellular and extracellular fluid . in kidneys urea is filtered out of blood by glomerulli and is partially being reabsorbed with water .
the most frequently determined clinical indices for estimating renal function depends upon concentration of urea in the serum .
it is useful in differential diagnosis of acute renal failure and pre renal condition where blood urea nitrogen 
urea clearance is a poor indicator of glomerular filtration rate as its overproduction rate depends on several non renal factors , including diet and urea cycle enzymes .
increased blood urea nitrogen ( bun ) is seen associated with kidney disease or failure , blockage of the urinary tract by a kidney stone , congestive heart failure , dehydration , fever , shock and bleeding in the digestive tract .
the high bun levels can sometimes occur during late pregnancy or result from eating large amounts of protein - rich foods .
if the bun level is higher than 100 mg / dl it points to severe kidney damage whereas decreased bun is observed in fluid excess .
low levels are also seen in trauma , surgery , opioids , malnutrition , and anabolic steroid use .
cystatin c has been proposed to be a marker as it is produced by all nucleated cells at a constant rate and is freely filtrated by the glomeruli and completely catabolized in the proximal tubules .
the concentration of serum cystatin c is mainly determined by glomerular filtration , which makes cystatin c an endogenous marker of glomerular filtration rate . in a meta analysis study by dharnidharka et
al found cystatin c was superior to serum creatinine as a marker of glomerular filtration rate .
other studies have shown similar results when compared with other markers such as a 1-microglobulin and  2-microglobulin .
cystatin c was found to be an effective marker for glomerular filtration rate in patients with cirrhosis following liver transplantation .
cystatin c has been found more useful for detecting early renal impairment in both type 1 and type 2 diabetic patients .
moreover cystatin c was also found to be associated with mild kidney dysfunction with increased risk for cardiovascular events , peripheral arterial disease and heart failure .
this protein is filtered at glomerulus and then reabsorbed in proximal tubule or excreted in urine and hence have potential to meet the criteria for use as a marker of glomerular filtration rate .
-trace protein is a low - molecular weight glycoprotein belonging to the lipocalin protein family with 168 amino acids and a molecular weight of 2300029000 , depending on the degree of glycosylation .
it has been reported to be a better indicator of reduced glomerular filtration rate than serum creatinine .
serum  -trace protein has been found to be elevated in patients with renal diseases .
however , when compared , cystatin c is still a better indicator than serum -trace protein .
fructose polymer inulin ( mw 5kda ) satisfies the criteria as an ideal marker of glomerular filtration rate .
rapid measurement of glomerular filtration rate by an inulin single - bolus technique would be practically useful .
a new technique of measuring iohexol clearance using timed dried capillary blood spots was shown by mafham m et al .
blood spot iohexol clearance showed potential in estimating glomerular filtration rate accurately in large - scale epidemiological studies especially among individuals without established chronic kidney disease .
plasma clearance after single injection of iohexol gives a good estimate of glomerular filtration rate and is advantageous for the patients and clinicians .
a new technique of measuring iohexol clearance using timed dried capillary blood spots was shown by mafham m et al .
blood spot iohexol clearance showed potential in estimating glomerular filtration rate accurately in large - scale epidemiological studies especially among individuals without established chronic kidney disease .
plasma clearance after single injection of iohexol gives a good estimate of glomerular filtration rate and is advantageous for the patients and clinicians .
some of them to mention are 125iodine ( i)-iothalamate , 51credta ethylenediamine tetra acetic acid , 99mtc - dtpa ( diethylene triamine penta acetic acid ) and 99mtc mercapto acetyl triglycine .
renal 125iodine ( i)-iothalamate clearance , is a simple and accurate test after a single subcutaneous injection , to measure glomerular filtration rate in adults . efficiency of 125 iodine ( i)-iothalamate was shown by geeta bajaj et al .
the same author found renal clearance of 125 iodine ( i)-iothalamate was reproducible , simple , and practical in healthy children and those with mild and advanced renal disease . in one of the study the mean renal extraction of cystatin c was equal to the mean renal extraction of 125 iodine ( i)-iothalamate in hypertensive patients , suggesting tubular secretion of cystatin c. it was possible to get an accurate determination of 5lcr - edta clearance from a single - plasma sample in adults by applying the mean sojourn time - based approach previously shown to be very precise for determination of 99mtc - dtpa single - sample clearance .
