Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome.

BACKGROUND: We designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS). METHODS: Patients with IMN were divided into 2 groups, and MZR combined with PSL was administered for 2 years. PSL was initially prescribed at 40 mg/day and tapered. MZR was given once-a-day at 150 mg and 3-times-a-day at 50 mg each to groups 1 and 2. Serum MZR concentrations from 0 to 4 h after administration were examined within one month of treatment. The concentration curve and peak serum level (C max) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR. RESULTS: At 2 years, 10 of 19 patients (52.6 %) in group 1 and 7 of 18 patients (38.9 %) in group 2 achieved complete remission (CR). The time-to-remission curve using the Kaplan-Meier technique revealed an increase in the cumulative CR rate in group 1, but no significant difference between the groups. Meanwhile, there was a significant difference in C max between groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 µg/mL, p = 0.04), and C max levels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that C max more than 1.1 µg/mL was necessary for CR in once-a-day administration. CONCLUSION: Administration of MZR once a day is useful when combined with PSL for treatment of IMN with SRNS. In addition, it is important to assay the serum concentration of MZR and to determine C max, and more than 1.1 µg/mL of C max is necessary for CR.

A Prospective Observational Survey on the Long-Term Effect of LDL Apheresis on Drug-Resistant Nephrotic Syndrome.

BACKGROUND/AIMS: LDL apheresis (LDL-A) is used for drug-resistant nephrotic syndrome (NS) as an alternative therapy to induce remission by improvement of hyperlipidemia. Several clinical studies have suggested the efficacy of LDL-A for refractory NS, but the level of evidence remains insufficient. A multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was conducted to evaluate its clinical efficacy with high-level evidence. METHODS: Patients with NS who showed resistance to primary medication for at least 4 weeks were prospectively recruited to the study and treated with LDL-A. The long-term outcome was evaluated based on the rate of remission of NS 2 years after treatment. Factors affecting the outcome were also examined. RESULTS: A total of 58 refractory NS patients from 40 facilities were recruited and enrolled as subjects of the POLARIS study. Of the 44 subjects followed for 2 years, 21 (47.7%) showed remission of NS based on a urinary protein (UP) level <1.0 g/day. The UP level immediately after LDL-A and the rates of improvement of UP, serum albumin, serum creatinine, eGFR, and total and LDL cholesterol after the treatment session significantly affected the outcome. CONCLUSIONS: Almost half of the cases of drug-resistant NS showed remission 2 years after LDL-A. Improvement of nephrotic parameters at termination of the LDL-A treatment was a predictor of a favorable outcome.

Immediate therapeutic efficacy of low-density lipoprotein apheresis for drug-resistant nephrotic syndrome: evidence from the short-term results from the POLARIS Study.

BACKGROUND: Hyperlipidemia is not merely a complication but a major exacerbating factor in longstanding nephrotic syndrome (NS). Low-density lipoprotein apheresis (LDL-A) has been reported to ameliorate dyslipidemia and induce rapid remission of NS. Several clinical studies have suggested the therapeutic efficacy of LDL-A, but the level of clinical evidence is insufficient. Therefore, a multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was initiated in Japan. METHOD: Patients with drug-resistant NS were prospectively recruited into the study and treated with LDL-A in facilities that were registered in advance. In the POLARIS study design, the clinical data are to be followed up for 2 years. In the current study, we aimed at evaluating the short-term efficacy based on the treatment outcome of LDL-A immediately after completion of treatment. RESULTS: Along with rapid improvement of hyperlipidemia, LDL-A significantly improved proteinuria and hypoproteinemia after treatment. More than half of the patients showed remission of NS based on the urinary protein level at the completion of LDL-A. The duration of NS before the start of treatment was significantly shorter in patients who responded to LDL-A. CONCLUSIONS: An analysis of patients registered in the POLARIS study indicated that LDL-A has short-term efficacy for drug-resistant NS. Rapid relief of dyslipidemia by LDL-A may provide early remission in about half of the NS patients who are resistant to conventional medication. Completion of the POLARIS study may reveal additional long-term effects of LDL-A in these patients.

Parasites alter the pathological phenotype of lupus nephritis.

