Influence of renin-angiotensin system on serum parathyroid hormone levels in uremic patients.

INTRODUCTION: The aim of this study was to investigate the factors influencing serum parathyroid (PTH) levels, including medications for treating chronic kidney disease-mineral and bone metabolism disorder (CKD-MBD) in patients with end-stage renal disease. METHODS: We enrolled 1,076 patients in nine Japanese facilities who had begun hemodialysis (HD) due to ESRD. We investigated the relationships between intact PTH (iPTH) levels and clinical parameters and medications just prior to beginning HD. RESULTS: Significant decreases in serum iPTH levels were seen in males, in the presence of diabetes mellitus (DM), and with administration of renin-angiotensin system inhibitors (RASIs). Significant correlations were found between serum calcium and iPTH levels. In the patients administered RASIs, there was a significant decrease in serum iPTH levels with DM, male gender, and administration of active vitamin D sterols (VDs) compared with those not administered RASIs, although serum-corrected calcium levels were not different. Multiple regression analysis found gender, age, presence of DM, and serum calcium and phosphate levels to be significant contributing factors. In addition, administration of angiotensin II receptor blockers (ARBs) may also be a contributing factor to iPTH levels at the beginning HD (p = 0.050). CONCLUSIONS: In this study, serum iPTH levels were related to administration of ARBs besides gender, age, the presence of DM and serum calcium levels. Our study suggests that the RA system involve serum iPTH levels in uremic patients.

[Case of acute kidney injury related to intravenous zoledronic acid in a patient with multiple myeloma].

We report the first case of acute kidney injury related to intravenous zoledronic acid (ZA)in a patient with multiple myeloma in Japan. A 37-year-old male was diagnosed as having multiple myeloma (MM) of the Bence Jones lambda type. He showed a good response to two courses of vincristine, adriamycin and dexamethasone (VAD) therapy, and remarkable reduction was seen in plasma cells in bone marrow from 38.4% to 6.8% and 24-hour urine protein from 18.5 g/dL to 2.8 g/dL. At that time, serum Cr(s-Cr) of 0.7 mg/dL and calcium of 9.3 mg/dL were in the normal range. ZA was administered intravenously at the dose of 4 mg for the first time. Subsequently, he developed a fever of up to 39.4 degrees C and used NSAIDs and cefepime. Four days later, s-Cr increasd rapidly to 7.3 mg/ dL and he received hemodialysis (HD) therapy. Four weeks later, renal biopsy was performed and demonstrated cast nephropathy (CN) and acute tubular necrosis. Seven months later, renal function had improved. ZA may be an identifiable precipitating factor of CN. We recommend that ZA should be used with caution, especially hypovolemia and NSAIDs, in patients with MM and renal insufficiency.

Mobilization of bone marrow cells by leukocytapheresis in patients with ulcerative colitis.

While several trials have suggested that leukocytapheresis by filtration can benefit patients with active ulcerative colitis (UC), mechanisms underlying these benefits are largely unknown. We studied how leukocytapheresis mobilizes bone marrow cells into the peripheral circulation in patients with active UC. Leukocytapheresis transiently reduced peripheral leukocytes, followed by an overshoot increase with emergence of immature leukocytes. The numbers of colonies and CD34(+) cells were comparable between UC patients and normal controls. Shortly after leukocytapheresis, the numbers of both colonies and CD34(+) cells increased significantly in UC patients (P < 0.0001 and P = 0.0372, respectively). This was not associated with changes in the concentration of circulating cytokines or epinephrine. These results indicate that leukocytapheresis mobilizes bone marrow cells into the circulation. This cell replacement may partly explain the therapeutic benefit in UC. The functional role of the mobilized bone marrow cells in affected intestine remains to be characterized.

Carbonic-adsorbent AST-120 reduces overload of indoxyl sulfate and the plasma level of TGF-beta1 in patients with chronic renal failure.

