摘要:

After transplantation the kidney is subjected to rejection and other deleterious factors including ischemic damage, acute tubular necrosis, rejection and the use of cyclosporine A (CsA) or FK506. As a result, kidney damage may be generalized with azotemia as its hallmark. These tubular syndromes may cause profound changes in the acid base balance and in the level of certain blood electrolytes and minerals. As a general rule, the renal tubular acidosis (RTA) that appears early following transplantation disappears spontaneously and is predominantly a sequela to acute renal failure. On the other hand, defects occurring in the late posttransplant period are often due to chronic rejection or CsA-induced nephrotoxicity. Secondary hyperparathyroidism, urinary tract infection and obstructive uropathy may also play a contributory urinary role in the pathogenesis of RTA. Chronic RTA following transplantation may interfere with bone metabolism and at times lead to nephrocalcinosis and nephrolithiasis. Therefore, if the condition is prolonged, a supplement of bicarbonate should be given if for no other reason than to protect the skeleton. As these patients may develop either hyperkalemia or hypokalemia, treatment with potassium supplements or potassium-sparing diuretics should be carried out with caution and under constant surveillance. Furthermore, magnesium replacement may be advisable if hypomagnesemia by decreased proximal reabsorption becomes clinically evident. Tubular dysfunction may occur following renal transplantation even in patients with maintained glomerular filtration rate and may induce a number of clinical problems including deterioration of renal graft function.

ISSN:1660-8151    

DOI:10.1159/000189443

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Sixteen kidney transplant (KT) patients (10 men, 6 women, aged 49 ± 10 years) with chronic hepatitis C α-interferon (IFN-α) therapy (Intron A®, Schering Plough) at a dose of 3 × 106 units subcutaneously 3 times a week. The treatment was scheduled for 24 consecutive weeks. Each patient had had stable renal function for at least 12 months prior to IFN-α therapy (mean serum creatinine, SCr, 121 ± 38 mmol/l). Fourteen patients were receiving cyclosporin-A (CsA)-based immunosuppression and 2 patients were on conventional therapy. The patients’ SCr was checked every 2 weeks while on IFN-α, or weekly if it increased more than 15% from baseline. IFN-α was withdrawn if SCr increased more than 25% from baseline, in which case a kidney biopsy was performed. Six patients experienced either acute (n = 5) or subacute (n = 1) renal failure within 7-24 weeks after the onset of IFN-α therapy. Their mean SCr increased from 105 ± 31 to 207 ± 63 mmol/l (p = 0.02) with de novo proteinuria in 1 case (1 g/day) and an increase in preexisting proteinuria in 2. The other 3 patients did not develop proteinuria. In each case, histological study showed diffuse interstitial edema associated with dilation of the peritubular capillaries, whereas mild inflammatory infiltrates were present in only 3 cases and mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There were no vascular lesions. IFN-α was withdrawn in these 6 patients, in association with methylprednisolone pulses in 5 cases. Renal function improved in 2 cases, stabilized in 1 and progressed to end-stage renal failure in 3 within 4-12 months. Four of these patients had iterative renal biopsies which showed diffuse interstitial fibrosis in each case. The patients who developed renal failure did not statistically differ at the start of the study from those who did not, with respect to the following: baseline immunosuppression, HLA matching, total peripheral blood lymphocyte count or peripheral blood lymphocyte subtypes. IFN-α therapy was associated with acute or subacute renal failure in 37% of the patients. The most prominent histological finding was diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. In conclusion, we do not recommend IFN-α therapy for KT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure are b

ISSN:1660-8151    

DOI:10.1159/000189444

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Fifty-two patients with postrenal transplant erythrocytosis were treated with an angiotensin-converting enzyme inhibitor (lisinopril or enalapril) for a median of 13 months (range 0-44). A significant fall in haemoglobin of 1.8 ± 1.6 g dl-1 (range -0.8 to 6.6) occurred over the first 3 months (p < 0.0001). The haemoglobin then remained stable for as long as 3 years. Both enalapril and lisinopril were equally effective. Therapy was withdrawn in 16 patients (31 %) because of decline in renal function (6), anaemia (5), hypotension (3), hyperkalaemia (1) or erectile impotence (1) – complications which were all reversible. Angiotensin-converting enzyme inhibitors in low dose are a safe and effective long-term therapy for postrenal transplant erythrocytos