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus and manifests with considerable phenotypic and histological heterogeneity. In particular, diffuse proliferative lupus nephritis (DPLN) and membranous lupus nephritis (MLN) represent morphologic forms that are polar opposites. DPLN is associated with autoimmune responses dominated by Th1 immune response associated with high levels of interferon (IFN)-γ. In contrast, a Th2 cytokine response is associated with the pathogenesis of MLN. MRL/lpr mice develop human LN-like immune complex-associated nephritis and provide a suitable histological model for human DPLN. Infection with Schistosoma mansoni skewed a Th2-type immune response induction and IL-10 in MRL/lpr mice, drastically changing the pathophysiology of glomerulonephritis from DPLN to MLN accompanied by increased IgG1 and IgE in the sera. T cells in 32-week-old MRL/lpr mice infected with S. mansoni expressed significantly more IL-4 and IL-10 than T cells of uninfected mice; T cells with IFN-γ were comparable between infected and uninfected MR/lpr mice. Thus, the helminthic infection modified the cytokine microenvironment and altered the pathological phenotype of autoimmune nephritis.

Significance of combined cyclosporine-prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial.

BACKGROUND: Combined treatment with cyclosporine microemulsion preconcentrate (CyA MEPC) and steroids has been widely used for idiopathic membranous nephropathy (IMN) associated with steroid-resistant nephrotic syndrome (SRNS). Recent studies have shown that once-a-day and preprandial administration of CyA MEPC is more advantageous than the conventional twice-a-day administration in achieving the target blood CyA concentration at 2 h post dose (C2). We designed a randomized trial to compare these administrations. METHODS: IMN patients with SRNS (age 16-75 years) were divided prospectively and randomly into 2 groups. In group 1 (n = 23), 2-3 mg/kg body weight (BW) CyA MEPC was given orally once a day before breakfast. In group 2 (n = 25), 1.5 mg/kg BW CyA MEPC was given twice a day before meals. CyA + prednisolone was continued for 48 weeks. RESULTS: Group 1 showed a significantly higher cumulative complete remission (CR) rate (p = 0.0282), but not when incomplete remission 1 (ICR1; urine protein 0.3-1.0 g/day) was added (p = 0.314). Because a C2 of 600 ng/mL was determined as the best cut-off point, groups 1 and 2 were further divided into subgroups A (C2 ≥600 ng/mL) and B (C2 <600 ng/mL). Groups 1A and 2A revealed significantly higher cumulative remission (CR + ICR1) (p = 0.0069) and CR-alone (p = 0.0028) rates. On the other hand, 3 patients with high CyA levels (C2 >900 ng/mL) in Group 1A were withdrawn from the study because of complications. CONCLUSION: CyA + prednisolone treatment is effective for IMN with associated SRNS at a C2 of ≥600 ng/mL. To achieve remission, preprandial once-a-day administration of CyA at 2-3 mg/kg BW may be the most appropriate option. However, we should adjust the dosage of CyA by therapeutic drug monitoring to avoid complications.

Wernicke's encephalopathy that developed during the introduction period of peritoneal dialysis.

A 43-year-old man was admitted with end-stage renal disease caused by IgA nephropathy, and was treated with maintenance peritoneal dialysis. The patient developed general fatigue and appetite loss, and his symptoms were gradually aggravated by depression. After approximately 2 months on dialysis, the patient presented with altered consciousness and ophthalmoplegia. Wernicke's encephalopathy was diagnosed based on the presence of classic symptoms and the findings on magnetic resonance imaging. Thiamine replacement therapy was immediately initiated. The patient recovered from most of his neurological symptoms; however, the sequela of Korsakoff syndrome remained. A marginal thiamine deficiency in combination with predisposing factors must be considered when treating dialysis patients.

Various roles of Th cytokine mRNA expression in different forms of glomerulonephritis.

