Hiroshi Nishitani

Roles of hypoalbuminemia and lipoprotein lipase on hyperlipoproteinemia in continuous ambulatory peritoneal dialysis

To assess the mechanism of serum lipoprotein abnormalities in continuous ambulatory peritoneal dialysis (CAPD), we measured serum lipids, apolipoproteins, and postheparin lipases in 46 patients with end-stage renal disease (ESRD) treated on CAPD, 26 patients on hemodialysis (HD), and 29 healthy subjects. HD patients had higher serum triglyceride levels than the healthy controls, showing type IV and type III phenotypes. They had significantly lower activities of hepatic triglyceride lipase (HTGL) in postheparin plasma compared with controls, and postheparin lipoprotein lipase (LPL) was also decreased by 15%, although the latter change was not statistically significant. CAPD patients had elevated levels in triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (apo) B, showing type IV, III, and II (IIb and IIa) phenotypes. The mean LPL and HTGL activities in CAPD patients were not different from those of HD patients. CAPD patients with hyperlipoproteinemia had significantly higher serum albumin levels than those with normolipidemia. There was a significant positive correlation between albumin and apo B levels in CAPD patients. In hyperlipidemic CAPD patients, there was no difference in serum albumin concentrations or HTGL activities among lipoprotein phenotypes, whereas LPL activities were significantly higher in the patients with type II than those with type IV hyperlipoproteinemia. These results suggest that there was some linkage between alterations in serum albumin and lipoproteins, and that LPL was related to phenotypic variation of hyperlipoproteinemia in CAPD.

Clinical Effects of Long-Term Use of Neutralized Dialysate for Continuous Ambulatory Peritoneal Dialysis

The long-term effects of neutralized dialysate used in continuous ambulatory peritoneal dialysis (CAPD) were evaluated in 8 well-controlled patients. Twelve milliliters of 8.4% sodium bicarbonate was added to Dianeal PD-1 immediately before every administration. The final pH was 6.8 and the concentration of sodium bicarbonate was 6 mmol/l. The final sodium level was 138 mEq/l. This dialysate was used for 5 months. For 2 months before and 3 months after this period, Dianeal PD-2 was used as the dialysate for comparison. Blood bicarbonate levels significantly improved during the use of the neutralized dialysate. Blood sodium, chloride and magnesium levels and the effluent volume significantly increased. Sodium balance improved during the period when neutralized dialysate was used. Total leukocyte counts in the effluent decreased, and leukocyte viability increased. Abdominal distention, abdominal pain during instillation, nausea and headache improved. No side effects, including peritonitis, occurred during the trial of neutralized dialysate. The results suggest that this dialysate was less irritating to the peritoneal membrane than the control dialysate and that the therapeutic effects were satisfactory.

Serum and corpuscular nickel and zinc in chronic hemodialysis patients

Serum and corpuscular nickel and zinc concentrations in 30 chronic hemodialysis patients were examined. Serum nickel and zinc levels before dialysis were 0.22 +/- 0.03 microgram/dl (normal value: 0.56 +/- 0.08 microgram/dl) and 70.0 +/- 13.4 micrograms/dl (normal value: 96 +/- 8 micrograms/dl) low, respectively. However, corpuscular nickel and zinc levels before dialysis were high: 1.25 +/- 0.24 microgram/dl (normal value: 0.88 +/- 0.17 microgram/dl) and 1,299 +/- 146 micrograms/dl (normal value: 1,120 +/- 80 micrograms/dl). Serum zinc levels significantly increased after dialysis, but serum nickel concentrations did not significantly increase during dialysis. Corpuscular nickel and zinc concentrations did not significantly change during dialysis.

Serum Levels of Acetate and TCA Cycle Intermediates during Hemodialysis in Relation to Symptoms

In order to study the metabolism of acetate transferred from dialysate, the plasma concentrations of organic acids including the tricarboxylic acid cycle (TCA cycle) intermediates were measured during hemodialysis in a comparative study between acetate dialysate and bicarbonate dialysate in 17 patients on maintenance hemodialysis treatment. Continuous measurements of serum concentrations of these organic acids during hemodialysis were performed using the filtrate obtained through an ultrafiltrate sampling device. The organic acids were measured by isotachophoresis. Serum acetate, malate and citrate concentration increased with time in acetate dialysis compared with bicarbonate dialysis. Correlations were found between these organic acids. Isocitrate became detectable when the serum acetate concentration was over 7 mmol/l which was correlated to the acetate concentration, and was accompanied by the development of symptoms. The above results suggest that an acetate overload on the patients during acetate dialysis affects acetate metabolism through the TCA cycle resulting in an accumulation of organic acids in the serum and the development of symptoms.

