JOURNAL
OF SURGICAL
RESEARCH
48,552-556
(1990)
Nephrolithiasis and Urine Ion Changes in Ulcerative Colitis Patients Undergoing Colectomy and Endorectal lleal Pullthrough MATTHIAS STELZNER, M.D., J. DUNCAN PHILLIPS, M.D., SALEH SALEH, M.D.,* AND ERIC W. FONKALSRUD, M.D.l The Departments
of Surgery and *Medicine,
Presented at the Annual Meeting
of the Association
UCLA School of Medicine,
for Academic Surgery, Louisville,
Press,
Kentucky,
90024
November
15-18, 1989
with inflammatory bowel disease who have undergone colectomy and construction of a permanent ileostomy [ 7, 81. Bambach et al. [8] found stones in 27 of 305 patients (8.9%) who had undergone proctocolectomy and ileostomy without small bowel resection, and in 9 of 61 patients (14.8%) with an additional partial small bowel resection. During the past decade over 2500 patients with ulcerative colitis have undergone total colectomy, mucosal proctectomy, and endorectal pullthrough with construction of an ileal reservoir (PTR) in the United States. It appears that this new operation may offer several physiologic advantages over standard ileostomy, including the prolongation of small intestinal transit time and increased intestinal water absorption with reduced fecal fluid loss [9, lo]. Whether the PTR procedure influences the incidence of urinary stone formation has not been determined. The present investigation was designed to obtain information regarding changes in the urinary ion excretion in patients with ulcerative colitis who undergo a PTR operation in order to estimate their risk of urinary stone formation.
Nephrolithiasis occurs in 5 to 13% of patients with ulcerative colitis (UC) who undergo colectomy and abdominal ileostomy, presumably from chronic dehydration and urinary concentration. Whether endorectal ileal pullthrough with ileal reservoir (PTR) changes the incidence of stones (primarily calcium oxalate) after colectomy is not known. Urinary excretion of Na2+, K+, Ca2+, Mg2+, phosphate, urate, oxalate, and citrate was measured in a prospective study of 12 UC patients undergoing PTR with temporary end ileostomy. Twenty-four-hour urine samples were obtained before colectomy (tJ, after colectomy but before ileostomy closure (t2), and 5 months after ileostomy closure (t3). Urine volumes decreased from 831 * 101 cc (mean + SE) at tI to 715 f 101 cc at t2 and then increased to 1278 f 421 cc at t3 (significant, with P < 0.01 by t test). Urinary excretions of Mg’+, oxalate, and citrate were low in UC patients compared to those in controls (15 healthy adult volunteers). Excretion of Ca2+ increased significantly following temporary ileostomy while excretion of Mg2+ fell. Excretion of Ca2’ fell and excretion of Mg2+ and citrate increased following PTR. We conclude that PTR patients have increased urine volumes and urinary ion changes known to decrease the risk of developing renal stones. o 1990 Academic
Los Angeles, California
METHODS
Inc.
Informed consent for voluntary study participation was obtained from 12 patients (7 males, 5 females) with ulcerative colitis undergoing the PTR procedure, in accordance with the Helsinki Declaration of 1975. Twentyfour-hour urine volumes and excretion of sodium, potassium, calcium, magnesium, phosphate, urate, oxalate, and citrate were measured in a prospective controlled fashion and compared to those of 15 healthy adult controls. Study patients ranged in age from 18 to 58 years (mean = 32.2). All patients had a history of long-standing ulcerative colitis with a mean duration of 8.3 years. Nine of the 12 patients had pancolitis. Each of the 12 had received highdose corticosteroid therapy for more than 4 months. The operation was performed in two stages separated by an interval of 4 months, as previously described [ll]. During the first operation, total colectomy, mucosal proctectomy, and creation of a 15-cm-lateral ileal reservoir
INTRODUCTION The incidence of nephrolithiasis is believed to be increased in patients with ulcerative colitis (UC) and Crohn’s disease, as well as certain other gastrointestinal disorders particularly in association with high urine oxalate levels [l, 21. Although some earlier reports do not mention nephrolithiasis as a complication in patients with UC [3-51, others have reported that nephrolithiasis develops in 2.0 to 6.4% of these patients [l, 6, 71. Nephrolithiasis occurs even more frequently in those patients 1 To whom correspondence and reprint requests should be addressed at Rm 72-126 CHS, Division of Pediatric Surgery, Dept. of Surgery, UCLA School of Medicine, Los Angeles, CA 90024. 0022-4804/90 $1.50 Copyright 0 1990 by Academic Press, All rights of reproduction in any form
