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You are watching: When plasma glucose concentration exceeds the renal plasma threshold,

Walker HK, hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. Third edition. Boston: Butterworths; 1990.


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Definition

Glucosuria, glucose in the urine, results from theglomerular filtration of much more glucose than the renal tubule have the right to absorb. It wake up in every normalindividuals in amounts up to 25 mg/dl (1–5). Abnormally increased glucosuria , results from either an elevated plasmaglucose, one impaired renal glucose absorptive capacity, or both.

The plasma glucoseconcentration over which significant glucosuria occurs is called the renalthreshold for glucose. Its value is variable, and also deviations occur both above and below thecommonly embraced "normal" threshold the 180 mg/dl. In diabetic patients, the worth is report tovary indigenous 54 come 300 mg/dl (6–14). Return glucosuria higher than 25 mg/dl is taken into consideration pathologic, plenty of commercial semiquantitative urine tests because that glucosuria that are accessible to patient fail to detect glucosuria until it reaches a level of 50–250 mg/dl (4).

The association between blood and also urine glucose was very first observed in the eighteenth century by Matthew Dobson, an English physician. For many years to pee glucose trial and error was the major method offered to monitor glycemic control in diabetes mellitus. Early methods of pee glucose detection had evaporation of pee to reveal sugar crystals and urine street fermentation through yeast. Methods based on copper reduction were arisen by von Fehling in the nineteenth century and also by Benedict at the turn of the twenty century. In 1941, the Ames agency marketed Clinitest, a copper palliation method, and followed it through Clinistix, a glucose oxidase-based determination. Due to the fact that then, several companies have actually marketed glucose oxidase-based tests.

Measurement that glucosuria is an indirect index of the blood glucose concentration, however, and also tests because that urine glucose should be construed with caution. Technical concerns such together test sensitivity and also variability of renal glucose threshold have to be taken into account. Furthermore, the social stigma sometimes linked with handling a body waste product (15) deserve to be a factor to consider in terms of patient acceptance of the monitoring technique.

These limitations, together with the advancement of residence blood glucose monitoring, have actually led come a decrease in the use of pee glucose for monitoring in diabetes mellitus. Self-monitoring that capillary blood glucose is currently the wanted method. Nevertheless, assessment of glucosuria to produce usable data (6,16). The is particularly appropriate security tool in health treatment settings whereby socioeconomic or education constraints (17) preclude the usage of an ext sophisticated techniques (e.g., residence capillary blood glucose monitoring, glycosylated hemoglobin measurement, and also frequent plasma glucose determinations). Selected patients continue to uncover urine glucose experimentation convenient, noninvasive, inexpensive, and also useful (18).


Technique

Sample arsenal for semiquantitative decision of glucosuria in the hospital or the home can take many forms: "24-hour collection" for all at once control; "fractional collection" in 4- come 6-hour block throughout the day to approximate manage points; "first voided point out urine" who interval is determined by the time because the previous urination; and "second voided clues urine" which assesses glucosuria in a details short interval because a discarded "first void." since of the countless factors that alter glucosuria, and because of the time hold-up between glucose filtration at the glomerulus and its illustration in the void, the is no surprising that numerous studies show that alters in the concentration the glucosuria between the very first and 2nd voided urine specimens execute not accurately reflect documented change or absence of adjust in plasma glucose (12,19,20). These monitorings were substantiated by various other studies showing that first and 2nd urine void tests for glucosuria agree just from 62% to 81% of the time (16).

Techniques for measuring glucosuria space based upon one of two people glucose oxidase (specific for glucose) or copper sulfate reduction (nonspecific: detects to reduce substances consisting of glucose, fructose, lactose, pentoses, galactose, homogentisic acid, and ascorbic acid). Test-Tape and also a range of "stick" or "strip" test such together Chemstrip (uG and uGK), Clinistix, Diastix, and Uristix room glucose oxidase based. Clinitest is copper sulfate palliation based. In the glucose oxidase-based technique, hydrogen peroxide is generated and reacts with horseradish peroxidase to produce nascent oxygen. It in turn oxidizes orthotoluidine to produce the blue or purple color that is read. In the Tes-Tape process, oxidized orthotoluidine is reacted with the yellow dye tartrazine to create a greater variety of color advancement (21).

Multifactorial impacts on the presence and degree the glucosuria have produced varying conclusions about how glucosuria should be reported and also used in surveillance diabetic control. Confusion is reduced if the absolute value of glucosuria is reported making use of the "percent scale" now contained with all methods (except Clinistix) together recommended by the ADA Committee ~ above Materials and also Therapeutic Agents (22,23).

