Low Na concentration solution for CAPD.
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Biomedical subjects
Publications and source records attributed to O Sakai.
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In peritoneal dialysis, sodium (Na) passes through the peritoneal membrane to a lesser extent than H2O and thus hypotonic fluid is removed indicating that Na removal is inefficient. Therefore we developed an ultra-low Na dialysate (ULNaD) [Na 98 mmol/liter, osmolality 340 mOsm/kg, glucose (G), 2.48%] to facilitate trans-peritoneal Na removal. The aim of the study was to examine (a) the fluid and Na kinetics of this solution, and (b) the clinical effect in the overhydrated patient. Regarding the former, in six cases, changes in the effluent Na levels during a 240-minute dwell of ULNaD were measured at 60-minute intervals. In eighteen cases, the transperitoneal net-Na removal (Na removal) and drained ultrafiltration (UF) volume after a 240-minute dwell of ULNaD were measured and compared to two types of standard Na dialysate (SNaD) [Na 132 mmol/liter, 1.36% G (348 mOsm/kg) and 2.27% G (396 mOsm/kg)]. The effluent Na levels increased gradually until the end of the dwelling. Drained UF volume of ULNaD (224 +/- 25 ml) was more than 1.36% G SNaD (77 +/- 33 ml, p < 0.01), but it was less than 2.27% G SNaD (341 +/- 32 ml, p < 0.01). However, a significant increase in Na removal by ULNaD (78.1 +/- 5.6 mmol) was found compared with both SNaD solutions (12.6 +/- 6.4 mmol in 1.36% G solution, p < 0.001; 27.8 +/- 5.1 mmol in 2.27% G solution, p < 0.001, respectively). Regarding the latter study aim, in six overhydrated patients with a Na excess, SNaD was replaced with ULNaD once a day for 7 consecutive days. At the end of the study as compared to the pre-values, a significant reduction in body weight (-2.5 +/- 1.0%, p < 0.05) and mean arterial pressure (-12.3 +/- 3.5%, p < 0.001) was observed. An increased drainage of daily UF volume (+86.5 +/- 31.1%, p < 0.05) and a markedly increased daily Na removal (+131.1 +/- 24.2%, p < 0.01) were also observed. The results of this study suggest that ULNaD actually facilitates trans-peritoneal Na removal mainly by diffusion force, and that ULNaD could benefit overhydrated patients with a Na excess.
Cardiovascular complications in renal replacement therapy remain prevalent today. The question, "Is atherosclerosis accelerated in peritoneal dialysis (PD) patients," has not been resolved. Many cross-sectional studies have revealed that there are more atherogenic lipid profiles in continuous ambulatory peritoneal dialysis (CAPD) than in other dialytic modalities. However, it is not certain that CAPD per se may contribute to lipid abnormalities in continuing PD for a long time. Therefore, we tried to assess whether CAPD itself may change lipid profiles in the long-term period on CAPD. We measured conventional lipid profiles in 16 stable CAPD patients in whom total cholesterol (T.chol.) levels remained under 240 mg/dL at the time of starting observation. Diabetic end-stage renal disease (DMESRD) patients were excluded from this study. Blood sampling was performed under strict conditions indicating overnight fasting with 10 hours dwell of 2 L of 1.5% Dianeal. Plasma levels of T.chol., triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and atherogenic lipoprotein (apo B/A-I) did not show significant changes by serial measurements from the sixth month to the thirtieth month following the commencement of CAPD as their initial dialysis treatment. Recently it is reported that high plasma levels of Lp(a) lipoprotein are an independent risk factor in cardiovascular events in renal replacement therapy because Lp(a) has a close relation to intravascular thrombosis and acceleration of atherosclerosis. We found that the incident of vascular accidents was five episodes among 33 patients with higher (> 31 mg/dL) Lp(a) levels, while there was only one episode in 45 patients with lower (< 30 mg/dL) Lp(a) levels (p < 0.05, odds ratio: 7.9). However, severity of aortic calcification and incidence of positive treadmill test showed no difference in these two groups. No significant correlation was observed between duration on CAPD and plasma Lp(a) levels. From the fact mentioned above, we speculate that CAPD does not essentially affect lipid profiles if determined under the strict condition of blood sampling. In order to evaluate the atherosclerosis noninvasively, we have measured aortic pulse wave velocity (AoPWV) in 33 stable CAPD patients excluding those with DMESRD by two years' interval. Fifteen cases (46%) increased in AoPWV, however, lipid profiles did not differ from those of nonadvanced patients. Calcification of arteries is further evidence of acceleration in atherosclerotic change. Therefore, we have graded severity of abdominal aortic calcification into three categories: grade I denoted nil calcification, grade II denoted patchy calcification, and grade III denoted calcification along the entire abdominal wall, having a lead-pipe shape by lateral view of plain abdominal x-ray film. There were significant differences in the duration of CAPD (grade I: 41 months, grade II: 60 months, grade III: 68 months). AoPWV showed least in the grade I group, faster in grade II, and fastest in grade III, while lipid profiles did not show significant differences in three categories. From the analysis of serial changes of lipid profiles, AoPWV and aortic calcification, CAPD may present some risk of accelerating atherosclerosis, at least in some patients on long-term treatment. Risk factors contributing to acceleration of atherosclerosis is result not from lipid abnormalities, but from other factors which remained to be seen, for example, abnormalities in calcium metabolism.
