ISSN:1660-8151    

DOI:10.1159/000188731

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The use of 1 α-hydroxyvitamin D3 [ 1 α(OH)D3] derivatives in a uremic patient is justified only in the treatment of hyperparathyroidism (i.e. when plasma intact parathyroid hormone -PTH – levels are above five or three times the upper limit of normal according to whether the patient is on continuous ambulatory peritoneal dialysis or on hemodialysis and between 0.5-1.5, 1-2 and 2-3 times the upper limit of normal for a creatinine clearance of, respectively, 30, between 30 and 10, or below 10 ml/min/1.73m2). The following prerequisites have however to be satisfied: (1) a good vitamin D3 repletion should be secured by plasma 25(OH)D levels of 20-30 ng/ml (if necessary by administration of native vitamin D or 25(OH)D3), and (2) phosphate retention (which is aggravated by the increased phosphate intestinal absorption induced by the 1α(OH)D derivatives) and the consequent possible hyperphosphatemia should be prevented or corrected by the oral administration of alkaline salts of calcium given before the meals as phosphate binders without inducing hypercalcemia. These prerequisites explain the narrow therapeutical margin of lα(OH)D3 derivatives in uremic patients before dialysis (more so in the adult than in the child) and the possible broadening of this margin in the patients on dialysis by the use of low dialysate calcium concentrations (1.25-1.00 mmol/l) in order to prevent hypercalcemia by inducing a negative perdialytic calcium balance. Once hyperphosphatemia is prevented by oral calcium, 1α(OH)D3 derivatives have the advantage to suppress the transcription of the prepro PTH gene by a mechanism independent of an increase in plasma calcium. Controlled randomized trials have not confirmed the claimed advantage in efficacy and safety of the parenteral versus the oral route nor of the intermittent versus the daily mode of their administration. The advantages of using the so called ‘nonhy-percalcemic hyperphosphatemic’ vitamin D3 derivatives in combination with oral calcium over 1α(OH)D3 derivatives in the treatment of uremic hyperparathyroidism are still waiting for clinical demonstration. Vitamin D derivatives have no place in the treatment of aluminic bone diseases which necessitate long term deferoxamine treatment and prevention of aluminum exposure by the dialysate and the phosphate binders. They are not indicated in the treatment of’idiopathic’ adynamic bone disease which is due to uremia per se combined with an excessive PTH suppression for the degree of renal failure. This low bone turnover pattern is associated with an increased risk of hypercalcemia and hyperphosphatemia and necessitates only a stimulation of PTH secretion by inducing a negative calcium balance with a lower dialysate calcium concentration or simply by discontinuing the oral calcium supplement in the uremic patient not yet dialyzed. In rare cases this pattern is due to a granulomatosis and is correcte

ISSN:1660-8151    

DOI:10.1159/000188732

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

To test the effect of parathyroidectomy on thyrotropic and lactotropic function, a thyrotropin-releasing hormone (TRH) test was performed before and between the 2nd and 3rd month after operation in 13 haemodialysed patients with secondary hyperparathyroidism. The thyrotropin response to TRH was higher in the postoperative period as compared with the values before the operation (p < 0.01). The prolactin response to TRH did not differ from the values before the operation. No correlations between thyrotropin response and serum parathyroid hormone (PTH), ionised calcium and haemoglobin or haematocrit were found. The lower sensitivity of the thyrotropic system to TRH in patients with renal osteopathy is not dependent on serum PTH or calcium.

ISSN:1660-8151    

DOI:10.1159/000188733

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The aim was to investigate circulating levels of immunoreactive endothelin (ir-ET) in atherosclerotic renovascular hypertension (RVH), and to assess the role of the kidneys in its overall plasma concentration. We studied 16 hypertensive patients with renal artery stenosis evidenced by angiography and admitted to hospital for the diagnostic evaluation of RVH by renal vein plasma renin activity (PRA) determinations. The right femoral vein was catheter-ized to simultaneously measure PRA and ir-ET in both renal veins and inferior vena cava below the origin of the renal veins. RVH was present in 9 patients as indicated by diagnostic PRA renal vein ratios and the remaining 7 patients were considered to have essential hypertension (EH). Patients with RVH showed a marked increase in systemic plasma ir-ET concentration (10.3 ± 0.9 pg/ml) as compared to hypertensives without RVH (6.2 ± 0.6 pg/ml, p < 0.005). Despite a significant increase of PRA in the vein of the ischemic (IK) versus the contralateral (CK) kidney in patients with RVH, no significant differences in ir-ET concentration were observed between both kidneys. These results indicate that patients with RVH have increased circulating levels of ir-ET. However, the higher systemic plasma ir-ET do not arise from the renal circulation, since plasma ir-ET is significantly higher in systemic circulation than in renal vein

