Hyperoxaluria
and
nephrolithiasis
after
John
Q.
Stauffer,
M.D.,
of
regulated acids
calcium
may
Management
calculi
and
intestinal
renal
oxalate
a diet Am.
bypass1
The American
important leading
low
and
J. C/in.
in oxalate Nutr.
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/1/64/4649773 by Queen Mary University of London user on 22 August 2018
jejunoileal
enhanced
determinant fatty to
fat
2
30: 64-71,
bypass
absorption
for acids.
are of
passive
dietary
at
oxalate.
and bile
salts
diffusion
calcium
increased
dietary
hyperabsorption
Malabsorbed
increased
content,
may and
of
of 750
be fatty
oxalate.
mg/day,
and
bowel
dis-
1977.
Renal ease
of Clinical
and
of
and
permeability,
disease
Journal
resection,
because
of calcium
It has been known for some that there is an association between gastrointestinal diseases and an increased risk for formation of renal calculi. Calcium urolithiasis associated with active peptic ulcer disease may be the presenting manifestation of primary hyperparathyroidism (1), and patients with chronic peptic ulcer disease may develop nephrocalcinosis after prolonged treatment with an absorbable alkali and milk (2). Another group of patients develops calcium-containing renal calculi without demonstrable abnormalities in parathyroid function or structural changes in the gastrointestinal tract. It has been shown that this group of patients has increased absorption of dietary calcium, and this condition had been called idiopathic hyperabsonptive hypercalcunia (3). Coe and Kavalach (4) emphasized the prevalence of gastrointestinal diseases in patients with renal calculi in a review of 230 consecutive patients presenting with nephrolithiasis during a 5-year period. In this group a cause for stone formation could be determined in only 84 patients, and the remaining 146 individuals had calcium stone formation secondary to unexplained hypencalcunia. In the 84 patients in whom a specific diagnosis was established, 18 (7.8%) had an underlying gastrointestinal disease. In this group, nine had inflammatory bowel disease, seven had chronic diarrheal states, and two developed stones after jejunoileal bypass. 64
calculi
is an
concentration
intestinal
includes
cholestyramine.
Renal
of
intraluminal alter
ileal disease, ileal
oxalate
solubility by
jejunoileal
with
Patients
forming
Intraluminal
oxalate
F.I4.C.P.
ABSTRACT risk
calcium
calculi
and
inflammatory
The association between inflammatory bowel disease and the increased risk of kidney stone formation was further emphasized by the observations of Denen et al. (5) and Gelzayd et al. (6). In reviews of large groups of patients with either ulcerative colitis on regional entenitis they observed a definite increase in the risk of forming nenal calculi. The overall incidence was approximately 6.3%. In this combined group, although many of the calculi analyzed were composed of uric acid, a majority of the stones were found to be calcium-containing, and many were composed entirely of calcium oxalate. Renal
calculi
after
jejunoileal
bypass
In 1973 Dickstein and Frame (7) noted a high incidence of renal calculi after jejunoileal bypass. They reported a 6-year experience in 34 patients who had undergone intestinal bypass. Twenty-three of these patients had had a jejunocolonic bypass and averaged a 100-pound weight loss postoperatively. Eleven patients had undergone jejunoileal by-
‘From Center, 2
the Department Syracuse,
These
studies
of Medicine,
New
York.
were
supported
Upstate
by Clinical
Medical Research
Center Grant RR 00229 from the Division of Research Facilities and Resources, and Grant AM 17968-01 from the National Institute of Arthritis, Metabolism and Digestive Diseases, United States Public Health Service.
Nutrition
30: JANUARY
1977,
pp. 64-71.
Printed
in U.S.A.
