renal diseases contribute a major component to morbidity and mortality ; with a prevalence of 17.2% . it has become a global problem necessitating early detection , evaluation , and preventive management to delay progression and to prevent adverse outcomes . the incidence of renal failure has doubled in the last 15 years . with progressive renal failure , glomerular filtration rate reduces below 15 ml / min leading to accumulation of metabolic byproducts such as urea and creatinine along with imbalance of electrolytes in serum . this necessitates renal replacement therapy ( rrt ) to avoid the serious complications leading to death . alternate to rrt , constant timely hemodialysis at regular intervals can be life - sustaining tool for these chronic renal failure patients . frequency of dialysis or time to initiate dialysis remains the key factor for maintaining homeostasis and to improve the quality of life of these patients . constant monitoring of serum levels of metabolic byproducts such as creatinine , urea , and potassium is needed . repeated venipuncture increases patient 's infection risks . saliva is considered as a filtrate of the blood where various molecules pass through transcellular ( passive intracellular diffusion and active transport ) or paracellular routes ( extracellular ultrafiltration ) into saliva . as a result , saliva is equivalent to serum , thereby reflecting the physiological state of the body . studies have shown variations in salivary levels of urea , creatinine , sodium , and potassium in renal failure patients . based on the availability of improved salivary diagnostic systems , this study was designed to test the diagnostic accuracy of salivary levels of creatinine , urea , sodium , potassium , and calcium using diagnostic validity test , receiver operator characteristic ( roc ) curve , and we also aimed to determine cutoff values for salivary creatinine , urea , sodium , potassium , and calcium as indicators of dialysis need in patients with renal failure . the study group consisted of 41 recently diagnosed renal failure patients undergoing dialysis for the first time while 41 healthy age- and sex - matched individuals constituted the control group . written informed consent individuals with other diseases , medications , and habits that affect water and electrolyte balance were excluded from the study . under aseptic conditions , the samples were centrifuged at 2000 revolutions / min ( rpm ) for 23 min to obtain serum . all participants were instructed to avoid eating or drinking for 2 h before collection of saliva . the samples were immediately transferred to a vaccine carrier with ice pack to avoid biochemical changes and carried to the laboratory . the samples were centrifuged at 4000 rpm for 10 min to obtain supernatant saliva . in renal failure patients , blood and saliva urea , creatinine , sodium , potassium , calcium , and phosphorus levels were determined in serum and supernatant saliva using semi - autoanalyzer . comparison of levels of serum and salivary urea , creatinine , sodium , potassium , calcium , and phosphorus between renal failure cases and age- and sex - matched healthy controls was done using unpaired t - test . pearson 's correlation coefficient was used to measure the degree of relationship between salivary and serum parameters . pearson 's correlation coefficient has been represented as r value , which signifies the extent of linear relationship between two variables ( serum and salivary parameters ) . any value between 1 and 0 indicates negative correlation and between 0 and + 1 indicates positive correlation . 1 indicates perfect negative linear relationship , + 1 indicates perfect positive linear relationship , and 0 indicates two variables are independent of each other . diagnostic values of salivary parameters were assessed using diagnostic validity tests and were confirmed using roc curve . comparison of levels of serum and salivary urea , creatinine , sodium , potassium , calcium , and phosphorus between renal failure cases and age- and sex - matched healthy controls was done using unpaired t - test . pearson 's correlation coefficient was used to measure the degree of relationship between salivary and serum parameters . pearson 's correlation coefficient has been represented as r value , which signifies the extent of linear relationship between two variables ( serum and salivary parameters ) . any value between 1 and 0 indicates negative correlation and between 0 and + 1 indicates positive correlation . 1 indicates perfect negative linear relationship , + 1 indicates perfect positive linear relationship , and 0 indicates two variables are independent of each other . diagnostic values of salivary parameters were assessed using diagnostic validity tests and were confirmed using roc curve . the values of urea and creatinine were significantly high in serum and saliva of cases when compared to controls . a statistically significant positive correlation was detected between serum and salivary urea concentration [ r = + 0.81 , graph 1 , p = 0.00 ] and between serum and salivary creatinine concentration [ r = + 0.65 , graph 2 , p = 0.00 , table 1 ] . area under the curve in roc for salivary urea [ graph 3a ] and creatinine [ graph 3b ] was 0.9 , suggestive of excellent diagnostic accuracy [ table 2 ] . correlation of serum and salivary parameters in cases and controls ( a ) receiver operating characteristic curve for salivary urea , ( b ) receiver operating characteristic curve for salivary creatinine . combined table of diagnostic validity tests for all the variables the sodium levels were increased significantly