BACKGROUND: Kidney disease is characterized by injurious immune responses to self or foreign antigens. The development and maintenance of immune responses generally involves activation of T lymphocytes. We evaluated mRNA expression patterns of T-cell cytokines to identify the principal Th-cell subset involved in the development of antineutrophil cytoplasmic antigen-associated pauci-immune crescentic glomerulonephritis (ANCAGN), membranoproliferative glomerulonephritis (MPGN), and membranous nephropathy (MN). METHODS: Kidney biopsy specimens from ANCAGN (17), MPGN (11), and MN (14) patients were evaluated for mRNA expression of various T-cell cytokines. RESULTS: Interferon-γ mRNA expression was detected in both ANCAGN and MPGN, but not in MN patients. Furthermore, mRNA expression of interleukin (IL)-12, a Th1-associated cytokine, was lower in MN patients than in ANCAGN and MPGN patients. In contrast, a significantly higher expression of IL-4 and IL-5 was observed in MN than in ANCAGN and MPGN patients. In the analyses of Th17-associated cytokine expression, a significantly higher expression of IL-6 and IL-17 was observed in ANCAGN than in MPGN and MN patients. No significant differences were observed in the expression of these cytokines between MPGN and MN patients. With regard to Treg-associated cytokines, a significantly higher IL-10 expression was observed in MN than in ANCAGN patients, and a significantly higher transforming growth factor-ß expression was observed in MN than in ANCAGN and MPGN patients. Similarly, Foxp3 expression was significantly higher in MN. CONCLUSION: Th1 and Th17 immune responses in ANCAGN, the Th1 response in MPGN, and Th2 and Treg responses in MN patients may be integral for the distinct histological features of these diseases.

The efficacy of incretin therapy in patients with type 2 diabetes undergoing hemodialysis.

BACKGROUND: Although incretin therapy is clinically available in patients with type 2 diabetes undergoing hemodialysis, no study has yet examined whether incretin therapy is capable of maintaining glycemic control in this group of patients when switched from insulin therapy. In this study, we examined the efficacy of incretin therapy in patients with insulin-treated type 2 diabetes undergoing hemodialysis. METHODS: Ten type 2 diabetic patients undergoing hemodialysis received daily 0.3 mg liraglutide, 50 mg vildagliptin, and 6.25 mg alogliptin switched from insulin therapy on both the day of hemodialysis and the non-hemodialysis day. Blood glucose level was monitored by continuous glucose monitoring. After blood glucose control by insulin, patients were treated with three types of incretin therapy in a randomized crossover manner, with continuous glucose monitoring performed for each treatment. RESULTS: During treatment with incretin therapies, severe hyperglycemia and ketosis were not observed in any patients. Maximum blood glucose and mean blood glucose on the day of hemodialysis were significantly lower after treatment with liraglutide compared with treatment with alogliptin (p < 0.05), but not with vildagliptin. The standard deviation value, a marker of glucose fluctuation, on the non-hemodialysis day was significantly lower after treatment with liraglutide compared with treatment with insulin and alogliptin (p < 0.05), but not with vildagliptin. Furthermore, the duration of hyperglycemia was significantly shorter after treatment with liraglutide on both the hemodialysis and non-hemodialysis days compared with treatment with alogliptin (p < 0.05), but not with vildagliptin. CONCLUSIONS: The data presented here suggest that patients with type 2 diabetes undergoing hemodialysis and insulin therapy could be treated with incretin therapy in some cases.

Total and HMW adiponectin is independently associated with B-type natriuretic peptide and anemia in chronic hemodialysis patients.

OBJECTIVE: A number of vasculo-protective roles have been reported for adiponectin. In contrast, higher, rather than lower, plasma adiponectin levels are associated with an increased risk of cardiovascular disease and mortality in patients undergoing hemodialysis (HD). The mechanisms by which high adiponectin levels are associated with adverse outcome are unclear. METHODS: This study measured the level of total and high molecular weight (HMW) adiponectins in 70 patients with HD patients (age: 65.2±8.6 years, man/woman: 30/40), and examined the association between adiponectins, metabolic and echocardiographic parameters. RESULTS: Women had a significantly higher total, HMW levels and HMW to total ratio than men. The levels of total and HMW adiponectin were positively correlated with those of HDL-cholesterol and B-type natriuretic peptide (BNP) levels, and negatively associated with body mass index (BMI), triglyceride, high sensitive-C reactive protein (CRP) and hemoglobin levels. A multiple linear regression analysis showed that HMW adiponectin had an independent association with BMI (ß=-0.270, p=0.003), HDL-cholesterol (ß=0.356, p<0.001), hemoglobin (ß=-0.180, p=0.034) and BNP (ß=0.200, p=0.014) as total did adiponectin. CONCLUSION: Anemia and BNP levels had independent influence on the total and HMW adiponectin levels in chronic HD patients.

