Renal Osteodystrophy in Patients on Continuous Ambulatory Peritoneal Dialysis Satoshi Hisano, M.D.' , lchiroh Yamane, M.D.', Kohji Ueda, M.D.l, and Masataka KawagoeZ 'Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka; Tedin Bioscience Laboratories, Hino, Tokyo

Twelve patients on continuous ambulatory peritoneal dialysis (CAPD) were studied in order to evaluate the progression of renal osteodystrophy (ROD). All patients received doses of 0.01 - 0.02 pg/kg of 1 alpha vitamin D3 (la - D3) and 0.1 - 0.15 g/kg of calcium carbonate for 12 - 18 months. Serum total protein, total calcium (Ca), creatinine, inorganic phosphate, alkaline phosphatase (ALP), and n-terminal parathyroid hormone were measured regularly. The radiological bone appearance for ROD or rickets and the height standard deviation score were compared between the outset and the end of this study. An increase of Ca values and a decrease of ALP values correlated with a suppression of hyperparathyroidism, and the hyperphosphatemia was controlled in the majority of our patients throughout this study. Two patients had ROD and rickets a t the outset of this study, and all patients but one had neither ROD nor rickets at the end of this study. Growth retardation improved or remained stable in 10 patients. Our results indicate that adequate doses of la - D3 and calcium carbonate are effective in the prevention of ROD and rickets in patients on CAPD. (Acta Paediatr Jpn I990; 32: 44 50)

-

Key Words

Renal osteodystrophy, Chronic renal failure, Continuous ambulatory peritoneal dialysis, Vitamin D

Introduction Renal osteodystrophy (ROD) is a major complication in patients with chronic renal failure. ROD may lead to short stature, bone pain, bone fracture, and bony deformities in patients with chronic renal failure [ 11 .

Received July 13,1989 Revised October 16,1989 Accepted October 26,1989 Correspondence address: Satoshi Hisano, M.D., Department of Pediatrics, Faculty of Medicine, Kyushu University, 3-1 -1 Maidashi, Higashi-ku, Fukuoka 812, Japan

Continuous ambulatory peritoneal dialysis (CAPD) has been reported to be effective in controlling the progression of ROD in adults [2] and in children [3,4]. Paunier et a1 [4], Salusky et a1 [5],and Fine et a1 [6] reported that ROD improved in children on CAPD if the serum total calcium value was raised to 10.5 to 11.5 mg/dl by increasing the vitamin D dosage in order to suppress the serum parathyroid hormone secretion. We prescribed 1 alpha vitamin D3 ( l a - D3) and calcium carbonate for 12 patients on CAPD in order to prevent the progression of ROD. Our study describes a prospective evaluation of the prevention of ROD in patients on CAPD.

Renal osteodystrophy on CAPD 45

Subjects and Methods Twelve patients, aged two to 16 years, who underwent CAPD at the Department of Pediatrics, Kyushu University Hospital, were studied in an attempt to evaluate the ROD (Table 1). The primary diseases for renal failure were chronic glomerulonephritis in four patients, hypoplastic or dysplastic kidney in three, lupus nephritis in one, and chronic pyelonephritis in one, and those of the remaining three patients were unknown. These 12 patients had a history of neither liver disease nor liver dysfunction. All patients received 4 - 5 exchanges/day, 0.5 - 1.5 liters/exchanges of 1.5% or 2.5% dextrose Dianeal s o hti on (Bax t er Laboratories) containing calcium (3.5 meq/L). Diet and fluid restriction ,were minimal. Prednisolone treatment had been discontinued in patient 4 with focal glomerular sclerosis one year before the study. Patient 10 was treated with prednisolone at a dose of 1 0 m g on alternate days throughout the study because of lupus nephritis. Neither of these two patients had any bone disease at the outset of the study. Eight patients (patients 1 - 4, 6 - 7, and 9 - 10) had received a dose of 0.01 - 0.02 pg/kg of l a - D3 3 - 6 months prior to the initiation of CAPD and the remaining four had received this agent after the initiation of CAPD. Three patients (patients 1, 3, and 5 ) had received a dose of 0.1 g/kg of aluminum hydroxide for 3 - 6 months until the outset of the study. In the study program, all patients, who were treated with CAPD for 3 - 6 months, received doses of 0.01 - 0.02 pg/ kg of l a - D3 and 0.1 - 0.15 g/kg of calcium carbonate for 12 - 18 months (a mean period of 13.4 months). None of these patients received aluminum hydroxide treatment throughout this study. Blood chemistries values including serum total protein, creatinine, total calcium (Ca), inorganic phosphate (P), and alkaline phosphatase (ALP) were measured using standard clinical laboratory techniques at monthly intervals. N-terminal fragment parathyroid hormone (n-PTH) was measured at both the outset and the end of this study by radioimmuno-