Heat-insoluble cryoglobulin in a patient with essential type I cryoglobulinemia and massive cryoglobulin-occlusive glomerulonephritis

We report a case of type I essential cryoglobulinemia with massive cryoglobulin-occlusive glomerulonephritis, in which the clinical course and the physical characteristics of the cryoglobulin were unusual. Nine years before appearance of cryoglobulin, this 54-year-old man noted edema and purpura of the lower extremities. Renal biopsy performed 2 years later showed large amounts of amorphous, weakly eosinophilic, weakly periodic acid-Schiff (PAS)-positive materials occluding the glomerular capillaries. Immunostaining showed the material to be weakly immunoglobulin (Ig) G positive, and electron microscopy showed homogeneous, electron-dense deposits. Nephrotic syndrome and azotemia did not respond to steroid treatment, and dialysis was begun 5 years after the biopsy. A small amount of cryoglobulin was first detected 2 years later, 9 years after the onset of disease. The cryoglobulin had a white gelatinous appearance, was resistant to resuspension, and did not redissolve when rewarmed to 37 degrees C. Immunoelectrophoresis of the cryoglobulin, which partially dissolved at 54 degrees C, showed it to be composed of monoclonal IgG-kappa and a small amount of albumin. We consider that the unusual physical characteristics of the cryoglobulin in this case precipitated a massive cryoglobulin-occlusive glomerulonephritis, which progressed to end-stage renal failure in the absence of significant cryoglobulinemia during the initial onset of disease.

Decreased Bone Mineral Density in Diabetic Patients on Hemodialysis

Renal osteodystrophy in hemodialyzed patients with DM-HD shows different features from that in non-DM,HD. Two studies were done. One was a comparison of BMD in 30 non-DM,HD patients and 30 DM-HD patients. The second was a comparison of possible factors affecting calcium metabolism in the higher and lower BMD groups (n = 20/21) in the DM-HD patients. BMD was measured by dual-energy X-ray absorptiometry (DEXA; Hologic QDR 1,000/W) in the third lumbar vertebra (L3), head, pelvis, and whole body. The BMDs of the DM-HD group were lower in these areas and whole body than that in the non-DM,HD group. A significant difference was found in the head BMD (p less than 0.05). In the second study, factors which may contribute to the differences in BMD were compared in the DM-HD patients divided into higher and lower BMD of the head. The group with higher head BMD had a value 110% of the mean value or more. Clinical and biochemical test results (age, the time since the first dialysis, body weight, the degree of obesity, height, serum calcium, serum phosphate, serum aluminum, serum c-PTH level and the dose of 1 alpha-OH-D3) were compared. The degree of obesity of the patients with higher BMD was significantly larger than that with lower BMD (p less than 0.005).

Concentrations of Thyroxine-Binding Globulin in Sera and Peritoneal Dialysates in Patients on Chronic Peritoneal Ambulatory Dialysis

Losses in thyroxine-binding globulin (TBG) in peritoneal dialysate and thyroid function were evaluated in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), in comparison to patients on hemodialysis (HD) without TBG loss in the dialysate. The TBG concentration in the peritoneal dialysate was 0.26 +/- 0.09 microgram/ml (mean +/- SD, n = 24), with a daily loss of 2.47 +/- 0.94 mg. The serum TBG level in CAPD patients was 21.0 +/- 4.71 micrograms/ml (n = 24), which was not significantly different from that in HD patients (20.0 +/- 5.72 micrograms/ml, n = 24) or in healthy Japanese subjects. The serum TBG level correlated positively with the TBG loss and TBG level in the peritoneal dialysate (p less than 0.001). The serum T4 level in CAPD patients (4.93 +/- 1.38 microgram/dl, n = 24) was significantly greater than in HD patients (4.08 +/- 1.30 microgram/dl, n = 24, p less than 0.05).

Acetate Kinetics during Hemodialysis and Hemofiltration

A comparison was made between acetate dynamics in hemodialysis (HD) with acetate dialysate and hemofiltration (HF) using acetate substitution fluid. Acetate kinetics was calculated from removed HCO-3 (Rbc), generated HCO-3 (Gbc) and loaded CH3COO- (Lac) during each treatment. Rbc and Gbc were 99 ± 17 and 137 ± 18 mmol/h in HF, and 114 ± 23 and 128 ± 27 mmol/h in HD, respectively. Lac was 142 ± 25 mmol/h in HF and 162 ± 27 mmol/h in HD. Accordingly, the conversion rate (CR) from acetate to bicarbonate was 98 ± 18% in HF and 79 ± 9% in HD. Although the net load of acetate was comparable, CR was significantly greater in HF, resulting in a significantly smaller increment of the serum acetate level. Therefore, fewer symptoms are seen and better normalization of acidosis can be achieved in HF.