Association of hypoalbuminemia with severe anemia in patients with diabetic nephrosclerosis.

BACKGROUND: Anemia in patients with early diabetes mellitus nephrosclerosis (DMN) is more severe than in patients with kidney disease of other origins, and the mechanism for this remains unclear. In this study, we carried out a retrospective study in order to identify the factors associated with anemia in patients with DMN. METHODS: To elucidate the factors that influence the severity of anemia in patients with DMN, we carried out a retrospective follow-up study of 124 biopsy-proven DMN cases [mean (SE) age, 55.3 (1.2) years; range, 18-78 years; male/female, 80/44]. First, a cluster analysis was performed using red blood cell counts and hemoglobin (Hb) and hematocrit levels. We then divided the clusters with regard to renal prognosis and survival and carried out simple and multifactorial analysis of clinical data, including the body mass index, age, systolic blood pressure (BP), diastolic BP, duration after the diagnosis of diabetes mellitus, serum albumin levels, blood urea nitrogen (BUN) concentrations, serum creatinine concentrations, the estimated glomerular filtration rate (eGFR) validated in the Japanese population, iron levels, total cholesterol levels, triglyceride levels, fasting blood sugar levels, HbA1c levels, urinary protein secretion, and pathohistological parameters. RESULTS: The factors that were significantly associated with the cluster group that showed severe anemia were sex (p = 0.0162), hypoalbuminemia (p < 0.0001), high BUN concentrations (p = 0.0020), low eGFR (p = 0.0104), and Kimmelstiel-Wilson nodules (p = 0.0022). In addition, hypoalbuminemia (p = 0.0277), high BUN concentrations (p = 0.0338), and a low eGFR (p = 0.0417) were significantly associated with this group in a multifactorial analysis. CONCLUSION: Our data strongly suggest that hypoalbuminemia is associated with severe anemia in DMN patients.

The proportion and metabolic effects of adiponectin multimeric isoforms in patients with chronic kidney disease on maintenance hemodialysis.

Adiponectin circulates at least in three major forms of oligomeric complexes in plasma: a low-molecular-weight (LMW) trimer, a middle-molecular-weight (MMW) hexamer, and high-molecular-weight (HMW) adiponectin. Although it has been reported that adiponectin has the favorable metabolic properties for humans, the roles of these multimers in the patients with the end-stage renal disease (ESRD) were unidentified. We determined the level of total and multimeric adiponectin in 71 patients with nondiabetic ESRD treated with hemodialysis (HD) using a commercially available kit of enzyme-linked immunosorbent assay (ELISA). Correlations between metabolic variables and total and multimeric adiponectin were examined by Spearman's correlations analysis. Forward stepwise multiple linear regression analysis was also performed to determine the factors independently associated with them. Female patients had significantly higher total, HMW, and MMW levels than male patients did. According to homeostasis model of assessment of insulin resistance (HOMA-IR), value was associated not only with HMW but also with MMW and LMW. In multivariate analyses, HMW showed independently and positively associated with high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), and sex as total adiponectin did. Unexpectedly, LMW adiponectin was independently and negatively correlated with TG and high-sensitive C-reactive protein (hs-CRP). Not only HMW adiponectin but also LMW adiponectin track with favorable metabolic effects in the patient with the ESRD.

[Case of suspicious lansoprazole-associated collagenous colitis in ANCA-associated nephritis].