HYPEROXALURIA
AND
NEPHROLITHIASIS
pass and had an average weight loss of 85 pounds. Eleven of 34 patients (32.4%) were found to have renal calculi, and nine of these I 1 had undergone jejunocolonic bypass . The interval between the shunt procedure and the first occurrence or knowledge ofstone formation ranged from 24 days to 6 years . The average interval was 1 year and 8 months . Three of the patients had a history of calculi before the shunt procedure, but preoperative intravenous pyelograms did not demonstrate retained calculi. This suggested that recurrent stone formation occurred after the shunt procedure. Several of the stone formers were found to have an elevated urinary oxalate excretion, and of the six stones analyzed, all contained calcium oxalate. Subsequently, O’Leary et al. (8) reported their experience in 3 1 morbidly obese patients who had been followed for at least 6 months after a jejunoileal bypass. The average weight loss after shunt was 84 pounds, and seven of 31 patients (22.6%) were found to have renal calculi. Six of the stone formers had either calcium oxalate on radiopaque stones. In a more recent study by Gregory et al. (9), 435 patients were evaluated after jejunoileal bypass. Two hundred and sixty-five patients had jejunoileal end-to-side anastomosis (14 inches of jejunum and 4 inches of ileum), whereas 172 patients had jejunoileal end-to-end anastomosis (12 inches of jejunum and 6 inches of ileum). Twenty-four of the 435 patients were found to have recurrent renal calculi, an incidence of approximately 6%. The stones obtained from 12 of the 24 patients consisted entirely of calcium oxalate. The 24-hr urinary oxalate excretion was determined in 156 obese patients preoperatively. The urinary oxalate was normal in 80 (O.2 Resect,,,,
m -115cm
P 30cm cm
FIG. 1. Change in urinary oxalate excretion in patients with ileal disease. Urinary oxalate is normal in patients with short resections (Group A) and abnormal with longer resections (Group B). Cholestyramine is effective in reducing urinary oxalate excretion in Group B (reprinted with permission from Ann. Internal Med. 79: 383, 1973).
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/1/64/4649773 by Queen Mary University of London user on 22 August 2018
2
4
6
8
0
2
Do”
FIG. 2. Urinary oxalate excretion is dependent on dietary oxalate concentration. In a patient with a 42-cm ileal resection, urinary oxalate excretion returns to normal on a low-oxalate diet (reprinted with permission from Ann. Internal Med. 79: 383, 1973).
occurred in his patients only after at least 30 cm of ileum had been resected (Fig. 3). Patients with longen nesections seemed to have higher elevations of urinary oxalate excretion. Earnest et al. (17) confirmed these observations, although in their study hypenoxalunia occurred only after 50 cm of ileal resection. They were able to correlate hypenoxalunia with the degree of steatonrhea. Earnest et al. (17) also demonstrated that patients with a colectomy did not have hypenoxalunia. In patients with extensive ileal resection, they showed that hyperoxalunia was directly related to dietary oxalate and fat content. Diets high in oxalate and saturated fat led to the highest urinary oxalate excretion. This confirmed observations of Andersson and Jagenbung (18) that a low saturated fat diet led to a reduction in urinary oxalate excretion in patients with ileal disease. Hyperoxaluria
a 20
0
0
FFER
without
bowel
resection
The foregoing studies suggested that enhanced absorption of dietary oxalate which occurred in malabsonption syndromes was the result of altered intraluminal solubility of oxalate (16-18). This hypothesis suggests that malabsorbed free fatty acids combine with intnaluminal calcium to form soaps. Because calcium is sequestered by fats, oxalate remains in solution as a soluble salt and available for absorption. If this hypothesis is
HYPEROXALURIA
AND
NEPHROLITHIASIS
correct, then patients with steatorrhea without inflammatory bowel disease or mucosal abnormalities should have hypenoxalunia. In the initial report by Smith et al.(l 1) in 1972, two of seven patients with bacterial overgrowth and six of 15 patients with intestinal disease, including adult celiac disease and cirrhosis, were noted to have hypenoxaluna. Subsequently, Stauffer et al. (19) demonstrated elevated urinary oxalate excretion in four patients with pancreatic insufficiency and two patients with adult celiac disease. In the patients with pancreatic insufficiency no reduction in urinary oxalate excretion was obtained when fecal fat malabsonption was reduced by treatment with pancreatic extracts. These patients had severe malabsonption in spite of treatment and were on a diet high in oxalate content during the test period. These individuals had a further increase in urinary oxalate excretion when dietary calcium was decreased, suggesting that intnaluminal solubility did play a role in the hyperabsorption. In a later report by McDonald et al. (20), patients with nontnopical sprue who had hypenoxalunia were found to have a reduction in urinary oxalate when they were in remission on a gluten-free diet. Hyperoxaluria
calcium
and dietary
To confirm the importance of intnaluminal solubility of oxalate in determining the absorption of dietary oxalate, a series of patients with regional entenitis with ileal
80
a
60
S
g
S 40
I
S
2
9
6
20 00
8 0
50 Length
of resected
00 segment
50 (cm)
FIG. 3. Urinary oxalate excretion is compared to the length of ileum resected. Patients with resections greater than 30-cm have increased urinary oxalate excretion (reprinted with permission from Ann. Internal Med. 79: 383, 1973).