BACKGROUND: We previously reported a significant increase in plasma TGF-beta1 in patients with chronic renal failure (CRF). Progression of CRF may be caused by persistent renal production of TGF-beta1. In CRF rat models, an oral carbonic absorbent (AST-120) reduces the expression of the TGF-beta1 gene in the kidney, and delays the progression of CRF, in part by alleviating the overload of indoxyl sulfate. The aim of this study was to evaluate the effect of AST-120 on plasma levels of indoxyl sulfate and TGF-beta1 in CRF patients. METHODS: Ten CRF patients (aged 59.3 +/- 9.5 years, 5 men, serum creatinine 4.37 +/- 1.72 mg/dl) were enrolled in this study. All patients maintained a regular dietary therapy and the same medication throughout the study. AST-120 was added at a dose of 6 g/day. Parameters including the slope of the reciprocal of the serum creatinine-time plot, plasma indoxyl sulfate level, and plasma and urinary levels of TGF-beta1 were compared before and after the treatment with AST-120. The mean observation periods before and after the treatment were 9.7 +/- 2.8 and 6.5 +/- 2.9 months, respectively. RESULTS: Administration of AST-120 significantly reduced the plasma levels of indoxyl sulfate (1.42 +/- 1.50 vs. 1.26 +/- 1.40 mg/dl, P < 0.05) and TGF-beta1 (17.9 +/- 7.2 vs. 10.6 +/- 4.7 ng/ml, P < 0.05) and improved the slope of the reciprocal of serum creatinine (-0.061 +/- 0.041 vs. -0.032 +/- 0.055 dl/mg/year, P < 0.05). CONCLUSIONS: These results support the notion that indoxyl sulfate and TGF-beta1 may be involved in the progression of CRF, and that the oral adsorbent AST-120 may suppress the progression, at least in part, by reducing overproduction of TGF-beta1.

Granulocytapheresis (GCAP) for severe alcoholic hepatitis-A preliminary report.

AIM: To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis. METHODS: We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered. RESULTS: The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself. CONCLUSION: GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.

Assessment of therapeutic effect in patients with secondary hyperparathyroidism using bone scintigraphy.

OBJECTIVE: The semi-quantitative method of bone scintigraphy [bone to soft tissue (B/ST) ratio] has been used in diagnosing and evaluating systemic metabolic bone diseases. The aim of this study is to evaluate of the therapeutic effect of secondary hyperparathyroidism (SHP). METHODS: The subjects were ten hemodialysis patients with SHP. Seven patients underwent parathyroidectomy (PTX), and 22-Oxacalcitoriol (derivative of 1,25-dihydroxyvitamin D3) (OCT) was given to three patients. Bone scintigraphy and blood tests [intact parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium (Ca), phosphorus (P), bone alkaline phosphatase (BALP), and deoxypridinoline (DPYD)] were performed before and after treatment. Regions of interest were drown around cranium, lumbar vertebrae, femoral neck and soft tissue of left medial thigh to calculate the B/ST ratio. RESULT: The B/ST ratios of cranium, lumbar vertebrae, and femoral neck were reduced significantly after PTX (cranium, p = 0.0079, lumbar vertebrae, p = 0.0282, femoral neck, p = 0.0252). Intact PTH, ALP, Ca, P, BALP and DPYD levels were reduced significantly after PTX (intact PTH, p = 0.003, Ca, p = 0.0005, P, p = 0.0393, ALP, p = 0.0051, DPYD, p = 0.0232, BALP, p = 0.0324). After OCT administration, the B/ST ratio of each bony region showed tendency to diminish, although not significantly. Intact PTH levels were reduced significantly, although ALP, BALP, and DPYD levels were not. Ca and P levels were increased significantly because of the medicinal action of OCT. CONCLUSION: The B/ST ratio of cranium may be non-invasive method and have potential in evaluating the therapeutic effect of SHP.

Evaluation of exercise-induced acute renal failure in renal hypouricemia using Tc-99m DTPA renography.

We present a case of a thirty-eight-year-old man who had exercise-induced acute renal failure (exercise-induced ARF). He experienced oliguria, general fatigue, and vague discomfort in the lower abdomen after he exercised. As he had suffered from hypouricemia before, he was diagnosed as having exercise-induced ARF associated with hypouricemia. Enhanced computed tomography (CT) images showed patchy wedge-shaped contrast enhancement on his bilateral kidneys, consistent with characteristic observations for exercise-induced ARF. Tc-99m diethylene triamine pentaacetic acid (DPTA) renography revealed decreases in both the renal blood flow (RBF) and glomerular filtration rate (GFR), and revealed parenchymal dysfunction of the bilateral kidneys. Renogram revealed a hypofunctional pattern on the bilateral kidneys. CT images and Tc-99m DTPA renography also had improved when the symptoms of exercised-induced ARF indicated improvement. It has been hypothesized that one cause of exercise-induced ARF may be renal vasocontraction. Although CT images are useful in evaluating exercise-induced ARF, Tc-99m DTPA renography can more easily and safely evaluate renal function. We also show that Tc-99m DTPA renography is useful in precisely evaluating the degree of improvement of exercise-induced ARF.