with cases both in serum and saliva compared to controls . a statistically significant positive correlation was detected between serum and salivary sodium concentration [ r = + 0.74 , p = 0.00 , table 1 ] . diagnostic accuracy and area under curve in roc for salivary sodium were 73% and 0.7 , respectively , suggestive of good diagnostic accuracy [ table 2 ] . a slightly negative correlation was detected between serum and salivary potassium concentration [ r = 0.03 , p = 0.88 , table 1 ] . diagnostic accuracy of salivary potassium was 89% and area under the curve in roc was 0.9 , suggestive of excellent diagnostic accuracy [ table 2 ] . the values of serum and salivary calcium showed slight reduction in cases when compared to controls . the values of serum and salivary phosphorus showed slight increase in cases compared to controls . correlation between serum and salivary calcium ( r = + 0.29 , p = 0.06 ) and between serum and salivary phosphorus [ r = + 0.271 , p = 0.09 , table 1 ] was not statistically significant . hence , cutoff value and diagnostic validity tests were not applicable . the achieved diagnostic accuracy of salivary urea , creatinine , sodium , and potassium in this study proved that saliva can be used as noninvasive diagnostic fluid in renal failure patients to monitor the levels of above - mentioned parameters . salivary levels of urea , creatinine , sodium , and potassium were proportional with their serum counterparts , and the mean values of the same are discussed in table 3 . mean values and cutoff values of serum and salivary urea , creatinine , sodium , potassium , calcium , and phosphorus cutoff values of the salivary levels of individual parameters were also evaluated . the cutoff values were evaluated in comparison with serum levels , which means any value of a parameter above the cutoff value would be considered as abnormal . the values of urea and creatinine were significantly high in serum and saliva of cases when compared to controls . a statistically significant positive correlation was detected between serum and salivary urea concentration [ r = + 0.81 , graph 1 , p = 0.00 ] and between serum and salivary creatinine concentration [ r = + 0.65 , graph 2 , p = 0.00 , table 1 ] . area under the curve in roc for salivary urea [ graph 3a ] and creatinine [ graph 3b ] was 0.9 , suggestive of excellent diagnostic accuracy [ table 2 ] . correlation of serum and salivary parameters in cases and controls ( a ) receiver operating characteristic curve for salivary urea , ( b ) receiver operating characteristic curve for salivary creatinine . the sodium levels were increased significantly with cases both in serum and saliva compared to controls . a statistically significant positive correlation was detected between serum and salivary sodium concentration [ r = + 0.74 , p = 0.00 , table 1 ] . diagnostic accuracy and area under curve in roc for salivary sodium were 73% and 0.7 , respectively , suggestive of good diagnostic accuracy [ table 2 ] . a slightly negative correlation was detected between serum and salivary potassium concentration [ r = 0.03 , p = 0.88 , table 1 ] . diagnostic accuracy of salivary potassium was 89% and area under the curve in roc was 0.9 , suggestive of excellent diagnostic accuracy [ table 2 ] . the values of serum and salivary calcium showed slight reduction in cases when compared to controls . the values of serum and salivary phosphorus showed slight increase in cases compared to controls . correlation between serum and salivary calcium ( r = + 0.29 , p = 0.06 ) and between serum and salivary phosphorus [ r = + 0.271 , p = 0.09 , table 1 ] was not statistically significant . the achieved diagnostic accuracy of salivary urea , creatinine , sodium , and potassium in this study proved that saliva can be used as noninvasive diagnostic fluid in renal failure patients to monitor the levels of above - mentioned parameters . salivary levels of urea , creatinine , sodium , and potassium were proportional with their serum counterparts , and the mean values of the same are discussed in table 3 . mean values and cutoff values of serum and salivary urea , creatinine , sodium , potassium , calcium , and phosphorus cutoff values of the salivary levels of individual parameters were also evaluated . the cutoff values were evaluated in comparison with serum levels , which means any value of a parameter above the cutoff value would be considered as abnormal . kidneys regulate the volume and composition of the extracellular fluid to maintain homeostasis by constantly processing the plasma by filtration , reabsorption , and secretion of substances , thereby help in preserving the internal environment of the body . renal damage reduces glomerular filtration capacity of kidneys and leads to increased serum levels of metabolic byproducts . among the byproducts , urea and creatinine dialysis is used to remove excess metabolic byproducts in cases of renal failure . during renal failure , continuous monitoring of serum levels of metabolic byproducts decides the need for dialysis . among all the metabolic byproducts , urea , creatinine , and potassium levels have been considered to be decisive indicators for initiation of dialysis . considering the disadvantages of invasive serum collection method and ease of saliva collection , saliva is a filtrate of serum and has been explored as an alternative to serum . in this study , we examined the use of saliva as an alternative to monitor the metabolic byproducts of kidney failure . sialometric parameters vary with age and sex . after reaching maximum development at the age of 15 years , salivary gland