- Email: [email protected]
A Comparison of Renal Function in Spinal Cord Injury Patients with and Without Reflux
Vol. 104, Sept. Printed in U.S.A.
THE JouRNAL OF UROLOGY
Copyright© 1970 by The Williams & Wilkins Co.
A COMPARISON OF RENAL FUNCTION IN SPINAL CORD INJURY PATIENTS WITH AND WITHOUT RE.FLUX LOUIS J. MARCHETTI*
AND
PAUL GONICKt
From the Section of Urology, Kingsbridge Veterans Administration Hospital, Bronx, and the Columbia University, New York, New York
The use of broad-spectrum antibiotics and the judicious use of catheter drainage have done much to add to longevity among paraplegics. However, renal failure and its antecedent causes are still the major causes of death. Following World War I, 80 per cent of the paraplegics were dead within a few weeks as a result of either urinary infection or decubitus ulcers or a combination of both. 1 In a recent study Wadewitz and associates reported on a group of World War II and Korean War paraplegics.2 In 1960 the World War II group had been followed an average of 14 years post-injury and at that time had a 25 per cent mortality rate. The Korean War group, with an average of 13-year post-injury followup, had a 14 per cent mortality rate. Renal disease was found to be the most frequent cause of death in both groups, accounting for 40 per cent in the World War II group and 50 per cent in the Korean War group. Hackler and associates listed the most common causes of decreased renal function in the paraplegic as pyelonephritis, renal amyloidosis, renal calculus disease, non-obstructive hydronephrosis and vesicoureteral reflux. 3 While much has been done to advance the treatment of pyelonephritis and renal calculus disease in the patient with a spinal cord injury, the management and treatment of vesicoureteral reflux are still controversial. PURPOSE
Our study was undertaken to evaluate and compare the renal function and radiographic Accepted for publication September 28, 1969. * Current address: Ehrling Bergquist Air Force Hospital, Offutt Air Force Base, Omaha, Nebraska 68113. t Current address: Hahnemann Medical School, Philadelphia, Pennsylvania 19102. 1 Barber, K. E. and Cross, R. R., Jr.: The urinary tract as a cause of death in paraplegia. J. Urol., 67: 494, 1952. 2 Wadewitz, P., Langlois, P. J. and Bunts, R. C.: Present urologic status of the World War 2 paraplegic: 20-year followup. Comparison with status of the 10-year Korean War paraplegic. J. Urol., 98: 706, 1967. 3 Hackler, R. H., Dalton, J. J., Jr.: and Bunts, R. C.: Changing concepts in the preservation of renal function in the paraplegic. J. Urol., 94: 107, 1965.
changes in spinal cord injury patients exhibiting bilateral vesicoureteral reflux with those who did not have reflux. In doing so, several other groups of patients both with and without reflux were evaluated. METHOD
Since July 1967, as part of the evaluation of each new spinal cord injury and at subsequent revisits, the following base line urological diagnostic studies were performed: complete blood count (CBC), blood urea nitrogen (BUN), serum creatinine, excretory urograms (IVPs), 12-hour endogenous creatinine clearance, cystogram, urinalysis and urine culture. The records of 194 spinal cord injury patients who had undergone evaluation one or more times were reviewed. Of these, 73 lacked complete data to be included in this study and 3 had ileal conduits and were excluded from this study. The remaining 118 patients were separated as follows: 1) bilateral reflux-those showing bilateral vesicoureteral reflux, 2) no reflux-those having 2 kidneys and no evidence of reflux, 3) unilateral reflux-patients with 2 kidneys and unilateral reflux, 4) reflux, 1 kidney-vesicoureteral reflux in a solitary kidney and 5) no reflux, 1 kidney-patients with l kidney and no evidence of reflux (see table). RESULTS
BUN and serum creatinine values. Of the 34 patients with reflux, 4 patients had an elevated BUN (normal, 10-20) and 1 had an abnormal serum creatinine level (normal, 1.0-2.0). Of cases without reflux, 5 patients had an abnormal DUN level and 2 had abnormal serum creatinine values" Urinary drainage. Of the 34 patients who exhibited some degree of reflux, 25 (73.5 per cent) have been maintained on urethral catheter drainage, 3 patients (8.8 per cent) use condom drainage, 2 (5.8 per cent) use suprapubic cystostomy drainage and 4 (11.6 per cent) underwent ilea! conduit urinary diversion. Of the 84 patients without reflux, 43 (51.2 per cent) are maintained on urethral catheter while 36 (42.9 per cent) are on condom drainage. One
365
366
MARCHETTI AND GONICK
Condition
No. Pts.