5lcr edta- glomerular filtration rate is suggested for systemic lupus erythematosus patient with suspected renal involvement even when the serum creatinine concentration and creatinine clearance are normal .
the limitation of this marker is that glomerular filtration rate measured by 5lcr edta can be overestimated in patients with severe oedema .
clinically the appearance of significant amount of protein in urine is one of the earliest sign of almost all renal diseases .
estimation of proteinuria helps in differentiating between tubulointerstitial and glomerular diseases and also to follow the progress of renal disease and to assess the response to therapy .
normally excretion in most healthy adults is between 20 - 150 mg of protein in urine over 24 hrs .
proteinuria more than 3.5 gm / day is taken to be diagnostic of nephrotic syndrome .
panels of protein measurement including albumin ,  2-macroglobulin , igg and  2- microglobulin have been employed in differential diagnosis of prerenal and postrenal disease .
it has been recommended the use of the protein / creatinine ratio as an index of quantitative proteinuria in 24 hour urine collection .
the use of the clearance of haptoglobin , in particular provided valuable diagnostic information in cases in which the routine methods gave borderline values for the index of proteinuria . during pregnancy proteinuria assay in 24 hour urine sample
one of the investigations for proteinuria is semi - quantitative dipstick urinalysis as this method is relatively low cost and easily performed.in pregnancy automated dipstick urinalysis is a more accurate screening test for the detection of proteinuria than visual testing .
the finding of dipstick proteinuria should be confirmed by either a 24 hour urine collection or a protein - creatinine ratio .
tubular function tests involve evaluation of functions of the proximal tubule ( i.e. tubular handling of sodium , glucose , phosphate , calcium , bicarbonate and amino acids ) and distal tubule ( urinary acidification and concentration ) .
tsukahara h et al assessed the renal proximal tubular function in neonates by measuring urinary  2-microglobulin concentrations .
chen jy et al showed that in sick neonates the urinary  2-microglobulin and n - acetyl--d - glucosaminidase were the early markers of renal tubular dysfunction .
they concluded that the elevated levels of urinary  2-microglobulin and n - acetyl--d - glucosaminidase in neonates born with meconium - stained amniotic fluid indicated the existence of tubular dysfunction , probably due to prenatal distress .
serum osmolality was measured directly using osmometry , or estimated based on the direct measurement of the concentrations of the osmotically active substances ( i.e. sodium , glucose , blood urea nitrogen , and ethanol ) .
the difference between the measured osmolality and the calculated molarity is referred to as the osmole gap .
lalo pa et al observed severe hyponatraemia in some of the patients by measuring urine osmolality and urine sodium . according to jeff ms
there are some genes which are involved in urine concentration which may encode solute - transport proteins and the vasopressin receptors .
these molecular mechanisms show the reduction in urine - concentrating ability with aging that predicts various changes in kidney function . while landon s et al showed that aquaporin-1 has a physiologic role in renal function and is also essential for maximal urinary concentrating ability . in a complete deficiency of aquaporin-1
electrolyte panel is frequently used to screen for an electrolyte or acid - base imbalance and to monitor the effect of treatment on a known imbalance that is affecting bodily organ function .
the test for electrolytes includes the measurement of sodium , potassium , chloride , and bicarbonate for both diagnosis and management of renal , endocrine , acid - base , water balance , and many other conditions .
the combination of decreased filtration and decreased secretion of potassium in distal tubule during renal failure cause increased plasma potassium .
clinically the appearance of significant amount of protein in urine is one of the earliest sign of almost all renal diseases .