ISSN:1660-8151    

DOI:10.1159/000189445

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

To investigate the significance of intraglomerular coagulation and fíbrinolysis in IgA nephropathy (IgA-N) and Henoch-Schönlein purpura nephritis (HSPN), the distribution of intact cross-linked fibrin (XFb) modulated by plasmin activity was examined in 25 patients with IgA-N and in 12 with HSPN. In addition to the conventional method detecting fibrin-related antigen (FRA) with an antibody against fibrinogen, the enhanced intensity of immunoreactivity of cross-linked FRA (XL-FRA) using the monoclonal antibody DD3B6/22 after plasmin exposure was evaluated to assess intraglomerular deposition of intact XFb. Also, intraglomerular invasion of macrophages was detected using the monoclonal antibody KP1 against CD68. Sixteen of a total of 37 specimens (43%) showed increased intensity of XL-FRA staining after plasmin treatment which is considered to reflect the distribution of intact XFb. Increases in the intensity of XL-FRA staining were observed mainly in mesangium and partially along glomerular capillary loops and also in a few cases in the crescents. The incidence (67%) of increases in XL-FRA staining after plasmin exposure in HSPN specimens was significantly higher than that in IgA-N specimens (32%; p < 0.05). In the group positive for XL-FRA after plasmin exposure, the numbers of macrophages per glomerulus were significantly higher (n = 15; mean ± SD = 1.6 ± 0.9) than in the negative group (n = 6; 0.5 ± 0.6; p < 0.01). In HSPN, the number of macrophages per glomerulus (n = 8; 1.9 ± 1.0) was higher than that in IgA-N (n = 13; 0.9 ± 0.9; p < 0.05). Based on these results, we conclude that XFb is often produced and distributed in intact form in the glomeruli both in IgA-N and HSPN, associated with a relatively low intraglomerular plasmin activity, and that intraglomerular coagulation may progress in accordance with macrophage infiltration, especially i

ISSN:1660-8151    

DOI:10.1159/000189446

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

At present, there are very few studies that look at the effect of uremia, prednisone and cyclosporine therapy on the lipid profiles of children. This effect is important because of the potential association of hyperlipidemia and increased risk of cardiovascular morbidity and mortality and glomerulosclerosis. We measured fasting lipid profiles in 73 children. There were 21 controls, 18 patients treated with cyclosporine and prednisone, 9 patients treated with cyclosporine alone and 25 dialysis patients. Lipoprotein (a) levels were measured using direct binding ‘sandwich’ ELISA. Uremic children had higher levels of triglycerides and very-low-density lipoprotein as compared with the control group. Children receiving combination of cyclosporine and prednisone also had higher total cholesterol, triglycerides, low-density lipoprotein, very-low-density lipoprotein as compared to the control group. However, children receiving cyclosporine monotherapy had lipid profiles similar to the control group. Patients receiving cyclosporine and prednisone had higher total cholesterol, high-density lipoprotein and low-density lipoprotein as compared with the dialysis group. Evaluating lipoprotein (a) levels, children on cyclosporine monotherapy had lower lipoprotein (a) levels as compared with children on dialysis and those receiving both combination therapy. The total cholesterol/ high-density lipoprotein-cholesterol ratio (TC/HDL) was similar among the study groups. In summary, uremic children and children receiving steroids with cyclosporine have elevated lipid levels. However, the increased risk for atherosclerosis is not evident because of similar levels of lipoprotein (a) and TC/HDL ratios among the study gro