%
Pts. With Abnormal IVP (%)
Bil. reflux No reflux Unil. reflux Reflux, 1 kidney No reflux, 1 kidney
13 81
11.0 68.6 16.1 1.7 2.5
8 (61.5) 20 (24. 7) 6 (31.5) 0 2
19
2
patient with a solitary kidney is drained by a U-tube nephrostomy and 3 patients have died. Infection. The last urine culture in 1 patient with unilateral reflux was reported as sterile. However, the patient was on antibiotics at the time the culture was collected and previous urine cultures showed infection. All patients with bilateral reflux demonstrated significant urinary infection. Of the 84 patients without reflux, 23 revealed a sterile last urine culture. Thirteen of the 23 were also on antibiotics at the time of the culture and had previous positive urine cultures. Thus only 10 of the total of 118 patients were actually thought to be free of urinary tract infection. All 10 patients are maintained on co,idom drainage. Radiographic changes. Radiographic changes exhibited by patients in all our groups were considered abnormal if they coincided with any of the changes delineated by Hackler and associates. 3 Clearance values. Comparison of the mean endogenous creatinine clearance values of the patients demonstrating bilateral reflux with those with 2 kidneys and no reflux showed no significant difference. However, examination of the range of clearance values found in the group without reflux revealed 3 abnormal values which seemed to indicate laboratory error. Inspection of the patients' records revealed no error so these figures had to be included. It is thought that their exclusion would have made the difference between the 2 groups significant. Comparison of the number of abnormal clearance values (below 70 ml./minute) shows that almost half of the patients with bilateral reflux had abnormal values. Only 20 per cent of the cases without reflux had low values. Statistical analysis revealed this to be a significant difference. (In the comparison of patients with bilateral reflux with patients without reflux and with 2 kidneys, the x2 value was 4.9 and the p value was 0.025.)
No. Pts. With Mean Clearance Value (ml. /min.)
86.6 ± 10.1 105.5 ± 4. 9 98.7±8.2 97. 9 60. 3
Range of Clearance (ml./min.)
39.9-169.6 2. 5-269. 0 60.5-160.3 68.8-127.0 17.0-100.0
Decreased
Clearance Value(%) 6 (46.1) 15 (17. 8) 4 (21.0) 1
DISCUSSION
Attempts to accurately measure renal function of a patient have led to many and varied procedures. A simple, rapid method of making such a determination is still not available. The DUN level proved to be a poor indicator of changes in renal function as changes in this measurement did not occur until 75 per cent of renal function was destroyed. 4 The use of IVPs as an indicator of renal function vrns also a poor one for 2 reasons: 1) the use of modern high concentration contrast agents and 2) the extrarenal excretion of these ugents tended to give incorrect estimates of renal function. 2 • 5 Doggart and Silver came to the conclusion that "the performance of a clearance test for an endogenous substance appears to offer the best compromise between convenience and accuracy". 6 They found the presence of reflux would make accurate urine collection difficult despite the presence of an indwelling Foley cutheter. The collection of urine for a 12 to 24-hour period reduced this error. In studying the creatinine clearance levels in 280 paraplegics, these investigators determined that ne,v patients had relatively normal values while those who were paraplegic for long periods of time showed more evidence of renal failure and therefore lower creatinine clearance levels. In 1952 Hutch found the incidence of reflux in patients who have been paraplegics for 3 years was 13 per cent und found that it was not until after the third year that severe damage to renal function occurred. 7 Despite the presence of hy4 Dossetor, J. B.: Creatininemia versus uremia. The relative significance of blood urea nitrogen and serum creatinine concentrations in azotemia. Ann. Intern. Med., 65: 1287, 1966. 5 Chamberlain, M. J. and Sherwood, T.: Extrarenal excretion of diatrizoate in renal failure. Brit. J. Radial., 39: 765, 1966. 6 Doggart, J. R. and Silver, J. R.: Renal function studies in paraplegic patients. Paraplegia, 1: 202, 1963. 7 Hutch, J. A.: Vesico-ureteral reflux in the paraplegic: cause and correlation. J. Urol., 68:
457, 1952.
