Cytokines and adhesion molecules in renal vasculitis and lupus nephritis

Background: Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules. Methods: Plasma levels and urinary excretion of tumour necrosis factor-&agr; (TNF-&agr;), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 15 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated. Results: Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-&agr; (9.27±3.19% vs 0.58±0.02%, P<0.01), IL-6 (120.79±65.83% vs 1.89±0.34%, P<0.01) and increased fractional excretion of IL-8 (23.34±6.38% vs 2.56±1.07%, P<0.01) and sVCAM-1 (0.81±0.33% vs 0.03±0.02%, P<0.01) compared with controls. Urinary excretion of TNF-&agr; and IL-6 and fractional excretion of TNF-&agr;, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-&agr; (20.52±2.01 pg/ml vs 12.33±0.23 pg/ml, P<0.05) and sVCAM-1 (1537.88±276.36 ng/ml vs 692.26±44.42 ng/ml, P<0.05) and increased urinary excretion of TNF-&agr; (2.81±0.51 &mgr;g/mol creat vs 0.98±0.05 &mgr;g/mol creat, P<0.01), IL-8 (35.78±14.03 &mgr;g/mol creat vs 12.46±5.19 &mgr;g/mol creat, P<0.05) and sVCAM-1 (48.98±20.20 &mgr;g/mol creat vs 2.92±1.35 &mgr;g/mol creat, P<0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-&agr; (18.10±0.57 pg/ml vs 12.33±0.23 pg/ml, P<0.05). Conclusions: Urinary excretion and fractional excretion, but not plasma levels of selected proinflammatory cytokines (TNF-&agr;, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.     

Does long-term treatment of renal anaemia with recombinant erythropoietin influence oxidative stress in haemodialysed patients?

Background. Patients with end-stage renal failure undergoing haemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) were demonstrated in plasma of uraemic patients, indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The aim of our investigation was to examine the role of renal anaemia in oxidative stress in HD patients. Methods. MDA and 4-hydroxynonenal (HNE) were measured in three groups of patients undergoing HD: group I comprised eight patients with a blood haemoglobin (Hb) <10 g/dl (mean Hb=8.1±1.3 g/dl), and group II were eight patients with a Hb <10 g/dl (mean Hb=12.4±1.9 g/dl); none of these 16 patients had been treated with human recombinant erythropoietin (rHuEpo). Group III comprised 27 patients with a mean Hb of 10.5±1.6 g/dl after long-term rHuEpo treatment. Results. Mean plasma concentrations of both MDA and HNE were significantly higher (P<0.0001) in all 43 HD patients than in 20 healthy controls (MDA 2.85±0.25 vs 0.37± &mgr;M, HNE 0.32± vs 0.10±0.01 &mgr;M). Comprising the three groups, it was shown that HD patients with a Hb <10 g/dl had significantly higher plasma levels of LPO products (MDA 3.81±0.86 &mgr;M, HNE 0.45±0.07 &mgr;M) than HD patients with a Hb > 10 g/dl (MDA 2.77±0.58 &mgr;M, HNE 0.25±0.05 &mgr;M), and than HD patients treated with rHuEpo (MDA 2.50±0.12 &mgr;M, HNE 0.29±0.03 &mgr;M). Furthermore, an inverse correlation between plasma concentration of LPO products and haemoglobin levels was seen (r=0.62, P<0.0001). Conclusion. Radical generation in HD patients might be caused in part by renal anemia itself. Treatment with rHuEpo may decrease radical generation effectively in HD patients due to the increase in the number of red blood cells and blood haemoglobin concentration. Keywords: erythropoietin; haemodialysis; HNE; lipid peroxidation; MDA; renal anaemia      

Insulin resistance is a common denominator of post-transplant diabetes mellitus and impaired glucose tolerance in renal transplant recipients