estimation of proteinuria helps in differentiating between tubulointerstitial and glomerular diseases and also to follow the progress of renal disease and to assess the response to therapy .
normally excretion in most healthy adults is between 20 - 150 mg of protein in urine over 24 hrs .
proteinuria more than 3.5 gm / day is taken to be diagnostic of nephrotic syndrome .
panels of protein measurement including albumin ,  2-macroglobulin , igg and  2- microglobulin have been employed in differential diagnosis of prerenal and postrenal disease .
it has been recommended the use of the protein / creatinine ratio as an index of quantitative proteinuria in 24 hour urine collection .
the use of the clearance of haptoglobin , in particular provided valuable diagnostic information in cases in which the routine methods gave borderline values for the index of proteinuria . during pregnancy proteinuria assay in 24 hour urine sample
one of the investigations for proteinuria is semi - quantitative dipstick urinalysis as this method is relatively low cost and easily performed.in pregnancy automated dipstick urinalysis is a more accurate screening test for the detection of proteinuria than visual testing .
the finding of dipstick proteinuria should be confirmed by either a 24 hour urine collection or a protein - creatinine ratio .
tubular function tests involve evaluation of functions of the proximal tubule ( i.e. tubular handling of sodium , glucose , phosphate , calcium , bicarbonate and amino acids ) and distal tubule ( urinary acidification and concentration ) .
tsukahara h et al assessed the renal proximal tubular function in neonates by measuring urinary  2-microglobulin concentrations .
chen jy et al showed that in sick neonates the urinary  2-microglobulin and n - acetyl--d - glucosaminidase were the early markers of renal tubular dysfunction .
they concluded that the elevated levels of urinary  2-microglobulin and n - acetyl--d - glucosaminidase in neonates born with meconium - stained amniotic fluid indicated the existence of tubular dysfunction , probably due to prenatal distress .
serum osmolality was measured directly using osmometry , or estimated based on the direct measurement of the concentrations of the osmotically active substances ( i.e. sodium , glucose , blood urea nitrogen , and ethanol ) .
the difference between the measured osmolality and the calculated molarity is referred to as the osmole gap .
lalo pa et al observed severe hyponatraemia in some of the patients by measuring urine osmolality and urine sodium . according to jeff ms
there are some genes which are involved in urine concentration which may encode solute - transport proteins and the vasopressin receptors .
these molecular mechanisms show the reduction in urine - concentrating ability with aging that predicts various changes in kidney function . while landon s et al showed that aquaporin-1 has a physiologic role in renal function and is also essential for maximal urinary concentrating ability . in a complete deficiency of aquaporin-1
electrolyte panel is frequently used to screen for an electrolyte or acid - base imbalance and to monitor the effect of treatment on a known imbalance that is affecting bodily organ function .
the test for electrolytes includes the measurement of sodium , potassium , chloride , and bicarbonate for both diagnosis and management of renal , endocrine , acid - base , water balance , and many other conditions .
the combination of decreased filtration and decreased secretion of potassium in distal tubule during renal failure cause increased plasma potassium .
the above discussed glomerular and tubular function markers are effective in proper assessment of renal function tests . these markers act as an indicator of biological , pathologic processes , or pharmacologic responses to a therapeutic intervention .
 background : the markers of renal function test assess the normal functioning of kidneys . 
 these markers may be radioactive and non radioactive . 
 they indicate the glomerular filtration rate , concentrating and diluting capacity of kidneys ( tubular function ) . if there is an increase or decrease in the valves of these markers it indicates dysfunction of kidney.aim:the aim of this review is to compare and analyze the present and newer markers of renal function tests which help in diagnosis of clinical disorders.material & methods : an extensive literature survey was done aiming to compare and compile renal function tests makers required in diagnosis of diseases.results:creatinine , urea , uric acid and electrolytes are makers for routine analysis whereas several studies have confirmed and consolidated the usefulness of markers such as cystatin c and -trace protein.conclusion:we conclude that further investigation is necessary to define these biomarkers in terms of usefulness in assessing renal function . 