Surgical complications and graft survival in pediatric kidney transplant recipients treated with a steroid-free protocol: experiences from a Danish university hospital.

BACKGROUND: The outcome of pediatric kidney transplantation depends on several factors, among these are the complications, which occur in relation to the surgical procedure. In this study, we present our experience with pediatric kidney transplantation in a steroid-free immunosuppression regimen, from a surgical point of view. METHODS: Patient charts of pediatric kidney transplantations in the period 1998-2011 were reviewed. Surgical complications, acute rejection, and patient and graft survivals were recorded. RESULTS: Sixty-one renal transplantations were performed in 58 patients. Thirty patients (49.1%) experienced a surgical complication, of which 11 (18%) required an explorative laparotomy. Overall the five-year Kaplan-Meier patient survival rate was 96.2% and the graft survival rate was 88.6%. Nine patients (14.7%) had an acute rejection episode within the first year after transplantation. No correlation was observed between surgical complications and acute rejection episodes or graft loss. CONCLUSIONS: This study indicated a high incidence of surgical complications among pediatric kidney transplantations when using a steroid-free immunosuppression regimen. Despite this, we observed high overall patient and graft survival, supporting the trend toward steroids avoidance in pediatric kidney transplantation.

Transmission of angiosarcomas from a common multiorgan donor to four transplant recipients.

We describe the donor tumor transmission of metastatic angiosarcomas to four transplant recipients through transplantation of deceased-donor organs, i.e. kidneys, lung and liver, from an apparently unaffected common female multiorgan donor. Fluorescent in situ hybridization of angiosarcoma cells confirmed that the tumor was of female donor's origin in male kidney recipients. Recent literature associated increased urokinase-plasminogen-activator-receptor (uPAR) and plasma soluble urokinase-plasminogen-activator-receptor (suPAR) levels with metastatic malignancies. Now we found that, compared to baseline levels, both deceased-donor kidney recipients showed increased uPAR transcripts in mononuclear cells as well as increased plasma suPAR levels after the diagnosis of metastatic angiosarcomas, i.e. 4 months after donor tumor transmission. These results show an association of uPAR/suPAR in donor tumor transmission of metastatic angiosarcomas in humans.

Mechanisms of renal NaCl retention in proteinuric disease.

In diseases with proteinuria, for example nephrotic syndrome and pre-eclampsia, there often are suppression of plasma renin-angiotensin-aldosterone system components, expansion of extracellular volume and avid renal sodium retention. Mechanisms of sodium retention in proteinuria are reviewed. In animal models of nephrotic syndrome, the amiloride-sensitive epithelial sodium channel ENaC is activated while more proximal renal Na(+) transporters are down-regulated. With suppressed plasma aldosterone concentration and little change in ENaC abundance in nephrotic syndrome, the alternative modality of proteolytic activation of ENaC has been explored. Proteolysis leads to putative release of an inhibitory peptide from the extracellular domain of the γ ENaC subunit. This leads to full activation of the channel. Plasminogen has been demonstrated in urine from patients with nephrotic syndrome and pre-eclampsia. Urine plasminogen correlates with urine albumin and is activated to plasmin within the urinary space by urokinase-type plasminogen activator. This agrees with aberrant filtration across an injured glomerular barrier independent of the primary disease. Pure plasmin and urine samples containing plasmin activate inward current in single murine collecting duct cells. In this study, it is shown that human lymphocytes may be used to uncover the effect of urine plasmin on amiloride- and aprotinin-sensitive inward currents. Data from hypertensive rat models show that protease inhibitors may attenuate blood pressure. Aberrant filtration of plasminogen and conversion within the urinary space to plasmin may activate γ ENaC proteolytically and contribute to inappropriate NaCl retention and oedema in acute proteinuric conditions and to hypertension in diseases with chronic microalbuminuria/proteinuria.

Improved renal function after early conversion from a calcineurin inhibitor to everolimus: a randomized trial in kidney transplantation.

