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Urinary lactic dehydrogenase as a marker of renal injury in blunt trauma patients with hematuria
ORIGINAL CONTRIBUTION dehydrogenase, urinary lactic, trauma; trauma, renal, blunt
Urinary Lactic Dehydrogenase as a Marker of Renal Injury in Blunt Trauma Patients With Hematuria We evaluated the use of urinary lactic dehydrogenase (LDH) in predicting renal injury in a convenience sample of 36 blunt trauma patients with hematuria. The mean ± SEM urinary LDH for the five patients with renal injuries was 129.4 + 35 U/L, which was not significantly different from the mean urinary LDH levels in either the 22 patients without demonstrable genitourinary or retroperitoneal injuries (92.9 ± 20.7 U/L) or the nine patients with nonrenal genitourinary or retroperitoneaI injuries (I65 + 46 U/L). Urinary LDH at a threshold of 135 U/L was more specific (75% vs 53%, P < .01) and more accurate (74% vs 57%, P < .0I) than hematuria at a threshold of 50 red blood cells per high-power f i d d in predicting lacerations of the kidney or ureter; urinary LDH was less sensitive than hematuria at these thresholds (67% vs 100%), but not significantly. We conclude that urinary LDH is a nonspecific marker of cellular disruption anywhere along the genitourinary tract in otherwise healthy blunt trauma patients. [Henneman PL, Bar'Or D, Marx JA: Urinary lactic dehydrogenase as a marker of renal injury in blunt trauma patients with hematuria. Ann Emerg Med August 1988;17:797~800.]
INTRODUCTION Our ability to predict the presence of renal injury after blunt trauma is limited. Clinical findings are unreliable. Red blood cells in the urine are difficult to interpret because they lack sensitivity for certain injuries, notably those of the renal pedicle and ureter, and they lack specificity because many patients with gross hematuria have no discernible urologic injury.l,z Guidelines for evaluation of patients with suspected blunt renal trauma range from very conservative (ie, intravenous pyelogram for everyone with blunt trauma) to more liberal (ie, intravenous pyelogram for patients with more than 50 red blood cells per high-power field [RBC/hpf]}.3-7 In an effort to improve our ability to predict blunt renal injury, we evaluated the use of urinary lactic dehydrogenase (LDH}. LDH is an intracellnlar enzyme with a molecular weight of 134,000 that is present in all cells and is released only after cell wall disruption. 8 Urinary LDH has been used as a marker and screening aid in renal carcinoma, renal tuberculosis, nephroptosis, and renal artery thrombosis. 9-1z Because molecules larger than 70,000 molecular weight (tool wt) do not normally pass through glomerular filtration, LDH appears in the urine only after breakdown of cell walls within the genitourinary tract. We hypothesized that urinary LDH might be a sensitive and specific marker for renal injury in healthy patients and tested this hypothesis in a pilot study of 36 blunt trauma patients with hematuria.
Philip L Henneman, MD* Torrance, California David Bar'Or, MDt Englewood, Colorado John A Marx, MD¢ Denver, Colorado From the Departments of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California;* Swedish Medical Center, Englewood, Colorado;I- and Denver General Hospital, Denver, Colorado.:~ Received for publication February 5, 1988. Revision received April 1, 1988. Accepted for publication May 16, 1988. Address for reprints: Philip L Henneman, MD, Department of Emergency Medicine, Harbor-UCLA Medical Center, 1000 W Carson Street, Torrance, California 90509.
METHODS A convenience sample of 36 blunt trauma patients with hematuria was used in this study. These patients were seen over an 18-month period and represented only a fraction of the blunt trauma patients seen in the Department of Emergency Medicine at Denver General Hospital. Hematuria was noted in all patients with a dipstick (Labstix ®, Miles Inc, Elkhart, Indiana), and 34 patients had documented microscopic hematuria. All underwent intravenous pyelogram and had simultaneous determinations of urine and serum LDH as part of their initial evaluation. There were no exclusion crite17:8August 1988
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797/59
URINARY LDH Henneman, Bar'Or & Marx
ria for patients with underlying renal disease, but no patient had k n o w n renal abnormalities on entry into the study. Intravenous pyelograms were performed in a standard fashion and interpreted by staff radiologists. Patients with pelvic fractures also underwent cystourethrograms. Renal contusions were diagnosed radiographically by a decreased nephrogram, and renal lacerations were diagnosed by either discontinuities within a nephrogram or by e x t r a v a s a t i o n of dye a r o u n d a nephrogram. Patients were classified by the presence or absence of injuries as determined by direct vision during surgery or radiographically, Patients with normal radiographic studies and no injuries noted by other means were believed to have clinically insignificant urological injuries. The degree of microscopic hematuria was determined after centrifuging the urine for five minutes at 10 g and discarding the supernatant; the remaining sediment was observed under x 40 magnification, and the average n u m b e r of RBC/hpf was calculated. The number of hpfs examined was not standardized, and house staff were not blinded to the study. Urine from blunt trauma patients undergoing intravenous pyelograms was also sent to the laboratory, where it was spun at 10 g for five minutes. Urine supernatant then was tested for h e m o g l o b i n w i t h a dipstick. Specimens that tested positive for hemoglobin were excluded from the study to eliminate RBC and RBC hemolysis as factors c o n t r i b u t i n g to elevated LDH measurements in urine. We were unable to determine how m a n y urine specimens could not be evaluated because of hemoglobin in the supemarant. L D H in u r i n e s u p e r n a t a n t a n d serum was assayed by measurement of the absorbance changes at 340 n m caused by oxidation of nicotinamideadenine dinucleotide during the lactate to pyruvate conversion at alkaline pH and expressed in units per liter. 13 Urinary LDH was not used in patient management. Associated injuries in the 36 patients included three splenic injuries, one liver l a c e r a t i o n , t h r e e p n e u mothoraces, two skull fractures, two intracranial hemorrhages, four spinal fractures, eight pelvic fractures, and eight extremity fractures. 60/798
Urine LDH levels were expressed as mean + SEM. Comparison of LDH levels was by t test, and comparison of dependent proportions (ie, sensitivity, specificity, and accuracy) was by the binomial test with normal approximations. Significance was defined as P < .05.