ISSN:1660-8151    

DOI:10.1159/000188734

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Increased plasma porphyrins have been described in patients with chronic renal failure (CRF). We measured plasma levels of porphyrins and the activity in erythrocytes of porphobilinogen deaminase (PBG-D), one of the key enzymes in heme biosynthesis, in CRF patients not yet on dialysis and in patients on intermittent hemodialysis (IHD) or chronic ambulatory peritoneal dialysis (CAPD), some of whom were being treated with recombinant human erythropoietin (rHuEPO). In addition, the amount of immuno-detectable PBG-D (Ig PBG-D) per 100 units standard PBG-D activity (Ig PBG-D/100 U) and the total amount of Ig PBG-D, using polyclonal antibodies, were determined in erythrocytes of all patients and controls to detect changes in biodegradation of this enzyme. Plasma porphyrins were increased in CRF patients not yet on dialysis and even higher in both patient groups on dialysis compared with controls. Plasma porphyrins were higher in patients on IHD than in patients on CAPD. The activity of PBG-D was increased and Ig PBG-D/100 U was decreased in patients on IHD compared with CRF patients not yet on dialysis and patients on CAPD. Reticulocyte counts were also greater in patients on IHD than in CRF patients not yet on dialysis and patients on CAPD. Ig PBG-D was increased in both groups of patients on dialysis and treated with rHuEPO compared with patients not treated with rHuEPO. In conclusion: (1) in patients on IHD, an increased production of porphyrins is, at least partly, caused by an increased PBG-D activity, and (2) an increased PBG-D activity and a decrease in Ig PBG-D/100 U in patients on IHD could be explained by the presence of a (relatively) young erythroid cell population in which a larger part of PBG-D has not yet been degraded.

ISSN:1660-8151    

DOI:10.1159/000188735

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We studied paraffin sections of renal biopsies from 7 patients with crescentic glomerulonephritis (CGN) by in situ hybridisation, to detect sites of interleu-kin-2 receptor (IL-2R) mRNA expression. Frozen sections from a further patient with CGN were studied by immunohistochemistry with a monoclonal antibody to CD25, to detect IL-2R protein. Positive control sections were taken from biopsies of acute cellular renal transplant rejection and negative controls from biopsies of membranous glomerulonephritis. No autoradiographic signal was detected in negative controls. IL·2R mRNA expression was seen in rejected transplants and in sections from 4 of 7 patients with CGN. Expression was seen in cortical interstitial cells, renal tubular epithelial cells, cells within glomerular crescents and in one glomerulus at the margin of Bowman’s capsule. Tubular cell expression of IL·2R protein was confirmed by immunohistochemistry. We have confirmed that IL·2R mRNA expression occurs locally within the kidney in CGN and have identified expression in tubular epithelial cells. The results suggest that local activation of immunocompetent cells occurs in the kidney and may be of significance in the pathogenesis of

ISSN:1660-8151    

DOI:10.1159/000188736

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The cytokines tumor necrosis factor-α (TNF-α) and its soluble TNF receptors 55 and 75 (sTNFR55, sTNFR75), interleukin-1β (IL-1β) and interleukin-6 (IL·6) were measured in plasma from 13 patients with the hemolytic uremic syndrome (HUS) on admission. No significant changes in the plasma levels of TNF-α and IL-1β were detected in the HUS patients as compared to the plasma levels of the control groups. Levels of IL-6 were significantly elevated in the plasma of those HUS patients who had extrarenal manifestations, consisting of seizures, loss of consciousness, coma and pancreatic necrosis. Although the exact function of IL-6 in the plasma of HUS patients is still unknown and the group of HUS patients is small, plasma IL-6 is associated with the severity and outcome of the disease. Plasma levels of sTNR55 and sTNFR75 were significantly elevated in all HUS patients compared to the healthy controls, but they were also elevated in the children with chronic renal failure. This indicates that elevated levels of circulating sTNFR should be carefully interpreted when kidney failure