ISSN:1660-8151    

DOI:10.1159/000189447

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The function of the adenohypophyseal-gonadal axis in haemodialyzed male patients is modified: the serum testosterone level is low, and the gonadotropin levels are increased. The pathogenetic role of secondary hyperparathyroidism in this disorder has not previously been defined. The area under the curve (AUC) and the secretion kinetics of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone after administration of LH-releasing hormone were examined in 7 dialyzed men with secondary hyperparathyroidism (mean age 36.2, range 20-47 years) before and 3 and 6 months after parathyroidectomy (PTX). The operation was successful in all 7 patients, as intact parathyroid hormone declined markedly during both postoperative periods as compared with the values before PTX: 81 ± (SEM) 34 and 138 ± 57 ng/l versus 965 ± 116 ng/l (p < 0.01 and p < 0.01). The testosterone AUC prior to PTX (63 ± 115 nmol/l × min) and 3 months (-4 ± 36 nmol/l × min) and 6 months after PTX (-62 ± 69) did not differ significantly, as was the case with LHAUC(1,110 ± 223 and 1,214 ± 331 and 1,020 ± 314 U/l × min, respectively) and follicle-stimulating hormone AUC (525 ± 334 and 634 ± 347 and 533 ± 264 U/l × min, respectively). The secretion kinetics of all three hormones was atypical as compared with healthy men of similar age, but it did not change after PTX. There were no correlations between the sexual indicators and parathyroid hormone, 1,25(OH)2D3, calcium, or phosphate during the individual periods. These findings indicate that secondary hyperparathyroidism is probably not involved in the dysfunction of the adenohypophyseal-gonadal axis

ISSN:1660-8151    

DOI:10.1159/000189448

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We have previously reported a high prevalence of endemic renal tubular acidosis (EnRTA) in the northeast of Thailand, and our subsequent studies provided evidence that K deficiency exists in the same region. Since tubulointerstitial damage is associated with K deficiency, we postulate that this might be implicated in the pathogenesis of EnRTA and, if so, that a spectrum of tubulointerstitial abnormalities can be anticipated. In this study we evaluated renal acidification ability in 4 patients and in 11 of their relatives. We used a 3-day acid load (NH4CI 0.1 g/kg/day) followed by 20 mg oral furosemide and monitored the maximal renal concentrating ability using water deprivation and intranasal 1-deamino-D-arginine vasopressin. The results showed that the subjects could be divided into three groups: normal relatives of the patients, those with suspected renal tubular acidosis, and patients with overt EnRTA who had chronic metabolic acidosis and a low rate of excretion of NH+4. The rate of excretion of K was very low (20 ± 4 mmol/day) in patients with EnRTA and in their relatives with suspected EnRTA. The transtubular K concentration gradient was also very low in their relatives, especially in patients with suspected EnRTA (2.8 ± 0.2). With a 3-day NH4C1 load, the rate of excretion of N+4 was very low in patients with EnRTA (32 ± 9 mmol/day), and the relatives with suspected EnRTA also had a decreased capacity to excrete N+4 (50 ± 14 mmol/day). In contrast, the normal relatives excreted 92 ± 12mmol of NH+4/day. The patients with EnRTA could not lower their urine pH to less than 5.5 after the acid loading (6.2 ± 0.3). After furosemide (20 mg), the NH4 excretion in the patients with EnRTA was lower than in the normal relatives. Moreover, the minimum urine pH in patients with EnRTA did not fall (6.1 ± 0.2), but there was a fall to 4.8 ± 0.1 in the patients with suspected EnRTA after furosemide treatment. In conclusion, there was a spectrum of tubulointerstitial abnormalities ranging from suspected to overt distal RTA in a geographic area known to have a high prevalence of K deficiency. K deficiency might be the important pathogenetic factor of EnRTA in the northeast of T