Vol, 32 No. 1 February 1990

assay (normal adult value: 0.23 - 0.63 ng/ml) in the Teijin Bioscience Laboratories. Radiographs of hands, wrists, and knees were examined at both the outset and the end of this study. The radiographs were evaluated according to the presence of subperiosteal erosion of the cortices of long bones and phalanges for the diagnosis of ROD, or increased thickness or fraying of the radiolucent zone in the region of the growth plates for the diagnosis of rickets [3]. The bone age was evaluated according to the atlas of Greulich and Pyle [7], and this bone age was determined by the following formula: Percent bone age = Observed bone age/Chronological bone age X 100. Heights were measured in all patients at both the outset and the end of this study. Heights were expressed as standard deviation score (SDS) according to the formula: SDS=Observed height (cm) - Expected mean height for age (cm)/ Standard deviation in height for age (cm). Standard deviation in height for age and expected mean height (fiftieth percentile) for age were obtained from the standard growth curve of Japanese. A student’s t test was used in the statistical analysis of the data.

Results Comparison of biochemistries values between the outset and the end of the study The biochemistries values listed in Table 1 are shown, except for n-PTH, by the total mean value of at least three consecutive determinants at both the outset and the end of this study. Hypoproteinemia was evident in three patients (patients 2, 3, and 12) throughout this study. The serum creatinine value decreased or remained stable in nine patients throughout this study. The normal value of serum total Ca was observed in only four patients (patients 1 and 6 - 8) at the outset of this study, and the serum total Ca value increased up to the normal range or above in all patients throughout this study. The serum total Ca value increased up to 12.3 mg/dl in patient 5 at the end of this study, and Ca precipitated on the conjunctiva bulbi. This Ca precipitation disappeared by the de-

46 Hisano et al. Table 1. Comparison of biochemistries values between the outset and the end of the study Patient No.

Sex

1

F

2

M

%y 9

8

T.Pr. (g/dl) A B 6.1 6.4

*

*

4

F

F

2

4

F

11

5.2 5.4

11.1

F

4

F

10

F

9

F

14

F

15

15

M

16

582

277

f

t

0.1

0.3

0.2

1.2 1.0

86

123

7.0

8.4

9.8

6.6 4.7

759

193

i

+

+

f

0.5 0.4

46

16

4.8 5.6

5.4

8.3

7.3

9.2

8.9 6.6

1169

285

f

f

0.3

0.2

0.3

8.1

10.5

+

+

0.6

0.4

0.6

5.8 6.2

4.2

3.5

f

f

0.2 0.2

0.3

0.2

l 4

3;

5.1 6.4

11.6

6.6

8.3

12.3

?

1

+

+

*

*

f

t

i

0.4 0.4

157

68

5.5

3.3

257

218

f

f

+

f

0.8 0.6

+

9.6

3.6

+

f

+

67

19

580

115

+

+

i

0.2 0.5

0.6

0.4

0.3

0.4

0.4 0.8

96

62

6.5 6.5

2.5

2.4

9.5

11.6

4.2 3.6

399

384

f

f

i

f

f

i

0.2 0.3

0.3

0.4

0.8

0.3

0.2 0.3

112

64

6.4 6.8

2.7

2.3

9.9

10.3

4.0 3.9

252

384

f

f

+

f

f

f

+

f

0.2 0.2

0.6

0.4

0.6

0.3

6.1 7.1

8.7

9.3

10.4

10.6

f

*

f

f

0.5 0.5

0.6

0.2

0.6

0.5

7.1 6.6

8.2

f

+

f

+

0.6

i

*

0.2

36

112

6.5 6.2

157

200

f

*

1.2 0.8

92

26

6.2 4.1

218

55

f

i

t

f

10.6

8.2

11.3

f

f

f

f

0.2 0.3

0.3

0.2

0.8

0.3

0.6 0 6

26

14

6.0 6.5

8.5

8.2

8.4

10.6

7.4 6.2

65

85

+

f

f

f

+

t

0.3

0.2

0.3

0.5

8.3

10.1

5

f

t

f

6.4 6.2

+

t

+

f

0.6 0.4

3

12

8.0 4.7

169

381

f

f

7.9

7.6

f

f

0.2

0.8

06.