552 Inc. reserved.
STELZNER
ET AL.: URINE
IONS
IN ULCERATIVE
COLITIS
TABLE Urine
Ion Excretion
mole/mole, creatinine Na+ K+ Ca2+ (X100) M$f (X100) Phosphate (X100) Urate (X100) Oxalate (X100) Citrate (X100) pH (pH units)
+ + f f f f f f
5 0.5** 5 3* 13” 5 0.4* 1**
5.60 rt 0.115**
UNDERGOING
and pH in Patients
with
Ulcerative
Colitis
tz 16 4 85 16 83 20 1 7
553
COLECTOMY
1
h 22 3 36 23 54 25 2 5
PATIENTS
+ * f f f f f f
6 0.5* 26* 4* 23* 4 0.3* 2*
5.53 f 0.097**
t3 63 5 32 24 62 22 2 14
k h f + f f f f
15* 1.0 7 4* lo** 3 0.3* 3*
5.70 f 0.165**
N 12 f 8 7f2 34 * 5 48 f 8 264 2~55 26 f 5 3 f 1.2 28 f 7 6.10 k 0.100
Note. ti, before colectomy; tP, after cutaneous ileostomy; t3, after PTR; N, normal controls. Values expressed as means f SEM; *, significantly different from N with P < 0.05; **, significantly different from N with P < 0.01.
was performed. The reservoir was drawn through the rectal muscularis and sutured to the anal mucosa. A temporary end ileostomy was constructed. During the second operation, the ileostomy was mobilized and an ileo-ileal anastomosis was performed. Perioperative corticosteroids and antibiotics were given according to a standardized regimen. Other postoperative medications including antidiarrheals or bulk-forming agents were given intermittently as necessary. For urine ion excretion, 24-hr urine specimens were obtained from each patient 2 days prior to both the first stage (tr) and the second stage operations (tz). A third urine specimen was obtained 4 months after cutaneous ileostomy closure (ts). All patients were consuming their regular home diets during the entire sampling periods. Patients did not receive any recommendations regarding oral fluid intake in order to obtain unbiased urine volume values reflecting actual “normal life” conditions. All urine samples were stored at 4°C and measurements were performed within 24 hr. Values of sodium, potassium, calcium, magnesium, phosphate, creatinine, chloride, uric acid, oxalate, citrate, and pH were measured using standard laboratory methods: sodium and potassium by flame emission photometry, calcium and magnesium by atomic absorption spectrophotometry, phosphate and creatinine by autoanalyzer, chloride by automated chloride titration, and pH by pH meter. Uric acid [12], oxalate [13], and citrate [14] were measured by techniques described previously. Results are expressed as moles of ion per mole of creatinine. Oral fluid intakes were not recorded. Saturation of the urine was calculated as relative supersaturation on a log 10 scale as described by Marshall and Robertson [15]. Relative supersaturation values for calcium oxalate, brushite, octocalcium phosphate, uric acid, and sodium acid urate were calculated using nomograms described previously by these authors. On this supersaturation scale, a urine at the solubility product has a value of zero and a urine at the formation product has the value of one. Negative values indicate undersat-
uration of the urine for the particular substrate and a very low probability of crystal formation. Values between zero and one are characteristic for the metastable region of supersaturation where growth of free existing crystal may occur but spontaneous crystal formation is unlikely if there are no nucleating agents. Values greater than one reflect the region of absolute supersaturation and indicate that there is a high probability of spontaneous precipitation of the particular substrate. Results are expressed as means + SEM. Statistical comparisons were made using the Student t test, with P < 0.05 considered significant. RESULTS
All 12 patients underwent the PTR procedure without major complications. Before ileostomy closure, two patients developed rectal strictures successfully treated by transanal dilatation. They continued to use anal dilators intermittently for 3 months following closure of the ileostomy and showed a satisfactory evacuation pattern during the long-term postoperative follow-up. When the- third urine sample was taken, all patients considered themselves to be continent. However, three patients experienced fecal staining once or twice a week and one patient had nocturnal fecal staining more than twice a week. The mean stool frequency was 7.9 per 24 hr. None of the patients experienced reservoir inflammation during the period of study. At the time of the third urine collection (t3), only four patients were still using psyllium hydrophilic mucilloid (Metamucil), diphenoxylate hydrochloride with atropine sulfate (Lomotil), or other antidiarrheal agents regularly. Patients with functioning ileal reservoirs demonstrated significantly increased sodium excretion compared to normal controls (Table 1). Potassium excretion was low preoperatively when compared to normal control values and after cutaneous ileostomy. However, potassium excretion increased to control values after PTR. During the
554
JOURNAL
OF SURGICAL
RESEARCH:
ileostomy period, patients showed a marked hypercalcuria, which returned to normal levels with the functioning reservoir. Magnesium excretion was low, compared to controls, at all time points. Excretions of phosphate increased slightly with the ileostomy, but remained far below normal values. Uric acid excretion showed minimal change during the entire period of study. Patients with a functioning ileal reservoir (t3) showed significantly higher urine citrate concentrations than those during the ti and t2 periods, but their citrate concentrations were less than half of normal values. Urine pH values were significantly lower in the three groups of patients than in controls (Table 1). The 24-hr urine volume was lowest during the ileostomy period, but increased by almost 80% once intestinal continuity was restored and the ileal reservoir was functioning (Table 2). The saturation of urine with calcium oxalate, uric acid, sodium urate, and calcium phosphate was calculated (Fig. 1). In all three groups of patients, metastable urine concentrations were found for calcium oxalate. Uric acid and sodium urate crystal formation appeared more likely in patients with ulcerative colitis or an ileostomy than in those with an ileal reservoir. Urine concentrations were below the solubility product for calcium phosphates in all three groups of patients. None of the 12 patients developed urinary stones during the 7-month study period. DISCUSSION
In this prospective study, changes in urinary ion excretion were measured in 12 patients undergoing colectomy and the PTR procedure. Patients with active ulcerative colitis and those following ileostomy creation had significantly reduced urine volumes compared to those of patients after the PTR procedure and to those of normal controls. The reduced volume in ileostomy patients was accompanied by an increased urinary excretion of calcium, but not of oxalate or uric acid. Changes in urine volumes may have been influenced by changes in medications, since the majority of patients received corticosteroids before colectomy and 4 patients continued to use antidiarrheals in varying dosages at the end of the study. Urine saturation, expressed by an activity product ratio, can be precisely calculated after obtaining activity prod-
TABLE Urine
Volume per 24 hr (ml)
Volume
in Patients
2 with
Ulcerative
Colitis
h
tz
t3
N
831 + 101*
715 f 101*
1278 f 420
1300f65
Note. tl, before colectomy; t2, after cutaneous ileostomy; t3, after PTR; N, normal controls. Values expressed as means f SEM, *, significantly different from N by t test, with 2’
OF SURGICAL
RESEARCH
48,552-556
(1990)
Nephrolithiasis and Urine Ion Changes in Ulcerative Colitis Patients Undergoing Colectomy and Endorectal lleal Pullthrough MATTHIAS STELZNER, M.D., J. DUNCAN PHILLIPS, M.D., SALEH SALEH, M.D.,* AND ERIC W. FONKALSRUD, M.D.l The Departments
of Surgery and *Medicine,
Presented at the Annual Meeting
of the Association
UCLA School of Medicine,
for Academic Surgery, Louisville,
Press,
Kentucky,
90024
November
15-18, 1989
with inflammatory bowel disease who have undergone colectomy and construction of a permanent ileostomy [ 7, 81. Bambach et al. [8] found stones in 27 of 305 patients (8.9%) who had undergone proctocolectomy and ileostomy without small bowel resection, and in 9 of 61 patients (14.8%) with an additional partial small bowel resection. During the past decade over 2500 patients with ulcerative colitis have undergone total colectomy, mucosal proctectomy, and endorectal pullthrough with construction of an ileal reservoir (PTR) in the United States. It appears that this new operation may offer several physiologic advantages over standard ileostomy, including the prolongation of small intestinal transit time and increased intestinal water absorption with reduced fecal fluid loss [9, lo]. Whether the PTR procedure influences the incidence of urinary stone formation has not been determined. The present investigation was designed to obtain information regarding changes in the urinary ion excretion in patients with ulcerative colitis who undergo a PTR operation in order to estimate their risk of urinary stone formation.
Nephrolithiasis occurs in 5 to 13% of patients with ulcerative colitis (UC) who undergo colectomy and abdominal ileostomy, presumably from chronic dehydration and urinary concentration. Whether endorectal ileal pullthrough with ileal reservoir (PTR) changes the incidence of stones (primarily calcium oxalate) after colectomy is not known. Urinary excretion of Na2+, K+, Ca2+, Mg2+, phosphate, urate, oxalate, and citrate was measured in a prospective study of 12 UC patients undergoing PTR with temporary end ileostomy. Twenty-four-hour urine samples were obtained before colectomy (tJ, after colectomy but before ileostomy closure (t2), and 5 months after ileostomy closure (t3). Urine volumes decreased from 831 * 101 cc (mean + SE) at tI to 715 f 101 cc at t2 and then increased to 1278 f 421 cc at t3 (significant, with P < 0.01 by t test). Urinary excretions of Mg’+, oxalate, and citrate were low in UC patients compared to those in controls (15 healthy adult volunteers). Excretion of Ca2+ increased significantly following temporary ileostomy while excretion of Mg2+ fell. Excretion of Ca2’ fell and excretion of Mg2+ and citrate increased following PTR. We conclude that PTR patients have increased urine volumes and urinary ion changes known to decrease the risk of developing renal stones. o 1990 Academic
Los Angeles, California
METHODS
Inc.