RENAL FUNCTION IN SPINAL CORD INJURY PATIENTS
dronephrosis, hydroureter and calycectasis in 25 per cent of his cases in the first 3 years, it was not until the third year that "severe damage" was demonstrated. This was associated with a sharp rise in the incidence of vesicoureteral reflux. Hackler and associates graded the radiographic changes found on the IVPs of their paraplegic patients and found that when reflux had persisted for more than 4 years, 29 per cent had more "severe" changes. 3 Lalli and Lapides suggested that reflux associated with urinary infection is the cause of renal deterioration, not the reflux itself. 8 While neither their study nor ours could definitely prove whether reflux or infection is the cause of renal deterioration in patients with reflux, our study showed that the combination of bilateral reflux with urinary tract infection resulted in greater renal damage. These previous studies have shown that deterioration of renal function and the incidence of reflux increase with the time following spinal cord injury. That there is an association between the two has been suggested by Hutch. SUMMARY The endogenous creatinine clearance values, serum creatinine level, BUN, CBC, urine culture and method of drainage of urine of 118 patients with spinal cord injury were examined and compared. Thirteen .0 per cent) of the patients exhibited bilateral vesicoureteral reflux and 81 (68.6 per cent) had 2 kidneys but demonstrated no evidence of reflux. Comparison of these 2 groups was undertaken to determine if a significant difference existed in renal function. Two significant differences were found in patients with reflux. The number of patients with bilateral re8 Lalli, A. F. and Lapides, J.: Long-term followup of ureteroneocystostomy without antireflux technique. J. Urol., 100: 441, 1968.
367
flux having abnormal creatinine clearance values was 3 times that found in patients without reflux. Radiographic changes consistent with renal deterioration were again 3 times more common in the paraplegic patient with bilateral reflux. The BUN and serum creatinine values again were found to be poor indicators of renal deterioration in these patients. It remains to be determined whether reflux alone and/or infection is the etiological agent for renal destruction in paraplegic patients. What is apparent is that the combination of bilateral reflux and urinary infection results in a greater degree of renal damage than that produced either agent alone. We conclude that this combination is a harbinger of increased renal damage in spinal cord injury patients and an effort must be made, in their presence, to sterilize the urinary tract. The known relationship of urinary tract infection, in the presence of retention catheters, makes every effort to free the paraplegic patient from such catheters vital to the preservation of renal function. Furthermore, we feel that such attempts to preserve renal function must be begun before demonstrable renal deterioration occurs since later attempts may not reverse the process. REFERENCES
DAMANSKI, M.: Hydronephrosis and hydroureter in paraplegia: a clinical study. J. Urol., 89: 660, 1963. RETIEF, P. J. AND KEY, A.G.: Urinary diversion in paraplegia. Paraplegia, 4: 225, 1967. Ross, J. C.: II. Diversion of urine in paraplegia. Paraplegia, 4: 209, 1967. SAMELLAS, W. AND RumN, B.: Management of upper urinary tract complications in multiple sclerosis by means of urinary diversion to an ilea! conduit. J. Urol., 93: 548, 1965. WooDHEAD, D. M. AND PoRcH, P. P., JR.: Cutaneous uretero-ileostomy for neurogenic vesical dysfunction. J. Urol., !ll: 253, 1964.