6.0

0.2

0.6 0.3

26

36

5.2 6.0

11.1

8.6

8.0

9.6

5.0 3.7

220

135

f

f

16

12

+ f

*

*

0.2 0.2

*

0.6

+

0.2

t

0.3

i

0.2

.f

f

5

f

0.8 0.2

n-PTH (ndml) A B 3.8 1.0

4.8 1.0

9.6 5.0

2.0 0.4

f

t

0.2 12

f

0.4

+

0.2 0.3

M

*

0.2

f

11

8.3 7.2

f

0.6

f

10

10.6

*

1.2

f

9

9.5

ALP (IU/L) A B

0.3 0.4

f

8

*

(mg/dl) A B

f

f

7

15.3

P

T. Ca. (mddl) A B

f

f

6

*

0.2

+

5

15.3

0.3 0.5 f

3

Cr (mddl) A B

1.7 0.5

4.6

2.3

2.0 0.9

2.4 0.3

2.0 1.5

1.9 0.7

2.0 0.6

1.4 0.4

~

(mean t SD) Abbreviations; T.Pr.; total protein, Cr: creatinine, T.Ca.:total calcium, P; inorganic phosphate, ALP: alkaline phosphatase, n-PTH; n terminal fragment parathyroid hormone, A: outset of the study, B; end of the study

crease down to 11 mg/dl of the serum Ca. The serum inorganic P decreased in all patients. In evaluating the age and the sex dependence in the serum ALP value [8], five patients (patients l - 3 and 5 - 6) had high values of ALP at the outset of this study. Only three patients (patients 6 - 7, and 11) had high values of ALP

at the end of this study, and the ALP value became normal in the remaining nine patients by the end of this study. The high value of n-PTH was evident in all patients at the outset, and the value of n-PTH improved in all patients throughout this study. However, the value of n-PTH remained high

Acta Paediatr Jpn

Renal osteodystrophy on CAPD 47 in six patients (patients 1 - 3, 6 - 7, and 9) at the end of this study.

There was no significant difference in the total mean value of serum ALP between the outset and the end of this study.

~ e ~ t i o n s hbetween ip serum total calcium value or alkaline phosphatase value and n-PTH value The relationship between the serum total Ca value or the serum ALP value and the serum n-PTH value are shown in Figs. 1 and 2. There was a significant negative correlation between the serum total Ca and n-PTH value (r = -0.52, p < 0.01) and there was a significant positive correlation between the serum ALP value and n-PTH value (r = 0.79, p < 0.01).

Comparison of radiological bone findings and height standard deviation score between the outset and the end of the study Table 3 shows the radiological bone findings and the height SDS at the outset and the end of this study. Patient 3 had the radiological bone findings of both ROD and rickets throughout this study. Patient 6 had also the radiological bone findings of both ROD and rickets at the outset, but these bone findings were completely healed during this study. The bone age was low in four patients (patients 3 - 4 and 6 - 7) throughout this study. The height SDS > -2 was evident in four patients (patients l - 2 and 9 - 10) at the outset, and this SDS > -2 in 7 patients (patients 1 - 4 and 8 - 10) at the end of this study. The height SDS improved or remained stable in 10 patients (patients 1, 3 - 4, and 6 - 12) throughout this

Comparison of the total mean value of biochemistries between the outset and the end of the study The data in Table 2 show the total mean value of biochemistries between the outset and the end of this study. A significant difference was observed in the total mean values of serum total protein, total Ca, inorganic P, and n-PTH between the outset and the end of this study.

10.

0 9-

2

\

z E:: 8

v

a,

v1

8-

Y = -0.85~

7-

+ 10.35

r = -0.52 6-

p

5-

4’

< 0.01

0

0

0

\

0

8

9

%rum

10

11

12

total calcium (mg/dl)

Fig. 1 : Relationship between serum total calcium and n-PTH values.

Vol. 32 No. I February 1990

48 Hisano et al.

’”t

0

9

8

I Y = 0.007X + 0.11 r = 0.79 p

2’

0 0

O

f

< 0.01

0

l

0 L

0

1

2

3

4

5

6

7

8

9

1

0

1

1

2 (Y100)

1

Serum alkaline phosphatase (IU/L) Fig. 2: Relationship between serum alkaline phosphatase and n-PTH values. Table 2. Comparison of the total mean value of biochemistries between the outset and the end of the study Biochemistries value

A

P

3

5.9 ? 0.1 8.1 * 3.9 8.1 ?: 0.9 6.7 5 1.8

Total protein Creatinine Total calcium Inorganic phosphate

(g/dl) (mg/dl) (mg/dl) (mg/dl)

Alkaline phosphatase

(IU/L)

402

t

319

226

f

117

n-PTH

(ng/ml)

3.3

&

2.4

1.3

t

1.4

6.3 f 0.5 7.5 3.6 10.5 ? 0.9 4.8 t 1.4

< <

Renal osteodystrophy in patients on continuous ambulatory peritoneal dialysis.

Twelve patients on continuous ambulatory peritoneal dialysis (CAPD) were studied in order to evaluate the progression of renal osteodystrophy (ROD). A...
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