Attainment of the Japanese Society for Dialysis Therapy Guidelines for the Management of Secondary Hyperparathyroidism in Chronic Hemodialysis Patients in Our Clinic

Attainment of the Japanese Society for Dialysis TherapyGuidelines for the Management of Secondary

Hyperparathyroidism in Chronic Hemodialysis Patientsin Our Clinic

Yuzuru Sato, Rieko Eriguchi, Junko Umakoshi, and Masakazu Kato

Sato Junkankika Naika, Matsuyama, Ehime, Japan

Abstract: The treatment according to the Japanese Societyfor Dialysis Therapy guidelines was performed in 189patients on maintenance dialysis in our clinic.The mean ageof the patients was 64.9 years and the mean dialysis periodwas 6.3 years. The underlying disease was diabetic nephr-opathy in 40.7% of the patients, chronic glomerulonephritisin 30.2%, and nephrosclerosis in 13.8%. In May 2006before the use of JSDT guidelines, patients with phospho-rus and calcium concentrations in the control goal rangewere most frequently observed (69.8%), followed inorder by those with a high concentration of phosphorusalone (13.8%), those with a low concentration of phospho-rus alone (2.6%), those with a high concentration ofcalcium alone (10.1%), those with high concentration ofboth phosphorus and calcium (3.7%). Treatment accordingto JSDT guidelines was performed for 6 months in thesepatients. In January 2007, the group with both phosphorusand calcium concentrations in the goal range accounted for

82.2%, showing improvement. The intact PTH concentra-tion in patients with normal phosphorus and calcium con-centration was in the reference range (60–180 pg/ml) inabout 50% of the patients, high (>180 pg/ml) in 35%, low(<60 pg/ml) in 10% during the study periods. The intactPTH concentration was often about 40 pg/ml in patientswith a concentration <60 pg/ml, 120 pg/ml in those with aconcentration of 60–180 pg/ml, and 200–250 pg/ml in thosewith a concentration >180 pg/ml.The concentration of NTxwas significantly higher in the patients with an intact PTHconcentration >180 pg/ml than in those with a concetrationof <60 pg/ml or those with a concentration of 60–180 pg/mland significantly increased with time. Key Words: Bonealkaline phosphatase (BAP), Chronic kidney disease–mineral and bone disorder, Japanese Society for DialysisTherapy guidelines, N-telopeptides of type I collagen(NTx), Secondary hyperparathyroidism.

Concerning the present status of chronic dialysis inJapan according to the types of institutions providingdialysis therapy, 45% of the institutions are privateclinics, and 47.6% (about 120 000) of 250 000 dialysispatients are also treated in private clinics such as ours(Table 1). The Guidelines for the Management of Sec-ondary Hyperparathyroidism in Chronic DialysisPatients (JSDT guidelines) recently proposed by theJapanese Society for Dialysis Therapy (JSDT) statethat they “accurately interpret the results of routineexamination” at the beginning of its policy. Thisshows the importance of the basis that clinical physi-

cians who examine the highest number of patientsshould accurately evaluate the results of routineexamination. In this study, we report the applicationof the JSDT guidelines in our clinic (Table 2).

PATIENTS AND METHODS

Since small-scale private clinics are rooted in thelocal community, various geographic biases areconsidered. Our clinic is located in Matsuyama City,Ehime Prefecture. Matsuyama City has a populationof 510 000 and its special products include tangerines,Citrus iyo, and kiwi fruit, which are foods with a highpotassium content. A national nutritional survey offood intakes according to prefectures shows thatMatsuyama is ranked 7th for fish and shellfish,

Address correspondence and reprint requests to Dr YuzuruSato, Sato Junkankika Naika, 4-10-25 Asoda-cho, Matsuyama,Ehime 790-09522, Japan. Email: [email protected]

Therapeutic Apheresis and Dialysis 11(Supplement 1):S48–S53doi: 10.1111/j.1744-9987.2007.00521.x© 2007 The AuthorsJournal compilation © 2007 International Society for Apheresis

S48

mailto:[email protected]

indicating a high intake, 22nd for meat, indicating amiddle rank, and 36th for milk and dairy products,indicating a low intake. People in this prefecture areconsidered to be conservative, traditional, and lackforethought.

