Evaluation Of Spot Urine Protein Creatinine Ratio As An .
OPENACCESS Freely available onlineClinical & Medical BiochemistryResearch ArticleEvaluation of Spot Urine Protein Creatinine Ratio as an Index ofQuantitative Proteinuria in Varying Renal DisordersSantosh KV*, Anandhi N, Tirupathi PDepartment of Biochemistry, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, India.ABSTRACTThis study is conducted to evaluate the correlation between 24 hrs urine protein and urine Protein CreatinineRatio (PCR) in spot urine sample and if found comparable the estimation of spot protein creatinine ratio could beadopted as an alternative method for quantification of proteinuria in our clinical lab setting.Keywords: Protein creatinine Ratio; Proteinuria; Kidney; Chronic kidney disease; ProteinINTRODUCTIONKidney disease is a worldwide health crisis and it is 12 th mostcommon cause of death causing 1.1 million deaths worldwideas per the global burden of disease study done by nationalkidney foundation in USA [1]. Almost 10% of world populationis affected by chronic kidney disease and it is more commonin women than in men. 17% of Indians have some form ofchronic kidney disease and two lakh patients need dialysis everyyear in India. Through proper statistics it is assumed as 50% ofpopulation having renal disorders see the nephrologists in thelast stage of their kidney disease [2]. According to a programconducted for screening of Chronic Kidney Disease (CKD) inChennai by Kidney Help Trust, the prevalence of CKD was 13.9percent in a rural population [3].Proteinuria is an important sign of kidney disease impartingpowerful diagnostic and prognostic information. It is a cornerstoneof the workup for CKD, AKI, and hematuria and preeclampsia. Itis the earliest marker of the glomerular disease occurring beforea reduction in GFR [4]. Early screening for kidney diseases bymeasuring 24 hr urine protein is very useful in prevention ofchronic kidney disease. Proteinuria also indicates the progressionof kidney disease and also helps to assess the effects of the therapygiven to the patient [5]. Routinely proteinuria is estimated alongwith serum urea and serum creatinine [3]. A normal serumcreatinine level does not necessarily mean that all is well withthe kidney. It is estimated that a loss of 50% of the functions ofnephrons leads to (approximate) doubling of serum creatinineconcentration.Protein estimation in 24 hrs urine is a reference gold standardmethod for the estimation of proteinuria [6]. However suchtimed urine collection is a cumbersome task and inconvenientto patients. It has many disadvantages and is prone to errors dueto sample collection. Hence an alternate method for estimatingproteinuria is essential [6]. Estimating protein creatinine ratio inspot urine sample, will be a convenient method for estimatingthe proteinuria which is done by estimating spot urine protein,creatinine and calculating protein creatinine ratio from it. Thisstudy is conducted to evaluate the correlation between 24 hrsurine protein and urine Protein Creatinine Ratio (PCR) in spoturine sample and if found comparable the estimation of spotprotein creatinine ratio could be adopted as an alternative methodfor quantification of proteinuria in our clinical lab setting.AimTo compare the results of spot urine protein creatinine ratio with24 hrs urine proteinObjective To do 24 hrs urine protein To do spot urine protein creatinine and calculate the proteincreatinine ratioCorrespondence to: Santosh KV, Department Of Biochemistry, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, India,Tel: 91 7358337721; E-Mail: vsantoshkumar27@gmail.comReceived: March 05, 2021; Accepted: March 19, 2021; Published: March 26, 2021Citation: Santosh KV, Anandhi N, Tirupathi P (2021) Evaluation of Spot Urine Protein Creatinine Ratio as an Index of Quantitative Proteinuria inVarying Renal Disorders. Clin Med Bio Chem. 7:2.Copyright: 2021 Santosh KV, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clin Med Biochem , an open access journalISSN: 2471-2663
Volume 7 Issue 2