RESULTS There were 29 m e n and seven women in the study population, w i t h a mean age of 32 years (range, 3 to 88). Five p a t i e n t s had renal injuries - three had renal lacerations and two had renal contusions. One of the patients with a renal laceration also had a ureter laceration. Two patients underwent surgical repair of their renal and ureter lacerations. The third with a renal laceration had extravasation of dye on the initial intravenous pyelogram and had a normal intravenous pyelogram after three days of observation. One of the patients w i t h a renal contusion had a horseshoe kidney and a congenital ureteropelvic obstruction that required repair. The fifth patient w i t h a c o n t u s i o n o r i g i n a l l y was thought to have a renal laceration on i n t r a v e n o u s p y e l o g r a p h y , b u t at l a p a r o t o m y only a renal c o n t u s i o n was discovered. Eight patients had abnormal radiographic studies without demonstrable renal, ureter, or bladder injuries; one had a perinephric hematoma, two had retroperitoneal hematomas, four had pelvic h e m a t o m a s , and one had a bladder contusion. One patient with a single nephrogram had a congenitally absent kidney at laparotomy; this pat i e n t was c l a s s i f i e d as h a v i n g a clinically insignificant urological injury. The last 22 patients had normal radiographic studies; one of these patients had a perinephric hematoma at laparotomy. The mean urinary LDH for all patients in the study was 113.1 ___ 17.5 U/L (range, 0 to 455 U/L). For the 22 patients w i t h o u t demonstrable genitourinary or retroperitoneal injury, the mean urinary LDH was 92.9 _+ 20.7 U/L (range, 0 to 303 U/L); for the five patients with renal injuries, the mean urinary L D H was 129.4 + 35 U/L (range, 14 to 221 U/L). Differences in mean urinary LDH were not significantly different (P > .1). The two patients with isolated renal lacerations had urinary LDH levels of 165 U/L and 14 U/L, and the patient with a lacAnnals ofEmergency Medicine
eration of the kidney and ureter had a urinary LDH of 150 U/L. The two patients with renal contusions had urinary LDH levels of 97 U/L and 221 U/L. Urinary LDH for the nine patients with nonrenal genitourinary or retroperitoneal injuries was 165 + 46 U/L (two perinephric hematomas - - 79 U/L and 455 U/L; two retroperitoneal hematomas - - 240 U/L and 41 U/L; four pelvic hematomas - - 10 U/L, 116 U/L, 129 U/L, and 279 U/L; one bladder contusion - - 132 U/L), which was not significantly different from either the 22 p a t i e n t s w i t h o u t d e m o n s t r a b l e genitourinary or retroperitoneal injuries or the five patients with recognized renal or ureter injuries. If all genitourinary or retroperitoneal injuries were considered, urinary LDH was most accurate at a threshold of 96 U/L w i t h a sensitivity, specificity, and accuracy of 71%. At this threshold, u r i n a r y L D H had a sensitivity of 67%, specificity of 58%, and accuracy of 60% for lacerations of the kidney or ureter (significant injuries) and a sensitivity of 80%, specificity of 61%, and accuracy of 64% for any renal injury (contusion or laceration). If only significant injuries were considered, urinary LDH was most accurate at a threshold of 135 U/L, with a sensitivity of 67%, specificity of 75%, and accuracy of 74%. At this threshold, urinary LDH had a sensitivity of 80%, specificity of 61%, and accuracy of 64% for renal and ureter contusions or lacerations. To improve the sensitivity of urinary L D H to m o r e t h a n 90%, the threshold would have to be lowered to 14 U/L, which would have decreased the accuracy to 17% for significant injuries and 25% for renal injuries. If the eight patients w i t h pelvic fractures were excluded to consider only patients with upper tract injuries, urinary LDH at a threshold of 135 U/L would have had the same sensitivity as w h e n pelvic fractures were included but a specificity of 89% and an accuracy of 86% for significant injuries (Table). T h i r t y - f o u r p a t i e n t s had microscopic urinalyses documented. Of the 16 patients with less than 50 RBC/hpf, n o n e had renal injuries. One had a perinephric hematoma, two had retro. peritoneal injuries, and two had pelvic h e m a t o m a s . N o n e required surgical intervention for these injuries. Of the 18 patients with more than 50 RBC/ 17:8 August 1988 17:
TABLE. Comparison of urinary LDH and hematuria in predicting urologic injuries
All Patients$
Renal Injuries* LDH P RBC (135 U/L) (50/hpf)
Significant Injuriest LDH P RBC (135 U/L) (50/hpf)
Sensitivity
60%
NS
100%
67%
NS
100%
Specificity
77%
< .01
55%
76%
< .01
52%
Accuracy
75%
< .05
62%
75%
< .01
56%
Patients Without Pelvic Fractures§ Sensitivity
60%
NS
100%
67%
NS
100%
Specificity
83%
< .01
59%
89%
< .01
54%
Accuracy
79%
< .05
67%
86%
< .01
59%
*Renal injuries included lacerations and contusions of the kidney. 1Significant injuries included lacerations of the kidney or ureter. ¢Thirty-six patients had urinary LDH determinations, and 34 had documented microscopic urinalyses. Two patients with dipstick-. positive urines and normal intravenous pyelograms were not included because they did not have microscopic urinalyses. §Eight patients with pelvic fractures were excluded to consider only upper-tract urologic injuries.