Our clinic was established in 1991. At present,there are five physicians, consisting of four internalmedicine physicians and a urologist. The number ofpatients as of 2006 is about 260.

The JSDT guidelines were proposed in 2006. In ourinstitution, treatment according to these guidelineswas performed in 189 patients on maintenance dialy-sis in May 2006. Their mean age was 64.9 years, andthe dialysis period was 1–5 years in 50%, 5–10 yearsin 30%, and 10 years or more in 20% of the patients(mean dialysis period, 6.3 years). The underlyingdisease was diabetic nephropathy in 40.7% of the

patients, chronic glomerulonephritis in 30.2%, andnephrosclerosis in 13.8% (Table 3).

The dialysis time was most frequently 4 h, whichwas observed in 78.8% of the patients. Most patientsunderwent dialysis 3 times/week.The dialysis methodwas hemodialysis (HD) in 61.4% of the patientsand online hemodiafiltration (HDF) in 38.4%,38.6%. The replacement volume was 36–60 L, andthe calcium concentration in the dialysate was2.5 mEq/L, which was adopted after the proposal ofthe Kidney Disease Outcomes Quality Initiative(K/DOQI) guidelines. Most patients were trans-ferred to our institution after the introduction ofdialysis in the central community hospital. The inter-val between introduction and transfer was 3 monthsor less in 86.2%, and 6 months or less in 96.3%(Table 4).

TABLE 1. Patients with chronic dialysis according to medical institutions

Number of institutions Number of patients (%)

National/public universities 52 790 0.3Private universities 60 3 051 1.2National 39 681 0.3Prefectural/municipal 444 20 410 7.9Social insurance 65 4 188 1.6Koseiren (Prefectural Welfare Federation of Agricultural cooperatives) 119 8 954 3.5Other public 184 11 555 4.5Private general 110 7 615 3.0Private 1079 77 767 30.2Private clinic 1788 (45.4%) 122 754 47.6

Total 3940 257 765

Present status of chronic maintenance dialysis in Japan, 2005 (from reference 1).

TABLE 2. Policy of the Japanese Society for Dialysis Therapy guidelines

1. The results of routine examination are accurately interpreted.2. Control of the serum P and Ca concentrations is given priority.Serum P: 3.5–6.0 mg/dL Corrected serum Ca: 8.4–10.0 mg/dL3. Only when these concentrations are attained, the parathyroid hormone (PTH) concentration is appropriately adjusted. Intact PTH:

60–180 pg/mL4. However, in cases of severe hyperparathyroidism not responding to medical treatment, intervention is adopted without further

medical treatment.

TABLE 3. Background of patients (I)

Subjects: 189 patients (111 males and 78 females) on maintenance dialysis in our hospital in May 2006

Age: 64.9 � 11.7 years (24–90 years)

Dialysis period: 6.3 � 5.1 years1–5 year 50.3%5–10 year 29.1%�10 year 20.6%

Underlying disease: Diabetic nephropathy 40.7%Chronic glomerulonephritis 30.2%Nephrosclerosis 13.8%Polycystic kidney 5.8%Others 9.5%

Mineral Control on Hemodialysis Patients S49

© 2007 The AuthorsJournal compilation © 2007 International Society for Apheresis Ther Apher Dial, Vol. 11, Supplement 1, 2007

A blood examination was performed every twoweeks, and intact PTH (iPTH) was measured 4 times/year in February, May, August, and November. Injec-tions were changed every two weeks, based on theresults of blood examination. Concerning changes ininjections, the doses of calcium carbonate, sevelamerhydrochloride, and vitamin D were changed, andother agents such as aluminum hydroxide were notused. Due to outside prescriptions, pharmaceuticalcounseling was not performed, but importance wasgiven to nutritional guidance by nutritionists.