Santosh kv, et al. To compare both the resultsReview of literatureKidney is regarded as one of the highly differentiated organs in thebody. At the end of embryonic development almost 30 differentcells will together form a multitude of filtering capillaries andsegmented nephrons enveloped by a dynamic equilibrium. Thiscellular diversity has control over various complex physiologicprocesses, endocrine functions, intra glomerular hemodynamics,solute and water transport, acid base balance and removal ofdrugs metabolites and they are all accompanied by intricatemechanism of renal response [7].OPENACCESS Freely available onlinethe hilum of the left kidney;B: CT scan in the axial plane showing location of the kidneys inrelation to the vertebral column (V) [8].Shape and measurementsShape: Bean shaped.Measurements: Length: 11 cm. (left kidney is slightly longer andnarrower).Width: 6 cm.Thickness: (anteroposterior) 3 cm.Weight: 150 g in males; 135 g in females (Figure 2).Anatomy of kidneyKidneys are the major excretory organs in our body. They alsohave Synonyms: Ren: kidney (in Latin); Nephrons: kidney (inGreek). The kidneys are two bean-shaped, reddish-brown organswithin the abdomen situated on the posterior abdominal wall [8].LocationKidneys lie on the posterior abdominal wall, one on each sideof the vertebral column, behind the peritoneum, opposite 12ththoracic and upper three lumbar (T12–L3) vertebrae. Theyoccupy epigastric, hypochondriac, lumbar and umbilical regions1.The right kidney lies at a slightly lower level than the left onedue to the presence of liver on the right side.2.The left kidney is little nearer to the median plane than theright.3.Their long axes are slightly oblique (being directed downwardand laterally) so that their upper ends or poles are nearer toeach other than the lower poles. The upper poles are 2.5cm away from the midline, the hilum are 5 cm away fromthe midline, and the lower poles are 7.5 cm away from themidline.4.Both kidneys move downward in vertical direction for 2.5cm during respiration.5.Trans pyloric plane passes through the upper part of thehilum of the right kidney and through the lower part of thehilum of the left kidney [9] (Figure 1).Figure 2: External Features.Each kidney presents the following external features:1.Two poles (superior and inferior).2.Two surfaces (anterior and posterior).3.Two borders (medial and lateral).4.A hilum [10].Poles1.The superior (upper) pole than the inferior pole.2.The inferior (lower) pole is thin and pointed and lies 2.5 cmabove the iliac crest.Surfaces1.The anterior surface is convex and faces anterolaterally.2.The posterior surface is flat and faces posteromedially [10].Borders1.The medial border of each kidney is convex above and belownear the poles and concave in the middle. It slopes downwardand laterally, and presents a vertical fissure in its middle partcalled hilum/hilus which has anterior and posterior lips.2.The lateral border of each kidney is convex.HilumFigure1: Location of the kidneys.A: Surface projection in relation to the anterior abdominal wall.The figure in the inset on the right shows the vertebral levels ofthe kidneys. The Trans pyloric plane (TPP) passes through theupper part of the hilum of the right kidney and the lower part ofClin Med Biochem , Vol. 7 Iss. 2The medial border (central part) of the kidney presents a deepvertical slit called hilum. It transmits, from before backward, thefollowing structures:1.Renal vein.2.Renal artery.3.Renal pelvis.2
Santosh kv, et al.4.OPENSubsidiary branch of renal artery.In addition to the above structures the hilum also transmitslymphatic’s and nerves, the latter being sympathetic and mainlyvasomotor in nature [10].When the kidney is split longitudinally, it presents the kidneyproper and the renal sinus [10].Kidney properThe naked eye examination of the kidney proper presents an outercortex and an inner medulla. The cortex is located just below therenal capsule and extends between the renal pyramids (vide infra)as renal columns (columns of Bertini). The cortex appears paleyellow with granular texture. The medulla is composed of 5–11dark conical masses called renal pyramids (pyramids of Malpighi).The apices of renal pyramids form nipple-like projections—the renal papillae which invaginate the minor calyces. A renalpyramid along with its covering cortical tissue forms a lobe ofthe kidney.Macroscopic structure of the kidney as seen in the longitudinalsection. Numerous nipple-like elevations (renal papillae) indentthe wall of the sinus. The renal pelvis within the sinus is dividedinto two or three large branches, called major calyces, whichfurther divides to form 5–11 short branches called minor calyces.Each minor calyx expands as it approaches the wall of renal sinus,and its expanded end is indented and molded around the renalpapilla (Figure 3).ACCESS Freely available