Background. Post-transplant diabetes mellitus is a known complication of steroid therapy in renal transplant recipients. Both insulin resistance and insulin deficiency have been shown to be necessary for development of post-transplant diabetes mellitus. It is not known whether recipients with impaired glucose tolerance have similar degree of insulin resistance or deficient insulin response as recipients with post-transplant diabetes mellitus. Methods. To address this question, we used an oral glucose tolerance test to categorize 46 renal transplant recipients on triple immunosuppressive medication to groups with normal glucose tolerance, impaired glucose tolerance or post-transplant diabetes mellitus. Insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp. Insulin response was calculated from the increase in serum insulin concentration during the oral glucose tolerance test. Results. Twenty-five were categorized to normal glucose tolerance, 15 to impaired glucose tolerance and six to post-transplant diabetes mellitus. There were no statistically significant differences between the groups regarding prednisolone dose, azathiprine dose, use of {beta}-blocker, age, gender, weight, waist-hip ratio, body mass index, donor source, smoking habits, or first-degree relatives with histories of diabetes mellitus. The impaired glucose tolerance and post-transplant diabetes mellitus groups showed a significant reduction in insulin-stimulated glucose disposal rate (mg/kg^.min) compared to the normal glucose tolerance group (4.6±1.6 and 3.4±1.3 respectively vs 7.1±2.4, P<0.05). The insulin response (picomol/l) was not different between the normal glucose tolerance and impaired glucose tolerance groups but was significantly reduced in the post-transplant diabetes mellitus group (448±310 and 450±291 respectively vs 170±128, P<0.05).Conclusion. Insulin resistance is a common denominator of post-transplant diabetes mellitus and impaired glucose tolerance in renal transplant recipients.     

Esophageal replacement with colon in children using either the intrathoracic or retrosternal route: An analysis of both surgical and long-term results

A total of 28 colon esophageal replacements performed in children for long gap esophageal atresia (22 patients), and intractable caustic stricture (6 patients) were reviewed. Emphasis was placed on identifying the pros and cons of the different reconstruction techniques: intrathoracic route (ITR) (19 patients) and retrosternal route (RSR) (9 patients). No hospital mortality occurred, whereas a higher morbidity rate occurred among patients operated on using the ITR as opposed to the RSR (68%vs 55%;P not significant). Six patients developed an anastomotic fistula (21% with the ITRvs 22% with the RSR;P not significant), whereas an anastomotic stenosis occurred in 13 patients (67% with the RSR, and 37% with the ITR;P<0.07). Overall, dysphagia was the most prevalent symptom at 3 months follow-up, but had significantly decreased at the final follow-up (54%vs 16%;P<0.0027). Functional results improved significantly during the follow-up (score 1–2vs score 3–4; Fisher test:P=0.001). However, despite the higher morbidity rate, better functional results were achieved using the ITR as opposed to the RSR.     

Effect of different membranes on amino-acid losses during haemodialysis

Background: We analysed amino-acid losses during haemodialysis, their influence on plasma amino-acid concentration, and their possible effects on nutritional state. Methods: Five patients were dialysed with three membranes: cuprophan (CUP), polysulphone (PS), and polyacrylonitrile AN69 (PAN). We compared anthropometric and biochemical parameters after 6 months in patients dialysed with CUP respect to patients with PAN. Results: Total losses of amino acids were higher with PAN than with PS and CUP (6.1±2.3 vs 3.8±1.3, P <0.05, and 3.7±1.3 g/session, P <0.01 respectively). Losses of essential amino acids (EAA) and non-essential amino acids (NEAA) were also higher with PAN respect to PS and CUP (1.8±0.8 vs 1±0.3 and 0.8±0.3, and 4.3±1.6 vs 2.8±1 and 2.9±1.1 g/session, P <0.05). The percentage reduction for plasma EAA and NEAA were lower with CUP respect to PS and PAN (11±5% and 20±14% vs 25±10% and 33±11%, and 30±11% and 25±17% respectively, P <0.05). There was no difference in the nutritional state between patients with CUP and PAN. However, plasma valine in patients with PAN was lower than in those with CUP (1.88±0.12 vs 2.13±0.32 mg/dl) and almost reached statistical significance. Conclusions: New synthetic membranes are advantageous with respect to conventional ones, but a disadvantage is the higher amino-acid losses, especially with polyacrylonitrile. Long-term studies are necessary to evaluate the impact of amino-acid losses on nutritional state in patients dialysed with these membranes.     