Informed consent for voluntary study participation was obtained from 12 patients (7 males, 5 females) with ulcerative colitis undergoing the PTR procedure, in accordance with the Helsinki Declaration of 1975. Twentyfour-hour urine volumes and excretion of sodium, potassium, calcium, magnesium, phosphate, urate, oxalate, and citrate were measured in a prospective controlled fashion and compared to those of 15 healthy adult controls. Study patients ranged in age from 18 to 58 years (mean = 32.2). All patients had a history of long-standing ulcerative colitis with a mean duration of 8.3 years. Nine of the 12 patients had pancolitis. Each of the 12 had received highdose corticosteroid therapy for more than 4 months. The operation was performed in two stages separated by an interval of 4 months, as previously described [ll]. During the first operation, total colectomy, mucosal proctectomy, and creation of a 15-cm-lateral ileal reservoir
INTRODUCTION The incidence of nephrolithiasis is believed to be increased in patients with ulcerative colitis (UC) and Crohn’s disease, as well as certain other gastrointestinal disorders particularly in association with high urine oxalate levels [l, 21. Although some earlier reports do not mention nephrolithiasis as a complication in patients with UC [3-51, others have reported that nephrolithiasis develops in 2.0 to 6.4% of these patients [l, 6, 71. Nephrolithiasis occurs even more frequently in those patients 1 To whom correspondence and reprint requests should be addressed at Rm 72-126 CHS, Division of Pediatric Surgery, Dept. of Surgery, UCLA School of Medicine, Los Angeles, CA 90024. 0022-4804/90 $1.50 Copyright 0 1990 by Academic Press, All rights of reproduction in any form
552 Inc. reserved.
STELZNER
ET AL.: URINE
IONS
IN ULCERATIVE
COLITIS
TABLE Urine
Ion Excretion
mole/mole, creatinine Na+ K+ Ca2+ (X100) M$f (X100) Phosphate (X100) Urate (X100) Oxalate (X100) Citrate (X100) pH (pH units)
+ + f f f f f f
5 0.5** 5 3* 13” 5 0.4* 1**
5.60 rt 0.115**
UNDERGOING
and pH in Patients
with
Ulcerative
Colitis
tz 16 4 85 16 83 20 1 7
553
COLECTOMY
1
h 22 3 36 23 54 25 2 5
PATIENTS
+ * f f f f f f
6 0.5* 26* 4* 23* 4 0.3* 2*
5.53 f 0.097**
t3 63 5 32 24 62 22 2 14
k h f + f f f f
15* 1.0 7 4* lo** 3 0.3* 3*
5.70 f 0.165**
N 12 f 8 7f2 34 * 5 48 f 8 264 2~55 26 f 5 3 f 1.2 28 f 7 6.10 k 0.100
Note. ti, before colectomy; tP, after cutaneous ileostomy; t3, after PTR; N, normal controls. Values expressed as means f SEM; *, significantly different from N with P < 0.05; **, significantly different from N with P < 0.01.
