Renal Failure, ll(4) 213-219 (1989-1990)

The Lack of Clinical Value of Laboratory Parameters in Predicting Outcome in Acute Renal Failure

Zijad Durakovic*, MD, PhD, Asaf Durakovic'f, MD, PhD, FACP, and Senadin DurakovicS, Chemlng, PhD

*Department of Internal Medicine, Rebro University Hospital Medical Faculty University of Zagreb Croatia, Yugoslavia tDepartment of Radiology and Nuclear Medicine Oak Ridge Associated Universities Oak Ridge, Tennessee, and Washington, DC, U.S.A. $Department of Biotechnology, Faculty of Biotechnology University of Zagreb Croatia, Yugoslavia

ABSTRACT

In 55 patients with either the oliguric and nonoliguric form of acute renal failure, some laboratory parameters for the analysis of prerenal and intrinsic types of acute renal failure were examined. The parameters were analyzed within 7 days of the clinically known beginning of the illness. m e parameters were analyzed as follows: sodium in urine, creatinine urinelplasma ratio, urine osmolality, osmolality urine/plasma ratio, renal failure index, and fractional excretion ofjiltered sodium. Hemodialysis was pei$ormed in 29 of the 55 patients. The oligunc form of acute renal failure was present in 49 of the 55 patients. In relation to renal failure index, prerenal acute renal failure was present in 7patients and intrinsic acute renal failure in 48. It appears that in patients with a clinical diagnosis of prerenal acute renal failure, the urinary parameters do not separate them from those with acute tubular necrosis. It also appears that in patients with laboratory diagnosis ofprerenal acute renal failure (i.e., a RFT < l .O) , the response to treatment is unpredictable and in fact may have a worse prognosis than in those with a RFI > 1.0 (517 deaths vs 10/48 deaths).

To the memory of our beloved mother, Remza Durakovic.

213 Copyright 0 1990 by Marcel Dekker, Inc.

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Nyu

Med

ical

Cen

ter

on 1

1/05

/14

For

pers

onal

use

onl

y.

214 Durakovic, Durakovic, and Durakovic

Acute renal failure (ARF) is the condilion in which there is a sudden reduction of the excretional function of previously healthy kidneys, which cannot be improved with correction of extrarenal factors (1-9). In ARF nor- mal diuresis can be present (5-7) in as many as 20%-30% of all patients. When confronted with a patients with ARF there is often a dilemma as to whether it is a case of prerenal or intrinsic ARF (6-14). Because of the diag- nostic and therapeutic dilemmas, we analyzed laboratory parameters in patients with ARF in order to analyze the values of these parameters in everyday clinical work in- volved in the care of patients with AR.F. The purpose of this work was to answer the question whether an analysis of various parameters in acute renal failure can be cor- related to the response to the treatment or to the eventual outcome.

PATIENTS AND METIHODS

From October 1982 to April 1986, prospective research was carried out on laboratory parameters in patients re- ferred for ARF is they satisfied the following criteria: (a) no preexistent renal disease, (b) no chronic renal disease in acute exacerbation, (c) no diuretic: therapy received, (d) start of illness within 7 days, where known, and (e) no previous hemodialysis carried out. The data of the in- itial analyse are given in Table 1. In all partients the following were dletermined: sodium

in 24-h urine, the urine/plasma creatinine ratio, the urine osmolality , the urine/plasma osmo1a:lity ratio, the renal

failure index (ratio between urine sodium and urine/ plasma creatinine ratio), and the fractional excretion of filtered sodium (urine/plasma sodium ratio and urine/ plasma creatinine ratio).

The group consisted of 55 patients (23 women and 22 men) treated in the Department of Internal Medicine, Rebro University Hospital, average age 46.3 f 19.9 years. The etiology of ARF in the 55 patietns was sepsis of various causes in 12, acute pancreatitis in 7, post- operative condition in 7, leptospirosis in 5, polytrauma in 3, heart failure (cardiogenic shock) in 5 , poisoning with acetic acid in 2, drug poisoning in 2, complication dur- ing pregnancy or after delivery in 2, acute exacerbation of chronic liver disease with dehydration in 2, poly- arteriitis nodosa in 1 , thrombosis of the abdominal aorta in 1 , malignant lymphoma with hyperuricaemia during therapy in 1, intoxication with insecticide in 1, acute pyelonephritis with dehydration in 1 , hemorrhage from a duodenal ulcer with metastatic liver carcinoma in 1, and acute glomerulonephritis in 2. The initiation of hemo- dialysis depends on the practice of the physician in charge and also on the patient’s status (severity of azotemia, volume overload, electrolyte disorders, etc .).