Rhabdomyolysis induced by psychotropic drugs.

A 41-year-old man experienced continuous convulsions, unconsciousness, and a high temperature. His laboratory findings revealed an increase in serum creatine phosphokinase, serum myoglobulin, and urinary myoglobulin levels. He had taken many psychotropic drugs as treatment for schizophrenia and was very dehydrated. Because a diagnosis of rhabdomyolysis was suspected, Tc-99m HMDP bone scintigraphy was performed. It showed diffusely increased soft tissue uptake in his shoulder girdles, vertebral area, psoas iliac muscles, and gluteofemoral muscles, leading to a diagnosis of rhabdomyolysis. Bone scintigraphy is useful in making an early diagnosis and evaluating the location and degree of muscle injury in rhabdomyolysis.

Usefulness of whole PTH assay in patients with renal osteodystrophy--correlation with bone scintigraphy.

OBJECTIVE: Intact parathyroid hormone (PTH) assay has recently been reported to be effective in evaluating both 1-84 PTH (whole PTH) and inactive 7-84 PTH. Inactive 7-84 PTH is considered to be increased in hemodialysis patients and to prevent the effects of 1-84 PTH, and intact PTH is considered to overestimate the PTH activity in these patients. As such, a whole PTH assay has recently been developed. The purpose of this study was to examine the usefulness of a whole PTH assay using the bone to soft tissue (B/ST) ratio on bone scintigraphy. METHOD: Twenty-five hemodialysis patients were included in our study. In all patients, bone scintigraphy and a blood test [whole PTH, intact PTH, alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P)] were performed. Regions of interest (ROIs) were drawn around the cranium, lumbar vertebrae, left femoral neck, and soft tissue of the medial left thigh to obtain the B/ST ratio. RESULTS: The B/ST ratio of the cranium and left femoral neck correlated with whole PTH and intact PTH. In particular, the B/ST ratio of the cranium correlated most significantly with the value of whole PTH. Whole PTH levels correlated with intact PTH levels (r = 0.891, p < 0.0001). CONCLUSION: Our data indicate that a whole PTH assay may be useful in evaluating PTH activity using the B/ST ratio. The B/ST ratio of the cranium may reflect the bone metabolism of hemodialysis patients.

Comparison of histological findings and parathyroid scintigraphy in hemodialysis patients with secondary hyperparathyroid glands.

To determine the usefulness of parathyroid scintigraphy in histological estimation for secondary hyperparathyroidism (2HPT) using Tc-99m sestamibi or Tc-99m tetrofosmin. Tc-99m sestamibi (MIBI) and Tc-99m tetrofosmin (Tetro) parathyroid imaging following double-phase study, magnetic resonance imaging (MRI), and ultrasound were performed on 14 patients with 2HPT. All patients underwent parathyroidectomy. The uptake of two tracers in parathyroid areas was compared with the histopathologic findings. Forty-nine parathyroid glands were surgically explored and histologically proven to be hyperplastic. Of these, 42 were diagnosed with nodular type (N-type) hyperplasia, and 7 with diffuse type (D-type) hyperplasia. MIBI and Tetro parathyroid imagings detected 34 and 35 parathyroid glands, respectively. The sensitivity of MIBI was determined to be 76.2% (32/42) for N-type, and 28.6% (2/7) for D-type. The sensitivity of Tetro was determined to be 78.6% (33/42) for N-type and 28.6% (2/7) for D-type. The sensitivity of both MIBI and Tetro was significantly higher for N-type than for D-type, 76.2% (32/42) vs. 28.6% (2/7) in MIBI, P = 0.022; 78.6% (33/42) vs. 28.6% (2/7) in Tetro, P = 0.015. The sensitivity of MRI was determined to be 76.2% (32/42) for N-type and 42.9% (3/7) for D-type, and the sensitivity of ultrasound was 71.4% (30/42) for N-type and 71.4% (5/7) for D-type. There was no significant difference in the sensitivity of MRI or ultrasound between N-type and D-type. The uptake ratios of MIBI and Tetro were also greater for N-type than for D-type. The detectability of both MIBI and Tetro was greater for N-type than for D-type. Tc-99m MIBI or Tc-99m Tetro parathyroid scintigraphy therefore may be used clinically to distinguish N-type from D-type parathyroid gland hyperplasia.