In January 2003, a 70-year-old female consulted a doctor for a fever of unknown origin. She had microscopic hematuria, proteinuria, BUN 41 mg/dL, Cr 2.1 mg/dL and MPO-ANCA 44 U/mL, and was suspected of having ANCA-associated nephritis. A renal biopsy was not conducted because the patient had just one kidney. She was treated with prednisolone (PSL ; 40 mg/day). Subsequently, because of Cr level improvement, the amount of PSL was decreased. In October 2006, the patient again had microscopic hematuria, proteinuria and a slightly elevated Cr level. Lowering of BP and dehydration caused by a common cold were considered to be the cause of her renal dysfunction. She was admitted to Fukuoka University Hospital for 2 weeks, where she received diet therapy and a changed medication schedule in which furosemide was stopped and the dose of enalapril was decreased from 5 mg/day to 2.5 mg/day. Because the MPO-ANCA level was < 10 EU, the amount of PSL was not changed. After 11 months, treatment with lansoprazole at 30 mg/day was started. At the end of the same month, however, she exhibited gait disturbance due to swelling, redness and tenderness in the bilateral pedal joints. After one month of receiving lansoprazole, she experienced a high fever and an elevated Cr level. Accordingly she was again admitted to the hospital, where she was diagnosed with venous thrombosis in the lower limbs, and warfarization was begun. Her condition improved, gradually, and she was discharged from the hospital. After the discharge, she began to exhibit watery diarrhea three to four times per day. Therefore, treatment with warfarin potassium was stopped 50 days after it was begun. In spite of the cessation of warfarization, the diarrhea continued. She underwent bacterial culturing and lower endoscopic examinations (no biopsy was done), which showed erosion of the colon, but the cause of the diarrhea was not found. After 181 days of treatment with lansoprazole, administration of this drug was stopped. The symptoms disappeared within 5 days. There have been few reports of collagenous colitis with chronic diarrhea, but a good prognosis has been described in these cases. Clinicians should consider drug treatment as a possible cause of collagenous colitis in the case of patients with chronic diarrhea of unknown origin during the administration of medication.

Anemia and hypertension are risk factors for both renal prognosis and survival in patients with diabetes mellitus.

BACKGROUND: Diabetic nephrosclerosis is the most common cause of renal failure in the industrialized countries. At the same time, the mortality rate of patients with diabetes mellitus is high. METHODS: To clarify the factors influencing the prognosis and survival of patients with diabetic nephrosclerosis, we carried out a retrospective follow-up study of 166 cases (age, 55.6 +/- 1.0 years; male/female, 110/56) by simple and multifactorial analyses of clinical data recorded at time of renal biopsy, including survival after diagnosis of diabetic mellitus (months), body mass index (BMI) (kg/m(2)) [body weight/(body height)(2)], age (years), mean blood pressure (mBP) (mmHg) [diastolic BP + (systolic BP - diastolic BP)/3], serum levels of albumin (mg/dl), urea nitrogen (BUN) (mg/dl), serum creatinine (s-Cr) (mg/dl), total cholesterol (mg/dl), triglyceride (mg/dl), and fasting blood sugar (FBS) (mg/dl), hematocrit (%), HbA1c (%), urinary protein secretion (g/day), insulin resistance, BP control (good, <140/90 mmHg or poor, > or =140/90 mmHg) after biopsies, and pathomorphological parameters at the biopsy. RESULTS: We found a significant association between renal prognosis and several factors, e.g., hypoalbuminemia, anemia, high levels of BUN and s-Cr, hypercholesteremia, hypertriglyceridemia at biopsy, poor control of BP after biopsies, Kimmelstiel-Wilson nodule, and severe glomerular and tubulointerstitial damages at the biopsy. In addition, associations between survival and factors such as low value of BMI, elderly age at the biopsy, and poor control of BP after biopsies were significant. By multivariate analysis we also found a significant association of renal prognosis with anemia, BUN, severe glomerular damage at the biopsy, and poor control of BP after biopsies. At the same time, poor control of BP after biopsies had a significant association with survival. On Kaplan-Meier analysis, anemia at biopsy and hypertension after biopsies are risk factors for both renal prognosis and survival in diabetes mellitus patients. CONCLUSIONS: Our data strongly suggest that good control of BP after biopsies and anemia at the biopsy play pivotal roles in the prognosis and survival of patients with diabetic glomerulosclerosis.

Amelioration of diabetic nephropathy in OLETF rats by prostaglandin I(2) analog, beraprost sodium.