In an open-label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric-coated mycophenolate sodium and corticosteroids. The primary endpoint, change in measured GFR (mGFR) from week 7 to month 12, was significantly greater with everolimus than controls: 4.9 (11.8) mL/min versus 0.0 (12.9) mL/min (p = 0.012; analysis of covariance [ANCOVA]). Per protocol analysis demonstrated a more marked difference: an increase of 8.7 (11.2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p < 0.001; ANCOVA). There were no differences in graft or patient survival. The 12-month incidence of biopsy-proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All but two episodes of BPAR in each group were mild. Adverse events occurred in 95.1% of everolimus patients and 90.0% controls (p = 0.19), with serious adverse events in 53.9% and 38.0%, respectively (p = 0.025). Discontinuation because of adverse events was more frequent with everolimus (25.5%) than controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI-treated controls but discontinuations and BPAR were more frequent.

Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 is not responsible for sodium retention in nephrotic rats.

AIM: In mineralocorticoid target cells 11-beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) converts glucocorticoids into non-active metabolites thereby protecting the mineralocorticoid receptor (MR) from stimulation by glucocorticoids. In nephrotic syndrome, a decreased activity of 11betaHSD2 has been suggested to allow glucocorticoids to stimulate MR, thereby contributing to sodium retention. We tested this hypothesis in the puromycin aminonucleoside model of nephrotic syndrome in rats. METHODS: Complete sodium and potassium intakes and excretions (faeces and urine) were measured in rats in metabolic cages. RNase protection assay of mRNA and Western blotting of protein were used to estimate renocortical expression of 11betaHSD2 and of the MR downstream effector serum and glucocorticoid induced kinase (SGK). In an intervention series, dexamethasone was given [10 microg (100 g bw)(-1)] to suppress endogenous glucocorticoids in the proteinuric stage during active sodium retention. RESULTS: Nephrotic rats developed proteinuria, positive sodium balance, decreased plasma aldosterone concentration, and decreased urinary Na(+)/K(+) ratio. 11betaHSD2 mRNA expression was down-regulated but protein expression was unchanged. SGK mRNA and phosphorylated SGK protein were up-regulated while total SGK protein expression was unchanged. Dexamethasone treatment, which suppressed plasma corticosterone concentration, did not correct sodium balance or fluid retention in nephrotic rats. CONCLUSION: Our results do not support the hypothesis that stimulation of the MR by endogenous glucocorticoids induces sodium and fluid retention in experimental nephrotic syndrome in rats.

Effect of grapefruit juice on Sandimmun Neoral absorption among stable renal allograft recipients.

BACKGROUND: The oral formulation of cyclosporin A (CsA)-Sandimmun-has a highly variable absorption. The development of a CsA microemulsion-Sandimmun Neoral-resulted in increased bioavailability, and decreased variability of absorption. The first oral formulation (Sandimmun) interacted with numerous other drugs and grapefruit juice. Several of these interactions might be explained by decreased pre-systemic metabolism by a cytochrome-enzyme (e.g. CYP3A4) located in the enteral mucosa, and/or via the P-glycoprotein-mediated decreased transport of CsA back from enterocytes into the gut lumen. The purpose of this pharmacokinetic study was to investigate the interaction between Sandimmun Neoral and grapefruit juice. METHOD: Eight stable renal transplant recipients were studied during two 8-h sessions in a randomized cross-over design with 4 weeks interval. Following an overnight fast the patients ingested their habitual morning dose of Neoral either with water or with grapefruit juice. During the 8-h study period 10 blood samples were taken for determination of CsA concentration. These results formed the basis for calculation of area under curve (AUC), and half-life (t(1/2)). Maximum concentration (C(max)) and time until C(max) (t(max)) were obtained from the concentration-time profile. RESULTS: The median AUC increased by 38% (12-194%) (P<0.05) following co-administration of Neoral with grapefruit juice. There were no significant changes in C(max), t(max), and t((1/2)). CONCLUSION: Co-administration of Sandimmun Neoral with grapefruit juice resulted in an increased bioavailability of CsA, indicating unchanged pre-systemic enterocyte first-pass metabolism as compared to Sandimmun. There was no impact of an oral grapefruit juice load on systemic clearance of CsA. It seems prudent to advise renal allograft recipients treated with Sandimmun Neoral not to ingest their medication with grapefruit juice.