Calcified plaque is common in the carotid and femoral arteries of dialysis patients without clinical vascular disease

Background. Cardiac and vascular mortality are common in end-stage renal disease (ERSD) and are often attributed to accelerated atherosclerosis. Subjects and methods. We studied 24 non-diabetic ESRD patients without cardiac or vascular disease (M = 12, F = 12) and 24 age-, sex- and race-matched healthy controls. All underwent B-mode ultrasound for carotid and femoral intima-media thickness (IMT) and plaque (% stenosis) together with blood pressure (BP), and echocardiograms to determine left ventricular mass. Results. Both BP and mean IMT were similar in patients and controls. However, discrete plaque was present in 71% (17/24) of patients compared with 21% (5/24) of controls (P = 0.001), and % stenosis was greater in patients (carotid 12.2 ± 11% vs 2.3 ± 5.9%, P <0.0004; femoral 16.4 ± 19.1% vs 3.1 ± 6.4%, P <0.003). Plaque was soft/atheromatous in 3 of the 5 controls, but not in any of the 17 patients (P = 0.007), all of whom had calcified lesions. BP and cholesterol were not correlated with IMT or plaque in patients, but in control subjects carotid IMT was correlated with systolic BP (r = 0.66, P <0.0005) and diastolic BP (r = 0.45, P <0.03). In patients, the only independent variables related to vascular morphology were serum albumin which was inversely related to IMT (P <0.03) and to plaque (carotid P <0.05, femoral P <0.02) and age, which was related to femoral plaque only (P <0.04). Left ventricular end-diastolic internal dimension not LVMI, correlated positively with carotid IMT (P <0.04). Conclusion. Our results show that calcified plaque is common in ESRD patients and hypoalbuminaemia may be an associated factor. Keywords: B-mode ultrasound; carotid and femoral artery; end-stage renal disease; calcification      

Prevalence, determinants, and clinical significance of hyperhomocyst(e)inaemia in renal-transplant recipients

Background: Previous studies have demonstrated that hyperhomocyst(e)inaemia is present in patients with impaired renal function and is correlated with cardiovascular disease. Because conflicting data are available on the prevalence, determinants, and clinical significance of hyperhomocyst(e)inaemia in renal-transplant recipients, we conducted the largest cross-sectional study on homocysteine determinants and clinical correlates in renal transplant recipients. Methods: Plasma homocyst(e)ine concentrations and factors known to influence homocysteine metabolism were analysed in 224 renal transplant recipients. Atherosclerotic complications were evaluated with respect to plasma homocysteine concentrations. Results: Mean plasma homocyst(e)ine was 21.3±9.7 &mgr;mol/l. After adjusting for age, gender, transplant duration and creatinine clearance, patients with and without cyclosporin A (CsA) had similar plasma homocyst(e)ine concentrations (16.9±5.9 &mgr;mol/l in CsA(+) patients vs 16.3±5.2 &mgr;mol/l in CsA(-) patients; P=0.3). We found a significant inverse relationship between plasma homocyst(e)ine and folate concentrations in both CsA(+) (r=-0.243; P<0.005) and CsA(-) (r=-0.396; P<0.05) patients. Patients with a past history of cardiovascular events had higher plasma homocyst(e)ine concentrations (25.2±11.7 mmol/l vs 20.5±8.8 mmol/l; P<0.005). Conclusion: Homocyst(e)inaemia is closely related to renal function and folate concentration in renal-transplant recipients. CsA does not seem to have direct effects on homocysteine metabolism. Hyperhomocyst(e)inaemia is associated with cardiovascular disease in renal-transplant recipients. Prospective placebo-controlled homocysteine-lowering therapy studies are required in this patient category.     