Statistical analysis was carried out by means of the r test and correlation coefficient (15).

RESULTS

Of the 55 patients, 49 had oliguria (less than 400 mL in 24-h urine), and 6 were not oliguric. The creatinine

Table 1 Renal Failure Parameters, Modijied ( I , 2 , 19)

Fractional Renal excretion of Sodium Creatinine Urine

Clinical Diuresis, in urine, urine/plasma, osmolality , Osmolality failure filtered sodium picture mL/24 h mmol/L mmol/L mOsm/kg urine/plasma index (RFI) (FEN,%) Within normal diuresis 1500 110-120 > 170 >700 >2.4 50 .7 50 .7

Acute renal failure

P r e r e n al s 500 < 20 > 40 >500 >1.5 <1 <1

Oliguric 400 > 25 < 20 <350 5 1 . 1 (1.5) > 1 > I

Renal Nonoliguric 600 > 25 < 20 <350 5 1 . 1 (1.5) > 1 > 1

RFI = Urine sodium/(Creatinine urinelplasrna). FEN^ 96 = (Sodium urine/Plasma)/Creatinine urinelPlasma x 100.

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Nyu

Med

ical

Cen

ter

on 1

1/05

/14

For

pers

onal

use

onl

y.

Clinical Value of Laboratory Parameters 215

quotient for urine and plasma was somewhat higher in those with oliguria. The urine osmolality and the osmolali- ty quotient were higher in nonoliguric patients while the RFI and FEN, were of similar value in both groups (shown in Table 2).

Of the 55 patients, the time from onset of ARF to ar- rival at the clinic was known in only 33, and all were oliguric. This time was 2.03 f 1.53 days. The average number of dialyses in the oliguric group was 8.8 f 6.5, while in one nonoliguric patient this amounted to 8.0.

Table 3 shows the parameters of ARF according to the diagnoses at the onset: renal or prerenal.

Of the 55 patients, 5 had leptospirosis, 2 had acute glomerulonephritis, 1 had urate nephropathy, 1 had thrombosed aorta, and 1 had polyarteriitis nodosa. In those 10 patients, parameters were analyzed separately because those diagnoses may have had urinary characteristics different from those of subjects with acute tubular necro- sis. Complete anuria was presented in 3 out of 10 patients. The creatinine quotient or the renal group was found to be lower than for the prerenal group; this was also true for urine osmolality and the osmolality quotient, RFI and FEN,. In a patient with a clinical diagnosis of “prerenal

acute renal failure,” the urinary parameters do not separate them from those with “acute tubular necrosis. ”

Table 4 presents the parameters of ARF according to the procedure of hemodialysis carried out in 29 patients, RFI and FEN, were higher in this group than in the gorup not treated by hemodialysis.

Table 5 presents the groups of patients with RFI values lower or higher than 1 .O. In the group of 7 patients with RFI lower than 1 .O, sodium in urine amounted to approx- imately 22 mmol/L. The clinical diagnoses of these pa- tients were acute myocardial infarction with heart failure in one, sepsis-peritonitis diffusa in one, liver cirrhosis with actue necrosis and severe jaundice in one, dehydra- tion in one, liver primary carcinoma with bleeding from gastric ulcer and also acute pancreatitis in one, coma dur- ing morphine intoxication and pneumonia in one, and toxic pneumonia with acute respiratory failure and melaena in one. In the group with RFI above 1.0, sodium in urine was approximately 63 mmol/L. The creatinine quotient in those patients with RFI lower than 1.0 amounted to 48, and in those with Rm higher than 1 .O this amounted to approximately 9. The parameters of FEN, differed greatly (0.43:13.36).