In order to investigate endothelial cell dysfunction in patients with impaired renal function, we measured circulating endothelin (ET-1) and thrombomodulin (Tm) concentrations used as markers for endothelial cell injury in patients with renal failure. 1) ET-1 and Tm were significantly higher in patients with renal failure and pre-dialysis patients than in normal subjects. Tm in CRF patients was significantly greater than that in ARF patients. In contrast, ET-1 was significantly greater in ARF than in CRF. 2) A positive correlation was found between serum creatinine concentration (Cr) and Tm in pre-dialysis patients. However, no correlation was found between Cr and ET-1. 3) A positive correlation was found between Tm and the duration of dialysis in HD patients, but not in CAPD patients. 4) With the improvement of renal function after regular HD treatment, a substantial reduction was found in ARF patients in both Tm and ET-1, but not in CRF patients. The present study suggests the presence of endothelial cell dysfunction in patients with impaired renal function. The progression of endothelial cell damage may differ between patients on HD and those on CAPD. In addition, it is suggested that endothelial cell dysfunction reverses in ARF patients with improved renal function.
We have encountered a 49-year-old female with persistent proteinuria and hematuria. Blood pressure, renal function, physical findings and chest X-p showed no abnormality, but blood tests disclosed mild thrombocytopenia, elevated serum ACE activity, serum lysozyme activity and serum IgA concentration. Abdominal echography and CT revealed multiple nodules in her spleen. In order to make a definite diagnosis and exclude the possibilities of malignant lymphoma or metastatic malignant tumor, splenectomy, and open renal biopsy were performed at the same time. On histological examinations, light microscopic appearance of the spleen was characterized by non-caseating granulomas compatible with sarcoidosis. Renal biopsy specimen showed diffuse proliferative glomerulonephritis with positive staining of IgA predominantly located in the mesangial area, compatible with IgA nephropathy. The present case may provide suggestive evidence for a link between sarcoidosis and IgA nephropathy in the pathogenesis. IgA nephropathy complicated by sarcoidosis is rare, and thus is of particular interest because common immunological abnormalities might be considered in the disease process of both diseases. We feel that despite a low index of suspicion, physicians must be alert to the possibility of IgA nephritis associated with sarcoidosis. The literature is reviewed regarding the relationship between IgA nephropathy and sarcoidosis.
Recently, several reports have suggested that there is a higher incidence of low turnover bone in the absence of aluminium exposure in peritoneal dialysis patients than in hemodialysis patients. Relative hypoparathyroidism with mild hypercalcemia, induced by a positive calcium balance, is considered to be one of the major causes of this disorder. Thus, we recruited 9 continuous ambulatory peritoneal dialysis (CAPD) patients with relative hypoparathyroidism and low bone turnover [intact parathyroid hormone (iPTH) < 50 pg/mL, intact osteocalcin < 10.0 ng/mL] who had been prescribed 1.75 mmol/L calcium (Ca) dialysate for 5.0 +/- 0.3 years. They were then treated by low Ca (1.25 mmol/L) dialysate for nine months without vitamin D and aluminum administration. Intact PTH and bone metabolic markers [intact osteocalcin, alkaline phosphatase (ALP)] were measured every three months. Intact PTH levels increased from 21.1 +/- 3.8 to 159.2 +/- 32.8 pg/mL after the first three months; thereafter, those levels were maintained at around 150 pg/mL. On the other hand, intact osteocalcin levels rose consecutively from 6.7 +/- 1.2 to reach 22.0 +/- 3.8 ng/mL after nine months. Interestingly, the pattern of time course changes between PTH and intact osteocalcin was different. ALP activity did not change during the nine-month period. Corrected serum calcium was significantly decreased (p < 0.001) to approximately 0.25 mmol/L within one month, and the level remained almost the same thereafter. The serum phosphate level did not change without adjusting the original dose of calcium carbonate as a phosphate binder. We concluded that low Ca dialysate (1.25 mmol/L) is effective for the treatment of CAPD-related hypoparathyroidism with low bone turnover.