THE JouRNAL OF UROLOGY
Copyright© 1970 by The Williams & Wilkins Co.
A COMPARISON OF RENAL FUNCTION IN SPINAL CORD INJURY PATIENTS WITH AND WITHOUT RE.FLUX LOUIS J. MARCHETTI*
AND
PAUL GONICKt
From the Section of Urology, Kingsbridge Veterans Administration Hospital, Bronx, and the Columbia University, New York, New York
The use of broad-spectrum antibiotics and the judicious use of catheter drainage have done much to add to longevity among paraplegics. However, renal failure and its antecedent causes are still the major causes of death. Following World War I, 80 per cent of the paraplegics were dead within a few weeks as a result of either urinary infection or decubitus ulcers or a combination of both. 1 In a recent study Wadewitz and associates reported on a group of World War II and Korean War paraplegics.2 In 1960 the World War II group had been followed an average of 14 years post-injury and at that time had a 25 per cent mortality rate. The Korean War group, with an average of 13-year post-injury followup, had a 14 per cent mortality rate. Renal disease was found to be the most frequent cause of death in both groups, accounting for 40 per cent in the World War II group and 50 per cent in the Korean War group. Hackler and associates listed the most common causes of decreased renal function in the paraplegic as pyelonephritis, renal amyloidosis, renal calculus disease, non-obstructive hydronephrosis and vesicoureteral reflux. 3 While much has been done to advance the treatment of pyelonephritis and renal calculus disease in the patient with a spinal cord injury, the management and treatment of vesicoureteral reflux are still controversial. PURPOSE
Our study was undertaken to evaluate and compare the renal function and radiographic Accepted for publication September 28, 1969. * Current address: Ehrling Bergquist Air Force Hospital, Offutt Air Force Base, Omaha, Nebraska 68113. t Current address: Hahnemann Medical School, Philadelphia, Pennsylvania 19102. 1 Barber, K. E. and Cross, R. R., Jr.: The urinary tract as a cause of death in paraplegia. J. Urol., 67: 494, 1952. 2 Wadewitz, P., Langlois, P. J. and Bunts, R. C.: Present urologic status of the World War 2 paraplegic: 20-year followup. Comparison with status of the 10-year Korean War paraplegic. J. Urol., 98: 706, 1967. 3 Hackler, R. H., Dalton, J. J., Jr.: and Bunts, R. C.: Changing concepts in the preservation of renal function in the paraplegic. J. Urol., 94: 107, 1965.
changes in spinal cord injury patients exhibiting bilateral vesicoureteral reflux with those who did not have reflux. In doing so, several other groups of patients both with and without reflux were evaluated. METHOD
Since July 1967, as part of the evaluation of each new spinal cord injury and at subsequent revisits, the following base line urological diagnostic studies were performed: complete blood count (CBC), blood urea nitrogen (BUN), serum creatinine, excretory urograms (IVPs), 12-hour endogenous creatinine clearance, cystogram, urinalysis and urine culture. The records of 194 spinal cord injury patients who had undergone evaluation one or more times were reviewed. Of these, 73 lacked complete data to be included in this study and 3 had ileal conduits and were excluded from this study. The remaining 118 patients were separated as follows: 1) bilateral reflux-those showing bilateral vesicoureteral reflux, 2) no reflux-those having 2 kidneys and no evidence of reflux, 3) unilateral reflux-patients with 2 kidneys and unilateral reflux, 4) reflux, 1 kidney-vesicoureteral reflux in a solitary kidney and 5) no reflux, 1 kidney-patients with l kidney and no evidence of reflux (see table). RESULTS
BUN and serum creatinine values. Of the 34 patients with reflux, 4 patients had an elevated BUN (normal, 10-20) and 1 had an abnormal serum creatinine level (normal, 1.0-2.0). Of cases without reflux, 5 patients had an abnormal DUN level and 2 had abnormal serum creatinine values" Urinary drainage. Of the 34 patients who exhibited some degree of reflux, 25 (73.5 per cent) have been maintained on urethral catheter drainage, 3 patients (8.8 per cent) use condom drainage, 2 (5.8 per cent) use suprapubic cystostomy drainage and 4 (11.6 per cent) underwent ilea! conduit urinary diversion. Of the 84 patients without reflux, 43 (51.2 per cent) are maintained on urethral catheter while 36 (42.9 per cent) are on condom drainage. One
365
366
MARCHETTI AND GONICK
Condition
No. Pts.