Table 2

Parameters of Acute Renal Failure in Relation to Diuresis

Acute renal failure, f SD Statistical significance,

Parameters Oliguric Nonoliguric P

Urine sodium, 58.13 f 31.90 58.70 f 18.84 mmol/L

Creatinine urine/plasma, 14.94 f 17.82 8.81 f 9.78 mmol/L

Urine osmolality, 340.78 f 100.66 298.33 k 24.24 < .02

Osmolality 1.06 f 0.32 0.82 f 0.15 < .02

mOsm/kg

urinelplasma

Renal Failure 15.92 f 21.68 15.80 f 13.19 Index

Fractional excretion of 11.25 f 15.84 11.76 f 10.19 filtered sodium

Age (average 47.84 f 19.56 35.58 f 20.51 in years)

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Nyu

Med

ical

Cen

ter

on 1

1/05

/14

For

pers

onal

use

onl

y.

216 Durakovic, Durakovic, and Durakovic

Table 3

Parameters of Acute Renal Failure in Relation to Diagnosis at the Beginning of the Illness

Acute renal failure in relation to the diagnoses, f SD Statistical

Prerenal Acute tubular necrosis significance, Parameters (N = 10) (N = 45) P

Urine sodium, 67.70 f 12.10 56.09 f 28.74 mmol/L

Creatinine urine/plasma, 859 f 4.92 15.54 f 18.65 mmol/L

Urine osmolality, 297.08 f 67.38 343.52 f 14.63 mOsm/kg

Osmolality urine/ plasma

0.93 f 0.21 1.08 f 0.32

Renal Failure 15.62 f 21.60 15.29 * 20.91 Index

Fractional excretion of 11.56 f 16.07 11.26 f 15.26 filtered sodium

Age (average 29.70 f 19.10 50.27 f 18.13 in years)

Hemodialysis: Done Not done

5 5

24 21

c .05

< .01

In only 1 of 7 patients with RFI lower than 1.0 was hemodialysis carried out on three occitsions, while in the group with RFI higher than 1 .O an average of 9.0 f 6.1 dialyses were carried out.

There was a very high correlation between the renal failure index and the fractional excretion of filtered sodium

Table 6 presents the outcome of illness. Of the 49 oliguric patients, 33 survived (67%), 15 died (31 %), and 1 female patient continued treatment and still receives dialysis because of complete anuria following acute pan- creatitis. Of those with nonoliguric ARF, the course of illness was satisfactory in all 6 patients. After hemodialysis of the 29 dialyzed patients, 21 patients improved (72%) and 7 (24%) died. Of the 26 patients not dialyzed, 18

(r = .99953, P < .001).

recovered and 8 died: 3 with cardiogenic shock due to myocardial infarction, 1 with pneumonia, 2 in the final phase of deompensated liver cirrhosis, 1 with a primary liver carcinoma, and 1 during sepsis. It appears that in patients with a laboratory diagnosis of “prerenal acute renal failure” (i.e., a RFI < 1 .O) the response to treat- ment is unpredictable and in fact may have a worse prog- nosis (5/7 deaths) than those with a RFI > 1.0 (10/48 deaths).

DISCUSSION

All of the patients suffered a sudden reduction in renal function, according to the accepted definition. Eleven

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Nyu

Med

ical

Cen

ter

on 1

1/05

/14

For

pers

onal

use

onl

y.

Clinical Value of Laboratory Parameters 217

Table 4

Parameters of Acute Renal Failure in Relation to Use of Hemodalysis

Acute renal failure in relation to dialysis f SD Statistical

Done Not done significance, Parameters (N = 29) (N = 26) P

Urine sodium, 62.51 f 32.95 53.38 f 27.70 mmol/L

Creatinine urinelplasma, mmol/L

9.11 f 11.94 20.03 f 20.29

Urine osrnolality, 308.70 f 60.88 364.30 f 116.8 mOsm/kg

Osmolality urine/ plasma

0.92 f 0.19 1.15 f 0.37

< .02

< .05

c .01

Renal Failure 18.25 f 18.75 12.11 f 22.86 Index

Fractional excretion of 13.44 It 13.75 9.26 f 17.22 filtered sodium

Age (average 41.68 f 16.78 51.92 f 21.93 in years)

Urine volume, 1031 f 1404 1606 f 1116 mL/24 h

percent had a nonoliguric form of ARF and 89 % had the oliguric form. These data of the nonoliguric form of ARF differ from others: 28% (l) , 59% (5) and 46% (11). The difference between our results and those of others studies probably lies in the fact that too much time elapsed be- tween the onset of ARF in a patient and his transfer to a specialized hospital department. In the literature, data are given for 102 (l), 92 (5), 10 (13), 61 (16), 225 (17), 27 (18), and 28 (19).