was performed. The reservoir was drawn through the rectal muscularis and sutured to the anal mucosa. A temporary end ileostomy was constructed. During the second operation, the ileostomy was mobilized and an ileo-ileal anastomosis was performed. Perioperative corticosteroids and antibiotics were given according to a standardized regimen. Other postoperative medications including antidiarrheals or bulk-forming agents were given intermittently as necessary. For urine ion excretion, 24-hr urine specimens were obtained from each patient 2 days prior to both the first stage (tr) and the second stage operations (tz). A third urine specimen was obtained 4 months after cutaneous ileostomy closure (ts). All patients were consuming their regular home diets during the entire sampling periods. Patients did not receive any recommendations regarding oral fluid intake in order to obtain unbiased urine volume values reflecting actual “normal life” conditions. All urine samples were stored at 4°C and measurements were performed within 24 hr. Values of sodium, potassium, calcium, magnesium, phosphate, creatinine, chloride, uric acid, oxalate, citrate, and pH were measured using standard laboratory methods: sodium and potassium by flame emission photometry, calcium and magnesium by atomic absorption spectrophotometry, phosphate and creatinine by autoanalyzer, chloride by automated chloride titration, and pH by pH meter. Uric acid [12], oxalate [13], and citrate [14] were measured by techniques described previously. Results are expressed as moles of ion per mole of creatinine. Oral fluid intakes were not recorded. Saturation of the urine was calculated as relative supersaturation on a log 10 scale as described by Marshall and Robertson [15]. Relative supersaturation values for calcium oxalate, brushite, octocalcium phosphate, uric acid, and sodium acid urate were calculated using nomograms described previously by these authors. On this supersaturation scale, a urine at the solubility product has a value of zero and a urine at the formation product has the value of one. Negative values indicate undersat-
uration of the urine for the particular substrate and a very low probability of crystal formation. Values between zero and one are characteristic for the metastable region of supersaturation where growth of free existing crystal may occur but spontaneous crystal formation is unlikely if there are no nucleating agents. Values greater than one reflect the region of absolute supersaturation and indicate that there is a high probability of spontaneous precipitation of the particular substrate. Results are expressed as means + SEM. Statistical comparisons were made using the Student t test, with P < 0.05 considered significant. RESULTS
All 12 patients underwent the PTR procedure without major complications. Before ileostomy closure, two patients developed rectal strictures successfully treated by transanal dilatation. They continued to use anal dilators intermittently for 3 months following closure of the ileostomy and showed a satisfactory evacuation pattern during the long-term postoperative follow-up. When the- third urine sample was taken, all patients considered themselves to be continent. However, three patients experienced fecal staining once or twice a week and one patient had nocturnal fecal staining more than twice a week. The mean stool frequency was 7.9 per 24 hr. None of the patients experienced reservoir inflammation during the period of study. At the time of the third urine collection (t3), only four patients were still using psyllium hydrophilic mucilloid (Metamucil), diphenoxylate hydrochloride with atropine sulfate (Lomotil), or other antidiarrheal agents regularly. Patients with functioning ileal reservoirs demonstrated significantly increased sodium excretion compared to normal controls (Table 1). Potassium excretion was low preoperatively when compared to normal control values and after cutaneous ileostomy. However, potassium excretion increased to control values after PTR. During the
554
JOURNAL
OF SURGICAL
RESEARCH:
ileostomy period, patients showed a marked hypercalcuria, which returned to normal levels with the functioning reservoir. Magnesium excretion was low, compared to controls, at all time points. Excretions of phosphate increased slightly with the ileostomy, but remained far below normal values. Uric acid excretion showed minimal change during the entire period of study. Patients with a functioning ileal reservoir (t3) showed significantly higher urine citrate concentrations than those during the ti and t2 periods, but their citrate concentrations were less than half of normal values. Urine pH values were significantly lower in the three groups of patients than in controls (Table 1). The 24-hr urine volume was lowest during the ileostomy period, but increased by almost 80% once intestinal continuity was restored and the ileal reservoir was functioning (Table 2). The saturation of urine with calcium oxalate, uric acid, sodium urate, and calcium phosphate was calculated (Fig. 1). In all three groups of patients, metastable urine concentrations were found for calcium oxalate. Uric acid and sodium urate crystal formation appeared more likely in patients with ulcerative colitis or an ileostomy than in those with an ileal reservoir. Urine concentrations were below the solubility product for calcium phosphates in all three groups of patients. None of the 12 patients developed urinary stones during the 7-month study period. DISCUSSION
In this prospective study, changes in urinary ion excretion were measured in 12 patients undergoing colectomy and the PTR procedure. Patients with active ulcerative colitis and those following ileostomy creation had significantly reduced urine volumes compared to those of patients after the PTR procedure and to those of normal controls. The reduced volume in ileostomy patients was accompanied by an increased urinary excretion of calcium, but not of oxalate or uric acid. Changes in urine volumes may have been influenced by changes in medications, since the majority of patients received corticosteroids before colectomy and 4 patients continued to use antidiarrheals in varying dosages at the end of the study. Urine saturation, expressed by an activity product ratio, can be precisely calculated after obtaining activity prod-
TABLE Urine
Volume per 24 hr (ml)
Volume
in Patients
2 with
Ulcerative
Colitis
h
tz
t3
N
831 + 101*
715 f 101*
1278 f 420
1300f65
Note. tl, before colectomy; t2, after cutaneous ileostomy; t3, after PTR; N, normal controls. Values expressed as means f SEM, *, significantly different from N by t test, with 2’