The sensitivity of advertisement clinical "strip" methods have the right to be 10–15 mg/dl (4,7), back 50 mg/dl is generally detected (4). The accuracy the each an approach also varies with the lot of glucosuria. Because that example, Clinitest and Diastix agreed v spectrophotometric analysis 78% and 72% of the time, dong (24). Keto-Diastix and Clinitest to be both exact at lower concentrations; however, Clinitest was correct in 96% the samples recognized to save 4% glucose vice versa, Keto-Diastix was accurate just 40% of the moment at this concentration (25). Clinitest is marketed together a two-drop check that steps glucose concentration from 0.25 come 5.0 g/dl and also as a five-drop check that measures concentrations from <0.25 to 2.0 g/dl. Glucose concentrations over 2.0 g/dl, however, can reason the equipment to rotate a color comparable to than for the 1.0 g/dl reading, the "pass-through" phenomenon. One underestimation of the pee glucose can result (26). Overall, the two-drop copper sulfate procedure (Clinitest) was the most accurate in comparison through spectrophotometric analysis, an especially at reduced glucose concentration (27).

A glucose oxidase-based strip test (Chemstrip uG) has actually been report to offer greater accuracy in the clinical variety (28). It reportedly excludes top limit that "normal" worths (30 mg/dl) if detecting 60 mg/dl and also is equivalent to other techniques in the 100–250 mg/dl range. ~ above the various other hand, Clinitest, Diastix, and Tes-Tape had tendency to check out low between 500 and 2000 mg/dl, whereas Chemstrip uG check out high at 2000 mg/dl.


Problems through Glucosuria measure up Techniques

There is significant literature about substances the can change the validity of tests for glucosuria. Conflict reports often result from the impacts of various concentrations of the problem in question or ethereal methodologic differences in test actions (15,16,21,23,28–37). However, achieve a urinary concentration of substances that can change the check is often challenging under typical clinical circumstances.

In addition to drugs provided in Table 139.1, limited evidence suggests that other agents (nalidixic acid, probenecid, chloral hydrate, hyaluronidase, nitrofurantoin, PAS, phenazopyridine, and also iodinated radiopaque agents) have the right to interfere v urine glucose experimentation (43). Ciprofloxacin, a quinolone antibiotic pertained to nalidixic acid, does no interfere through Clinitest (44), yet has been associated with false confident reactions in particular glucose oxidase tests (45).


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Practical concerns can also alter test results (46): (a) v Clinitest, angling that the dropper away from upright can change volumes that are crucial to specific results (47), (b) timing and also shaking can alter accessible oxygen and modify the reaction (48), and also (c) inattention may reason results to be missed: 58% of nurses routinely performing coincided Clinitest and Acetest procedures failed to recognize the "pass-through" phenomenon" (46).


Potential Errors in monitoring Glucosuria

Errors in color discrimination occur commonly during glucosuria monitoring. Patient of all age groups and also professionals read an ext accurately at the extremes of to pee glucose concentrations. Accuracy decreases as the true value viewpoints the midrange of the check (49). Many errors because that all teams are underestimates (50,51). Health treatment professionals have actually been trained to balance the error distribution (49), implying (hat the errors space not innate to the check procedures.

The acquired color vision deficiency caused by diabetic retinopathy itself may contribute much more to inaccuracies in glucosuria trial and error than any type of other element (52). The is mainly a blue–yellow defect and also therefore requires most tests for glucosuria. Severity of the diabetes-related defect correlates substantially with as whole severity the diabetic retinopathy and with the severity the macular an illness (52). This result of diabetes is severe sufficient to mask the regular loss of hue discrimination which occurs through age. However, hue discrimination can be transformed by ambient light and also by age. Reduced lighting can decrease hue distinguish in civilization with normal shade vision. Although testing in bright lighting did not boost results in nondiabetics, outcomes with diabetic people improved substantially (52). Patients with proliferate diabetic retinopathy or diabetic macular condition are more than likely at greater risk because that test errors once monitoring glucosuria.

Errors can additionally stem native the falacious ide of a "normal" renal threshold. Genuine variation in renal thresholds for glucose among individuals is a far-ranging reason why patients and health care professionals find urine test misleading and are frustrated with the data generated. Further, there is a far-reaching trend because that patients with greater renal thresholds for glucose to exhibit higher values because that glycosylated hemoglobin and also mean blood glucose (6,17): because glucosuria trial and error cannot warning of hypoglycemia, diabetic patients tend to keep results at close to threshold values. Therefore, in those patients that aim because that tight control, glucosuria testing should be abandoned when results are repetitively negative. Once administration has lugged blood glucose to the suggest of lacking glucosuria, there is no alternate to capillary blood glucose monitoring.