Desferrioxamine improves burst-forming unit-erythroid (BFU-E) proliferation in haemodialysis patients

Background: In chronic renal failure, desferrioxamine (DFO) may improve erythropoiesis independent from its aluminium (Al) chelating effect. The mechanism of this action is still unknown. Methods: To verify whether DFO influences proliferation of erythropoietic precursors, we studied 10 patients on chronic haemodialysis, free from malignancies or other haematological diseases, iron deficiency, bone marrow fibrosis, and Al toxicity. Al accumulation was excluded by the DFO test. Peripheral blood samples were drawn for basal burst-forming unit-erythroid (BFU-E) assay. Mononuclear cells were isolated by density gradient centrifugation with Ficoll-Hypaque, and incubated for 15 days with three different experimental conditions: (a) low-dose recombinant human erythropoietin (rHuEpo) (3 U/ml); (b) high dose rHuEpo, (30 U/ml); (c) both DFO (167 &mgr;g/ml) and rHuEpo (3 U/ml). We determined TIBC, transferrin, ferritin, reticulocytes, hypochromic erythrocytes, soluble transferrin receptor (sTR), haemoglobin (Hb), and haematocrit (Hct) at baseline and then every 14 days. Patients received 5 mg/kg DFO infused during the last hour of each dialysis session for 6 weeks; six patients remained in the study for an additional 6 more weeks. BFU-E assays were set up after 6 and 12 weeks of DFO therapy. Results: At baseline DFO had small effect on BFU-E proliferation (33.9±25 vs 30.4±25.9) and high-dose rHuEpo had a significant effect (45.15±27 vs 30.4±25.9, P<0.01). After 6 weeks of DFO therapy a significant increase in BFU-E proliferation was observed in all culture conditions (78.25±32 vs 30.45±25.9 standard culture, P<0.01; 110.9±30 vs45.15±27 high dose rHuEpo, P<0.01; 98.75±32 vs 45.15±27 DFO culture, P<0.01). Moreover, the increase in BFU-E proliferation was significant greater with DFO culture than standard culture (P<0.01). The same trend was found at the third BFU-E assay, performed in only six patients, when all culture conditions showed a further increase of erythroid precursor proliferation. However, the DFO culture was not significantly greater than the standard culture, while the high-dose rHuEpo was significantly greater than the DFO culture. Patients in group 1 (n=10), had a significant increase in reticulocytes (1.5±0.6 vs 1.72±0.3, P<0.01) and of hypochromic erythrocytes (HE) (5.6±5.1 vs 14.4±12.7, P<0.01), while sTR, Epo, Hb, and Hct were only minimally increased. Ferritin decreased significantly (448±224 vs 196±215, P<0.01) and TIBC and transferrin were unchanged. Conclusions: Thus DFO increases erythroid activity by BFU-E proliferation and increases reticulocytes in haemodialysis patients. Such an effect may be related to increased iron utilization. DFO may be a useful tool for anaemic patients with good iron stores and without Al overload. Key words: desferrioxamine; erythroid progenitors; erythropoiesis; haemodialysis      

Maintenance cyclosporin monotherapy after renal transplantation-clinical predictors of long-term outcome