If the onset of ARF is analyzed according to the diagnoses, it can be seen that in 10 (18%) patients the illness started for a prerenal reason, which is lower than in other publications: 2 1 % (5) and 29 % (1). Of the number quoted by us, diuresis was established in only 2 patients by the correction of extrarenal factors.

The diagnostic indicators in patients with diagnoses in- dicating prerenal acute renal failure, total anuria was pres- ent in 3 out of 10 patients, indicating severe illness. Perhaps this could explain the lack of difference between those two groups. The study may have been carried out late in the course of some patients with ARF.

We found prerenal ARF in 13 % , and in the other study ( 1) this was found to be 27 % and 47 % (2). It is very like- ly, therefore, that due to late recognition of functional oliguria in the strict sense, it is already occurring when the patient is transferred to a specialized department.

No significant difference was found between dialyzed and nondialyzed groups with regard to sodium in urine. The creatinine quotient was lower than 10, particularly in the dialyzed group, which indicates that the condition

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Nyu

Med

ical

Cen

ter

on 1

1/05

/14

For

pers

onal

use

onl

y.

218 Durakovic, Durakovic, and Durakovic

Table 5

Parameters of Acute Renal Failure in Relation to Renal Failure Index

Statistical Renal Failure Index, x * SD

< 1.0 > 1.0 significance, Parameters (N = 7) (N = 48) P

Urine sodium, 22.00 f 11.69 63.47 f 28.95 < .001 mmol/L

Creatinine

mmol/L urine/plasma, 48.62 f 21.07 9.26 * 8.98 < .001

Urine osmolality, 390.71 f 174.17 327.60 f 77.83 mOsm/kg

Osmolality 1.17 f 0.57 1.01 f 0.26 urinelplasma

Renal Failure 0.52 f 0.26 17.51 f 21.47 < .001 Index

Fractional excretion of 0.43 f 0.21 13.61 * 15.78 < .001 filtered sodium

Age (average 53.71 f 21.72 45.46 f 19.58 in years)

Table 6

Outcome of Illness in Patients with Acute Renal Failure

Outcome of Illness

Characteristics Well Chronicity Death

According to diagnosis at beginning Renal 31 1 13 Prerenal 8 0 2

According to diurasis 0 1 i g u ri c Nonoliguric

33 1 15 6 0 0

According to use of hemodialysis Done 21 1 7 Not done 18 0 8

According to Renal Failure Index > 1.0 37 1 10 < 1.0 2 0 5

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Nyu

Med

ical

Cen

ter

on 1

1/05

/14

For

pers

onal

use

onl

y.

Clinical Value of Laboratory Parameters 219

of the dialyzed group was more serious (none expected). In the dialyzed group, the osmolality quotient was lower and the RFI and FEN, were higher than in the nondia- lyzed group. Obviously, the clinical picture needs to be examined according to the given parameters in relation in applied therapeutic methods. If the RFI is taken as a discriminative parameter, it follows that 7 patients had a functional type.

The mean value of sodium in urine was 22, ranging up to 43, and was significantly more than 40 in patients with the intrinsic type of ARF, averaging 63 and ranging down to 26 (in 4 patients). This indicates that this parameter alone in not sufficiently discriminative, and absolute meaning should not be attached to it (12, 13, 15, 16). The creatinine quotient in ARF was 9.26, in the prerenal type 48.62. Neither the osmolality nor the osmolality quotient differed essentially between groups; therefore, neither of these two parameters is sufficiently discriminative in ARF.

The height of RFI in prerenal ARF amounted 0.87 at the most. This should probably be considered prerenal if it amounts to as much as 0.9, while the RFI was from 1 to 112; three had less than 2, five had between 2 and 3, and all others had more than 3. These data agree with those of Miller et al. (l) , who found an average value of RFI of more than 4. The values of FEN, in prerenal ARF (0.43) and in intrinsic ARF (13.16) differ from those in other reports (2). With regard to the outcome of the illness, prerenal ARF was lethal in 3 1 % , which is lower than in other data (3, 19). None of the patients ended in death with nonoliguric ARF, although in this group ARF was recognized later during the basic illness. These results do not agree with those in other studies, in which the lethality in nonoliguric ARF amounted to 80% (3), 20%-30% (7), and 85% (19).