The contents of nutritional guidance were asfollows: salt, �7 g/day; water, urine volume +300 mL;weight gain, 2% of dry weight every other day and3% of dry weight every three days; potassium,approximately 2000 mg before cooking; phosphorusintake, 900 mg/day; and goal serum phosphorus level,�5 mg/dL. Nutritional guidance was performed byfive full-time nutritionists after the results of eachblood examination were obtained (Table 5). As aresult, weight gain was stable (2–3% every other day,3–4% every three days).

RESULTS

The results of examination in May 2006 before theuse of JSDT guidelines were applied to the matrix of

the therapeutic control of serum phosphorus/calciumconcentrations shown by the guidelines. Patients withphosphorus and calcium concentrations in the controlgoal range were most frequently observed (69.8%),followed in order by those with a high concentrationof phosphorus alone, those with a low concentrationof phosphorus alone, those with a high concentra-tion of calcium alone, and those with high concentra-tions of both calcium and phosphorus (Fig. 1).

As shown in Table 6, in patients with both calciumand phosphorus concentrations in the goal range, thecorrected calcium concentration was 9.3 mg/dL,and the phosphorus concentration was 4.9 mg/dL. Inpatients with a high concentration of phosphorusalone, the phosphorus concentration was 6.7 mg/dL.In the patients with a high concentration of calciumalone, the calcium concentration was 10.5 mg/dL. Inthe patients with high concentrations of both calciumand phosphorus, the calcium concentration was

TABLE 4. Background of patients (II)

Dialysis time: 3 h 12 patients (6.3%)3.5 h 13 patients (6.9%)4 h 149 patients (78.8%)4.5 h 14 patients (7.4%)5 h 1 patient (0.5%)

Frequency of dialysis: 3 times/week 186 patients2 times/week 3 patients

Dialysis method: HD 116 patients (61.4%)On-line HDF 73 patients (38.6%)(Replacement volume: 36–60 L)

Ca concentration in dialysate: 2.5 mEq/L (from February 2004)Introduction institution: Matuyama Red Cross Hospital 130 patients (68.8%)

Ehime Prefectural Central Hospital 37 patients (19.6%)Interval between introduction and transfer to our hospital: <3 months

3–6 months129 patients (86.2%)19 patients (10.1%)

6–12 months 6 patients (3.2%)

HD, hemodialysis; HDF, hemodiafiltration.

TABLE 5. Contents of nutritional guidance

1. Salt restriction �7 g/day2. Water restriction Urine volume + 300 mLWeight gain 2–3% every other day, 3–4% every

three days3. Potassium restriction 2000–2200 mg/day (before cooking)4. Phosphorus restriction 900 mg/dayGoal serum P level �5.0 mg/dL

(Full-time nutritionists, 5)

0 0

132(69.8%)

0

26(13.8%)

19(10.1%)

7(2.6%)

5(2.6%)

Ca

P

Low

Low

High

High3.5 6.0

10.0

8.40mg/dL

mg/dL mg/dL

mg/dL

Examination results in May 2006

FIG. 1. Classification according to examination results in May2006.

Y Sato et al.S50

© 2007 The AuthorsJournal compilation © 2007 International Society for ApheresisTher Apher Dial, Vol. 11, Supplement 1, 2007

10.4 mg/dL, and the phosphorus concentration was6.8 mg/dL. In the patients with a low concentration ofphosphorus alone, the phosphorus concentration was3.3 mg/dL.

Treatment according to JSDT guidelines wasperformed for 6 months in these patients. Changesin examination values during this treatment periodwere as follows.

In the group with calcium and phosphorus concen-trations both in the control goal range, their concen-trations were almost stable despite slight monthlychanges such as an increase in phosphorus or calcium(Fig. 2).

In the group with a high concentration of phospho-rus alone, subsequent treatment reduced both serumphosphorus and calcium concentrations to the goalrange in about 50%-80% of the patients each month(Fig. 3).

In the group with a low concentration of phospho-rus alone, both the calcium and phosphorus concen-trations decreased to the goal range after about6 months in 70%-80% (Fig. 4).