Usefulness of bone uptake ratio of bone scintigraphy in hemodialysis patients.

OBJECTIVE: It is important to estimate the bone metabolism in patients with renal osteodystrophy. The methods of estimation must be noninvasive, accurate, and able to measure repeatedly. METHODS: The regions of interest on bone scintigraphy were drawn over the radius in 22 hemodialysis patients (10 males, 12 females). The bone/soft tissue ratio (B/ST ratio) was calculated for all patients. The bone soft tissue ratio of both skull (S) and radius (R) was obtained from the resultant count ratios. We investigated the correlation between intact parathyroid hormone (PTH), alkaline phosphatase (ALP) and the uptake ratios S and R. RESULTS: Intact PTH had a significantly linear correlation with R (r = 0.745, p < 0.0001) and S (r = 0.702, p = 0.0001). ALP also had a significantly linear correlation with R (r = 0.537, p = 0.009) and S (r = 0.772, p < 0.0001). CONCLUSION: The measurement of the bone soft tissue ratio of radius on bone scintigraphy was crucial for estimating renal osteodystrophy.

A clinical assessment of the relationship between bone scintigraphy and serum biochemical markers in hemodialysis patients.

BACKGROUND: Renal osteodystrophy is a metabolic bone disease and a common complication of end-stage chronic renal failure and maintenance dialysis treatment. In this study, we examined the correlation between quantifying bone scintigraphy and serum biochemical markers in hemodialysis patients. METHODS: Bone scintigraphy with technetium-99m-hydroxy-methylene-diphosphonate (99mTc-HMDP) was performed on 28 patients on maintenance hemodialysis. Bone scintigraphy was performed using a standard protocol and was quantified by setting regions of interest (ROIs) over selected regions. The bone-to-soft-tissue ratio (B/ST ratio) at each region was calculated in all patients. The B/ST ratios were then compared with serum biochemical markers. RESULTS: The B/ST ratio for the skull correlated well with serum bone-specific alkaline phosphatase (BAP) (r = 0.735, p < 0.001), serum deoxypyridinoline (DPD) (r = 0.806, p < 0.001) and intact parathyroid hormone (intact PTH) (r = 0.701, p < 0.001). The B/ST ratio for the lumbar spine correlated with intact PTH (r = 0.387, p < 0.05) but not with serum BAP or serum DPD. The B/ST ratio for the femoral neck correlated with serum DPD (r = 0.431, p < 0.05) and intact PTH (r = 0.449, p < 0.05) but not with serum BAP. CONCLUSIONS: Our data suggest that quantitative bone scintigraphy is a sensitive and useful method for evaluating bone metabolism in hemodialysis patients. The B/ST ratio for the skull may reflect changes of bone metabolism in hemodialysis patients.

Technetium-99 m sestamibi imaging in patients with subacute thyroiditis.

To determine if subacute thyroiditis (SAT) is associated with changes in the regional perfusion of the thyroid gland, we performed Tc-99 m sestamibi scans on eleven patients with SAT who had painful goiter and clinical thyrotoxicosis. Eleven patients had Tc-99 m pertechnetate and Tc-99 m sestamibi scintigraphy during the acute stage of SAT. The thyroid uptake ratio of sestamibi was compared with the laboratory data and color Doppler ultrasonography. Tc-99 m pertechnetate scintigraphy in the thyroid was markedly reduced during the acute stage of SAT. Conversely, Tc-99 m sestamibi showed diffuse increased uptake in the thyroid region, suggesting increased perfusion. On the other hand, there was near absence of vascularization in the acute phase and slight increase in the recovery phase by color Doppler ultrasonography. The clearance rate of Tc-99 m sestamibi during the early phase (from 10 min to 1 h) was decreased in the acute stage of SAT. The sestamibi uptake ratio correlated with serum immunosuppressive acidic protein (IAP) in the acute stage of SAT and the sestamibi uptake ratio in the recovery stage of SAT was correlated with serum thyrotropin levels. Tc-99 m sestamibi uptake in the early phase in the acute stage of SAT may reflect the inflammatory process associated with SAT.