Background. There is considerable debate about whether maintenance cyclosporin (CsA) monotherapy is advisable or not in renal transplantation. Methods. Between August 1984 and December 1989, 463 adult patients received a first cadaver graft. Initial immunosuppression was sequential: antilymphocyte or antithymocyte globulins (10-14 days), prednisone and azathioprine were combined and CsA was introduced (6-8 mg/kg/day) when the antilymphocyte or antithymocyte globulins were discontinued. When the graft function was stable and the peak of preformed lymphocytotoxic antibodies was &les:25% and/or the number of rejection episodes was ⩽1, the steroid therapy was stopped within 1.5-3 months after transplantation, and azathioprine within 3-12 months. Patients with both anti HLA antibodies >25% and more than one rejection episode were excluded. Cyclosporin doses were adapted for whole-blood trough levels between 100 and 200 ng/ml (monoclonal antibody radioimmunoassay or high-performance liquid chromatography). Cyclosporin monotherapy was attempted in 234 of the 463 patients. Results. At the end of the investigation in January 1993 (follow-up time >36 months, mean 60.5±4.5 months), 135 patients were receiving CsA without steroids or azathioprine. The 99 CsA monotherapy failures were due to rejection episodes in 48 cases, CsA A nephrotoxicity in 26 cases, and other causes in 25 cases, including five deaths and four with poor compliance. Renal function was stable in patients with successful CsA monotherapy: mean creatininaemia was 124±10 &mgr;mol/l at the time of CsA monotherapy inclusion and 129±10 &mgr;mol/l at the end of follow-up (mean time of CsA monotherapy 52±6 months). The parameters for predicting monotherapy success were age (43.2 versus 27.8, P=0.0014), timing of trial inclusion ⩾6 months post-transplant (7.9&;plusmn; versus 5.3&;plusmn;3.1 months, P=0.04), and excellent and stable renal function at the time of inclusion (124±10 versus 145±32 &mgr;mol/l, P<0.001). Conclusions. Maintenance CsA monotherapy was effective in 58% of low-immunological-risk first-graft patients and probably did not jeopardize overall results of our first grafts: patient and graft survival were respectively 90 and 73% at 6 years. We propose this policy to avoid long-term complications of glucocorticoid and azathioprine in selected compliant recipients with low immunological risk, follow-up time post-transplantation >6 months, and stable creatinaemia levels.     

Insulin resistance precedes microalbuminuria in patients with insulin-dependent diabetes mellitus

Background. Insulin resistance has been associated with hypertension and with renal complications in patients with type 1 diabetes mellitus. Causal relationships have not been fully explained. Methods. We investigated whether insulin resistance precedes microalbuminuria by measuring insulin resistance with a euglycaemic clamp in combination with indirect calorimetry in 16 uncomplicated type 1 diabetic patients and in six healthy control subjects. The patients had over 10 year duration of diabetes, and were expected to experience either a complication-free or complicated disease course within the next few years. They have thereafter been followed for the development of microalbuminuria for 3 years. Results. In a euglycaemic insulin clamp glucose disposal was lower in diabetic patients compared with control subjects (7.5±2.9 and 12.6±2.0 mg/kg LBM/min; P<0.002), mainly due to impaired glucose storage (4.3±2.3 vs 8.6±1.6 mg/kg LBM/min; P<0.001). Three years later seven IDDM patients had albumin excretion rate over 30 mg/24 h; glucose disposal (5.5±2.1 vs 9.0±2.2 mg/kg LBM/min; P<0.01) had been lower in patients who developed microalbuminuria compared with those who remained normoalbuminuric. Conclusions. Insulin resistance predicts the increment in urinary albumin excretion. Insulin resistance depends mainly on impaired glucose storage in uncomplicated IDDM.     