hpf, three had renal lacerations (one also had a ureter laceration), two had renal contusions, one had a perinephric hematoma, two had pelvic hematomas, and one had a bladder contusion. Two of these patients required surgical repair, one had an isolated renal laceration, and the other had lacerations of the kidney and ureter. If only significant injuries (lacerations of the kidney or ureter) were considered, urine with more than 50 RBC/hpf had a sensitivity of 100%, specificity of 52%, and accuracy of 56%; if any renal injuries were considered, hematuria had a sensitivity of 100%, specificity of 55%, and accuracy of 62%. If the eight patients with pelvic fractures were excluded, urine with more than 50 RBC/hpf would have had the same sensitivity as when pelvic fractures were included, but slightly higher accuracies of 67% for any renal injury and 59% for significant injuries. Urinary LDH at a threshold of 135 U/L was significantly more specific {76% vs 52%, P < .01} and more accurate (75% vs 56%, P < .01) in predicting significant injuries than hematuria at a threshold of 50 RBC/hpf (Table). These significant differences remained if patients with pelvic fractures were excluded. At these thresholds, urinary LDH was less sensitive than hematuria in predicting significant injuries (67% vs 100%), but not significantly. Urinary LDH was not related to the degree of h e m a t u r i a . For patients 17:8August 1988
without documented urinary or retroperitoneal injurg, urinary LDH was 48 + 6.8 U/L with 0 to 10 RBC/hpf, 194.6 + 51.6 U/L with 11 to 20 RBC/hpf, 25 + 9.6 U/L with 21 to 50 RBC/hpf, and 77 + 21 U/L with more than 50 RBC/ hpf. Urinary LDH was also not related to serum LDH in these same patients (correlation coefficient, 0.12). DISCUSSION Normal values for urinary LDH have been reported to be 22 _+ 6 U/L.11 The presence of LDH in the urine of normal persons is attributed to normal breakdown of cells within the urinary tract.9 Urinary LDH has been shown to be elevated in patients with renal tumors, renal tuberculosis, pyelonephritis, acute tubular necrosis, and nephrotic syndrome; it has been proposed that this is due to increased kidney cell necrosis and not passage of serum LDH into the urine.9,n LDH can enter the urine of otherwise healthy trauma patients in a limited number of ways: through RBC and RBC lysis within the urine, by cellular disruption along the genit o u r i n a r y tract, and. by free LDH (serum) that enters the urine with blood. By centrifuging the urine and dipsticking the centrifuged urine for hemoglobin, w e eliminated RBC and RBC lysis as contributing factors to elevated LDH measurement in urine. Because we found no relation between the number of RBC/hpf or serum LDH and urinary LDH in patients without
Annals Of Emergency Medicine
recognizable injuries, we suspect that serum LDH does not enter the urine with RBC in appreciable amounts, except possibly when large amounts of blood enter the urine. Our data suggest that blunt trauma patients w i t h h e m a t u r i a have increased cellular disruption along the genitourinary tract when compared with normal individuals, which resuits in increased levels of urinary LDH. Mean values for urinary LDH, however, were not significantly different for patients with or without recognized genitourinary injuries in our study. Two factors probably account for this finding. First, radiographic studies used to evaluate patients for possible genitourinary injury do not detect minor areas of trauma as signified by the large number of blunt trauma patients with hematuria and normal studies. 3 Second, all of our patients had hematuria, signifying cellular disruption somewhere along the genitourinary system. Urinary LDH, like hematuria, does not differentiate contusion from laceration. Urinary LDH appears to be a marker of cellular disruption but does not determine if the disruption is because of multiple small contusions or a single major contusion or a laceration. Urinary LDH, like hematuria, also does not differentiate renal from nonrenal injury. LDH isoenzyme analysis, however, m i g h t differentiate renal from nonrenal injury because kidney cells are rich in isoenzyme LDH-5. s 799/61
URINARY LDH Henneman, Bar'Or & Marx