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/1/64/4649773 by Queen Mary University of London user on 22 August 2018
TABLE
AFTER
67
BYPASS
I
Urinary oxalate and jejunoileal
excretion (mg/day) bypass with varying
in regional enteritis dietary calcium
Calcium Patient
(mg/day)#{176}
groups (no.)
Regional enteritis after ileectomy (6) Jejunoileal bypass preoperative (5) Jejunoileal bypass postoperative (4)
250
500
1,000
3.000
83
74
59
50
71
57
90.4” 102.7
204.7
a The unvarying component of the 100 g of fat and 500 mg of oxalate/day. after 250-mg calcium diet.
diet
consisted Before
b
of and
resection ranging from 50 to 150 cm was evaluated on a constant diet containing 100 g of fat and 500 mg of oxalate in the form of spinach and tea (19). The dietary calcium was changed from 250 to 3,000 mg/day by manipulation of the diet and addition of pulverized calcium gluconate tablets (Table 1). As dietary calcium was increased from 250 to 3,000 mg, a significant reduction in urinary oxalate excretion was noted. In two of these individuals, when dietary calcium was varied from 3,000 to 250 to 3,000 mg, urinary oxalate excretion was inversely related to dietary calcium. Hyperoxaluria
after
jejunoileal
bypass
The studies of Dickstein and Frame (7) in 1973 and, later, of O’Leary et al. (8) in 1974 suggested that abnormalities in oxalate metabolism might be the explanation for the increased incidence of renal calculi in patients after small bowel bypass. They documented that a majority of stones formed in these patients were composed of calcium oxalate. In a later study by Gregory et al. (9), abnormalities in urinary oxalate excretion were noted to occur after the bypass operation. In ongoing investigations in our laboratory, we have confirmed that preoperative urinary oxalate determinations in patients undergoing jejunoileal bypass for control of obesity were within normal range (Table 1). When these and other patients who have undergone jejunoileal bypass are studied postoperatively, the urinary oxalate excretion is
68
STAUFFER
abnormal. In shunted patients studied thus far, the urinary oxalate excretion has ranged from 75 to 302 mg/24 hr, whereas fecal fat excretion has ranged from 29 to 59 g/24 hr. Three of these six patients have formed recurrent calcium oxalate renal calculi. To test the hypothesis that intraluminal oxalate solubility is an important determinant for hyperabsorption after jejunoileal bypass, these patients were studied while dietary calcium was changed from 3,000 to 250 to 3,000 mg/day. The average urinary oxalate excretion on the 3,000-mg diet was 90.4 mg/24 hr. When dietary calcium was reduced to 250 mg, urinary oxalate excretion rose to a mean of 204.7 mg/24 hr, and fell to 102.7 mg/24 hr. when dietary calcium was again increased to 3,000 mg. The change in urinary oxalate excretion on the different calcium diets was significant (P < 0 D2). Urinary calcium excretion rose on the high-calcium diet, but the change was not statistically significant when compared to the low-calcium diet. An example of this response to changes in dietary calcium is seen in a single patient after jejunoileal bypass in Figure 4. This individual was unique in that his urinary calcium excretion was elevated, but the inverse relationship between dietary calcium and urinary oxalate excretion is readily apparent. Failure to reduce his urinary oxalate
excretion to normal with added dietary calcium may be related to the severe fecal fat malabsorption (29.3 g/day). Reduction in urinary calcium was obtained by the addition of hydrochlorothiazide 50 mg three times daily, but this was associated with a further increase in urinary oxalate excretion. Improvement in the urine composition was obtained with administration of cholestyramine and a low-oxalate, low-fat, and 750-mg calcium diet. Intraluminal sorption
factors
regulating
oxalate
ab-
The foregoing studies suggest that hyperabsorption of dietary oxalate in various intestinal diseases is related to steatorrhea. The degree of absorption appears to be regulated by the dietary calcium content, although high-calcium diets can not overcome hyperabsorption when fecal fat excretion is greater than 20 g/day. Studies have also shown (1, 21) that the colon may be the main site of enhanced absorption. The relationship between steatorrhea, dietary calcium, and urinary oxalate excretion is further emphasized when patients with different diseases are compared on standard diets (Fig. 5). Patients with regional entenitis, pancreatic insufficiency, adult celiac disease,
URINARY OXALATE EXCRETION AFTER JEJUNOILEAL BYPASS IN A PATIENT
1895 500
.c
. cci
cci
400 E
E 300
Id
I4
U -J
-J
200
4
x
4 U
0
(00
90
DAY FIG
.4. Urinary
lOO-g of cholesytramine oxalate,
oxalate
and calcium
fat diet. The dietary and
a low-fat,
excretion
in a single
calcium
is changed
low-oxalate,
and
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/1/64/4649773 by Queen Mary University of London user on 22 August 2018
from
750-mg
patient
after
junoileal
3,000 to 250 to 3,000 calcium diet is shown
bypass
when
studied
on a 500-mg
mg. The response to administration in the last 4 days.
