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Some exogenous markers have been proposed as alternatives, including radioactive contrast agents such as 51Cr-ethylenediaminetetraacetic acid (EDTA), 125I-iothalamate and Technetium99m-diethylenetriaminopentacetic acid (Tc99-DTPA) 5-7 .

The measurement of GFR using these radioisotopic labels is very accurate and can be used in very small and non-toxic quantities.

Tc99m-DTPA has a physical half-life of 6.02 hours 8 and can be difficult to use and measure. This allows for less exposure to radiation and quicker determination of glomerular filtration. The only thing that can be done with DTPA is the elimination of the urine.

The urine clearance is a widely used tool, however in some patients it can be unreliable due to incomplete collection of urine samples. Under the conditions of water diuresis, a constant urinary flow and adequate collection of urine samples can be maintained.

Various formulas have been developed to estimate the clearance. One of the most widely used formulas is the proposal in 1976 by Cockcroft and Gault 9 and more recently the equation developed by Levey as part of the MDRD study 10,11, however these formulas have shown variable results depending on the population studied.

The identification and proper classification of patients with kidneys disease is important.

The identification allows the early installation of the corresponding treatment and the prevention of the progression of the disease.

The aim was to compare 4 GFR measurement methods with inulin clearance from the point of view of correlation and concordance.

There are methods and material.

The nephrology department of the "Ignacio Chvez" National Institute of Cardiology performed 51 inulin, creatinine, and technetium clearance procedures from March 2004 to March 2005. The patients who had stable renal function in at least the last three consultations were included.

Patients who did not have enough water, pregnant women with alterations that prevent adequate urine collection, patients who were undergoing peritoneal dialysis or hemodialysis, and patients who did not have enough water could be indicated due to a medical contraindication.

All patients were given a daily water intake of at least 2 liters prior to the study. The studies began at approximately 8:00 a.m., with the patient fasting, with a hydration period that consisted of drinking water at a rate of 10-15 ml/Kg of weight for at least one hour prior to the study. maintaining a stable urinary flow (>4ml/min.), which was maintained during the rest of the study at values ​​of 2-10ml/min.

After the hydration period, Inutest® 25% was administered with a loading dose of 22.5 kg and a continuous IV injection for over an hour. Every 30 min for 5 periods,urine and blood samples were taken.

Blood and urine samples were obtained by venipuncture in the arm. The concentrations were measured in a standard colorimetric method. The GFR was adjusted to 1.73m2SC and the clearance was calculated using the formula U V/ .

Inulin was administered with Tc99m-DTPA.

A 1.5 mCi bolus was administered in a single dose, followed by a 2 mCi injection for the rest of the day. The same urine and blood samples were used for the analysis. The activity of each tube was recorded in a well counter for one minute.

Blood and urine samples were used to measure creatinine concentrations. The Jaffé technique was used to measure conjugate.

According to the original description, the Cockcroft-Gault formula was used to estimate the clearance of creatinine. The GFR was calculated using the MDRD equation: 170 serum creatinine0.999 age.

If the patient is black, the blood urea nitrogen is 0.170.

There is an analysis of the statistics.

Mean and standard deviation are expressed. A simple linear regression analysis was used to express the Pearson correlation coefficients for the two methods.

The analysis of concordance between two tests was done using a method called Bland and Altman. The difference between the estimated GFR and that measured by inulin against the average of both was shown in a graph. The lower limit is the mean of the difference minus 2 standard deviations and the upper limit is the mean of the difference plus 2 standard deviations. The limits of agreement are shown for each GFR measurement method. A significant p value was taken into account.

The package was used for Windows.

Results.

Fifty-one patients participated in the study, of which 16 (31.4%) were healthy subjects who were being studied as kidney donors, 12 (23.5%) patients had systemic arterial hypertension, 5 (9.8%) diabetic nephropathy, 4 (7.8%) ) focal segmental glomerulosclerosis, 3 (5.9%) patients with renal transplantation and 11 (21.6%) with various diseases (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Takayasu's arteritis and thin basement membrane disease).

The average age of the patients was 39.75 years of age, with an average weight of 67.97 grams, and 28 were men and 23 were women.

The average amount of water taken by the patients during the procedure was 2360 liters, with an average total diuresis of 1738 liters.

The average results of the different GFR measurement methods are as follows: inulin clearance 73 ± 40 ml/min/1.73 m2, technetium clearance 70 ± 38 ml/min/1.73 m2, creatinine clearance 73 ± 37 ml/ min/1.73 m2, Cockroft formula 75 ± 37 ml/min/1.73 m2 and Levey formula 67 ± 37 ml/min/1.73 m2.

There is a correlation between Irish Clearance and Tc99m-DTPA CLEARANCE.

In the total population studied, the average clearance of inulin was 73 ± 40 ml/min/1.73m2, while the average clearance of technetium was 70 ± 38 ml/min/1.73m2, the average being of the difference between both procedures of 2.62 ml/min/1.73m2.

The correlation between Inulin and Technetium was positive and significant.