These results show that both calcium and phospho-rus levels can be controlled by changing meals andmedication in all patients with a higher or lower con-centration of phosphorus alone.

On the other hand, in the group with a high con-centration of calcium alone, the control of bothcalcium and phosphorus concentrations in the goalrange was difficult. During the course, as interventiontherapy, parathyroidectomy (PTx) was performed in3 patients and percutaneous ethanol injectiontherapy (PEIT) in 1 patient. Even after 6 months,both the calcium and phosphorus concentrations

TABLE 6. Examination results in May 2006 (N = 189)

N Corrected CA P

Normal Ca/P 132 (69.8%) 9.3 � 0.4 4.9 � 0.6High P/normal Ca 26 (13.8%) 8.8 � 0.4 6.7 � 0.7High Ca/normal P 19 (10.1%) 10.5 � 0.4 5.4 � 0.4High Ca/P 7 (3.7%) 10.4 � 0.3 6.8 � 0.9Low P/normal Ca 5 (2.6%) 9.3 � 0.2 3.3 � 0.1

0%

20%

40%

60%

80%

100%

May 2006 Jun Jul

Normal Ca/P High P/normal Ca High Ca/normal P High Ca/PLow P/normal Ca Low Ca/normal P High Ca/low P Low Ca/P

Group with normal Ca and P (N = 132)

Jan 2007DecNovOctSepAug

FIG. 2. Group with normal Ca and P (N = 132).

0%

20%

40%

60%

80%

100%

May 2006 Jun Jul Aug


Group with high P and normal Ca (N= 26)

Jan 2007DecNovOctSep

FIG. 3. Group with normal Ca and high P (N = 26).

0%

20%

40%

60%

80%

100%

May 2006 Jun Jul Aug Sep Oct


Group with low P and normal Ca (N = 5)

Jan 2007DecNov

FIG. 4. Group with normal Ca and low P (N = 5).



were in the goal range in only about 50% of thepatients, and the calcium concentration remainedhigh (Fig. 5).

In the group with high concentrations of bothcalcium and phosphorus, their concentrationsentered the goal range in only 20–30% of the patients(Fig. 6). Therefore, the control of both the calcium

and phosphorus concentrations is difficult in patientswith a high calcium concentration.

The number of swollen glands was observed byparathyroid ultrasonography. Swollen glands wererarely detected in patients with normal concentra-tions of both calcium and phosphorus. In the groupwith a high concentration of calcium alone, 1 glandwas swollen in 4 of 19 patients, 2 glands in 2, and 3glands in 1. In the group with high concentrations ofboth calcium and phosphorus, 2 swollen glands wereobserved in 4 of 7 patients. The number of swollenglands was very high in patients with a high calciumconcentration (Table 7). However, the volume of thelargest gland was more than 500 mm3 in only 2patients.

The status in January 2007 was compared with thatin May 2006 at the initiation of the application ofJSDT guidelines using the matrix for therapeuticcontrol.The group with both calcium and phosphorusconcentrations in the goal range accounted for 69.8%at the initiation, but accounted for 82.2% in January2007, showing improvement (Fig. 7).

The JSDT guidelines give priority to the control ofcalcium and phosphorus concentrations in the goalrange over that of PTH, stating that PTH should becontrolled in the reference range after the control ofcalcium and phosphorus. Therefore, the distributionof intact PTH concentrations was evaluated in

0%

20%

40%

60%

80%

100%

May 2006 Jun Jul Aug Sep Oct Nov Dec Jan 2007


Group with high Ca and normal P (N = 19)(PTx, 3 patients; PEIT, 1)

FIG. 5. Group with high Ca and normal P (N = 19). PEIT, percu-taneous ethanol injection therapy; PTx, parathyroidectomy.

0%

20%

40%

60%

80%

100%


Group with high Ca and P (N = 7)

(Waiting for PTx, 1)

May 2006 Jun Jul Aug Sep Oct Nov Dec Jan 2007

FIG. 6. Group with high Ca and P (N = 7). PTx,parathyroidectomy.