HYPEROXALURIA STEATORRHEA 200
AND
AND
OXALATE
EXCRETION
o’er. 25OmgCo)cium
75 Do
NEPHROLITHIASIS
---
--
r:.70_-
500mgCalcium
-3000mgColcium
.-
-.-.#
50
-.--..
E
(00
-J OX 75 0 >-
cc
50
OX
z
cc
69
BYPASS
cholate significantly increased oxalate absorption (from 32.2 ± 9.4 to 330.4 ± 47.3 nmoles/min per g ofdry weight (P < 0.001)), and changed water absorption to water secretion Exposure of colonic mucosa to deoxycholate also increased absorption of urea, decreased tra nsm ucosal electrical potential difference, and increased colonic clearance of intravenously administered oxalate. In parallel studies using nicininoleic acid and oleic acid, a similar effect on increased oxalate absorption was demonstrated These studies suggested that bile salts and fatty acids increased colonic absorption of oxalate by a nonspecific alteration of colonic permeability. Hyperabsorption of dietary oxalate appears to be dependent upon both intraluminal and mucosal abnormalities initiated by malabsorption of fatty acids Malabsorption of bile salts in patients with ileectomies and jejunoileal bypass contributes to alterations in mucosal permeability. .
25 Ui IOX
AFTER
500’s
25
(0
20
FECAL
y!
FAT
3000
P.
4!O
057
P
and
nephrolithiasis
after
John
Q.
Stauffer,
M.D.,
of
regulated acids
calcium
may
Management
calculi
and
intestinal
renal
oxalate
a diet Am.
bypass1
The American
important leading
low
and
J. C/in.
in oxalate Nutr.
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/1/64/4649773 by Queen Mary University of London user on 22 August 2018
jejunoileal
enhanced
determinant fatty to
fat
2
30: 64-71,
bypass
absorption
for acids.
are of
passive
dietary
at
oxalate.
and bile
salts
diffusion
calcium
increased
dietary
hyperabsorption
Malabsorbed
increased
content,
may and
of
of 750
be fatty
oxalate.
mg/day,
and
bowel
dis-
1977.
Renal ease
of Clinical
and
of
and
permeability,
disease
Journal
resection,
because
of calcium
It has been known for some that there is an association between gastrointestinal diseases and an increased risk for formation of renal calculi. Calcium urolithiasis associated with active peptic ulcer disease may be the presenting manifestation of primary hyperparathyroidism (1), and patients with chronic peptic ulcer disease may develop nephrocalcinosis after prolonged treatment with an absorbable alkali and milk (2). Another group of patients develops calcium-containing renal calculi without demonstrable abnormalities in parathyroid function or structural changes in the gastrointestinal tract. It has been shown that this group of patients has increased absorption of dietary calcium, and this condition had been called idiopathic hyperabsonptive hypercalcunia (3). Coe and Kavalach (4) emphasized the prevalence of gastrointestinal diseases in patients with renal calculi in a review of 230 consecutive patients presenting with nephrolithiasis during a 5-year period. In this group a cause for stone formation could be determined in only 84 patients, and the remaining 146 individuals had calcium stone formation secondary to unexplained hypencalcunia. In the 84 patients in whom a specific diagnosis was established, 18 (7.8%) had an underlying gastrointestinal disease. In this group, nine had inflammatory bowel disease, seven had chronic diarrheal states, and two developed stones after jejunoileal bypass. 64
calculi
is an
concentration
intestinal
includes
cholestyramine.