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Tissue-type plasminogen activator (tPA) is an endothelium-derived vasoactive substance which is released to the blood stream by exercise, blood occlusion, and desmopressin (DDAVP). The increased capacity of the plasma tPA level raised by these factors is thought to reflect in vivo endothelial function. On the other hand, endothelial dysfunction has been reported in patients with hypercholesteremia as well as in those with diabetes mellitus. Therefore, diabetic patients with hypercholesteremia were administered 5 mg of simvastatin daily for one month and plasma tPA responses evoked by DDAVP were examined before and after treatment for hypercholesteremia. While the treatment of simvastatin for one month significantly reduced serum cholesterol levels from 257 +/- 12 mg to 206 +/- 10 mg (no change in HbA1c was observed during the study), plasma tPA levels and % delta vWF (von Willebrand factor) following DDAVP infusion significantly increased from 11.4 +/- 1.2 ng/ml to 13.4 +/- 1.4 ng/ml and from 69.3 +/- 23.4% to 126.5 +/- 47.4%, respectively. However, neither increase in plasma levels of guanosine 3', 5'-cyclic monophosphate (cGMP) nor change in the depressive response of blood pressure was observed following DDAVP infusion after the treatment of simvastatin. In addition, no change in urinary albumin excretion rate was observed with the treatment of hypercholesteremia. Therefore, it was suggested that improvement in hypercholesteremia may ameliorate vascular endothelial dysfunction in diabetic patients with hypercholesteremia and that hypercholesteremia may enhance endothelial dysfunction in these patients.
A 30-year-old woman with chronic renal failure (CRF) due to glycogen storage disease Type I (GSD I) was admitted for dialysis. Hemodialysis (HD) was introduced as the primary therapeutic modality. However, maintenance HD was very difficult to conduct because of hypotension during the HD sessions. Furthermore, hypoglycemia and metabolic disturbances persisted. After changing from HD to CAPD, fasting blood sugar was significantly elevated through a continuous glucose supply from the dialysate. The values of ketone, non-esterified fatty acid, blood urea nitrogen/creatinine (BUN/ Cr), and glucagon were improved. CAPD not only controlled uremia, but also ameliorated the metabolic disturbances of GSD I. Therefore, we conclude that CAPD is superior to HD as a dialytic modality for patients with CRF due to GSD I.
The serum levels of uric acid, hypoxanthine and xanthine tended to increase with the decrease of renal function. This mechanism was thought to be the decreased excretion of these materials from the kidney. More than ninety percent of the patients with renal insufficiency (Ccr < or = 30 ml/min) showed hyperuricemia. In general, the gouty arthritis was reported to be uncommon in the patients with secondary hyperuricemia due to renal insufficiency. However, the frequency of gouty arthritis was reported to be high in the patients with polycystic disease and lead nephropathy. The therapeutic standard for secondary hyperuricemia with renal insufficiency was not established. Allopurinol is the drug of choice for controlling hyperuricemia due to renal insufficiency in many cases. In renal insufficiency, the drug must be used cautiously and in reduced dosage because increased serum concentration of oxipurinol, active metabolite of allopurinol, may induce severe side effect.
Malnutrition is a serious complication in patients on long-term CAPD treatment. Accordingly, quantitative evaluation of nutritional status is a critical issue. This study aimed to assess nutritional status by dual photon energy x-ray absorptiometry (DEXA) in CAPD patients. Total lean body mass (D-TBM), right arm lean mass (D-RAM) and body fat percent (D-% FAT) measured by DEXA were compared with mid-arm muscle circumference (MAMC) and body fat percent (AP-% FAT) measured by anthropometrics (AP) in 51 CAPD patients. The subjects were stratified into groups by gender, age, duration on CAPD, and diabetes mellitus or non-diabetes. There was significant correlation between D-TBM, D-RAM and MAMC (r = 0.519, p = 0.001, r = 0.545, p = 0.001) or D-% FAT and AP-% FAT (r = 0.763, p = 0.0001). However, in the groups of females with over 50 years and over 48 months of dialysis duration, there was no correlation between D-TBM, D-RAM and MAMC. The DEXA method is useful in the quantitative evaluation of nutritional status of dialysis patients serially.
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Streptococcus pneumoniae is one of the important human pathogens in clinical microbiology. A polymerase chain reaction assay was designed to detect and identify S. pneumoniae through amplification of the ribosomal DNA spacer regions between the pneumococcal 16S-23S ribosomal RNA genes. Thirty-two Streptococcus and non-Streptococcus strains were tested to verify the specificity of the assay, and only S. pneumoniae strains gave a positive reaction. This method is a powerful technique for the rapid identification of S. pneumoniae.