Case of a parathyroidectomized patient observed longitudinally by ultrasonography. Relationship between the growth rates and 1,25-dihydroxyvitamin D3 receptor contents in the parathyroid glands.

Parathyroid glands enlarge gradually with the progression of secondary hyperparathyroidism. The significance of down-regulation of the 1,25-dihydroxyvitamin D receptor (VDR) in parathyroid glands has been emphasized. Here we report a case in whom the relationship between the growth rates of the parathyroid glands and their VDR content was examined. A 36-year-old man, who had been hemodialyzed for 8.8 years because of chronic renal failure due to chronic glomerulonephritis, developed severe secondary hyperparathyroidism. The first ultrasonographic examination of the parathyroid glands, performed 10 months before parathyroidectomy, revealed that the sizes of the right upper (RU) and left upper (LU) glands were 10 x 8 x 5 and 14 x 10 x 9 mm3, respectively, although the right lower (RL) and left lower (LL) glands were not detected. The second ultrasonographic examination performed 5 days before PTX revealed that the RU gland had enlarged up to 24 x 12 x 10 mm3, while the LU gland remained unchanged at 16 x 9 x 8 mm3. At this time, the sizes of the RL and LL glands were determined only in the longitudinal section to be 10 x 5 and 4 x 3 mm2, respectively. In the excised specimens, the sizes and weights of the RU and RL glands were 25 x 10 x 9 mm3 and 1,950 mg and 17 x 10 x 8 mm3 and 1,160 mg, respectively, while those of the LU and LL glands were 16 x 10 x 7 mm3 and 850 mg and 9 x 8 x 7 mm3 and 350 mg, respectively. Histopathologic study demonstrated that the RU and RL glands exhibited nodular hyperplasia, while the LU and LL glands exhibited diffuse hyperplasia. Using a ligand binding assay, the VDR content of the rapidly growing RU and RL glands were significantly reduced to 32.6 +/- 9.6 and 32.7 +/- 5.2 fmol/mg protein, respectively, as compared to that of the LU gland with no significant proliferating activity (111.8 +/- 0.8 fmol/mg protein). It is of great interest that the smallest LL gland, which showed some proliferating potential in spite of a histologic pattern of diffuse hyperplasia, has a VDR content of 41.0 +/- 2.6 fmol/mg protein. In summary, it was implied from this case that the VDR content in the parathyroid gland might reduce as the growth rate of the parathyroid gland increases and, furthermore, that the VDR content seems to depend to some degree on the histopathologic pattern rather than on gland weight.

ABSENCE OF MACROSCOPIC HEMATURIA IN A CASE OF IGA NEPHROPATHY AND GRAVES' DISEASE WITH ACUTE RENAL FAILURE

creatinine to 8.1 mg/dl in 2 days. The patient had experienced no macroscopic hematuria before admission. On admission, the patient’s blood pressure was 172/110 mm Hg and pulse 102 beats/min. The patient looked acutely ill and was disorientated. The thyroid was diffusely and moderately enlarged. No peripheral edema was found. Blood analysis gave the following readings: hemoglobin 15.2 g/dl, white blood cell count 14,100/mm3, total protein 6.2 g/dl, albumin 3.5 g/dl, BUN 270.3 mg/dl, creatinine 8.2 mg/dl, uric acid 31 mg/dl. Uri-nalysis results were as follows: protein 0.38 g/day, red blood cell count 15-20 per Dear Sir, The frequency of acute renal failure in IgA nephropathy has been reported to be 0.8-6.6% [1,2]. The etiology and pathogene-sis of acute damage to renal function in IgA nephropathy, however, have not been fully elucidated. Bennett and Kincaid-Smith [3] have suggested that acute renal failure results from glomerular crescents, while the role of obstructive tubular red blood cell casts in the pathogenesis of reversible acute renal failure has been emphasized by other reports [4, 5]. Episodes of macroscopic hematuria are indeed frequently reported to precede the occurrence of renal failure, suggesting that macroscopic hematuria affects renal function. The authors have recently experienced a case in which reversible acute renal failure associated with IgA nephropathy was not accompanied by any evidence of macroscopic hematuria. A 42-year-old man was admitted to this hospital suffering from acute renal failure. The patient had had an unknown type of neprhitis with proteinuria and hypertension when tonsillectomy was performed at the age of about 10 years. The patient had remained well until 5 years ago, when proteinuria and hypertension were found during an annual medical examination. Eight days before admission, the patient experienced fatigue and a sore throat followed by vomiting after a picnic excursion with his family. After vomiting coffee ground materials, the patient wa admitted to a nearby hospital, where intravenous fluid