Renal
of
intraluminal alter
ileal disease, ileal
oxalate
solubility by
jejunoileal
with
Patients
forming
Intraluminal
oxalate
F.I4.C.P.
ABSTRACT risk
calcium
calculi
and
inflammatory
The association between inflammatory bowel disease and the increased risk of kidney stone formation was further emphasized by the observations of Denen et al. (5) and Gelzayd et al. (6). In reviews of large groups of patients with either ulcerative colitis on regional entenitis they observed a definite increase in the risk of forming nenal calculi. The overall incidence was approximately 6.3%. In this combined group, although many of the calculi analyzed were composed of uric acid, a majority of the stones were found to be calcium-containing, and many were composed entirely of calcium oxalate. Renal
calculi
after
jejunoileal
bypass
In 1973 Dickstein and Frame (7) noted a high incidence of renal calculi after jejunoileal bypass. They reported a 6-year experience in 34 patients who had undergone intestinal bypass. Twenty-three of these patients had had a jejunocolonic bypass and averaged a 100-pound weight loss postoperatively. Eleven patients had undergone jejunoileal by-
‘From Center, 2
the Department Syracuse,
These
studies
of Medicine,
New
York.
were
supported
Upstate
by Clinical
Medical Research
Center Grant RR 00229 from the Division of Research Facilities and Resources, and Grant AM 17968-01 from the National Institute of Arthritis, Metabolism and Digestive Diseases, United States Public Health Service.
Nutrition
30: JANUARY
1977,
pp. 64-71.
Printed
in U.S.A.
HYPEROXALURIA
AND
NEPHROLITHIASIS
pass and had an average weight loss of 85 pounds. Eleven of 34 patients (32.4%) were found to have renal calculi, and nine of these I 1 had undergone jejunocolonic bypass . The interval between the shunt procedure and the first occurrence or knowledge ofstone formation ranged from 24 days to 6 years . The average interval was 1 year and 8 months . Three of the patients had a history of calculi before the shunt procedure, but preoperative intravenous pyelograms did not demonstrate retained calculi. This suggested that recurrent stone formation occurred after the shunt procedure. Several of the stone formers were found to have an elevated urinary oxalate excretion, and of the six stones analyzed, all contained calcium oxalate. Subsequently, O’Leary et al. (8) reported their experience in 3 1 morbidly obese patients who had been followed for at least 6 months after a jejunoileal bypass. The average weight loss after shunt was 84 pounds, and seven of 31 patients (22.6%) were found to have renal calculi. Six of the stone formers had either calcium oxalate on radiopaque stones. In a more recent study by Gregory et al. (9), 435 patients were evaluated after jejunoileal bypass. Two hundred and sixty-five patients had jejunoileal end-to-side anastomosis (14 inches of jejunum and 4 inches of ileum), whereas 172 patients had jejunoileal end-to-end anastomosis (12 inches of jejunum and 6 inches of ileum). Twenty-four of the 435 patients were found to have recurrent renal calculi, an incidence of approximately 6%. The stones obtained from 12 of the 24 patients consisted entirely of calcium oxalate. The 24-hr urinary oxalate excretion was determined in 156 obese patients preoperatively. The urinary oxalate was normal in 80 (O.2 Resect,,,,
m -115cm
P 30cm cm
FIG. 1. Change in urinary oxalate excretion in patients with ileal disease. Urinary oxalate is normal in patients with short resections (Group A) and abnormal with longer resections (Group B). Cholestyramine is effective in reducing urinary oxalate excretion in Group B (reprinted with permission from Ann. Internal Med. 79: 383, 1973).
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/1/64/4649773 by Queen Mary University of London user on 22 August 2018
2
4
6
8
0
2
Do”
FIG. 2. Urinary oxalate excretion is dependent on dietary oxalate concentration. In a patient with a 42-cm ileal resection, urinary oxalate excretion returns to normal on a low-oxalate diet (reprinted with permission from Ann. Internal Med. 79: 383, 1973).