%
Pts. With Abnormal IVP (%)
Bil. reflux No reflux Unil. reflux Reflux, 1 kidney No reflux, 1 kidney
13 81
11.0 68.6 16.1 1.7 2.5
8 (61.5) 20 (24. 7) 6 (31.5) 0 2
19
2
patient with a solitary kidney is drained by a U-tube nephrostomy and 3 patients have died. Infection. The last urine culture in 1 patient with unilateral reflux was reported as sterile. However, the patient was on antibiotics at the time the culture was collected and previous urine cultures showed infection. All patients with bilateral reflux demonstrated significant urinary infection. Of the 84 patients without reflux, 23 revealed a sterile last urine culture. Thirteen of the 23 were also on antibiotics at the time of the culture and had previous positive urine cultures. Thus only 10 of the total of 118 patients were actually thought to be free of urinary tract infection. All 10 patients are maintained on co,idom drainage. Radiographic changes. Radiographic changes exhibited by patients in all our groups were considered abnormal if they coincided with any of the changes delineated by Hackler and associates. 3 Clearance values. Comparison of the mean endogenous creatinine clearance values of the patients demonstrating bilateral reflux with those with 2 kidneys and no reflux showed no significant difference. However, examination of the range of clearance values found in the group without reflux revealed 3 abnormal values which seemed to indicate laboratory error. Inspection of the patients' records revealed no error so these figures had to be included. It is thought that their exclusion would have made the difference between the 2 groups significant. Comparison of the number of abnormal clearance values (below 70 ml./minute) shows that almost half of the patients with bilateral reflux had abnormal values. Only 20 per cent of the cases without reflux had low values. Statistical analysis revealed this to be a significant difference. (In the comparison of patients with bilateral reflux with patients without reflux and with 2 kidneys, the x2 value was 4.9 and the p value was 0.025.)
No. Pts. With Mean Clearance Value (ml. /min.)
86.6 ± 10.1 105.5 ± 4. 9 98.7±8.2 97. 9 60. 3
Range of Clearance (ml./min.)
39.9-169.6 2. 5-269. 0 60.5-160.3 68.8-127.0 17.0-100.0
Decreased
Clearance Value(%) 6 (46.1) 15 (17. 8) 4 (21.0) 1
DISCUSSION
Attempts to accurately measure renal function of a patient have led to many and varied procedures. A simple, rapid method of making such a determination is still not available. The DUN level proved to be a poor indicator of changes in renal function as changes in this measurement did not occur until 75 per cent of renal function was destroyed. 4 The use of IVPs as an indicator of renal function vrns also a poor one for 2 reasons: 1) the use of modern high concentration contrast agents and 2) the extrarenal excretion of these ugents tended to give incorrect estimates of renal function. 2 • 5 Doggart and Silver came to the conclusion that "the performance of a clearance test for an endogenous substance appears to offer the best compromise between convenience and accuracy". 6 They found the presence of reflux would make accurate urine collection difficult despite the presence of an indwelling Foley cutheter. The collection of urine for a 12 to 24-hour period reduced this error. In studying the creatinine clearance levels in 280 paraplegics, these investigators determined that ne,v patients had relatively normal values while those who were paraplegic for long periods of time showed more evidence of renal failure and therefore lower creatinine clearance levels. In 1952 Hutch found the incidence of reflux in patients who have been paraplegics for 3 years was 13 per cent und found that it was not until after the third year that severe damage to renal function occurred. 7 Despite the presence of hy4 Dossetor, J. B.: Creatininemia versus uremia. The relative significance of blood urea nitrogen and serum creatinine concentrations in azotemia. Ann. Intern. Med., 65: 1287, 1966. 5 Chamberlain, M. J. and Sherwood, T.: Extrarenal excretion of diatrizoate in renal failure. Brit. J. Radial., 39: 765, 1966. 6 Doggart, J. R. and Silver, J. R.: Renal function studies in paraplegic patients. Paraplegia, 1: 202, 1963. 7 Hutch, J. A.: Vesico-ureteral reflux in the paraplegic: cause and correlation. J. Urol., 68:
457, 1952.
