Ischemia times and donor serum creatinine in relation to renal graft failure

BACKGROUND: The results of renal transplantation are dependent on many variables. To simplify the decision process related to a kidney offer, the authors wondered which variables had the most important influence on the graft failure risk. METHODS: All transplant patients (n=1,124) between January 1981 and July 2000 were included in the analysis (2.6% had missing values). The variables included were donor and recipient age and gender, recipient original disease, race, donor origin, current smoking, cardiovascular disease, body weight, peak and current panel reactive antibody (PRA), number of preceding transplants, type and duration of renal replacement therapy, and time since failure of native kidneys. Also, human leukocyte antigen (HLA) identity or not, first and second warm and cold ischemia times, left or right kidney and fossa, donor kidney anatomy, donor serum creatinine and proteinuria, and transplantation year were included. RESULTS: In a multivariate model, cold ischemia time and its time-dependent variable significantly influenced the graft failure risk censored for death (P<0.0001) independent of any of the other risk factors. The influence primarily affected the risk in the first week after transplantation; thereafter, it gradually disappeared during the first year after transplantation. Donor serum creatinine also significantly influenced the graft failure risk in a time-dependent manner (P<0.0001). The risk of a high donor serum creatinine is already enlarged in the immediate postoperative phase and increases thereafter; the curve is closely related to the degree of the elevation. The other variables with a significant influence on the graft failure rate were, in order of decreasing significance, recipient age, donor gender, donor age, HLA identity, transplantation year, preceding transplantations, donor origin, and peak PRA. CONCLUSIONS: Donor serum creatinine and cold ischemia time are important time-dependent variables independently influencing the risk of graft failure censored for death. The best strategy for improving the results of cadaveric transplantations is to decrease the cold ischemia time and to allocate kidneys from donors with an elevated serum creatinine to low-risk recipients.     

Immunotherapy for renal cell carcinoma

Renal cell carcinoma (RCC) is the most prevalent malignancy within the kidney and the incidence is rising. Due to improved radiological evaluation over 50% of the renal cancers are found incidentally. Despite the fact that these incidentalomas are often confined to the kidney, around 50% of all patients diagnosed with kidney cancer will develop systemic disease. Metastatic RCC has a poor prognosis. Traditional treatment modalities like chemo- and radiotherapy show overall response percentages of 2-6%. In view of the observed spontaneous remissions of advanced renal cancer, immune mechanisms have been suggested to play a role in the natural disease course of RCC. At present, several non-specific cytokine regimens are used in the treatment of mRCC, e.g. interleukin-2 and interferon-alpha, in combination or as monotherapy or in combination with substances like 13-cis-retinoic acid and/or 5-fluorouracil. Collective data of trials evaluating cytokine-based therapies for mRCC show an overall response rate of approximately 15%, with 5% of the patients showing complete responses. More importantly, cytokine treatment clearly translates into a significant survival benefit in a subset of patients. Nevertheless, the toxicity profile of these cytokine regimens is significant. With the enhanced knowledge of tumor-immunology, the identification of immunogenic tumor proteins, and antibodies recognizing tumor-associated antigens, new treatment strategies with increased specificity and fewer side effects are of interest. Here we review the different immunotherapeutical modalities currently used as well as new approaches for the treatment of advanced RCC.     