ISSN:1660-8151    

DOI:10.1159/000188737

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effects of peritoneal albumin loss and the consequences of heterogeneous peritoneal solute transport on serum albumin levels were investigated in 25 adult patients on standard continuous ambulatory peritoneal dialysis (0-58 months). The patients were divided into three groups according to their albumin concentrations (g/l/1.73 m2) in 8-hour overnight effluents: group 1 ( l.l; n = 6). Significant differences (mean ± SD) were observed in serum albumin levels (4.4 ± 0.2, 3.7 ± 0.3, and 3.1 ± 0.5 g/dl, respectively) and in net ultrafiltration (0.37 ± 0.13, 0.19 ± 0.21, and -0.06 ± 0.20 liters/8 h/1.73m2, respectively). The serum albumin levels were strongly correlated with 8-hour peritoneal mass transfer, clearance of albumin, 8-hour effluent concentrations of protein and glucose, and ultrafiltration rate. Moreover, the serum albumin levels showed significant negative correlations with dialysate-to-serum ratios of small solutes (urea, creatinine, and uric acid) and macromolecules (IgG, IgA, and IgM) estimated from 8-, 4-, and 1-hour dwell times. In addition, an overnight dialysate glucose-to-protein ratio < 1.0 was highly predictive of low serum albumin levels ( < 3.5 g/dl) and poor ultrafiltration. From the results of this study we conclude that peritoneal loss of albumin as well as peritoneal transport of other solutes of wide size (‘permeability’) contribute to the low serum albumin levels during continuous ambulatory peritoneal dialysis, especially in patients with a high peritoneal pe

ISSN:1660-8151    

DOI:10.1159/000188738

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

A retrospective single-center cohort study was conducted on 35 patients with diffuse proliferative (WHO type IV) and/or membranous (type V) lupus nephritis (22 with type IV, 6 with type V, and 7 with type IV plus V) who had been treated with a sequential regimen comprising prednisolone and cyclophosphamide during active disease, followed by low-dose prednisolone and azathioprine maintenance. The follow-up period was 33.2 ± 4.5 months. At presentation, 32 (91.4%) patients were nephrotic, and an abnormal serum cre-atinine level was noted in 14 (48.3%) patients with type IV changes. Cyclophosphamide was given for 26.8 ± 2.8 weeks. 33 (94.3%) patients achieved complete or partial renal remissions: 77.3 and 22.7% of the type IV patients, 16.7 and 66.6% of the type V patients, and 14.3 and 71.4% of the type IV plus V patients, respectively (p < 0.0001 for type IV versus type V and for type IV versus type IV plus V). The duration of therapy before renal remissions and normalization of C3 were attained was similar among the three groups of patients. Disease relapse occurred in 4 (18.2%) of 22 type IV patients and in 1 of the 5 type V patients in remission. Mortality was not observed, and none of the patients had an increase in serum creatinine level to double the baseline value. Adverse effects related to therapy included: hair loss (42.9%), transient amenorrhea (53.6%), leukopenia (11.4%), febrile episodes (14.3%), and herpes zoster (28.6%). We conclude that sequential use of prednisolone and cyclophosphamide followed by low-dose prednisolone and azathioprine can achieve favorable therapeutic results in the majority of patients with diffuse proliferative and/or membranous lupus nephritis, without excessive toxici-tie

ISSN:1660-8151    

DOI:10.1159/000188739

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We report the results of a biochemical evaluation of long-term treatment of cystinuria with the SH compound tiopronin (2-mercaptopropionylglycine). The effects of tiopronin were studied by monitoring the urinary excretion of free cystine and the mixed disulfide between tiopronin and cysteine. Thirty-one patients with homozygous cystinuria were treated with tiopronin for 0.4-12 years (mean 7.8 years). The urinary concentration of free cystine was used to adjust the tiopronin dose. In 28 of the 31 patients a mean urinary cystine concentration of less than 1,200 μmol/1 (288 mg/l) was achieved with the final dose. The final daily doses of tiopronin ranged from 250 mg (1.5 mmol) to 3,000 mg (18.4 mmol; mean 1,540 mg; 9.4 mmol). In a majority of the patients the treatment reduced the 24-hour urinary free cystine excretion effectively, on average by 0.61 μmol (0.15 mg)/mg of tiopronin administered. No changes in the efficacy of tiopronin over time were observed, and the frequency of adverse effects was acceptable. To evaluate the effects of tiopronin on the metabolism of cystine we calculated the total urinary excretion of cystine as the sum of free cystine and the amount of cystine corresponding to the cysteine content of the tiopronin-cysteine disulfide. At low doses of tiopronin there was an increase in urinary excretion of the mixed disulfide as well as of total cystine, whereas higher doses were followed by an unexpected decrease in the urinary excretion of these compounds. We conclude that long-term treatment with tiopronin in cystinuria effectively reduces the urinary excretion of free cystine. Monitoring urinary cystine concentration is necessary to achieve adequate individualized doses of tiopronin. Assessment of the mixed tiopronin-cysteine disulfide and the urinary excretion of total cystine shows that tiopronin may interfere with cystine metabolism in a more complex way than through a simple disulfide exchange reaction with urinary cystin

ISSN:1660-8151    

DOI:10.1159/000188740

出版商:S. Karger AG    

年代:1995

数据来源: Karger