Basic Science

Although tiny amounts the glucose are existing in the to pee of all regular individuals, the ax glucosuria is traditionally reserved for pathologic amounts of urine glucose (more 보다 25 mg/dl in arbitrarily fresh urine). The renal tubule will certainly reabsorb practically all the glucose current in the regular glomerular filtrate. Glucosuria occurs when that balance is lost: when the amount of glucose in the glomerular filtrate exceeds the volume of the renal tubule to reabsorb it. The balance deserve to be shed either as soon as the plasma glucose is elevated (e.g., in diabetes mellitus) or as soon as the absorptive capacity of the tubule is impaired (e.g., in Fanconi syndrome, pregnancy, hereditary renal glucosuria, and acute tubular injury).


Renal Threshold because that Glucose

There is a an unfavorable correlation between the renal glucose threshold and also the creatinine clearance in kind I diabetics (7). Age, heart failure, renal an illness (e.g., diabetic glomerulosclerosis), and chronic hyperglycemia are recognized to raise the renal threshold for glucose. Pregnancy, hyperthyroidism, fever, and exercise decrease that (15). In renal an illness such as diabetic glomerulosclerosis, a reduced glomerular filtration price decreases delivery of glucose to the tubule for a offered plasma glucose level (53). Together a consequence, normal tubular reabsorption that filtered glucose permits the plasma glucose worth to rise markedly above the usual threshold prior to glucosuria occurs (4). Thus, just like age in normal individuals, glomerulosclerosis in long-standing diabetes is linked with a elevated renal threshold for glucose, and also the visibility or quantity of glucose in the urine i do not care of lesser surveillance value.

Renal thresholds in individual patients may (54) or may not adjust (6,10) in the quick term, but patients v proteinuria have actually consistently lower renal thresholds (mean 67 mg/dl) (6), and deteriorating renal function in normal individuals tends to an outcome in an raised threshold because that glucose (53).


Tubular Reabsorption the Glucose

If the renal tubule capacity for glucose reabsorption is impaired because that constitutional or gained reasons, glucosuria can occur with regular plasma glucose concentrations (4). The Fanconi syndrome, pregnancy, and also acute tubular necrosis are examples of this phenomenon. Normally, together the level that plasma glucose and also the filtered pack rises, renal tubular reabsorption the glucose rises linearly until a preferably tubular resorptive volume is got to (7). This maximal tubular reabsorptive capacity ranges from 0.9 to 2.0 mmol/min and is continuous for each individual (7). The exact same is true in diabetes. Patients with recent onset of form I diabetes exhibited a 20% increase in both glomerular filtration rate and also maximal tubular reabsorptive volume (55). In addition, a reduced glomerular filtration rate in permanent diabetes was accompanied through a lower maximal tubular reabsorptive rate (55). Glomerulo-tubular balance because that glucose was maintained in both instances (55).

The proximal convoluted renal tubule reabsorbs most of the filtered glucose fill both normally and also during hyperglycemia. The intermediate segment, between the late proximal and distal tubule, also can reabsorb glucose (56). The acts together a buffer to assist the solution to an enhanced glucose load; overt glucosuria walk not happen until the resorptive capacity is exceeded.

Finally, it has not been possible to demonstrate a correlation between urine flow, maximal tubular reabsorptive capacity, and renal threshold for glucose (7). In addition, the temporal lag between a far-ranging rise in plasma glucose and increased glucosuria varies in between 20 and also 120 min (6,15). This points deserve distinct attention when attempting to infer plasma glucose values from results of testing for glucosuria in stormy patients.


Related Pathophysiology

Glucose infusion researches in dogs created hyperglycemia and raised glomerular filtered fill to close to maximal tubular reabsorptive capacity without glucosuria (56). In spite of resultant decreased fractional proximal reabsorption, and also therefore increased glucose egress from the proximal convoluted tubule, the overfill glucose load was reabsorbed in the intermediary segment of the renal tubule. The overabundance filtered load might be presented to inhibit sodium and fluid reabsorption in the proximal tubule. However, sodium and glucose reabsorption can be dissociated and also equivalent infusions in which euglycemia was kept by added insulin had a similar effect, saying insulin mediation of the proximal inhibition that sodium and fluid reabsorption.