parenchyma will be gradually replaced by adipose and fibrovascular tissue leading to reduction in volume of acini in turn leading to sialometric alterations . in addition , women present smaller salivary glands in comparison with men ; this along with female hormonal pattern may contribute to variation in salivary parameters among the sexes . considering the above factors , age- and sex - matched controls salivary urea and creatinine levels showed positive correlation with serum levels both in cases and controls . the correlation of salivary urea and creatinine level so with serum further saliva as an ultra - filtrate of serum . in this study , the correlation coefficient of salivary and serum urea level was 0.8 while that of salivary and serum creatinine was 0.69 . although no previous explanation is available for this finding , the cause may be the lower molecular weight and size of urea at 60.03 d and 0.26 nm , respectively , in comparison with that of creatinine at 113 d and 0.3 nm , leading to a greater filtration of urea in comparison to creatinine . a significant positive correlation was found between salivary sodium level and serum sodium level , whereas slight negative correlation was obtained when salivary and serum potassium levels were compared and correlated . the salivary concentration of these ions ( sodium and potassium ) does not depend entirely on their serum concentration , and instead depend on differing , reabsorption of sodium and secretion of potassium in the striated ducts of salivary glands , thus explaining the increase potassium ion concentration in saliva than in serum . very high correlation coefficient of r = + 0.5 was found between serum and salivary potassium in patients undergoing dialysis by nagler . the reduction in serum and salivary calcium level is the consequence of a fall in 1,25 dihydroxycholecalciferol , an active metabolite of vitamin d synthesized in the kidney which plays a main role in calcium absorption from intestine , thereby causing dip in the calcium levels in serum and saliva . serum and salivary phosphorus values showed statistically nonsignificant increase in the study group and positive correlation was obtained between serum and salivary phosphorus but was statistically nonsignificant . our finding of increased level of salivary phosphorus was in agreement with a study done by savica et al . the increase in serum and salivary phosphorus levels can be explained by diminished phosphate load in the filtrate . the amount of the phosphate filtered is completely reabsorbed in the tubules , thus increasing plasma level of phosphorus . hence , hyperphosphatemia is dangerous due to increased risk of precipitation of calcium phosphate in soft tissue and in walls of blood vessels , contributing to cardiovascular calcification in renal failure patients . hence , increase in the level of salivary phosphorus is due to renal function deterioration . the salivary urea showed sensitivity , specificity , positive predictive value ( ppv ) , negative predictive value ( npv ) of 93% and overall diagnostic accuracy of salivary urea was found to be 93% in this study . this suggested that salivary urea has excellent diagnostic accuracy which was also confirmed by its score of 0.9 of area under the curve in roc . similar findings were obtained by other authors . however , comparatively , lesser values of sensitivity of 80% , specificity of 71% , ppv of 80% , and npv of 71% were demonstrated by zuniga et al . , whereas sensitivity of 80% , specificity of 90% , and area under the curve of 0.898 in roc were demonstrated by xai et al . the salivary creatinine showed sensitivity of 93% , specificity of 90% , ppv of 90% , npv of 93% , and overall diagnostic accuracy of 91% which suggested that salivary creatinine has excellent diagnostic accuracy , which was also confirmed by its score of 0.9 of area under the curve in roc . parallel findings were obtained by previous studies . however , comparatively , less diagnostic accuracy was demonstrated by xai et al . , in which sensitivity was 77% , specificity was 98% , and area under the curve was 0.897 in roc . minor disparity in the diagnostic accuracy of urea and creatinine between studies could be due to difference in sample size , method of estimation , time and method of sample collection . the salivary sodium showed sensitivity , specificity , ppv , npv of 73% and overall diagnostic accuracy of 73% , which suggested that salivary sodium had good diagnostic accuracy and was confirmed by its score of 0.7 of area under the curve in roc . the salivary potassium showed sensitivity of 83% , specificity of 78% , ppv of 79% , npv of 82% with overall diagnostic accuracy of 89% which suggested that salivary potassium had excellent diagnostic accuracy confirmed by its score of 0.9 of area under the curve in roc . based on the findings of this study , we concluded that salivary diagnostics is a simple , quick , noninvasive , inexpensive , highly accurate , and reliable technique to assess the serum levels of metabolic byproducts and electrolytes in patients with renal failure . the salivary urea , creatinine , sodium , and potassium are diagnostically accurate and can be used to monitor serum levels of metabolic byproducts such as urea and creatinine and for screening of high - risk patients to assess the need for dialysis . the authors of this manuscript declare that they have no conflicts of interest , real or perceived , financial or non - financial in this article . the authors of this manuscript declare that they have no conflicts of interest , real or perceived , financial or non - financial in this article .