The total population had a lower limit of -15ml/min/1.73m2 and an upper limit of 21ml/min/1.73m2 according to the concordance analysis. When analyzing only the group of healthy subjects (donors), a lower limit of agreement of -19 ml/min/1.73m2 (95% CI: -30; -8) and an upper limit of agreement of 28 ml/min/ 1.73m2 (95% CI: 17; 39).

There is a correlation between Irish clearance and Canadian clearance.

The average clearance was 73 + 37, with the difference between the inulin and creatinine method being -0.38.

The correlation was positive between the glomerular filtration rate and the inulin and creatinine clearance.

The total population had a lower limit of -22 liter/min/1.73m2 and an upper limit of 22 liter/min/1.73m2 according to the concordance analysis. When analyzing only the group of healthy subjects (donors), a lower limit of agreement of -29 ml/min/1.73m2 (95% CI: -44; -15) and an upper limit of agreement of 34 ml/min/ 1.73m2 (95% CI: 19; 48).

There is a correlation between Kilkenny Clearance and the Coca-Cola Formula.

The average clearance with the Cockcroft formula was 75 and the average difference was -2.42 liters/min/1.73m2).

There was a positive correlation with inulin clearance.

The total population had a lower limit of -44 ml/min/1.73m2 and an upper limit of 39 ml/min/1.73m2 according to the analysis. When analyzing only the group of healthy subjects (donors), a lower limit of agreement of -52 ml/min/1.73m2 (95% CI: -77; -27) and an upper limit of agreement of 55 ml/min/ 1.73m2 (95% CI: 30; 80).

There is a correlation between Irish Clearance and Levey's Formula.

The average clearance with the Levey formula was 67 + 37 ml/min/1.73m2, with the average difference compared to inulin being 7.31 ml/min/1.73m2, showing a significant positive correlation with inulin clearance. (r= 0.88, r2=0.78, p<0.01).

The total population had a lower limit of -42 ml/min/1.73m2 and an upper limit of 57 ml/min/1.73m2 according to the analysis. When analyzing only the group of healthy subjects (donors), a lower limit of agreement of -41 ml/min/1.73m2 (95% CI: -64; -18) and an upper limit of agreement of 58 ml/min/ 1.73m2 (95% CI: 35; 80).

The limits of agreement of the 4 tests are shown in Table 1.

Discussion.

The incidence and prevalence of kidney disease has increased in recent years, and is a global public health problem.

The increase may be the result of more progression to chronic renal failure, increased availability of treatment, and decreased mortality.

In the United States, it is estimated that by 2010 the number of people who will be treated with a transplant will increase from 340,000 to 13 million.

The cardiovascular type will be caused by the increase in the prevalence of kidney failure. The prevalence of early stages of kidney failure in the United States is higher than the prevalence of advanced disease.

It is important to detect the decline in the function of the kidneys in a timely manner so that treatment can be put in place to slow the progression of the disease.

Since its introduction, Inulin has been the ideal substance to measure glomerular filtration, but its clinical application is impractical since it is a compound that meets all the requirements.

It is known that the values of serum creatinine can be changed by a variety of factors, such as age, sex, and muscle mass. interference with chromogens can alter its determination. Likewise, it has been shown that it is not a reliable method since an approximate reduction of 50% of the GFR may be necessary to cause an increase in its serum levels. which prevents early detection of renal failure, so it has been recommended not to use serum creatinine in isolation to estimate the GFR.

The GFR can be estimated from prediction equations such as the Cockcroft-Gault equation and the abbreviated equation of the MDRD study, however, any formula that uses the creatinine level will depend on the method used for the determination.

The formula derived from the study has been evaluated in a number of studies and has shown conflicting results. In addition, it has turned out to be less accurate in patients with normal levels of creatinine in their urine.

I125-Iothalamate is a marker that has been used for many years and has proven to be a reliable marker of the function of the kidneys, however it is not currently available in our medium 20.

The use of 99mTc linked to DTPA began in the 70s, when the evaluation of brain and kidney function was published by Hauser 21. The results of clearance with technetium have been compared with the results of clearance with iothalamate.

The underestimation of GFR compared to inulin is due to the fact that technetium is only excreted through the kidneys and is bound to a range of 5-10%.

Continuous water intake and short-term urine collections are used to maintain a constant urine output. The blood and urine samples taken during the procedure allowed simultaneous determination of inulin, creatinine and technetium concentrations for later comparison.

There was a correlation between technetium and creatinine clearance with inulin clearance, but the concordance analysis showed the variability of technetium clearance with even greater dispersion of the data in the subgroup.

The range of variation in the comparison of creatinine clearance with inulin clearance was greater in the group of healthy patients.

On the other hand, the comparison of the clearance of inulin with the two formulas used, showed an adequate correlation for both cases and a great variability as far as the concordance study is concerned, since it was found that both formulas could underestimate or overestimate the GFR. by more than 40 ml/min in comparison with the inulin method, again being greater the degree of variation between the healthy subjects evaluated.

It is important to point out that the concordance analysis used in our study, proposed by Bland and Altman, has been increasingly used in studies that seek to compare two clinical measurement methods, but especially when trying to replace the "gold standard" with another equally reliable but easier to perform.

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