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We established spontaneously immortalized Schwann cell lines from long-term cultures of adult mouse dorsal root ganglia and peripheral nerves. One of the cell lines, designated IMS32, responded to mitogenic stimuli by platelet-derived growth factor (PDGF)-BB, acidic and basic fibroblast growth factors (aFGF, bFGF), and transforming growth factors (TGF)-beta 1 and -beta 2, as determined by bromodeoxyuridine (BrdU) incorporation and double immunofluorescence for S100 and BrdU. Furthermore, conditioned media (CM) obtained from IMS32 cells showed mitogenic activity for both IMS32 cells and long-term cultured Schwann cells. Western blot analysis revealed TGF-beta-like molecule in the CM, and the activity was absorbed with anti-TGF-beta neutralizing antibody. Reverse transcription followed by polymerase chain reaction (RT-PCR) of IMS32 RNA revealed that these cells expressed TGF-beta 1, -beta 2, and -beta 3 transcripts. When rat pheochromocytoma PC12 cells were incubated with the CM, they developed neurite growth. Coculture of PC12 and IMS32 cells also showed neurite growth of PC12 cells. RNA transcripts of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), ciliary neurotrophic factor (CNTF), and glial cell line-derived neurotrophic factor (GDNF) were detected from IMS32 cells by RT-PCR. In these, we sequenced the mouse GDNF cDNA coding region and observed 97% and 90% homologies to corresponding rat and human cDNA sequences, respectively. These results indicate that the immortalized Schwann cell line mitotically responds to various growth factors and secretes autocrine and paracrine growth-promoting activities in vitro.
Protein tyrosine kinases play an important role in cellular proliferation and differentiation of various cell types. To identify potential tyrosine kinases involved in glomerular functions we have utilized the polymerase chain reaction (PCR) and degenerate oligonucleotides for isolation of such genes from isolated glomeruli, cultured mesangial cell, and glomerular endothelial cells. Sequence analysis of PCR-amplified cDNAs resulted in the isolation of 24 tyrosine kinases. Here we describe for the first time the constitutive expression of 15 tyrosine kinases, tyro-1, tyro-4, tyro-6, hyk, Ptk-3, Ryk, tie, yes, lyn, tec, Jak1, Jak2, Jak3, c-abl, and flk, in renal glomeruli. In addition, Flt-1, an endothelial cell-specific receptor for vascular endothelial growth factor (VEGF), is expressed in renal mesangial cells and its gene expression is up-regulated upon the stimulation of platelet-derived growth factor (PDGF) with the concomitant up-regulation of VEGF. These data suggest that possible involvement of VEGF/Flt-1 system in cytokine-induced mesangial cell proliferations.
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Cadmium (Cd)-induced nephropathy was treated by triethylenepentaminehexaacetic acid (TTHA) in male Syrian hamsters. Hamsters injected three times a week with 3 mg/kg body wt CdCl2 showed proteinuria, urinary N-acetyl-beta-D-inglucosaminidase (NAG), and fractional excretion of sodium (FENa) when compared to saline-injected control. Cd-treated hamsters injected ip with TTHA 10 mg/kg body wt five times a week showed reduction of renal damage, including reductions in urinary protein (from 6.7 +/- 2.2 to 4.3 +/- 0.5 mg/d) and NAG (0.17 +/- 0.06 to 0.04 +/- 0.02 U/d). Urinary excretion of Cd was significantly increased (from 87 +/- 51.3 to 3052 +/- 1485 mg/L) by TTHA administration. Cd concentration in renal cortical tissue was slightly reduced (26.4 +/- 3.0 to 21.8 +/- 2.7 mg/g. protein). Excretion of malondialdehyde (MDA) was increased only in Cd-injected hamsters (to 2.1 +/- 1.6 nM/L), and elevated MDA in renal cortical tissue was not reduced by the administration of TTHA (1041 +/- 105 vs 1104 +/- 358 nM/g protein). Glutathione (GSH) concentration in the renal cortex was significantly elevated after Cd administration and further increased after TTHA administration (5.5 +/- 2.1 to 9.8 +/- 2.0 micrograms/50 mg protein). There were no marked effects on creatinine clearance (Ccr) and hematocrit. Moreover, renal morphological changes were improved significantly by treatment with TTHA. We demonstrated the efficacy of TTHA in the treatment of Cd-induced nephropathy in hamsters. Although the precise mechanism of the TTHA effects on Cd-induced nephropathy has not been elucidated, it might involve GSH reducing the elevated MDA concentration in renal tissue.