Our pilot study does not support the use of u r i n a r y L D H as a screening t e s t for r e n a l injury. H e m a t u r i a appears to be a better screening test t h a n u r i n a r y L D H for b l u n t renal injury because it is easy to p e r f o r m and inexp e n s i v e , r e q u i r e s l i t t l e t i m e to perf o r m , a n d is a s e n s i t i v e m a r k e r for renal injury. U r i n a r y L D H is m o r e expensive, requires specialized equipm e n t , t a k e s l o n g e r to p e r f o r m , a n d c a n n o t be d o n e if t h e significant hem o l y s i s has t a k e n place in t h e urine. T h e ideal s c r e e n i n g test s h o u l d be 100% s e n s i t i v e (no false-negative findings) and as close to 100% specific as p o s s i b l e to m i n i m i z e f a l s e - p o s i t i v e findings. Although we found hematuria to be 100% sensitive, larger studies h a v e f o u n d it to be less sensitive. Cass et al 3 reviewed the charts of 831 patients with blunt trauma and h e m a t u r i a and f o u n d t h a t h e m a t u r i a w i t h m o r e t h a n 50 R B C / h p f had a sens i t i v i t y of 8 2 % , s p e c i f i c i t y of 71%, and accuracy of 71% for predicting significant renal injuries. We found u r i n a r y L D H to be m o r e specific and a c c u r a t e t h a n h e m a t u r i a in predicting significant g e n i t o u r i n a r y injuries. T h e reason for this is unclear. Further i n v e s t i g a t i o n w i t h i s o e n z y m e a n a l y s i s m i g h t be w a r r a n t e d b e f o r e u r i n a r y L D H is discarded as a potent i a l t o o l i n t h e e v a l u a t i o n of b l u n t g e n i t o u r i n a r y trauma. CONCLUSION U r i n a r y L D H w a s e v a l u a t e d in a c o n v e n i e n c e s a m p l e of 36 b l u n t trauma patients with hematuria. The
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m e a n u r i n a r y L D H in t h e s e patients was 113.1 + 17.5 U/L, w h i c h was sign i f i c a n t l y h i g h e r t h a n p u b l i s h e d norm a l values for u r i n a r y LDH. U r i n a r y L D H in t h e five p a t i e n t s w i t h renal injuries was 129.4 _+ 35 U / L ; this was not significantly different from the u r i n a r y L D H levels in e i t h e r t h e 22 p a t i e n t s w i t h o u t d e m o n s t r a b l e genit o u r i n a r y or r e t r o p e r i t o n e a l i n j u r i e s (92.9 + 20.7 U/L) or the n i n e patients w i t h n o n r e n a l g e n i t o u r i n a r y or retrop e r i t o n e a l injuries (165 -+ 46 U/L). U r i n a r y L D H was n o t related either to t h e n u m b e r of RBCs in t h e u r i n e or to s e r u m L D H levels. U r i n a r y L D H at a t h r e s h o l d of 135 U / L was m o r e specific (75% vs 53%, P < .01) and m o r e accurate (74% vs 57%, P < .01) t h a n h e m a t u r i a w i t h m o r e t h a n 50 R B C / h p f i n p r e d i c t i n g l a c e r a t i o n of t h e k i d n e y or u r e t e r ; u r i n a r y L D H was less s e n s i t i v e t h a n h e m a t u r i a (66.7% vs 100%) at t h e s e thresholds b u t n o t significantly. We c o n c l u d e t h a t u r i n a r y L D H is a n o n s p e c i f i c m a r k e r of cellular d i s r u p t i o n a n y w h e r e a l o n g t h e genitourinary tract in otherwise h e a l t h y b l u n t t r a u m a patients.
The authors thank the nurses and physicians from the departments of Emergency Medicine and Surgery at Denver General Hospital who cared for these patients, and Sara Marini for her help in manuscript preparation.
REFERENCES
1. Levitt MA, Criss E, Koberick M: Should the emergency IVP be used more selectively in
Annals of Emergency Medicine
blunt renal trauma? Ann Emerg Med 1985;14: 959-965. 2. Cass AS: Blunt renal trauma in children. J Trauma 1983;23:123-127. 3. Cass AS, Luxenberg P, Gleich P, et ah Clinical indications for radiographic evaluation of blunt renal trauma. J Urol 1986;136:370-371. 4. Brower P, Paul J, Brosman SA: Urinary tract abnormalities presenting as a result of blunt abdominal trauma. J Trauma 1978;18:719-722. 5. Griffen WO, Belin RP, Ernst CB, et aI: Intravenous pyelography in abdominal trauma. J Trauma 1978;18:387-392. 6. Nicolaisen GS, McAnincia JW, Marshall GA, et al: Renal trauma: Re-evaluation of the indications for radiographic assessment. J Urol 1985; 133:183-187. 7. Guice K, Olham K, Eide B, et al: Hematuria after blunt trauma: When is pyelography useful? J Trauma 1983;23:305-311. 8. Wrobleski F, Gregory KF: Lactic dehydrogenase isoenzymes and their distribution in normal tissues and plasma and in disease states. Ann N Y Acad Sci USA 1961~94:912-932. 9. Rosalki SB, wilkinson J: Urinary lactic dehydrogenase in renal disease. Lancet 1959;2: 327-328. 10. Wacker WEC, Dorfman LE: Urinary lactate dehydrogenase activity. Screening method for detection of cancer of kidney and bladder. JAMA 1962; 181:972-978. 1I. Hautmann R: Diagnosis of renal disorders: Comparison of urinary enzyme patterns with corresponding tissue patterns. Curt ProbI Clin Biochem 1979;9:58-70. 12. Buser S, Hagmaier V, Locher JT, et ah Diagnostic relevance of urinary lactate dehydrogenase determination in nephroptosis and for the indication to nephropexy. Curt Probl Clin Biochem 1979;9:44-55. 13. Gay RJ, McComb RB, Bowers G: Optimum reaction conditions for human lactate dehydrogenase isoenzymes as they affect total lactate dehydrogenase activity. Clin Chem 1968; 14:740-753.