BACKGROUND: Strict control of blood glucose and blood pressure levels sometimes fails to delay the development of diabetic nephropathy, and an effective therapy is not yet available. The present study aimed to examine whether the prostaglandin I(2) analog beraprost sodium (BPS) ameliorates diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHOD: Fifty-week-old OLETF rats were divided into three groups according to treatment; 400 microg/kg body weight (BW) BPS, 200 microg/kg BW BPS, and 0.9% saline administration. Kidney histology, index of glomerulosclerosis, and glomerular volume were determined, and urine and serum chemistry were assessed. RESULTS: The values for urine protein excretion and serum blood urea nitrogen in BPS-treated rats were significantly lower than those in untreated rats. In rats treated with 400 microg/kg BW BPS, neither sclerotic changes nor inflammatory cell infiltration were observed. Index of glomerulosclerosis and glomerular volume were also significantly reduced compared with untreated rats. Intriguingly, BPS reduced the level of serum triglyceride. In the glomerulus of treated rats, advanced glycation end product formation and macrophage influx were suppressed in a dose-dependent manner. CONCLUSION: These findings indicate that BPS has a therapeutic effect on diabetic nephropathy in the OLETF rat, which suggests a potential application of this drug in the treatment of human diabetic nephropathy.

Prognostic factors for renal amyloidosis: a clinicopathological study using cluster analysis.

OBJECTIVE: There is no standardized therapy for renal amyloidosis, which shows rapid progression and poor prognosis. Here, we used cluster analysis to examine the correlation between amyloid-related renal damage and prognosis, and determined the clinicopathological prognostic factors for renal amyloidosis. METHODS AND PATIENTS: We analyzed 125 patients with renal amyloidosis (men/women: 43/82; mean age at renal biopsy: 58.8+/-11.1 years, +/-SD; range: 21-78 years). Cluster analysis was performed using clinical parameters, renal histological findings, type of renal amyloidosis, and follow-up data. We also analyzed survival data. RESULTS: We divided 125 cases (prognosis was checked in 97 [77.6%] cases) into three groups by cluster analysis. In the cluster groups, accelerated progression correlated with serum creatinine (s-Cr) levels at renal biopsy and histological grade of renal damage by amyloid deposition (p<0.0001). The most important prognostic factors were glomerular, tubulointerstitial, and vascular lesions induced by amyloid deposition at biopsy (p<0.0001). We also found that amyloid-A (AA) type amyloidosis correlated is more significantly with amyloid-mediated vascular (P=0.0010) and tubulointerstitial lesions (p=0.0705) than with amyloid-L (AL) type amyloidosis. Proteinuria and nephrotic syndrome were more severe in AL than AA amyloidosis (p=0.0836). The 10-year individual survival rate was about 20%, and most deaths were due to cardiovascular disease and infection. CONCLUSION: Our results indicate that the quantity of amyloid deposition in the kidney, and the extent of glomerular, tubulointerstitial, and vascular damage are significant renal prognostic factors in amyloidosis.

Relationship of predialytic intact parathyroid hormone on secondary hyperparathyroidism in chronic maintenance haemodialysis patients.

METHODS AND RESULTS: In order to clarify the predialytic factors influencing the onset of secondary hyperparathyroidism (SHPT) in patients on chronic maintenance haemodialysis, the time-course changes of serum levels of intact-PTH (i-PTH) during haemodialysis for 5 years were investigated. The subjects were 69 non-diabetic patients who had a serum aluminium level of less than 1.85 nmol/L at the end of observation. Patients were divided into two groups based on i-PTH levels obtained at the start of dialysis; the high group (H group) consisted of patients whose i-PTH levels were more than 22.00 pmol/L, the low group (L group) had levels less than 22.00 pmol/L. In the H group, i-PTH was 41.46 +/- 2.87 pmol/L at the start of dialysis (vs L group, P < 0.0001) and 15.82 +/- 2.85 pmol/L after haemodialysis initiation. In the L group, i-PTH levels did not significantly change and was 11.69 +/- 2.50 pmol/L 12 months after the start of dialysis (at the 12th month). However, at the 60th month, the i-PTH level was 33.24 +/- 5.30 pmol/L in the H group, and 9.85 +/- 2.13 pmol/L in the L group (P < 0.005). CONCLUSION: It is suggested that control of i-PTH levels in the predialytic period may be important to suppress SHPT throughout haemodialysis.