Remote Ischemic Preconditioning To Reduce Contrast-Induced Nephropathy: A Randomized Controlled Trial.

BACKGROUND: Despite the increasing use of pre- and post-hydration protocols and low osmolar instead of high osmolar iodine containing contrast media, the incidence of contrast induced nephropathy (CIN) is still significant. There is evidence that contrast media cause ischemia reperfusion injury of the renal medulla. Remote ischemic preconditioning (RIPC) is a non-invasive, safe, and low cost method to reduce ischemia reperfusion injury. The aim of this study is to investigate whether RIPC, as an adjunct to standard preventive measures, reduces contrast induced acute kidney injury in patients at risk of CIN. METHODS: The RIPCIN study is a multicenter, single blinded, randomized controlled trial in which 76 patients at risk of CIN received standard hydration combined with RIPC or hydration with sham preconditioning. RIPC was applied by four cycles of 5 min ischemia and 5 min reperfusion of the forearm. The primary outcome measure was the change in serum creatinine from baseline to 48 to 72 hours after contrast administration. RESULTS: With regard to the primary endpoint, no significant effect of RIPC was found. CIN occurred in four patients (2 sham and 2 RIPC). A pre-defined subgroup analysis of patients with a Mehran risk score ≥11, showed a significantly reduced change in serum creatinine from baseline to 48 to 72 hours in patients allocated to the RIPC group (Δ creatinine -3.3 ± 9.8 µmol/L) compared with the sham group (Δ creatinine +17.8 ± 20.1 µmol/L). CONCLUSION: RIPC, as an adjunct to standard preventive measures, does not improve serum creatinine levels after contrast administration in patients at risk of CIN according to the Dutch guideline. However, the present data indicate that RIPC might have beneficial effects in patients at a high or very high risk of CIN (Mehran score ≥ 11). The RIPCIN study is registered at: http://www.controlled-trials.com/ISRCTN76496973.

Components of pain assessment after laparoscopic donor nephrectomy.

BACKGROUND: Pain after laparoscopic surgery can be divided into three components: incisional or superficial wound pain, deep intra-abdominal pain and referred shoulder pain. Better understanding and adequate assessment of post-operative pain may be an important clue to the optimisation of recovery after laparoscopic surgery. Therefore, we performed a components of pain assessment after laparoscopic donor nephrectomy. METHODS: Twenty patients who underwent a laparoscopic donor nephrectomy were included in this prospective study. Pain was subdivided into three components: superficial wound pain, deep intra-abdominal pain and referred shoulder pain, and for each component a numeric rating scale (from 0 to 10) was obtained at 1, 24 and 48 h after surgery. RESULTS: Repeated measurements analysis of variance showed that during the first 48 h after surgery, the superficial wound and deep intra-abdominal pain components were significantly higher as compared with the referred shoulder pain component. Although the deep intra-abdominal pain component was slightly higher as compared with superficial wound pain, this difference was not significant (P = 0.097). Further assessment of superficial wound pain showed that the Pfannenstiel incision was the most significant determinant of this component of pain (P = 0.004), whereas deep intra-abdominal pain was significantly higher at the ipsilateral side of the abdomen (P = 0.015). DISCUSSION: The components of pain assessment revealed that pain related to the Pfannenstiel incision and the deep intra-abdominal pain component are the most important determinants of pain after laparoscopic donor nephrectomy. Further improvement of the management of post-operative pain should focus on these components of pain.

Poor early graft function impairs long-term outcome in living donor kidney transplantation.

BACKGROUND: Poor early graft function (EGF) after living donor kidney transplantation (LDKT) has been found to decrease rejection-free graft survival rates. However, its influence on long-term graft survival remains inconclusive. METHODS: Data were collected on 472 adult LDKTs performed between July 1996 and February 2010. Poor EGF was defined as the occurrence of delayed or slow graft function. Slow function was defined as serum creatinine above 3.0 mg/dL at postoperative day 5 without dialysis. RESULTS: The incidence of slow and delayed graft function was 9.3 and 4.4%, respectively. Recipient overweight, pretransplant dialysis and warm ischemia were identified as risk factors for the occurrence of poor EGF. The rejection-free survival was worse for poor EGF as compared to immediate graft function with an adjusted hazard ratio (HR) of 6.189 (95% CI 4.075-9.399; p < 0.001). Long-term graft survival was impaired in the poor EGF group with an adjusted HR of 4.206 (95% CI 1.839-9.621; p = 0.001). CONCLUSIONS: Poor EGF occurs in 13.7% of living donor kidney allograft recipients. Both, rejection-free and long-term graft survivals are significantly lower in patients with poor EGF as compared to patients with immediate graft function. These results underline the clinical relevance of poor EGF as phenomenon after LDKT.

Low-pressure pneumoperitoneum during laparoscopic donor nephrectomy to optimize live donors' comfort.