Effects of recruitment maneuver on atelectasis in anesthetized children

BACKGROUND: General anesthesia is known to promote atelectasis formation. High inspiratory pressures are required to reexpand healthy but collapsed alveoli. However, in the absence of positive end-expiratory pressure (PEEP), reexpanded alveoli collapse again. Using magnetic resonance imaging, the impact of an alveolar recruitment strategy on the amount and distribution of atelectasis was tested. METHODS: The authors prospectively randomized 24 children who met American Society of Anesthesiologists physical status I or II criteria, were aged 6 months-6 yr, and were undergoing cranial magnetic resonance imaging into three groups. After anesthesia induction, in the alveolar recruitment strategy (ARS) group, an alveolar recruitment maneuver was performed by manually ventilating the lungs with a peak airway pressure of 40 cm H2O and a PEEP of 15 cm H2O for 10 breaths. PEEP was then reduced to and kept at 5 cm H2O. The continuous positive airway pressure (CPAP) group received 5 cm H2O of continuous positive airway pressure without recruitment. The zero end-expiratory pressure (ZEEP) group received neither PEEP nor the recruitment maneuver. All patients breathed spontaneously during the procedure. After cranial magnetic resonance imaging, thoracic magnetic resonance imaging was performed. RESULTS: The atelectatic volume (median, first and third standard quartiles) detected in the ZEEP group was 1.25 (0.75-4.56) cm3 in the right lung and 4.25 (3.2-13.9) cm3 in the left lung. The CPAP group had 9.5 (3.1-23.7) cm3 of collapsed lung tissue in the right lung and 8.8 (5.3-28.5) cm3 in the left lung. Only one patient in the ARS group presented an atelectasis of less than 2 cm3. An uneven distribution of the atelectasis was observed within each lung and between the right and left lungs, with a clear predominance of the left basal paradiaphragmatic regions. CONCLUSION: Frequency of atelectasis was much less following the alveolar recruitment strategy, compared with children who did not have the maneuver performed. The mere application of 5 cm H2O of CPAP without a prior recruitment did not show the same treatment effect and showed no difference compared to the control group without PEEP.     

Clinical diagnosis of syndesmotic ankle instability: evaluation of stress tests behind the curtains

We studied the feasibility of clinical tests in the diagnosis of syndesmotic injury of the ankle. 9 investigators examined 12 persons twice, including 2 patients with an arthroscopically-confirmed syndesmotic injury. They sat behind a curtain that exposed only the lower legs. We found a statistically significant relation between the final arthroscopic diagnosis and the squeeze, fibula translation, Cotton, and external rotation tests as well as for limited dorsal flexion. None of the syndesmotic tests was uniformly positive in chronic syndesmotic injury. The external rotation test had the fewest false-positive results, the fibula translation test the most. The external rotation test had the smallest inter-observer variance. The physical diagnosis was missed in one fifth of all examinations. When in accordance with medical history and physical examination, positive stress tests should raise a high index of suspicion of syndesmotic instability. The final diagnosis of such instability, however, should be made by additional diagnostic imaging and/or arthroscopy.     

Role of transforming growth factor beta in peritoneal fibrosis

SUMMARY: Technique survival of peritoneal dialysis is seriously limited by the development of peritoneal fibrosis. the mesothelial cell layer lining the peritoneum is important in the pathogenesis of peritoneal fibrosis. Mesothelial cells are able to produce transforming growth factor beta (TGF-β), and respond to stimulation by this cytokine. In this review, we will detail the evidence available so far for the role of the complex interaction between TGF-β and mesothelial cells in the development of peritoneal fibrosis.     

Five‐year follow‐up after live donor nephrectomy – cross‐sectional and longitudinal analysis of a prospective cohort within the era of extended donor eligibility criteria

To establish the outcome of live kidney donors 5 years after donation, we investigated the risk for progressive renal function decline and quality of life (QoL). Data on estimated glomerular filtration rate (eGFR), creatinine, hypertension, QoL and survival were assessed in a prospective cohort of 190 donors, who donated between 2008 and 2010. Data were available for >90%. The mean age predonation was 52.8 ± 11.5 years, 30 donors having pre‐existent hypertension. The mean follow‐up was 5.1 ± 0.9 years. Eight donors had died due to non‐donation‐related causes. After 5 years, the mean eGFR was 60.2 (95% CI 58.7–62.7) ml/min/1.73 m², with a median serum creatinine of 105.1 (95% CI 102.5–107.8) μmol/l. eGFR decreased to 33.6% and was longitudinally lower among men than women and declining with age (P < 0.001), without any association on QoL. Donors with pre‐existent and new‐onset hypertension demonstrated no progressive decline of renal function overtime compared to nonhypertensives. No donors were found with proteinuria, microalbuminuria or at risk for end‐stage renal disease. After an initial decline postdonation, renal function remained unchanged overtime. Men and ageing seem to affect renal function overtime, while decreased renal function did not affect QoL. These data support further stimulation of living kidney donation programmes as seen from the perspective of donor safety.     