RENAL FUNCTION IN SPINAL CORD INJURY PATIENTS
dronephrosis, hydroureter and calycectasis in 25 per cent of his cases in the first 3 years, it was not until the third year that "severe damage" was demonstrated. This was associated with a sharp rise in the incidence of vesicoureteral reflux. Hackler and associates graded the radiographic changes found on the IVPs of their paraplegic patients and found that when reflux had persisted for more than 4 years, 29 per cent had more "severe" changes. 3 Lalli and Lapides suggested that reflux associated with urinary infection is the cause of renal deterioration, not the reflux itself. 8 While neither their study nor ours could definitely prove whether reflux or infection is the cause of renal deterioration in patients with reflux, our study showed that the combination of bilateral reflux with urinary tract infection resulted in greater renal damage. These previous studies have shown that deterioration of renal function and the incidence of reflux increase with the time following spinal cord injury. That there is an association between the two has been suggested by Hutch. SUMMARY The endogenous creatinine clearance values, serum creatinine level, BUN, CBC, urine culture and method of drainage of urine of 118 patients with spinal cord injury were examined and compared. Thirteen .0 per cent) of the patients exhibited bilateral vesicoureteral reflux and 81 (68.6 per cent) had 2 kidneys but demonstrated no evidence of reflux. Comparison of these 2 groups was undertaken to determine if a significant difference existed in renal function. Two significant differences were found in patients with reflux. The number of patients with bilateral re8 Lalli, A. F. and Lapides, J.: Long-term followup of ureteroneocystostomy without antireflux technique. J. Urol., 100: 441, 1968.
367
flux having abnormal creatinine clearance values was 3 times that found in patients without reflux. Radiographic changes consistent with renal deterioration were again 3 times more common in the paraplegic patient with bilateral reflux. The BUN and serum creatinine values again were found to be poor indicators of renal deterioration in these patients. It remains to be determined whether reflux alone and/or infection is the etiological agent for renal destruction in paraplegic patients. What is apparent is that the combination of bilateral reflux and urinary infection results in a greater degree of renal damage than that produced either agent alone. We conclude that this combination is a harbinger of increased renal damage in spinal cord injury patients and an effort must be made, in their presence, to sterilize the urinary tract. The known relationship of urinary tract infection, in the presence of retention catheters, makes every effort to free the paraplegic patient from such catheters vital to the preservation of renal function. Furthermore, we feel that such attempts to preserve renal function must be begun before demonstrable renal deterioration occurs since later attempts may not reverse the process. REFERENCES
DAMANSKI, M.: Hydronephrosis and hydroureter in paraplegia: a clinical study. J. Urol., 89: 660, 1963. RETIEF, P. J. AND KEY, A.G.: Urinary diversion in paraplegia. Paraplegia, 4: 225, 1967. Ross, J. C.: II. Diversion of urine in paraplegia. Paraplegia, 4: 209, 1967. SAMELLAS, W. AND RumN, B.: Management of upper urinary tract complications in multiple sclerosis by means of urinary diversion to an ilea! conduit. J. Urol., 93: 548, 1965. WooDHEAD, D. M. AND PoRcH, P. P., JR.: Cutaneous uretero-ileostomy for neurogenic vesical dysfunction. J. Urol., !ll: 253, 1964.