17:8 August 1988
Urinary Lactic Dehydrogenase as a Marker of Renal Injury in Blunt Trauma Patients With Hematuria We evaluated the use of urinary lactic dehydrogenase (LDH) in predicting renal injury in a convenience sample of 36 blunt trauma patients with hematuria. The mean ± SEM urinary LDH for the five patients with renal injuries was 129.4 + 35 U/L, which was not significantly different from the mean urinary LDH levels in either the 22 patients without demonstrable genitourinary or retroperitoneal injuries (92.9 ± 20.7 U/L) or the nine patients with nonrenal genitourinary or retroperitoneaI injuries (I65 + 46 U/L). Urinary LDH at a threshold of 135 U/L was more specific (75% vs 53%, P < .01) and more accurate (74% vs 57%, P < .0I) than hematuria at a threshold of 50 red blood cells per high-power f i d d in predicting lacerations of the kidney or ureter; urinary LDH was less sensitive than hematuria at these thresholds (67% vs 100%), but not significantly. We conclude that urinary LDH is a nonspecific marker of cellular disruption anywhere along the genitourinary tract in otherwise healthy blunt trauma patients. [Henneman PL, Bar'Or D, Marx JA: Urinary lactic dehydrogenase as a marker of renal injury in blunt trauma patients with hematuria. Ann Emerg Med August 1988;17:797~800.]
INTRODUCTION Our ability to predict the presence of renal injury after blunt trauma is limited. Clinical findings are unreliable. Red blood cells in the urine are difficult to interpret because they lack sensitivity for certain injuries, notably those of the renal pedicle and ureter, and they lack specificity because many patients with gross hematuria have no discernible urologic injury.l,z Guidelines for evaluation of patients with suspected blunt renal trauma range from very conservative (ie, intravenous pyelogram for everyone with blunt trauma) to more liberal (ie, intravenous pyelogram for patients with more than 50 red blood cells per high-power field [RBC/hpf]}.3-7 In an effort to improve our ability to predict blunt renal injury, we evaluated the use of urinary lactic dehydrogenase (LDH}. LDH is an intracellnlar enzyme with a molecular weight of 134,000 that is present in all cells and is released only after cell wall disruption. 8 Urinary LDH has been used as a marker and screening aid in renal carcinoma, renal tuberculosis, nephroptosis, and renal artery thrombosis. 9-1z Because molecules larger than 70,000 molecular weight (tool wt) do not normally pass through glomerular filtration, LDH appears in the urine only after breakdown of cell walls within the genitourinary tract. We hypothesized that urinary LDH might be a sensitive and specific marker for renal injury in healthy patients and tested this hypothesis in a pilot study of 36 blunt trauma patients with hematuria.
Philip L Henneman, MD* Torrance, California David Bar'Or, MDt Englewood, Colorado John A Marx, MD¢ Denver, Colorado From the Departments of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California;* Swedish Medical Center, Englewood, Colorado;I- and Denver General Hospital, Denver, Colorado.:~ Received for publication February 5, 1988. Revision received April 1, 1988. Accepted for publication May 16, 1988. Address for reprints: Philip L Henneman, MD, Department of Emergency Medicine, Harbor-UCLA Medical Center, 1000 W Carson Street, Torrance, California 90509.
METHODS A convenience sample of 36 blunt trauma patients with hematuria was used in this study. These patients were seen over an 18-month period and represented only a fraction of the blunt trauma patients seen in the Department of Emergency Medicine at Denver General Hospital. Hematuria was noted in all patients with a dipstick (Labstix ®, Miles Inc, Elkhart, Indiana), and 34 patients had documented microscopic hematuria. All underwent intravenous pyelogram and had simultaneous determinations of urine and serum LDH as part of their initial evaluation. There were no exclusion crite17:8August 1988
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797/59
URINARY LDH Henneman, Bar'Or & Marx
ria for patients with underlying renal disease, but no patient had k n o w n renal abnormalities on entry into the study. Intravenous pyelograms were performed in a standard fashion and interpreted by staff radiologists. Patients with pelvic fractures also underwent cystourethrograms. Renal contusions were diagnosed radiographically by a decreased nephrogram, and renal lacerations were diagnosed by either discontinuities within a nephrogram or by e x t r a v a s a t i o n of dye a r o u n d a nephrogram. Patients were classified by the presence or absence of injuries as determined by direct vision during surgery or radiographically, Patients with normal radiographic studies and no injuries noted by other means were believed to have clinically insignificant urological injuries. The degree of microscopic hematuria was determined after centrifuging the urine for five minutes at 10 g and discarding the supernatant; the remaining sediment was observed under x 40 magnification, and the average n u m b e r of RBC/hpf was calculated. The number of hpfs examined was not standardized, and house staff were not blinded to the study. Urine from blunt trauma patients undergoing intravenous pyelograms was also sent to the laboratory, where it was spun at 10 g for five minutes. Urine supernatant then was tested for h e m o g l o b i n w i t h a dipstick. Specimens that tested positive for hemoglobin were excluded from the study to eliminate RBC and RBC hemolysis as factors c o n t r i b u t i n g to elevated LDH measurements in urine. We were unable to determine how m a n y urine specimens could not be evaluated because of hemoglobin in the supemarant. L D H in u r i n e s u p e r n a t a n t a n d serum was assayed by measurement of the absorbance changes at 340 n m caused by oxidation of nicotinamideadenine dinucleotide during the lactate to pyruvate conversion at alkaline pH and expressed in units per liter. 13 Urinary LDH was not used in patient management. Associated injuries in the 36 patients included three splenic injuries, one liver l a c e r a t i o n , t h r e e p n e u mothoraces, two skull fractures, two intracranial hemorrhages, four spinal fractures, eight pelvic fractures, and eight extremity fractures. 60/798
Urine LDH levels were expressed as mean + SEM. Comparison of LDH levels was by t test, and comparison of dependent proportions (ie, sensitivity, specificity, and accuracy) was by the binomial test with normal approximations. Significance was defined as P < .05.