Endothelin and cardiovascular remodelling in end-stage renal disease

Background. Plasma endothelin (ET) is elevated in end-stage renal disease (ESRD), but the origin and consequences of this increase remain unclear. In the present study we analysed the relationships between plasma ET levels and cardiovascular alterations in ESRD. Methods and results. Common carotid artery (CCA) intima-media thickness (IMT) and diameter, atherosclerotic plaque occurrence, and left ventricular (LV) geometry and function were determined by ultrasound imaging in 76 haemodialysis patients and in 57 age-, sex-, and blood pressure-matched controls. Arterial stiffness was evaluated via carotid-femoral pulse wave velocity (CF-PWV), forearm post-ischaemic vasodilation was measured by venous plethysmography, and plasma ET levels were determined using a specific immunoenzymoassay. Compared with controls, ESRD patients had elevated plasma ET levels (1.6±1.4 vs 4.6±3.8 pg/ml; P<0.001), increased LV mass (P<0.001), increased CCA-IMT (P<0.001), a higher prevalence of atherosclerotic plaques (P<0.001) and increased CF-PWV (P<0.01). Plasma ET levels correlation positively with LV outflow velocity integral (r=0.57; P<0.0001), stroke index (P<0.01), and baseline forearm blood flow (P<0.001) which were all significantly higher in ESRD patients than in controls (P<0.01). After adjustment for age, blood pressure, haemoglobin levels, gender and body dimensions, plasma ET levels were significantly correlated to LV mass (r=0.46; P<0.001), CCA-IMT and CCA intima -media cross-sectional area (r=0.41; P<0.001), and CF-PWV (p<0.05). Post-ischaemic forearm vasodilation was decreased in ESRD (85±31 vs 119±28%; P<0.001) and there was a negative correlation between post-ischaemic flow recovery and ET levels (r=-0.49; P<0.001). In ESRD patients, plasma ET levels were positively and independently correlated with the prevalence of CCA atherosclerotic plaque (P<0.01). Conclusions. These results indicate that the increased plasma ET levels in ESRD patients are associated with left ventricular hypertrophy and arterial intima-media thickening, suggesting that increased ET concentrations in ESRD patients may be of pathophysiological significance in the process of cardiovascular remodelling.     

Increased urinary adrenomedullin excretion in children with urinary-tract infection

Background: Adrenomedullin (AM), a smooth-muscle relaxant peptide, is stimulated by cytokines and bacterial endotoxins. We hypothesized that urinary-tract infections may be associated with elevated urinary AM excretion. Methods: AM in urine was quantified in eleven children with urinary-tract infection and 11 age- and sex-matched controls by radioimmunoassay. RT-PCR was used to demonstrate local AM mRNA expression in the urinary tract. Results: In healthy controls but not in diseased children there was a significant correlation between AM and creatinine in urine (r-0.91, P<0.001). AM levels in children with urinary tract infection were significantly higher than in controls (0.6±0.41 vs 0.15±0.14 ng/&mgr;mol creatinine; P<0.001; (means±SD)). There was a significant correlation between white cell count and AM in urine (r-0.78, P<0.001). AM mRNA was expressed in renal tissue, renal pelvis, ureter, bladder, and urethra. Conclusion: The smooth-muscle relaxant peptide adrenomedullin that is synthesized in tissue of the human urinary tract is elevated in urine of patients with urinary-tract infections. A possible consequence might be the interference with the ureteral anti-reflux mechanisms.     

Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial

Background: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. Methods: To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 &mgr;g twice a week, n=10) or daily (0.75 &mgr;g a day, n=8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders. Results: Pharmacokinetic analysis after a single dose of 3.0 &mgr;g (pulse) vs 0.75 &mgr;g (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse=562±291 vs daily=454±113 pg/ml), calcium (pulse=2.32±0.20 vs daily=2.32±0.12 mmol/l) and phosphorus (pulse=1.32±0.52 vs daily=1.35±0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and rate of decline in PTH were similar (time: pulse=14.2±6.8 weeks, daily=12.2±7 weeks; rate: pulse=7.4±4.2 vs daily=8.4±4.2% PTH/week; P=NS). The serum calcium increased similarly in both groups. Hypercalcaemia (>2.9 mmol/l) was rare (pulse=3, daily=2 episodes). Conclusions: This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy. Key words: calcitriol; calcium balance; CAPD; dialysis; hyperparathyroidism; renal osteodystrophy      

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection

Background  Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. Methods  We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Results  Pre-transplant and post-operative levels of serum sCD30 were 58.10 ± 52.55 and 51.55 ± 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Conclusion  Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.     