onlineconvoluted tubule.2.Each collecting tubule begins as a junctional (connecting)tubule from the distal convoluted tubule. Many collectingtubules unite together to form collecting duct (duct ofBellini) which opens on the apex of renal papilla.The collecting tubules radiate from the renal pyramid into thecortical region to form radial striations called medullary rays. Thetotal capacity of renal pelvis and major and minor calyces is about8 ml (Figure 4).Figure 4: Nephron Structure.ProteinuriaUrine is formed by the ultrafiltration of plasma across glomeruli.Normally glomerular membrane does not allow the filtration ofprotein into urine because of narrow spaces in the glomerularmembrane [3].Glomerular barrier has three layers1.Fenestrated endothelium2.The basement membrane3.PodocytesAltogether form a size selective electrostatic filter. Electrostaticbarrier consists of negatively charged sialoproteins andproteoglycan [11] (Figure 5).Figure 3: Macroscopic StructureThe collecting tubules within the renal papilla open into theminor calyx by perforating its wall and capsule lining the Sinus.Thus, the pelvis of ureter (upper funnel-shaped part of the ureter)is connected with the kidney tissue through calyces [8].Microscopic structureHistologically, each kidney consists of 1 to 3 million of uriniferoustubules. Each uriniferous tubule consists of two components:nephron and collecting tubule [10].1.The nephron is the structural and functional unit of kidney.The number of nephrons in each kidney is about 1–3million. Each nephron consists of a glomerulus and a tubulesystem. The glomerulus is a tuft of capillaries surroundedby Bowman’s capsule. The tubular system consists of theproximal convoluted tubule, loop of Henle, and distalClin Med Biochem , Vol. 7 Iss. 2Figure 5: Glomerular Membranes.Illustration of glomerular filtration system. Each human kidneycontains 1 million glomeruli. An afferent arteriol branches intoseveral capillaries (glomerular tuft), the walls which constitutesfilter system. The plasma filtrate is led to the proximal tubulewhile the unfiltered blood returns to blood circulation. The3
Santosh kv, et al.filtration of the capillary wall contains the inner most fenestratedendothelium, glomerular basement, membrane and the porocyteswith their inter digitating foot processes. The slip diaphragmis uniformly wide porous filter between the foot processes. Todate the slip diaphragm has been shown to contain distinctcomponent s as shown above.Most proteins such as immunoglobulins both G and M are largeto pass through glomerular membrane [11]. Some have chargeof confrontation that prevents from traversing through filter. Atleast one half of the proteins in normal urine are tamm-horsfallproteins, which are localized to the thick ascending limb of loopof henle. The remaining proteins are filtered plasma proteins ofdifferent molecular sizes, mostly low molecular weight proteinssuch as transferrin, macroglobulin and intermediate sizedalbumin [11].Most filtered proteins at the glomerulus are reabsorbed in theproximal tubule. Slit diaphragm between podocytes has beenrecently discovered. These slit diaphragms contribute to thebarrier effect. Mutation in slit diaphragm can disrupt normalfunction and lead to proteinuria. Proteinuria may result fromincreased glomerular permeability due to damage to the integrityof glomerular filter [12]. Proteinuria can also occur when areduced number of functioning nephrons leads to increaseddiffusion of protein across remaining glomeruli.OPENACCESS Freely available onlineProteinuria is considered severe or in the “nephrotic range” whenprotein excretion is greater than 3.5 gm/day. When the proteinsin the urine have high molecular weight they are consideredto have glomerular origin. For proteins with the low molecularweight there is evidence that the defect causing proteinuria islikely related to abnormal proximal tubular reabsorption, oftenrelated to toxic damage of tubular cells. Proteinuria associatedwith progressive kidney disease is predominantly of glomerularorigin and mainly composed of plasma albumin [13].Causes of proteinuriaThe presence of proteinuria is not always an indicative of renaldisease. Proteinuria is broadly classified into1.Functional proteinuria2.Organic proteinuriaCauses of functional proteinuria Violent exercise Cold bathing Dehydration Emotional stress Fever Urinary tract infection PregnancyThe normal urinary protein excretion is less than 