International Urology and Nephrology 22 (6), pp. 573--579 (1990)

Residual Kidney Function and Plasma Urea Concentration in Patients with Chronic Renal Failure O. SCI-IOCK, J. ERBEN,* H. NADVORNiKOVA, V. TEPLAN, O. MARE~KOV~, I. SI~LA, V. REITSCHL~GEROV~, Institute for Clinical and Experimental Medicine, Prague-Kr~; * 1st Internal Clinic, Charles University, Hradec Krhlov6, Czechoslovakia (Received November 9, 1989) The relationships between the plasma levels of urea (Purea), renal clearance of urea (Cu~ea) and creatinine (Ccr) at an intake of 0.5 g protein/kg body weight/day were followed in 10 patients with chronic renal failure (CRF) under balance conditions. Under these conditions, Pureaattained a value of 30 mmol/1 when Cureahad decreased below 3.8 ml/min. By contrast, no correlation could be demonstrated between Purea and Cer under these conditions. The same relationships were followed in another group of 30 outpatients with CRF. Even in patients not followed under balance conditions, Cur~ determination makes it possible to establish whether the high increase in Purea is due to the decrease in residual renal function below the critical level or whether extrarenal factors are involved. Likewise, no significant correlation between Purea and Ccr could be demonstrated under these conditions. The findings suggest that Curea measurement in CRF patients helps to assess residual renal function in terms of Put= regulation and provides information that cannot be obtained by C~, measurement. Chronic renal failure is associated with a n u m b e r o f alterations in the c o m p o sition o f the internal environment. The extent of these alterations depends on the degree o f decrease in renal function and a n u m b e r o f extrarenal factors (metabolic and endocrine alterations, changes in extrarenal excretion and magnitude o f intake o f some substances, etc.). To determine the role played in impaired extracellular fluid composition by the decrease in residual renal function, and by the extrarenal factors responsible for it, is important f r o m the clinical point of view since recognition o f the main underlying cause m a y have its implications in the choice o f therapy. In clinical practice, residual renal function is most c o m m o n l y assessed on the basis o f creatinine clearance (Ccr) or by plasma creatinine estimation (Per) only. However, this m e t h o d o f investigation m a y not be satisfactory in every case b o t h because in the end stage o f chronic renal failure ( C R F ) the value o f Ccr no longer provides sufficiently accurate information on the glomerular filtration rate ( G F R ) , and because excretion o f a n u m b e r o f substances by residual nephrons changes significantly due to tubular function adaptation [2]. VSP, Utrecht Akad~miai Kiad6, Budapest

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Schiick et al.: Chronic r e nal f a i l u r e

The routinely monitored changes of internal environment in CRF include Purea determination. Even though urea is relatively little toxic [3], its plasma concentration should not exceed 30 retool/1 [4, 5]. Provided residual renal function has not declined below a certain level and the patient is in a balanced metabolic state, P .... can be maintained below the above level by suitable diet. An adequate decrease in protein intake (not endangering the body by undesirable metabolic changes) is 0.5 g/kg/day [6]. In case of more pronounced decreases in protein intake it is necessary to supplement amino acids or their ketoanalogs [7]. Thevalue of residual renal function still sufficient to prevent a rise in P . . . . over 30 mmol/1 under the conditions of a protein intake of 0.5 g/kg/day can be theoretically calculated (assuming constant faecal nitrogen elimination) on the basis of interrelations between protein intake, P .... and renal urea clearance [8, 9]. The critical value of Curea based on the above calculation (for the protein intake of 0.5 g/kg/day) should be in the region of 4 ml/min. In this study we tried to assess (l) to what extent these theoretical assumptions are applicable in clinical practice and, (2) whether C .... determination helps to assess residual renal function and provides for clinical practice information which could not be obtained by Ccr assessment.

Method

The nitrogen balance of individuals with CRF, hospitalized at the Metabolic Unit, was monitored for 3 weeks. This group of patients included six men and four women whose mean age was 52 (28-61) years. The cause of CRF was chronic glomerulonephritis in six cases, chronic pyelonephritis in three, and polycystic kidney in one case. The diet included protein of high biological quality, 0.5 g/kg body weight/day. Low-protein flour was used to prepare the baked products. Composition of the diet for a 70-kg individual was as follows: 35 g of proteins, 90 g of fats, 320 g of carbohydrates, 80--100 mmol of Na and 55 65 mmol of K, with individualized fluid intake. Energy input amounted to 9500 kJ. The diet was madeusinga computer program [10]. In these patients, the daily excretions of urea, creatinine, Na and K were measured, together with the plasma concentration of these substances and acid base balance, twice a week. Body weight was determined daily. Nitrogen faecal excretion was assessed in six cases. Another 29 patients with CRF were followed up on an outpatient basis without balance determination. The recommended diet contained 0.5 g/kg/day of protein and was prepared at home according to recipes provided by the Metabolic Unit. This group of patients comprised 18 men and 11 women with a mean age of 39 (22-60) years. The cause of CRF was chronic glomerulonephritis in nine cases, chronic pyelonephritis in four, polycystic kidney in three, other renal disease in seven cases, and the diagnosis was unclear in five subjects. In these patients the same biochemical parameters as in the preceding group were monitored once a week. Urea and creatinine concentrations were measured using a Hitachi autoanalyser, International Urology and Nephrology 22, 1990

Schiick et al. : Chronic r e n a l f a i l u r e

575

Na and K concentrations were determined by means of an Eppendorf flame photometer. Acid-base balance was assessed by the Astrup method. The respective clearance values were calculated by the standard method on the basis of the above concentrations and diuresis [9]. Nitrogen loss in stool was determined in daily portions. After drying the stool at 105 ~ the dried matter was weighed and homogenized. Nitrogen content was determined by kjeldahlization. Correlation analysis was used for statistical evaluation.