ISSN:1660-8151    

DOI:10.1159/000189449

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Correction of anemia with recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease has been associated with improvement of several abnormalities in hypothalamo-hypophyseal functions. The aim of the present work was to evaluate the growth hormone (GH) responses to GH-releasing hormone (GHRH) and clonidine stimulation, as well as the baseline concentrations of insulin-like growth factor I (IGF-I), before and after the correction of anemia with rhEPO in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine clinically stable patients (1 male, 8 female; mean age 55.4 years; mean duration of CAPD 14.1 months) were studied. Twelve normal volunteers were studied as controls. GHRH and clonidine stimulation tests were performed prior to starting rhEPO and again after partial correction of anemia with rhEPO therapy (60-130 U/ kg/week, s.c, for 12 weeks). Blood samples for GH were collected during 2 h after GHRH (100 μg i.v. in bolus) or clonidine (0.15 mg/m2, p.o.) administration. In basal plasma samples IGF-I concentrations were also measured. Mean ( ± SEM) blood hemoglobin concentration rose from 5.32 ± 0.25 to 7.22 ± 0.25 mmol/l (p < 0.001) after rhEPO treatment. GH responses to GHRH were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC)ofGH responses in CAPD patients (9.89 ± 4.01 μg/land 15.06 ± 6.02 μg·h/l, respectively) did not differ from those obtained in control subjects (14.58 ± 3.25 μg/l and 16.94 ± 4.31 μg·h/1, respectively). The study after correction of anemia showed an evident potentiation of GH values that reached statistically significant values at 60 and 90 min. GH AUC after rhEPO therapy rose to 25.61 ± 9.25 μg·h/l (p = 0.01). In control subjects, clonidine administration was followed by a GH release that reached a maximum at 90 min (7.67 ± 2.24 μg/l). However, CAPD patients exhibited a blunted response to clonidine both before (2.00 ± 0.78 μg/l) and after (2.78 ± 0.76 μg/l, NS) correction of the anemia with rhEPO. On the other hand, IGF-I concentrations after rhEPO therapy (32.05 ± 5.52 nmol/l) were not significantly different from those found prior to starting therapy (38.13 ± 8.44 nmol/l). In conclusion, these results suggest that correction of the anemia with rhEPO therapy potentiates GH responses to direct pitiutary stimulation with GHRH although it is unable to restore the blunted response of GH to clonidine that i

ISSN:1660-8151    

DOI:10.1159/000189450

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

This study aims to raise the possibility of methylguanidine, a peroxidative product of creatinine, as a measure of the peroxidative state. As a known standard, we measured the inhibitory effect of uremic serum on the NADPH-dependent microsomal lipid peroxidation. This is an established method for evaluating the peroxidative state and is compared to the effect of uremic serum on methylguanidine synthesis. The study shows decreased serum antioxidant activity in hemodialysis patients by both methods, though there is no correlation between them. These results support the use of methylguanidine as a peroxidative marker and suggest a difference in the reactive oxygen species involved in the reactions of methylguanidine synthesis and microsomal lipid peroxidation.

ISSN:1660-8151    

DOI:10.1159/000189451

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In order to clarify the relation between leukopenia during hemodialysis and leukocyte adhesiveness, the number of circulating leukocytes, their filterability through 5-μm diameter pores, and the concentration of neutrophil elastase in plasma were measured in peripheral blood collected at the beginning of hemodialysis (dialyzer, cuprophane membrane), 15 min into dialysis, and end of dialysis (duration of dialysis, 180 min) in 15 patients with chronic renal failure. Leukopenia was most marked at 15 min in all patients. In accordance with the change in number of circulating leukocytes, the filtration time of the leukocytes, as determined by a modification of the Nuclepore filtration method (filtered blood volume 0.5 ml, leukocyte count 2,500/μl, suction pressure 10 cm H2O, temperature 37 °C) was significantly longer at 15 min versus the beginning and end of the dialysis (p < 0.005 and p < 0.025, respectively). Addition of the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP; 20 nM), to the suspensions immediately increased the leukocyte filtration time. Such FMLP-induced increases were significantly greater at 15 min versus the beginning of dialysis (p < 0.05). This heightened sensitivity of cells to FMLP appeared to persist until the end of dialysis (p < 0.05 versus the beginning). Plasma levels of neutrophil elastases were highest at the end of dialysis versus those at the beginning and after 15 min (both p < 0.005). Results suggest that the changes in filterability of leukocytes may be related to decreases in their number in the circulation. Neutrophil elastase appeared to accumulate in plasma so that its maximal value at the end of dialysis would reflect the preceding changes in leukocyte rheolo

ISSN:1660-8151    

DOI:10.1159/000189452

出版商:S. Karger AG    

年代:1996

数据来源: Karger