150 mg/day.Normally only a small amount of protein is excreted (20 mg-150mg/day) and most of it is albumin. The reminder is almost entirelythe Tamm Horsefall Protein Uromucoid a constituent of urinarycast probably secreted by distal tubules [3]. Proteins of molecularweight 15000 Daltons-40000 Daltons filter more easily but inlesser quantities because of their low plasma concentrations. Inaddition the proportion of individual proteins excreted in urinedepend on the extent of their reabsorption by renal tubules,albumin represents approximately 60% of total protein excretedit is not completely removed from the filtrate by tubular cells [3]. Alimentary proteinuria Ortho static or postural proteinuria Orthostatic proteinuria is a benign condition occurring inyoung people proteinuria occurs in the upright positiondue to increased hydrostatic pressure in the renal veins. Adiagnosis of ortho static proteinuria is made when an earlymorning urine sample does not contain protein [13].Proteinuria is an important sign of kidney disease impartingpowerful diagnostic and prognostic information. It is a cornerstoneof the worker for ckd, aki, and hematuria and pre eclampsia. Itis the earliest marker of the glomerular disease occurring beforea reduction in GFR. Proteinuria is associated with hypertensionobesity and vascular disease it can be used to predict risks ofckd progression, cardiovascular disease. Proteinuria loweringtherapies may be Reno protective and monitoring proteinuria isa key aspect of assessing treatment response in a variety of kidneydiseases [13].Acute nephritic syndromeChanges in glomerular protein filtration and defects in tubularreabsorption cause appearance of proteins in the urine. At valuesexceeding 300 mg/day, or 200 mg/L, the condition is termedproteinuria. Smaller amounts of protein may appear in theurine in the early stages of progressive disease, such as diabeticnephropathy. Albumin excretion between 30 and 300 mg/day(20-200 mg/L) was previously termed micro albuminuria [7]. Altered transglomerulor passage of proteins Decreased tubular reabsorption Increased plasma concentration of proteins Addition of proteins to the tubular fluid Therefore important step in the clinical evaluation ofproteinuria is the classification of proteinuria.Clin Med Biochem , Vol. 7 Iss. 2Organic proteinuria: Proteinuria is seen in different stages ofvarious kidney diseases. Some the kidney diseases in which wecan see proteinuria areNephrotic syndromeAsymptomatic hematuria or proteinuria or a combination ofthese two Diabetic nephropathy Chronic kidney disease Acute kidney injury [13]Mechanism of protein in urineThe increased proteinuria can result from four mechanisms [14]4
Santosh kv, et al.Types of proteinuria1.Glomerular proteinuria: Increased filtration of macromolecule across the glomerular filtration barrier due to loss ofcharge size selectivity. In this type proteinuria will be greater than1 gm/day.2.Tubular proteinuria: Tubular damage or dysfunctionmay inhibit the normal reabsorption capacity of proximal tubule.Lower molecular weight proteins are excreted in urine. Classiccauses of tubular proteinuria are fanconis syndrome and dentsdisease.3.Over flow proteinuria: Normal or abnormal plasmaproteins produced in increased amounts are filtered at theglomerulus and exceeds the resorptive capacity of proximaltubule. Example: myeloma, myoglobin in rhabdomyolysis,hemoglobin in intravascular hemolysis.Post renal proteinuriaSmall amount of IgG or IgA are excreted in UTI or stones.Proteinuria is the cause and effect of several complications notonly at the kidney but also at the systemic level. Proteinuriahas been implicated as an effector of injury process involved inkidney disease progression. Proteinuria is a strong independentdeterminant of CKD progression, and also an independent riskfactor of progression to end stage renal disease (ESKD). Henceproteinuria should be treated accordingly [13].Detecting and quantifying proteinuriaScreening for proteinuria is done by reagent impregnated dipsticks which detects protein at concentration greater than 200mg/dl. If proteinuria is detected in this way we have to do aquantitative estimation of protein.Quantitative estimation of protein can be done by the followingmethods1.24 hours urine protein estimation2.Random single void urine protein creatinine ratio24 hours urine protein estimationMost patients with persistent proteinuria should undergo aquantitative measurement of protein excretion, which can be donewith a 24-hour urine specimen. 