RESULTS There were 29 m e n and seven women in the study population, w i t h a mean age of 32 years (range, 3 to 88). Five p a t i e n t s had renal injuries - three had renal lacerations and two had renal contusions. One of the patients with a renal laceration also had a ureter laceration. Two patients underwent surgical repair of their renal and ureter lacerations. The third with a renal laceration had extravasation of dye on the initial intravenous pyelogram and had a normal intravenous pyelogram after three days of observation. One of the patients w i t h a renal contusion had a horseshoe kidney and a congenital ureteropelvic obstruction that required repair. The fifth patient w i t h a c o n t u s i o n o r i g i n a l l y was thought to have a renal laceration on i n t r a v e n o u s p y e l o g r a p h y , b u t at l a p a r o t o m y only a renal c o n t u s i o n was discovered. Eight patients had abnormal radiographic studies without demonstrable renal, ureter, or bladder injuries; one had a perinephric hematoma, two had retroperitoneal hematomas, four had pelvic h e m a t o m a s , and one had a bladder contusion. One patient with a single nephrogram had a congenitally absent kidney at laparotomy; this pat i e n t was c l a s s i f i e d as h a v i n g a clinically insignificant urological injury. The last 22 patients had normal radiographic studies; one of these patients had a perinephric hematoma at laparotomy. The mean urinary LDH for all patients in the study was 113.1 ___ 17.5 U/L (range, 0 to 455 U/L). For the 22 patients w i t h o u t demonstrable genitourinary or retroperitoneal injury, the mean urinary LDH was 92.9 _+ 20.7 U/L (range, 0 to 303 U/L); for the five patients with renal injuries, the mean urinary L D H was 129.4 + 35 U/L (range, 14 to 221 U/L). Differences in mean urinary LDH were not significantly different (P > .1). The two patients with isolated renal lacerations had urinary LDH levels of 165 U/L and 14 U/L, and the patient with a lacAnnals ofEmergency Medicine
eration of the kidney and ureter had a urinary LDH of 150 U/L. The two patients with renal contusions had urinary LDH levels of 97 U/L and 221 U/L. Urinary LDH for the nine patients with nonrenal genitourinary or retroperitoneal injuries was 165 + 46 U/L (two perinephric hematomas - - 79 U/L and 455 U/L; two retroperitoneal hematomas - - 240 U/L and 41 U/L; four pelvic hematomas - - 10 U/L, 116 U/L, 129 U/L, and 279 U/L; one bladder contusion - - 132 U/L), which was not significantly different from either the 22 p a t i e n t s w i t h o u t d e m o n s t r a b l e genitourinary or retroperitoneal injuries or the five patients with recognized renal or ureter injuries. If all genitourinary or retroperitoneal injuries were considered, urinary LDH was most accurate at a threshold of 96 U/L w i t h a sensitivity, specificity, and accuracy of 71%. At this threshold, u r i n a r y L D H had a sensitivity of 67%, specificity of 58%, and accuracy of 60% for lacerations of the kidney or ureter (significant injuries) and a sensitivity of 80%, specificity of 61%, and accuracy of 64% for any renal injury (contusion or laceration). If only significant injuries were considered, urinary LDH was most accurate at a threshold of 135 U/L, with a sensitivity of 67%, specificity of 75%, and accuracy of 74%. At this threshold, urinary LDH had a sensitivity of 80%, specificity of 61%, and accuracy of 64% for renal and ureter contusions or lacerations. To improve the sensitivity of urinary L D H to m o r e t h a n 90%, the threshold would have to be lowered to 14 U/L, which would have decreased the accuracy to 17% for significant injuries and 25% for renal injuries. If the eight patients w i t h pelvic fractures were excluded to consider only patients with upper tract injuries, urinary LDH at a threshold of 135 U/L would have had the same sensitivity as w h e n pelvic fractures were included but a specificity of 89% and an accuracy of 86% for significant injuries (Table). T h i r t y - f o u r p a t i e n t s had microscopic urinalyses documented. Of the 16 patients with less than 50 RBC/hpf, n o n e had renal injuries. One had a perinephric hematoma, two had retro. peritoneal injuries, and two had pelvic h e m a t o m a s . N o n e required surgical intervention for these injuries. Of the 18 patients with more than 50 RBC/ 17:8 August 1988 17:
TABLE. Comparison of urinary LDH and hematuria in predicting urologic injuries
All Patients$
Renal Injuries* LDH P RBC (135 U/L) (50/hpf)
Significant Injuriest LDH P RBC (135 U/L) (50/hpf)
Sensitivity
60%
NS
100%
67%
NS
100%
Specificity
77%
< .01
55%
76%
< .01
52%
Accuracy
75%
< .05
62%
75%
< .01
56%
Patients Without Pelvic Fractures§ Sensitivity
60%
NS
100%
67%
NS
100%
Specificity
83%
< .01
59%
89%
< .01
54%
Accuracy
79%
< .05
67%
86%
< .01
59%
*Renal injuries included lacerations and contusions of the kidney. 1Significant injuries included lacerations of the kidney or ureter. ¢Thirty-six patients had urinary LDH determinations, and 34 had documented microscopic urinalyses. Two patients with dipstick-. positive urines and normal intravenous pyelograms were not included because they did not have microscopic urinalyses. §Eight patients with pelvic fractures were excluded to consider only upper-tract urologic injuries.