Staphylococcus aureus carriage in adult peritoneal dialysis patients and their spouses.

OBJECTIVE: We hypothesized that carriage of Staphylococcus aureus among continuous ambulatory peritoneal dialysis (CAPD) patients was influenced by their spouses. Furthermore, this carrier status was compared to previous Staph. aureus peritonitis episodes in order to identify the influence of Staph. aureus carriage on peritonitis rate. DESIGN: A combined prospective surveillance study (Staph. aureus carriage) and retrospective chart review (Staph. aureus peritonitis). SETTING: A single peritoneal dialysis unit in a county hospital. PATIENTS AND METHODS: Cultures from patients (n = 32) and spouses (n = 16) were obtained twice, with a 1-month interval, from the anterior nares, the umbilical, and one groin area. All positive cultures were phage typed. Retrospective chart review of all episodes of Staph. aureus peritonitis among the patients was carried out. RESULTS: Twelve of 32 patients (37.5%) and 5 of 16 spouses (31%) evaluated were carriers. Half of the spouses of patients who were Staph. aureus carriers, were also carriers, as opposed to 20% of spouses of noncarrier patients (p = 0.30). Patients and spouses always shared the same phage type. Among patients, Staph. aureus was found in the nose only (n = 9), in all three regions (n = 2), and extranasally only (n = 1). If only one nasal culture was used to establish carriage, the sensitivity and negative predictive value would be 92% and 95%, respectively. A trend toward a higher incidence (p = 0.062) of Staph. aureus peritonitis was found among carriers (patients), 0.37 versus 0.28 peritonitis episode/dialysis-year. CONCLUSIONS: Only one positive nasal culture was necessary when carriage of Staph. aureus was to be established. Staph. aureus carriage was found more often in patients who had previously suffered from Staph. aureus peritonitis. The phage types isolated remained fairly constant, and the patients and spouses often had the same carrier state and shared the same phage types, although transmission does not always take place.

Etoposide: more effective and less bone-marrow toxic than standard immunosuppressive therapy in systemic vasculitis?

In two patients suffering from ANCA-positive systemic vasculitis (one from Wegener's granulomatosis, the other from microscopic polyangiitis), who were both resistant to or could not tolerate standard immunosuppressive therapy, complete clinical and biochemical remission was obtained within few months, treating with cyclic etoposide. Etoposide therapy was found to be significantly less bone marrow toxic than standard immunosuppressive therapy.

Severe hypothyroidism masquerading as renal impairment.

A case of severe hypothyroidism in a 51-year old male is presented. The patient was especially complaining of weakness, stiffness and moderate pain in the proximal muscle groups together with rhinorrhea and nasal stenosis. Because of severely elevated S-creatine-kinase combined with reduced creatinine clearance and proteinuria, polymyositis with secondary glomerulopathy was suspected. Meanwhile, biopsies from skin, muscle, and kidney were normal. All symptoms disappeared 3 months after thyroid replacement therapy was initiated. S-TSH should be considered when evaluating patients with renal impairment of unknown etiology.

Continuous venovenous haemodialysis: a three-pump system.

A simple three-pump-based system for the performance of continuous venovenous haemodialysis is described. The method employs access to the circulation via a double-lumen catheter, and by means of a standard extracorporeal peristaltic pump the blood is circulated through a haemofiltration filter. Standard solutions for peritoneal dialysis are administered in a single-pass manner countercurrent to the blood flow. To control the dialysate flow through the filter, two separate pumps designed for intravenous infusion are used. Anticoagulation is achieved by means of continuous heparin infusion. This three-pump system is effective in controlling the fluid balance and the level of azotemia. Furthermore, this system makes haemodialysis possible in spite of severe haemodynamic instability. The system is easy to use and inexpensive. 3 patients participated in the study.