24 hours urine collection for urineprotein estimation is considered to be the Gold standard methodfor assessment of proteinuria. The patient should be instructedto discard the first morning void; a specimen of all subsequentvoiding should be collected, including the first morning void onthe second day. The urinary creatinine concentration should beincluded in the 24 hour measurement to determine the adequacyof the specimen. Creatinine is excreted in proportion to musclemass, and its concentration remains relatively constant on adaily basis. Young and middle-aged men excrete 16 to 26 mg perkg per day and women excrete 12 to 24 mg per kg per day. Inmalnourished and elderly persons, creatinine excretion may beless [15].However such timed urine collection has many disadvantagesClin Med Biochem , Vol. 7 Iss. 2OPENACCESS Freely available onlineand is prone to errors. 24 hours urine protein estimation isa cumbersome task with many errors including incompletecollections, bacterial growth, incorrect timings and incompletebladder emptying. These errors far exceed those caused by diurnalvariation in protein excretion. It also requires hospital admissionand cause inconvenience especially for repeated follow up [4].Random single void urine protein creatinine ratioThough 24 hours urine protein estimation is the gold standardmethod it has many limitations. Hence estimation of proteincreatinine ratio in random single voided urine sample is usedas an alternative method. This approach is based on the factthat in presence of stable glomerular filtration rate urinarycreatinine concentration is reported to be fairly constant [16].As creatinine concentration is fixed its concentration in urinevaries with hydration, the random urine protein creatinine rationullifies the effect of hydration on Protein estimation [4]. Thekidn
urine protein and urine Protein Creatinine Ratio (PCR) in spot urine sample and if found comparable the estimation of spot protein creatinine ratio could be adopted as an alternative method for quantification of proteinuria in our clinical lab setting. Aim To compare the results of spot urine protein creatinine
In our population, the spot urine protein: creatinine ratio is a poor screening tool for women at risk for preeclampsia during pregnancy. Keywords: spot urine protein:Creatinine ratio, pre-eclampsia screening, pre-eclampsia diagnosis . Introduction . Hypertensive disease aff
Formation of Urine: nitrogen-containing waste products of protein metabolism, urea and creatinine, pass on through tubules to be excreted in urine urine from all collecting ducts empties into renal pelvis urine moves down ureters to bladder empties via urethra Formation of Urine: in healthy nephron, neither protein nor RBCs filter into capsule
Alere Drug Screen Urine Test Strip Ask donor to provide a urine sample, collect the sample urine using pipette. Apply 3 drops of the urine to the speciment well of the test device. x3 Read the results at 5 minutes. A B C How it works Alere Drug Screen Urine Test
Types of Glomerular Disease 1/2 Proteinuria and blood in urine (hematuria) are the most common manifestations of glomerular diseases. Proteinuria can be classified by the amount of protein that leaks into the urine: Nephrotic: 3.5 grams of protein in 24 hour collection of urine-severe Sub nephrotic: 0.5-3.5 grams of protein in 24 hour collection of urine-moderate
following criteria: (1) routine urine qualitative analysis showing positive urine protein three times within 1 week; (2) 24-h urine protein quantification 150mg or urinary protein/creatinine (mg/mg) 0.2; or (3) a urine microalbumin above normal, three times within 1 week. Renal biopsy and pathological examination were per-
Dried Urine Testing Urine dried on filter paper strips is a convenient and practical way to test essential and toxic elements that are excreted into urine. ZRT Laboratory is a pioneer in commercial testing for elements using a simple, two-point (morning and night) urine collection, into which filter paper strips are dipped and then allowed to dry.
Glucose, urine UGluc g% or g/dL Negative Diabetes mellitus, low renal glucose threshold, kidney tubule diseases Protein, urine UProt mg% or mg/dL 0-30 mg/dL Exercise, fever, various types of kidney disease Bilirubin, urine UBili Negative Hemolysis Ketones, urine UKetone Ne
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