During the past several years, a number of cases have been reported in support of the notion that the fractional excretion of sodium (and thus the RFI) is not a discrimi- native parameter. That is, it does not predict who has “prerenal” ARF and who has acute tubular necrosis (4, 12-14, 17, 18,20-23). Our data support this conclusion.

Address correspondence and reprint requests to: Dr. Asaf Durakovic, Medical Division, Oak Ridge Associated Universities, Washington, DC, U.S.A.

REFERENCES

6.

7.

8.

9.

10.

1 1 .

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

Espinel CH: The FEN, test, use in the differential diagnosis of acute renal failure. J Am Med Assoc 236579-581, 1976. Hanington JT, &hen JJ: Acute oliguria. N Engl J Med 291:89-91,. 1975. Linton AL, Eliahou H, Solez K: Acute renal failure-a continu- ing enigma. Renal Failure 10:3-7, 1987. Anderson RJ, Linas SL, Berns AS, Henrich WL, Miller TR, Gabow PA, Schrier RW: Nonoliguric acute renal failure. N En& J Med 296:1134-1137, 1977. Oken DE: On the differential diagnosis of acute renal failure. Am J Med 71:916-921, 1981. Schrier R: Acute renal failure. J A m Med Assoc 247:2518-2521, 1982. Finn WF: Recovery from acute renal failure. In: Brenner BM, Lazarus JM (eds): Acute renal failure. Philadelphia, WB Saunders,

Finn WF, Chevalier A L Recovery from postischemic acute renal failure in the rat. Kidney Inr 16:113-123, 1979. Nanji AJ: Increased fractional excretion of sodium in prerenal azotemia: need for careful interpretation. Clin Chem 27: 1314-1315, 1981. Espinel CH, Gregory AW: Differential diagnosis of acute renal failure. Clin Nephrol 13:73-76, 1980. Corwin HL, Bonventre JV: Acute renal failure. Med Clin N Am

Corwin HL, Schreiber MJ, Fang LST: Low fractional excretion of sodium. Arch Int Med 144:981-982, 1984. Zarich S, Fang LST, Diamond JR: Fractional excretion of sodium. Arch Int Med 145:108-112, 1985. Sachs L: Angewundte sratistik, 4th ed. Berlin, Springer, 1975, pp

Fine LG, Eliahou H E Acute oliguric intrinsic renal failure diagnostic criteria and clinical features in 61 patients. Isr J Med Sci 5:1024-1031, 1969. Brosius FC, Lau K: Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. Am J Nephrol

Moran SM, Myers BD: Course of acute renal failure studied by a model of cratinine. Kidney Znr 27:928-937, 1984. Martinez-Vea A, Nadal P, Mas A, Nogue S, Bertran A, Pares A, Milla J: Nonoliguric acute renal failure in an intensive care unit. lntens Care Med 6:244-246, 1980. Pru C, Kjellstrand C: Urinary indices and chemistries in the dif- ferential diagnosis of prerenal failure and acute tubular necrosis. Sem Nephrol 5224-233, 1985. Walker JF, Cumming AD, Lindsay RM, Sibbald WJ, Solez K, Linton AL: The renal response produced by mn-hypotensive sepsis in a large animal model. Am J Kidney Dis 8:88-97, 1986. Adrendshorst WJ, Finn WF, Gottschalk CW: Pathogenesis of acute renal failure following temporary renal ischemia in the rat. Circ Res 37:558-568, 1975. Goldfarb D, Iaina A, Serban I, Gavendo S, Kapuler S, Eliahou HE: Beneficial effect of verapamil in ischemic acute renal failure in the rat. Proc Exp Biol Med 172:389-392, 1983.

1983, pp 753-774.

7011037-1054, 1986.

209-216.

6~450-457, 1986.

1. Miller TR, Anderson RJ, Linas SL, Henrich WL, Berns AS, Gabow PA, Schrier RW: Urinary diagnostic indices in acute renal failure. Ann lnt Med 89:47-50, 1978.

Ren

Fai

l Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Nyu

Med

ical

Cen

ter

on 1

1/05

/14

For

pers

onal

use

onl

y.