Differential immunogenicity of HLA mismatches in clinical transplantation

Although HLA matching is beneficial in clinical transplantation, it is not feasible to select a completely HLA matched donor for every potential recipient because of the enormous polymorphism of the HLA system. As a consequence, the majority of the recipients will be transplanted with a mismatched donor organ or hematopoietic stem cell transplant. For this large group of patients it is important to take advantage of the differential immunogenicity of HLA mismatches and to select for them a donor with HLA mismatches of low immunogenicity, the so-called acceptable mismatches. The differential immunogenicity of HLA mismatches can be determined by either retrospective analysis of graft survival data or by in vitro assays measuring T-cell and B-cell alloreactivity. A recently developed computer algorithm (HLAMatchmaker) can be instrumental in selecting donors with HLA mismatches, which do not lead to alloantibody formation. The theoretical background and practical implications of this acceptable mismatch approach are discussed.     

Comparison of oral transmucosal fentanyl citrate and an oral solution of meperidine, diazepam, and atropine for premedication in children

The safety and efficacy of premedication with oral transmucosal fentanyl citrate (OTFC) was compared with that of an orally administered solution of meperidine, diazepam, and atropine and no premedication in 59 children about to undergo elective operations. The patients were randomly assigned to receive no premedication (n = 19); 0.25 ml/kg of the oral solution (containing meperidine, 1.5 mg/kg, diazepam, 0.2 mg/kg, and atropine, 0.02 mg/kg, n = 20); or OTFC (15-20 micrograms/kg, n = 20). Children had activity (sedation) and anxiety scores, vital signs (including systolic and diastolic arterial blood pressures and heart and respiratory rates) and pulse oximetry determined oxygen saturation measured before and at 10-min intervals after premedication until they were taken to the operating room. Quality of induction and recovery was evaluated using scoring schedules; recovery times were measured and side effects noted. OTFC was readily accepted and provided significant reductions in preoperative activity (sedation) and anxiety starting after 30 min. After OTFC, sedation and anxiolysis were significantly greater than in children having no premedication but similar to children having the oral solution for premedication. Vital signs and oxygen saturations remained unchanged preoperatively in all groups. Induction and recovery evaluations and recovery times were similar in the three groups, although children having OTFC had the lowest requirements for narcotics in the recovery room. OTFC caused an 80% incidence of mild preoperative facial pruritus and a higher overall incidence of postoperative vomiting (37%) than premedication with the oral solution (5%) or no premedication (18%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Caries preventive efficacy of silver diammine fluoride (SDF) and ART sealants in a school-based daily fluoride toothbrushing program in the Philippines

Background

Occlusal surfaces of erupting and newly erupted permanent molars are particularly susceptible to caries.The objective of the study was to assess and compare the effect of a single application of 38% SDF with ART sealants and no treatment in preventing dentinal (D3) caries lesions on occlusal surfaces of permanent first molars of school children who participated in a daily school-based toothbrushing program with fluoride toothpaste.

Methods

The prospective community clinical trial in the Philippines was conducted over a period of 18 months and included 704 six- to eight-year-old school children in eight public elementary schools with a daily school-based fluoride toothpaste brushing program. Children were randomly assigned for SDF application or ART sealant treatment. Children from two of the eight schools did not receive SDF or ART sealant treatment and served as controls. SDF or ART sealant treatment was applied on sound occlusal surfaces of permanent first molars. Surfaces that were originally defined as sound at baseline but which changed to dentinal (D3) caries lesions were defined as surfaces with new caries (caries increment). Non-compliance to the daily toothbrushing program in three schools offered the opportunity to analyze the caries preventive effect of SDF and sealants separately in fluoride toothpaste brushing and in non-toothbrushing children.

Results

In the brushing group, caries increment in the SDF treatment group was comparable with the non-treatment group but caries increment in the sealant group was lower than in the non-treatment group with a statistically significant lower hazard ratio of 0.12 (0.02-0.61). In the non-brushing group, caries increment in the SDF treatment group and the sealant group was lower than the non-treatment group but the hazard ratio was only statistically significant for the sealant group (HR 0.33; 0.20-0.54). Caries increment was lower in toothbrushing children than in non-toothbrushing children. Hazard ratios reached statistical significance for the non-treated children (HR 0.43; 0.21-0.87) and the sealant-treated children (HR 0.15; 0.03-0.072).

Conclusions

A one-time application of 38% SDF on the occlusal surfaces of permanent first molars of six- to eight-year-old children is not an effective method to prevent dentinal (D3) caries lesions. ART sealants significantly reduced the onset of caries over a period of 18 months.

Trial registration number

German Clinical Trial Register DRKS00003427