occurred in his patients only after at least 30 cm of ileum had been resected (Fig. 3). Patients with longen nesections seemed to have higher elevations of urinary oxalate excretion. Earnest et al. (17) confirmed these observations, although in their study hypenoxalunia occurred only after 50 cm of ileal resection. They were able to correlate hypenoxalunia with the degree of steatonrhea. Earnest et al. (17) also demonstrated that patients with a colectomy did not have hypenoxalunia. In patients with extensive ileal resection, they showed that hyperoxalunia was directly related to dietary oxalate and fat content. Diets high in oxalate and saturated fat led to the highest urinary oxalate excretion. This confirmed observations of Andersson and Jagenbung (18) that a low saturated fat diet led to a reduction in urinary oxalate excretion in patients with ileal disease. Hyperoxaluria
a 20
0
0
FFER
without
bowel
resection
The foregoing studies suggested that enhanced absorption of dietary oxalate which occurred in malabsonption syndromes was the result of altered intraluminal solubility of oxalate (16-18). This hypothesis suggests that malabsorbed free fatty acids combine with intnaluminal calcium to form soaps. Because calcium is sequestered by fats, oxalate remains in solution as a soluble salt and available for absorption. If this hypothesis is
HYPEROXALURIA
AND
NEPHROLITHIASIS
correct, then patients with steatorrhea without inflammatory bowel disease or mucosal abnormalities should have hypenoxalunia. In the initial report by Smith et al.(l 1) in 1972, two of seven patients with bacterial overgrowth and six of 15 patients with intestinal disease, including adult celiac disease and cirrhosis, were noted to have hypenoxaluna. Subsequently, Stauffer et al. (19) demonstrated elevated urinary oxalate excretion in four patients with pancreatic insufficiency and two patients with adult celiac disease. In the patients with pancreatic insufficiency no reduction in urinary oxalate excretion was obtained when fecal fat malabsonption was reduced by treatment with pancreatic extracts. These patients had severe malabsonption in spite of treatment and were on a diet high in oxalate content during the test period. These individuals had a further increase in urinary oxalate excretion when dietary calcium was decreased, suggesting that intnaluminal solubility did play a role in the hyperabsorption. In a later report by McDonald et al. (20), patients with nontnopical sprue who had hypenoxalunia were found to have a reduction in urinary oxalate when they were in remission on a gluten-free diet. Hyperoxaluria
calcium
and dietary
To confirm the importance of intnaluminal solubility of oxalate in determining the absorption of dietary oxalate, a series of patients with regional entenitis with ileal
80
a
60
S
g
S 40
I
S
2
9
6
20 00
8 0
50 Length
of resected
00 segment
50 (cm)
FIG. 3. Urinary oxalate excretion is compared to the length of ileum resected. Patients with resections greater than 30-cm have increased urinary oxalate excretion (reprinted with permission from Ann. Internal Med. 79: 383, 1973).
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/1/64/4649773 by Queen Mary University of London user on 22 August 2018
TABLE
AFTER
67
BYPASS
I
Urinary oxalate and jejunoileal
excretion (mg/day) bypass with varying
in regional enteritis dietary calcium
Calcium Patient
(mg/day)#{176}
groups (no.)
Regional enteritis after ileectomy (6) Jejunoileal bypass preoperative (5) Jejunoileal bypass postoperative (4)
250
500
1,000
3.000
83
74
59
50
71
57
90.4” 102.7
204.7
a The unvarying component of the 100 g of fat and 500 mg of oxalate/day. after 250-mg calcium diet.
diet
consisted Before
b
of and
resection ranging from 50 to 150 cm was evaluated on a constant diet containing 100 g of fat and 500 mg of oxalate in the form of spinach and tea (19). The dietary calcium was changed from 250 to 3,000 mg/day by manipulation of the diet and addition of pulverized calcium gluconate tablets (Table 1). As dietary calcium was increased from 250 to 3,000 mg, a significant reduction in urinary oxalate excretion was noted. In two of these individuals, when dietary calcium was varied from 3,000 to 250 to 3,000 mg, urinary oxalate excretion was inversely related to dietary calcium. Hyperoxaluria
after
jejunoileal
bypass