TABLE 7. Number of swollen glands by parathyroid gland ultrasonography

None 1 gland 2 glands 3 glands 4 glands Others

Normal Ca/P 122 6 4 0 0High P/normal Ca 23 3 0 0 0High Ca/normal P 11 4 2 1 0 1†

High Ca/P 1 0 4 1 0 1‡

Low P/normal Ca 5 0 0 0 0

†Hyperparathyroidism of transplanted accessory thyroid. ‡Parathyromatosis.

May 2006 January 2007(N=175)(N=189)

Low

LowHigh

High

High

High

Low

Low 3.5 3.56.0 6.0

8.4 8.4

10.010.0

Results of treatment according to the JSDT guidelines

P P

CaCa

1.1% 4.0%

0 0 0 0 0 0

00

2.6%

2.6%10.1%

13.8%69.8% 1.1% 82.2% 10.9%

FIG. 7. Results of treatment according to the Japanese Society forDialysis Therapy (JSDT) guidelines. (Units are in mg/dL.)

Y Sato et al.S52

© 2007 The AuthorsJournal compilation © 2007 International Society for ApheresisTher Apher Dial, Vol. 11, Supplement 1, 2007

patients with normal calcium and phosphorus con-centrations at the initiation of guideline applicationand after 3 and 6 months. At each time point, theiPTH concentration was in the reference range (60–180 pg/mL) in about 50% of the patients, high(�181 pg/mL) in 35%, and low in 10%.

The intact PTH concentration was often about40 pg/mL in patients with a concentration <60 pg/mL,120 pg/mL in those with a concentration of60–180 pg/mL, and 200–250 pg/mL in those with aconcentration �181 pg/mL. Though no significantdifference was observed, the iPTH concentrationin the patients with a concentration �181 pg/mLincreased with time. The patients in this group with ahigh iPTH concentration were classified into thosewith a concentration of 180–300 pg/mL and thosewith a concentration �300 pg/mL. The percentage ofpatients with an iPTH concentration �300 pg/mL,despite calcium and phosphorus concentrations inthe goal range, increased with time (Fig. 8).

As a bone metabolism marker in patients with aniPTH concentration �181 pg/dL, BAP was evalu-ated.The BAP concentration in these patients gradu-ally increased, being higher than that in the other twogroups. The concentration of NTx serum as a boneresorption marker was also significantly higher inthe patients with an intact PTH concentration

�181 pg/mL than in those with a concentration of<60 pg/mL or those with a concentration of60–180 pg/mL (Fig. 9).

CONCLUSIONS

Treatment according to JSDT guidelines increasedthe percentage of patients in whom both calcium andphosphorus concentrations could be controlled from69.8% at the initiation of their application to 82.2%.However, some of the patients with a high bone turn-over despite normal calcium and phosphorus con-centrations showed a further increase in turnover.Treatment strategies for such cases should be evalu-ated in the future.

CONFLICT OF INTEREST

No conflict of interest has been declared by Y Sato,R Eriguchi, J Umakoshi or M Kato.

REFERENCE

1. Japanese Society for Dialysis Therapy Patient RegistrationCommittee.An Overview of Regular Dialysis Treatment in Japanas of December 31, 2005. CDROM: Japanese Society for Dialy-sis Therapy, Patient Registration Committee, 2005.

0

20

40

60

< 60 60 180 181 300 >301

Distribution of i-PHT concentrations in the group

with normal Ca and P

May

August

November

– –

(%)

FIG. 8. Distribution of intact parathyroid hormone (i-PTH)concentrations in the group with normal Ca and P.

i-PTH and NTx in the group with

normal Ca and P

i-PTH (pg/mL)

May

August

November

0

50

100

150

200

250

< 60 60–180 >181

P<0.01

**

*

(NMBCE/L)

FIG. 9. Intact parathyroid hormone (i-PTH) and NTx in thegroup with normal Ca and P.



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Attainment of the Japanese Society for Dialysis Therapy Guidelines for the Management of Secondary Hyperparathyroidism in Chronic Hemodialysis Patients in Our Clinic