hpf, three had renal lacerations (one also had a ureter laceration), two had renal contusions, one had a perinephric hematoma, two had pelvic hematomas, and one had a bladder contusion. Two of these patients required surgical repair, one had an isolated renal laceration, and the other had lacerations of the kidney and ureter. If only significant injuries (lacerations of the kidney or ureter) were considered, urine with more than 50 RBC/hpf had a sensitivity of 100%, specificity of 52%, and accuracy of 56%; if any renal injuries were considered, hematuria had a sensitivity of 100%, specificity of 55%, and accuracy of 62%. If the eight patients with pelvic fractures were excluded, urine with more than 50 RBC/hpf would have had the same sensitivity as when pelvic fractures were included, but slightly higher accuracies of 67% for any renal injury and 59% for significant injuries. Urinary LDH at a threshold of 135 U/L was significantly more specific {76% vs 52%, P < .01} and more accurate (75% vs 56%, P < .01) in predicting significant injuries than hematuria at a threshold of 50 RBC/hpf (Table). These significant differences remained if patients with pelvic fractures were excluded. At these thresholds, urinary LDH was less sensitive than hematuria in predicting significant injuries (67% vs 100%), but not significantly. Urinary LDH was not related to the degree of h e m a t u r i a . For patients 17:8August 1988
without documented urinary or retroperitoneal injurg, urinary LDH was 48 + 6.8 U/L with 0 to 10 RBC/hpf, 194.6 + 51.6 U/L with 11 to 20 RBC/hpf, 25 + 9.6 U/L with 21 to 50 RBC/hpf, and 77 + 21 U/L with more than 50 RBC/ hpf. Urinary LDH was also not related to serum LDH in these same patients (correlation coefficient, 0.12). DISCUSSION Normal values for urinary LDH have been reported to be 22 _+ 6 U/L.11 The presence of LDH in the urine of normal persons is attributed to normal breakdown of cells within the urinary tract.9 Urinary LDH has been shown to be elevated in patients with renal tumors, renal tuberculosis, pyelonephritis, acute tubular necrosis, and nephrotic syndrome; it has been proposed that this is due to increased kidney cell necrosis and not passage of serum LDH into the urine.9,n LDH can enter the urine of otherwise healthy trauma patients in a limited number of ways: through RBC and RBC lysis within the urine, by cellular disruption along the genit o u r i n a r y tract, and. by free LDH (serum) that enters the urine with blood. By centrifuging the urine and dipsticking the centrifuged urine for hemoglobin, w e eliminated RBC and RBC lysis as contributing factors to elevated LDH measurement in urine. Because we found no relation between the number of RBC/hpf or serum LDH and urinary LDH in patients without
Annals Of Emergency Medicine
recognizable injuries, we suspect that serum LDH does not enter the urine with RBC in appreciable amounts, except possibly when large amounts of blood enter the urine. Our data suggest that blunt trauma patients w i t h h e m a t u r i a have increased cellular disruption along the genitourinary tract when compared with normal individuals, which resuits in increased levels of urinary LDH. Mean values for urinary LDH, however, were not significantly different for patients with or without recognized genitourinary injuries in our study. Two factors probably account for this finding. First, radiographic studies used to evaluate patients for possible genitourinary injury do not detect minor areas of trauma as signified by the large number of blunt trauma patients with hematuria and normal studies. 3 Second, all of our patients had hematuria, signifying cellular disruption somewhere along the genitourinary system. Urinary LDH, like hematuria, does not differentiate contusion from laceration. Urinary LDH appears to be a marker of cellular disruption but does not determine if the disruption is because of multiple small contusions or a single major contusion or a laceration. Urinary LDH, like hematuria, also does not differentiate renal from nonrenal injury. LDH isoenzyme analysis, however, m i g h t differentiate renal from nonrenal injury because kidney cells are rich in isoenzyme LDH-5. s 799/61
URINARY LDH Henneman, Bar'Or & Marx