The studies of Dickstein and Frame (7) in 1973 and, later, of O’Leary et al. (8) in 1974 suggested that abnormalities in oxalate metabolism might be the explanation for the increased incidence of renal calculi in patients after small bowel bypass. They documented that a majority of stones formed in these patients were composed of calcium oxalate. In a later study by Gregory et al. (9), abnormalities in urinary oxalate excretion were noted to occur after the bypass operation. In ongoing investigations in our laboratory, we have confirmed that preoperative urinary oxalate determinations in patients undergoing jejunoileal bypass for control of obesity were within normal range (Table 1). When these and other patients who have undergone jejunoileal bypass are studied postoperatively, the urinary oxalate excretion is
68
STAUFFER
abnormal. In shunted patients studied thus far, the urinary oxalate excretion has ranged from 75 to 302 mg/24 hr, whereas fecal fat excretion has ranged from 29 to 59 g/24 hr. Three of these six patients have formed recurrent calcium oxalate renal calculi. To test the hypothesis that intraluminal oxalate solubility is an important determinant for hyperabsorption after jejunoileal bypass, these patients were studied while dietary calcium was changed from 3,000 to 250 to 3,000 mg/day. The average urinary oxalate excretion on the 3,000-mg diet was 90.4 mg/24 hr. When dietary calcium was reduced to 250 mg, urinary oxalate excretion rose to a mean of 204.7 mg/24 hr, and fell to 102.7 mg/24 hr. when dietary calcium was again increased to 3,000 mg. The change in urinary oxalate excretion on the different calcium diets was significant (P < 0 D2). Urinary calcium excretion rose on the high-calcium diet, but the change was not statistically significant when compared to the low-calcium diet. An example of this response to changes in dietary calcium is seen in a single patient after jejunoileal bypass in Figure 4. This individual was unique in that his urinary calcium excretion was elevated, but the inverse relationship between dietary calcium and urinary oxalate excretion is readily apparent. Failure to reduce his urinary oxalate
excretion to normal with added dietary calcium may be related to the severe fecal fat malabsorption (29.3 g/day). Reduction in urinary calcium was obtained by the addition of hydrochlorothiazide 50 mg three times daily, but this was associated with a further increase in urinary oxalate excretion. Improvement in the urine composition was obtained with administration of cholestyramine and a low-oxalate, low-fat, and 750-mg calcium diet. Intraluminal sorption
factors
regulating
oxalate
ab-
The foregoing studies suggest that hyperabsorption of dietary oxalate in various intestinal diseases is related to steatorrhea. The degree of absorption appears to be regulated by the dietary calcium content, although high-calcium diets can not overcome hyperabsorption when fecal fat excretion is greater than 20 g/day. Studies have also shown (1, 21) that the colon may be the main site of enhanced absorption. The relationship between steatorrhea, dietary calcium, and urinary oxalate excretion is further emphasized when patients with different diseases are compared on standard diets (Fig. 5). Patients with regional entenitis, pancreatic insufficiency, adult celiac disease,
URINARY OXALATE EXCRETION AFTER JEJUNOILEAL BYPASS IN A PATIENT
1895 500
.c
. cci
cci
400 E
E 300
Id
I4
U -J
-J
200
4
x
4 U
0
(00
90
DAY FIG
.4. Urinary
lOO-g of cholesytramine oxalate,
oxalate
and calcium
fat diet. The dietary and
a low-fat,
excretion
in a single
calcium
is changed
low-oxalate,
and
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/1/64/4649773 by Queen Mary University of London user on 22 August 2018
from
750-mg
patient
after
junoileal
3,000 to 250 to 3,000 calcium diet is shown
bypass
when
studied
on a 500-mg
mg. The response to administration in the last 4 days.
HYPEROXALURIA STEATORRHEA 200
AND
AND
OXALATE
EXCRETION
o’er. 25OmgCo)cium
75 Do
NEPHROLITHIASIS
---
--
r:.70_-
500mgCalcium
-3000mgColcium
.-
-.-.#
50
-.--..
E
(00
-J OX 75 0 >-
cc
50
OX
z
cc
69
BYPASS
cholate significantly increased oxalate absorption (from 32.2 ± 9.4 to 330.4 ± 47.3 nmoles/min per g ofdry weight (P < 0.001)), and changed water absorption to water secretion Exposure of colonic mucosa to deoxycholate also increased absorption of urea, decreased tra nsm ucosal electrical potential difference, and increased colonic clearance of intravenously administered oxalate. In parallel studies using nicininoleic acid and oleic acid, a similar effect on increased oxalate absorption was demonstrated These studies suggested that bile salts and fatty acids increased colonic absorption of oxalate by a nonspecific alteration of colonic permeability. Hyperabsorption of dietary oxalate appears to be dependent upon both intraluminal and mucosal abnormalities initiated by malabsorption of fatty acids Malabsorption of bile salts in patients with ileectomies and jejunoileal bypass contributes to alterations in mucosal permeability. .
25 Ui IOX
AFTER
500’s
25
(0
20
FECAL
y!
FAT
3000
P.
4!O
057
P