Rapid infusion that hypertonic glucose elicits various hemodynamic responses in normal and diabetic patient (55). Normal people raise renal plasma flow about 10% but exhibit no change in glomerular filtration rate. Diabetics exhibit no adjust in the renal plasma flow but experience a 9% fall in the glomerular filtration rate. The transforms in both groups create a far-reaching decrease in the filtration fraction, and in both teams there is rise in urinary salt excretion during glucose infusion.

Just together the renal threshold because that glucose may exhibit broad individual variations, the change in blood glucose essential to transform glucosuria might vary together well. A group of 65 insulin-dependent diabetic patients studied at home by capillary blood glucose security (6) had actually a median renal threshold because that glucosuria of 130 mg/dl v a variety of 54 come 180 mg/dl. The plasma glucose in ~ which your glucosuria got to 2% varied from 144 to 360 mg/dl, and also the plasma glucose adjust necessary to transform to 2% glucosuria varied from 36 come 288 mg/dl. There was no correlation in between individual renal threshold values and the delta plasma glucose important to accomplish 2% glucosuria.

Methodology used and also patient population characteristics appear to influence the factors that have the right to correlate v the renal threshold for glucosuria. Some find that neither age, expression of diabetes, metabolic control, nor the performance of tubular glucose reabsorption (splay) are associated with the renal glucose threshold (7). Others find a correlation v at least age and mean plasma glucose in patients there is no proteinuria (14). There is an train station correlation between maximal tubular reabsorption of glucose and age or duration of diabetes (7). Thus, in a random examine of glucosuria in 261 regular persons (5), the median value because that glucosuria in individuals aged 50 year or less was 36.5 mg/dl (95% confidence borders 12.0 to 61.0 mg/dl) and also no age- or sex-related distinctions were observed. However, in individuals over the period of 50 years, the median values were 25.0 mg/dl (5.0 come 35.0 mg/dl) in men and also 14.2 mg/dl (4.0 come 29.0 mg/dl) in women.

Renal glucosuria additionally occurs. However, the syndrome is rare if one adheres strictly come the criterion of far-reaching amounts that glucosuria after an overnight fast prior to considering a diagnosis of nondiabetic renal glucosuria. Its primary creates represent a collection of associated familial hereditary defects in i beg your pardon the renal threshold for glucose is transformed in 2 ways: (a) a reduced maximum price of glucose reabsorption in the tubule; and also (b) an altered relationship between the filtered glucose load and also glucose reabsorption the does not readjust maximal reabsorption however does rise the splay the the glucose titration curve. The filtered glucose fill at i m sorry glucosuria wake up is commonly reduced in both species and distinguishing in between them have the right to be difficult. The defects have the right to be either autosomal leading or autosomal recessive and the problems usually have no clinical manifestations. Therapy is not required. Their glucose absorption from the gut is normal other than for a tiny subgroup with an unified glucose and galactose malabsorption. A patient v complete absence of tubular glucose reabsorption has been reported (57). One additional type of renal glucosuria is reported to take place in patients through nephrotic syndromes (58) and in renal transplant patients recovering from tubular necrosis or acute refusal (59).


Clinical Significance

Measurement of glucosuria is potentially satisfactory for the reasonably stable patient with diet and/or oral agent controlled form II diabetes mellitus who infrequently requires administration adjustment, an especially if used in associate with regular assessment that plasma glucose, glycosylated hemoglobin, or fructosamine level. Since of that insensitivity to hypoglycemia, urine glucose trial and error cannot be typically recommended together a basis because that making therapeutic decisions in patients with form I diabetes or in strictly controlled type II patients taking insulin. It is also inadequate for use in the administration of diabetes in pregnant (60). However, urine experimentation in this patients remains crucial for ketones.

Quantitative 24-hour pee glucose determination is supported by some (61) together a way of assessing glucose control and dietary compliance. A reasonable score is the excretion of much less than 7% of ingested carbohydrate every day. The excretion of much greater amounts in asymptomatic, non-ketotic diabetics argues dietary noncompliance.

Measurement of glucosuria is inexpensive and noninvasive. Patient acceptance of duty for surveillance glucosuria can contribute to boosted control. In one study (9), the average blood glucose worth was substantially (p < .02) lower in patients who adhered to glucosuria surveillance instructions (176 ± 81 rng/dl) than in those that did not (200 ± 83 mg/dl).

In patients for whom capillary blood glucose monitoring is difficult or impractical for any kind of reason, us accept and work within the restrictions of security glucosuria in bespeak to attain the services which monitoring have the right to offer.


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