[Peritonitis among patients treated with continuous ambulatory peritoneal dialysis]. / Peritonitis blandt patienter behandlet med kontinuerlig ambulant peritonealdialyse.

A retrospective study of 51 consecutive patients treated with continuous ambulatory peritoneal dialysis (CAPD) during a total of 736 months is presented. Forty-one episodes of peritonitis were found. Thirty-three patients did not experience peritonitis. One patient had six episodes of peritonitis. The time to first and second episode of peritonitis was 487 days (16.2 months) and 1005 days (33.5 months) respectively. The incidence of peritonitis was 0.67 episodes per patient-year, and was not influenced by either sex, diabetes or previous abdominal surgery. The time to the first episode of peritonitis was equal in patients suffering from one vs two or more episodes of peritonitis. Two patients suffered from tunnel infection. Initial treatment with vancomysin and gentamycin (before knowing the results of microbiological culturing) was adequate in 90% of the peritonitis episodes. Sterile peritonitis was found in 12% of the cases. No relapse of peritonitis was observed. Six patients suffered from eleven cases of reinfection. An optimal surgical strategy as well as vancomycin plus gentamicin treatment of peritonitis are advised when a reduction in infection rates is required

Preventive effect of levothyroxine in patients operated for non-toxic goitre: a randomized trial of one hundred patients with nine years follow-up.

OBJECTIVE: Earlier reports have shown different effects of levothyroxine in the prevention of recurrence of non-toxic goitre after operation. These studies have been either retrospective or of short-term follow-up. This study was designed to evaluate the efficacy of long-term Eltroxin treatment (levothyroxine 0.1 mg daily) in the prevention of post-operative recurrence of non-toxic goitre. DESIGN: Randomized prospective non-placebo controlled study with 9 years follow-up. Group A (n = 40) received levothyroxine and group B (n = 60) did not. PATIENTS: One hundred patients consecutively operated for non-toxic goitre. All clinically and biochemically euthyroid and none taking any thyroid and/or antithyroid medication. MEASUREMENTS: T3, T4, TSH, thyroid antibodies (microsomal/thyroglobulin), weight and neck circumference were measured and thyroid palpation were done preoperatively, 3 and 12 months after surgery and thereafter yearly up to 9 years. RESULTS: Sixty-nine patients completed 9 years follow-up. Incidence of recurrence in group A vs group B was 14.5 vs 21.8% (P < 0.05) irrespective of type of operation, pathoanatomical diagnosis, removed amount or remnant size of the thyroid gland and level of TSH. CONCLUSION: No preventive effect on incidence of recurrence of goitre by Eltroxin 0.1 mg daily in patients operated for non-toxic sporadic goitre was observed.

[Use of glucocorticoids in acute exacerbation of bronchial asthma, parenterally of perorally?]. / Brug af glukokortikoider ved akut forvaerring af asthma bronchiale, parenteralt eller peroralt?

This is a review concerning the use of glucocorticoids in patients with acute bronchial asthma. Using peak expiratory flow (PEF), forced expired volume in one second (FEV1) and forced vital capacity (FVC) the time course of response shows a significant improvement in one to three hours, maximal effect in eight hours and still significant effect after thirty hours. The smallest dose tested is 15 mg prednisolone eight-hourly orally which seems as effective as methylprednisolone 250 mg six-hourly intravenously. Methylprednisolone-(sodium-acetate) 80 mg given as single dose, intramuscularly seems better than methylprednisolone 32 mg orally twice daily (reducing to 0 mg over eight days) in outpatient treatment of patients not taking glucocorticoids.