Results

Table 1 summarizes the results of examination in patients assessed under balance conditions. Their mean C~r value was 6.1 ml/min (range 4.4-7.6 ml/min). With a protein intake of 0.5 g/kg/day, urea excretion was on average 1.54.6 mmol/ 24 h (range 129 to 176 mmol/24 h). Faecal excretion of N was relatively low amounting to a mean 1.3 (___0.3) g/24 h (corresponding to 43 mmol of urea). The sum of urine and faecal excretion of N corresponded to its intake indicating a good nitrogen balance. The levels of plasma urea fluctuated between 23.0 and 49.0 mmol/1, with a mean value of 33.9 mmol/1. Renal urea clearance ranged between 1.8 and 5.5 ml/min, with a mean value of 3.3 ml/min. Table I Mean values and SD of creatinine clearance (C=), plasma urea concentration (P~rCa),urine urea excretion (Uurea V), faecal N excretion, urea clearance (Curia) in patients with chronic renal failure followed under balance conditions Cer ml/min 6.12

(___0.97)

Purea mmol]l 33.9

(+ 8.2)

Uurea V mmol/24 h 154.6

(q- 17.1)

Faecal N excretion g/24 h

Cure~ rnl/mirt

1.3

3.55

(__+0.3) (• 1.20)

Curea Cer" 0.54

(-t-0.15]

A close indirect correlation could be demonstrated between the values of Purea and Curea (Fig. 1). Using the equation characterizing this correlation, it can be calculated that the value of Purea = 30 mmol/1 is attained at a decrease in Curea to 3.8 ml/min. It is evident from the right side of Fig. 1 that no significant correlation between Pnre~ and Ccr could be demonstrated under the same conditions. Table 2 shows the results of measurement in patients who had not been followed under balance conditions. In this group, the mean value of Cot amounted to 7.6 ml/min with a range between 4.4 and 11.9 ml/min. Mean daily urea excretion in this group was higher than in that followed under balance conditions. Purea ranged between 23.0 and 58.0 mmol/1. Mean Curea value was 4.0 ml/min with a range of 2.8 and 6.3 ml/min. As can be seen in Fig. 2, the correlation between Pnrea International Uroloyy and Nephrology 22, 1990

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Schiick et al.: Chronic renal failure

Purea

Puree

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Ccr (mt/min)

Fig. 1. Relationship between plasma urea concentration (Pure.a) and urea clearance (Cu,,~), and between Pur~ and creatinine clearance (C=) in patients with chronic renal failure under balance conditions

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Purea (retool/I) 60

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Fig. 2. Relationship between plasma urea concentration (Purea) and urea clearance (Cu~), and between Pur~ and creatinine clearance (C=) in outpatients with chronic renal failure. Open circles indicate patients with urine urea excretion exceeding 200 mmol/24 h, closed circles those below 200 mmol]24 h International Urology and Nephrology 22, 1990

577

Schiick et aL : Chronic r e nal f a i l u r e

Table 2 Mean values and SD under the same conditions as shown in Table 1 in outpatients with chronic renal failure Cer ml/min

Pares mmol/l

Uurea V retool/24 h

Cure. ml/min

Curea Ccr

7.68 39.1 247.5 4.08 0.54 (--+2.34) (-+8.5) (-+93.9) (-+1.20) (-+0.10) and C~r,~ in this group showed a relatively large spread, the correlation was statistically non-significant. Figure 2 distinguishes patients whose urine urea excretion was over 200 retool/24 h (open circles) from those with daily urea excretion below this value. The right side of Fig. 2 gives the relationship between P .... and Ccr in the same patients documented at the left side of the figure. No statistically significant correlation could be demonstrated between the two parameters.