The absorption of iron is disturbed in recombinant human erythropoietin-treated peritoneal dialysis patients

Background. Intravenous iron supplementation is often necessary in recombinant human erythropoietin (r-HuEPO)-treated haemodialysis (HD) patients, but rarely in r-HuEPO-treated peritoneal dialysis (PD) patients. This may be due to differences in iron absorption or blood loss. Method. Iron absorption (whole-body counting after ingestion of a radiolabelled iron test dose) and iron metabolism were compared in eight iron-replete r-HuEPO-treated PD patients (serum ferritin 100-500 &mgr;g/l) and 68 healthy iron-replete controls (sufficient iron in bone marrow specimen). Results. Mucosal uptake (13.4±9.8), mucosal transfer (0.34±0.18) and iron retention (4.9±4.0) in PD patients was significantly lower than in controls (42.9±18.8%, P<0.0001, 0.63±0.18, P<0.0001, and 28.0±16.7%, P<0.0001). Conclusion. Iron absorption is impaired in PD patients, as we have shown previously for HD patients. One reason for higher iron needs in HD patients may be higher blood losses due to the dialysis procedure and blood sampling for laboratory tests.     

Inflammatory reactions after vascular prosthesis implantation: A comparison of gelatin-sealed and unsealed dacron prostheses

Despite widespread use of the gelatin-sealed knitted Dacron prosthesis (GDP) in clinical practice owing to its zero porosity, the biological impacts of this graft are still controversial. We conducted a randomized controlled study on 50 patients undergoing abdominal aortic aneurysm repair to evaluate the inflammatory reaction to GDP (n=25) and unsealed knitted Dacron prostheses (UDP, n=25). There were no significant differences in the mean age, size of the aneurysm, operative time, blood loss, or transfusion requirements between the GDP and UDP groups. During the first 7 postoperative days (PODs), slight fever and leukocytosis were noticed in both groups. Significant differences in maximum body temperature, leukocyte count, and plasma C-reactive protein concentration were observed between the GDP and VDP groups on POD 14: 37.2±0.5°C vs 36.9±0.3°C (P=0.019), 8,151±1,788/l vs 6,914±1,501/l (P=0.015), and 32.6±27.5mg/l vs 19.0±15.8mg/l (P=0.048), respectively. By POD 21, however, there were no detectable differences in these variables. Thus, we concluded that GDP caused an inflammatory reaction in the 2nd week after implantation, but ultimately there were no significant differences from UDP by the 3rd week.     

Long-term linear growth of children with severe steroid-responsive nephrotic syndrome

The present study was designed to evaluate the risk of permanent linear growth impairment in a selected group of 42 children with steroid-dependent nephrotic syndrome (SDNS) and 14 children with frequently relapsing nephrotic syndrome (FRNS). Longitudinal height measurements were available in all patients from the onset of the disease for a mean follow-up of 11.7±3.5 years. During the prepubertal period, patients lost 0.49±0.6 height SD score (HtSDS) (P<0.001). Twenty-three patients have reached their final height with an average loss of 0.92±0.8 HtSDS from the onset of their disease (P<0.001) and 0.68±0.7 from their target HtSDS (P<0.001). The pubertal growth spurt was mildly delayed in male but not female patients. Steroid therapy, calculated as the mean duration of prednisone (PDN) treatment or as the average cumulative PDN dose, was the only predictor of poor growth evolution. Partial catch-up growth occurred after PDN withdrawal. Children with early onset NS and adolescent patients, who were still receiving PDN after the age of 9 years in girls and 11 years in boys, were at higher risk for HtSDS loss. In conclusion, children with severe steroid-responsive NS are at risk of permanent growth retardation secondary to prolonged courses of steroid treatment.     

Thymic function, anti-thymocytes globulins, and cancer after renal transplantation

Background

Prolonged CD4 T cell lymphopenia after polyclonal antithymocyte globulins (ATG) is associated with an increased rate of cancers. Here, we examined whether pre-transplant thymic function estimated by TREC levels is predictive of cancer occurrence following ATG treatment.

Patients and methods

The impact of TREC on cancer occurrence was analyzed in 115 consecutive incident renal transplant recipients having received ATG.