Our pilot study does not support the use of u r i n a r y L D H as a screening t e s t for r e n a l injury. H e m a t u r i a appears to be a better screening test t h a n u r i n a r y L D H for b l u n t renal injury because it is easy to p e r f o r m and inexp e n s i v e , r e q u i r e s l i t t l e t i m e to perf o r m , a n d is a s e n s i t i v e m a r k e r for renal injury. U r i n a r y L D H is m o r e expensive, requires specialized equipm e n t , t a k e s l o n g e r to p e r f o r m , a n d c a n n o t be d o n e if t h e significant hem o l y s i s has t a k e n place in t h e urine. T h e ideal s c r e e n i n g test s h o u l d be 100% s e n s i t i v e (no false-negative findings) and as close to 100% specific as p o s s i b l e to m i n i m i z e f a l s e - p o s i t i v e findings. Although we found hematuria to be 100% sensitive, larger studies h a v e f o u n d it to be less sensitive. Cass et al 3 reviewed the charts of 831 patients with blunt trauma and h e m a t u r i a and f o u n d t h a t h e m a t u r i a w i t h m o r e t h a n 50 R B C / h p f had a sens i t i v i t y of 8 2 % , s p e c i f i c i t y of 71%, and accuracy of 71% for predicting significant renal injuries. We found u r i n a r y L D H to be m o r e specific and a c c u r a t e t h a n h e m a t u r i a in predicting significant g e n i t o u r i n a r y injuries. T h e reason for this is unclear. Further i n v e s t i g a t i o n w i t h i s o e n z y m e a n a l y s i s m i g h t be w a r r a n t e d b e f o r e u r i n a r y L D H is discarded as a potent i a l t o o l i n t h e e v a l u a t i o n of b l u n t g e n i t o u r i n a r y trauma. CONCLUSION U r i n a r y L D H w a s e v a l u a t e d in a c o n v e n i e n c e s a m p l e of 36 b l u n t trauma patients with hematuria. The
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m e a n u r i n a r y L D H in t h e s e patients was 113.1 + 17.5 U/L, w h i c h was sign i f i c a n t l y h i g h e r t h a n p u b l i s h e d norm a l values for u r i n a r y LDH. U r i n a r y L D H in t h e five p a t i e n t s w i t h renal injuries was 129.4 _+ 35 U / L ; this was not significantly different from the u r i n a r y L D H levels in e i t h e r t h e 22 p a t i e n t s w i t h o u t d e m o n s t r a b l e genit o u r i n a r y or r e t r o p e r i t o n e a l i n j u r i e s (92.9 + 20.7 U/L) or the n i n e patients w i t h n o n r e n a l g e n i t o u r i n a r y or retrop e r i t o n e a l injuries (165 -+ 46 U/L). U r i n a r y L D H was n o t related either to t h e n u m b e r of RBCs in t h e u r i n e or to s e r u m L D H levels. U r i n a r y L D H at a t h r e s h o l d of 135 U / L was m o r e specific (75% vs 53%, P < .01) and m o r e accurate (74% vs 57%, P < .01) t h a n h e m a t u r i a w i t h m o r e t h a n 50 R B C / h p f i n p r e d i c t i n g l a c e r a t i o n of t h e k i d n e y or u r e t e r ; u r i n a r y L D H was less s e n s i t i v e t h a n h e m a t u r i a (66.7% vs 100%) at t h e s e thresholds b u t n o t significantly. We c o n c l u d e t h a t u r i n a r y L D H is a n o n s p e c i f i c m a r k e r of cellular d i s r u p t i o n a n y w h e r e a l o n g t h e genitourinary tract in otherwise h e a l t h y b l u n t t r a u m a patients.
The authors thank the nurses and physicians from the departments of Emergency Medicine and Surgery at Denver General Hospital who cared for these patients, and Sara Marini for her help in manuscript preparation.
REFERENCES
1. Levitt MA, Criss E, Koberick M: Should the emergency IVP be used more selectively in
Annals of Emergency Medicine
blunt renal trauma? Ann Emerg Med 1985;14: 959-965. 2. Cass AS: Blunt renal trauma in children. J Trauma 1983;23:123-127. 3. Cass AS, Luxenberg P, Gleich P, et ah Clinical indications for radiographic evaluation of blunt renal trauma. J Urol 1986;136:370-371. 4. Brower P, Paul J, Brosman SA: Urinary tract abnormalities presenting as a result of blunt abdominal trauma. J Trauma 1978;18:719-722. 5. Griffen WO, Belin RP, Ernst CB, et aI: Intravenous pyelography in abdominal trauma. J Trauma 1978;18:387-392. 6. Nicolaisen GS, McAnincia JW, Marshall GA, et al: Renal trauma: Re-evaluation of the indications for radiographic assessment. J Urol 1985; 133:183-187. 7. Guice K, Olham K, Eide B, et al: Hematuria after blunt trauma: When is pyelography useful? J Trauma 1983;23:305-311. 8. Wrobleski F, Gregory KF: Lactic dehydrogenase isoenzymes and their distribution in normal tissues and plasma and in disease states. Ann N Y Acad Sci USA 1961~94:912-932. 9. Rosalki SB, wilkinson J: Urinary lactic dehydrogenase in renal disease. Lancet 1959;2: 327-328. 10. Wacker WEC, Dorfman LE: Urinary lactate dehydrogenase activity. Screening method for detection of cancer of kidney and bladder. JAMA 1962; 181:972-978. 1I. Hautmann R: Diagnosis of renal disorders: Comparison of urinary enzyme patterns with corresponding tissue patterns. Curt ProbI Clin Biochem 1979;9:58-70. 12. Buser S, Hagmaier V, Locher JT, et ah Diagnostic relevance of urinary lactate dehydrogenase determination in nephroptosis and for the indication to nephropexy. Curt Probl Clin Biochem 1979;9:44-55. 13. Gay RJ, McComb RB, Bowers G: Optimum reaction conditions for human lactate dehydrogenase isoenzymes as they affect total lactate dehydrogenase activity. Clin Chem 1968; 14:740-753.
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