Discussion

It is evident from our results that in patients followed under balance conditions it is possible to find a very close correlation between Purea and C .... in CRF patients. In agreement with the hypothesis, the critical value of Cu~eaat which Pure~ of 30 retool/1 is attained (under the conditions of a protein intake of 0.5 g/kg/day), is 3.8 ml/min. However, it is also evident from the results that the critical value of residual function (in terms of Purea regulation) cannot be characterized by the value of Ccr. When interpreting this finding, it should be remembered that the value of Cure~reflects not only the extent of the glomerular filtration rate but also the intensity of tubular urea reabsorption. It is well known from previous studies that tubular urea reabsorption is significantly decreased under the conditions of osmotic diuresis [13]. Patients with CRF develop, in their residual nephrons, osmotic diuresis decreasing tubular urea reabsorption and, consequently, Cure~approximates the value of inulin clearance [11, 12]. Despite this, the value of the Cur~/Ccr ratio in CRF patients is not an accurate marker of fractional urea exretion (tubular urea reabsorption) since Ccr significantly differs from inulin clearance, apparently as a result of the increase in tubular creatinine secretion [1 ]. The fact that the changes in the intensity of tubular creatinine secretion and the decline in the tubular urea reabsorption in residual nephrons may vary interindividually explains why no significant correlation could be found, even under balance conditions, between the values of Purea and Ccr. Another observation in agreement with this finding is that the C~rea/Ccr ratio showed a large spread of values between 0.32 and 0.73. Even though the correlation between Pur~a and Cur~ in patients not treated with low-protein diet under balance conditions was not close, Cu~e~ measurement appears to be useful in these cases. If, under these conditions, P~r~ is higher than International Urology and Nephrology 22, 1990

578

Schiick et al. : Chronic" renal failure

30 mmol/1 (with the recommended diet of 0.5 g/kg/day), it is possible to determine on the basis of Curea measurement whether the cause of the high Purea is a decrease in residual renal function below the critical level or whether extrarenal factors are involved. Of the latter, a high Pure~value is most often attributable to an inadequatelyhigh protein intake. In other cases increased metabolism oftissueprotein can be the main cause of the high value of P . . . . . It is evident from Fig. 2 that patients with Pure~higher than 30 mmol/1 can be divided into two groups. In one group (the right upper quadrant of the figure), although the values of C .... were above the critical level (3.8 ml/min), P .... values were higher than 30 mmol/1. In these cases extrarenal factors are apparently at play. As is evident from the figure, urea excretion in these patients was over 200 retool/24 h. Since no signs of a hypercatabolic state were clinically present, it can be reasonably assumed that the main cause of the high Pu~e~values in these cases was failure to observe the prescribed diet. As in these c a s e s C u r e a did not drop below critical level, it is possible to attain a decrease in Pu~,a below 30 mmol/1 if the protein intake has decreased adequately. In some patients (the left upper quadrant), however, C~r,~ can be seen below the critical level with a value of Purea o v e r 30 mmol/1. In these cases Pur~ cannot be modified even when observing the prescribed diet. As is evident from Fig. 2, another factor possibly playing a role in the high Purea value in some of these cases, besides the decrease in C~ea below the critical level, is the relatively high protein intake (open circles). Our results suggest that Ca~ea determination in patients with CRF provides valuable information in terms of P~r~ regulation and also about residual renal function that cannot be obtained by Ccr determination.

References 1. Brod, J.: The Kidney. Butterworths, London 1973. 2. Bricker, N. S., Klahr, S., Perkenson, M., Schultze, R. G. : Renal function in chronic renal disease. Medicine, 44, 263 (1965). 3. Dzfirik, R.: Uraemia. The Pathophysiology of Carbohydrate Metabolism. Publishing House of the Slovak Academy of Sciences, Bratislava 1973. 4. Vfilek, A. : Chronic Renal Insufficiency. Avicenum, Praha 1975. 5. Erben, J, : Residual function in chronic renal insufficiency under regular dialysis treatment, Sbor. Vdd. Praci Ldk. Fak. Hradec Kr6lovd, 23, 1 (1989). 6. Alverstrand, A., Bergstr6m, J.: Nutritional management. In: Suki, W. N., Massry, S. G. (eds): Therapy of Renal Disease and Related Disorders. Martinus Nijhoff, BostonThe Hague-Dordrecht-Lancaster 1984. 7. Heidland, A., Kult, J., Rockel, L., Heiderbreder, E. : Evaluation of essential amino acids and ketoacids in uremic patients on low-protein diet. Am. J. Clin. Nutr., 31, 1784

(1978). 8. Kassirer, J. P. : Clinical evaluation of kidney function -- glomerular function. N. En91. J. Med., 285, 385 (1971). 9. Schiick, O.: Examination of Kidney Function. Martinus Nijhoff, Boston-The HagueDordrecht-Lancaster 1984. International Uroloyy and Nephrology 22, 1990

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10. Teplan, V., Schfick, O., N~dvornikov/t, H., Lopot, F., Korandov/t, diet program. E D T N A - E R C , 4 J., 7, 11 (1987). 11. Chasis, H., Smith, H. W.: The excretion of urea in normal man glomerulonephritis. J. Clin. Invest., 17, 347 (1938). 12. Smith, H. W. : The Kidney. Structure and Function in Health and versity Press, New York 1951. 13. Shannon, J. A. : The renal reabsorption and excretion of urea under diuresis. A m . J. Physiol., 123, 182 (1938).

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V.: A frozen balance and in subjects with Disease, Oxford Uniconditions of extreme

International Urology and Nephrology 22, 1990

Residual kidney function and plasma urea concentration in patients with chronic renal failure.

The relationships between the plasma levels of urea (P(urea)), renal clearance of urea (C(urea)) and creatinine (Ccr) at an intake of 0.5 g protein/kg...
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