Results

Mean follow-up was 7.5 ± 2.6 years. After ATG induction, patients with the lowest pre-transplant TREC values had lower post-transplant CD4⁺ and CD4⁺ CD45RA⁺ CD45RO⁻ T cell counts, and a higher frequency of T cells with a regulatory phenotype (CD127⁺CD4⁺CD25⁺Foxp3⁺). Log-transformed pre-transplant TREC values were significantly lower in patients who developed cancer after transplantation (p < 0.0001). The cumulative incidence of cancer was higher in patients having the lowest pre-transplant TREC values (T1 [low]: 47.4%, T2 [medium]: 12.5%, and T3 [high]: 2.7%; p < 0.0001). In multivariate analysis, pre-transplant TREC value was the only predictive factor of cancer (HR, 0.39; 95% CI, 0.16 to 0.97, for one log (TREC/10⁶ PBMC); p = 0.046).

Conclusions

Pre-transplant thymic function is associated with an increased rate of post-transplant cancer in patients having received ATG. Omitting ATG in recipients with low pre-transplant TREC values should be considered.     

Pre-Transplantation Immune Cell Distribution and Early Post-Transplant Fungal Infection Are the Main Risk Factors of Liver Transplantation Recipients in Lower Model of End-Stage Liver Disease

Background

The prognosis of patients after liver transplantation (LTx) with high Model of End-Stage Liver Disease (MELD) score (>30) is predicted, but patients with lower MELD scores (<30) have no conclusive studies of pre- and post-transplant risk factors that influence the long-term outcome.

Clinical evaluation and follow-up outcome of presurgical plan by Dextroscope: a prospective controlled study in patients with skull base tumors

Background

Patient-specific approach design, comprehensive evaluation on perioperative data, and follow-up of postoperative life quality (KPS) were carried out to evaluate the application of VR technology of Dextroscope in procedures of patients with skull base tumors.

Methods

Eighty-four patients with skull base tumors involved in this research were randomized into 2 groups (test group and control group), each with 42 patients. Before operation, image data such as MR, MRA, or CTA of head were collected and imported into the Dextroscope workstation. The detailed preoperative plans were made in the test group, but no Dextroscope plans in control group. The resection rate of tumors, preoperative evaluation including the duration of operation, total blood loss, the postoperative LOS, the number of cases with cerebrovascular injury complications in operation, and postoperative KPS of patients on discharge and the sixth month follow-up in the 2 groups were recorded and compared.

Results

The total resection rate of tumors was 83.33% in test group and 71.42% in the control group (P > .05). The total resection rate of meningioma was 86.67% in test group and 76.47% in control group. The total resection rates of trigeminal Schwannoma in the 2 groups were all 100% (P > .05). The duration of operation and the postoperative LOS of each patient were 5.25 ± 0.64 hours and 8.50 ± 1.10 days in the test group and 7.36 ± 0.87 hours and 12.50 ± 1.52 days in the control group, respectively (P < .05). Total blood loss of each patient was 456.75 ± 55.76 mL in the test group and 523.85 ± 66.78 mL in the control group (P > 05). There were 3 cases with complications of cerebral vessels injury in the test group and 7 cases in the control group (P < .05). During follow-up, KPS of patients in the test group on discharge (85.75 ± 9.68) was significantly superior to that in the control group (81.66 ± 9.24; P < .05). The KPS of patients on the sixth-month follow-up in the test group was 92.35 ± 9.95, which was significantly superior to that in the control group (85.6 ± 9.34; P < .05). Karnofsky performance scores of patients in the test group improved significantly from discharge to the sixth month after procedure (P < .05), whereas there were adverse results in the test group (P < .05). The 2 cases with CSF leakage were cured completely.

Conclusion

The preoperative plans with VR technology in patients with skull base tumor or CSF leakage operations can help certain the diagnosis, individually locate the position of skull base lesions, and design patient-specific approach, which also facilitate to shorten operation duration and the postoperative LOS, reduce total blood loss and injury of vessels in operation, and improve the postoperative KPS.