Nowadays, laparoscopic donor nephrectomy (LDN) has become the gold standard to procure live donor kidneys. As the relationship between donor and recipient loosens, it becomes of even greater importance to optimize safety and comfort of the surgical procedure. Low-pressure pneumoperitoneum has been shown to reduce pain scores after laparoscopic cholecystectomy. Live kidney donors may also benefit from the use of low pressure during LDN. To evaluate feasibility and efficacy to reduce post-operative pain, we performed a randomized blinded study. Twenty donors were randomly assigned to standard (14 mmHg) or low (7 mmHg) pressure during LDN. One conversion from low to standard pressure was indicated by protocol due to lack of progression. Intention-to-treat analysis showed that low pressure resulted in a significantly longer skin-to-skin time (149 ± 86 vs. 111 ± 19 min), higher urine output during pneumoperitoneum (23 ± 35 vs. 11 ± 20 mL/h), lower cumulative overall pain score after 72 h (9.4 ± 3.2 vs. 13.5 ± 4.5), lower deep intra-abdominal pain score (11 ± 3.3 vs. 7.5 ± 3.1), and a lower cumulative overall referred pain score (1.8 ± 1.9 vs. 4.2 ± 3). Donor serum creatinine levels, complications, and quality of life dimensions were not significantly different. Our data show that low-pressure pneumoperitoneum during LDN is feasible and may contribute to increase live donors' comfort during the early post-operative phase.

Biological mechanisms influencing prosthetic bypass graft patency: possible targets for modern graft design.

In recent years, ample attention has been directed towards the mechanisms that play a major role in the process of vascular graft failure, especially graft thrombosis and intimal narrowing have been highlighted. In this article, a survey is conducted into the key mechanisms of the biological processes of intimal hyperplasia and ultimate graft failure. The sequence of biochemical events that lead to thrombosis of grafts is used as a guideline to describe possible counteracting prosthetic surface interventions in each separate phase of the process.

Preservation of kidneys from controlled donors after cardiac death.

BACKGROUND: Donation after cardiac death (DCD) expands the pool of donor kidneys, but is associated with warm ischaemic injury. Two methods are used to preserve kidneys from controlled DCD donors and reduce warm ischaemic injury: in situ preservation using a double-balloon triple-lumen catheter (DBTL) inserted via the femoral artery and direct cannulation of the aorta after rapid laparotomy. The aim of this study was to compare these two techniques. METHODS: This was a retrospective cohort study of 165 controlled DCD procedures in two regions in the Netherlands between 2000 and 2006. RESULTS: There were 102 donors in the DBTL group and 63 in the aortic group. In the aortic group the kidney discard rate was lower (4·8 versus 28·2 per cent; P < 0·001), and the warm (22 versus 27 min; P < 0·001) and the cold (19 versus 24 h; P < 0·001) ischaemia times were shorter than in the DBTL group. Risk factors for discard included preservation with the DBTL catheter (odds ratio (OR) 5·19, 95 per cent confidence interval 1·88 to 14·36; P = 0·001) and increasing donor age (1·05, 1·02 to 1·07; P < 0·001). Warm ischaemia time had a significant effect on graft failure (hazard ratio 1·04, 1·01 to 1·07; P = 0·009), and consequently graft survival was higher in the aortic cannulation group (86·2 per cent versus 76·8 per cent in the DBTL group at 1 year; P = 0·027). CONCLUSION: In this retrospective study, direct aortic cannulation appeared to be a better method to preserve controlled DCD kidneys.

Does a plain X-ray of the pelvis predict arterial complications in renal transplantation? A prospective study.

BACKGROUND: It is unknown whether if a plain X-ray of the iliac arteries (pelvic X-ray) is a reliable tool to detect calcifications and predict vascular complications. METHODS: In a prospective study, a pelvic X-ray was performed before transplantation in patients without evidence of peripheral vascular disease (n = 109) and vascular calcifications were scored. Vascular calcifications in the iliac arteries and complications were scored by the transplant surgeon during the operation (gold standard). RESULTS: Vascular calcifications were found on the pelvic X-ray in 33 patients (30.2%). The transplant surgeon identified vascular calcifications in 35%. Sensitivity and specificity of the pelvic X-ray for vascular calcifications in the iliac arteries were 48 and 82%, respectively. Technical problems with the arterial anastomosis due to vascular calcifications were observed in five patients. The negative predictive value and positive predictive value of a pelvic X-ray for complications with the arterial anastomosis were 99 and 14%, respectively. CONCLUSIONS: A pelvic X-ray is not a reliable tool to detect vascular calcifications. Technical problems with the arterial anastomosis due to calcifications are infrequent in the absence of vascular calcifications on the pelvic X-ray.

Validation of the Simulator for Testing and Rating Endovascular SkillS (STRESS)-machine in a setting of competence testing.

AIM: Endovascular skills are an integral part of modern-day vascular surgery. The STRESS machine has been developed to test these skills in vascular surgeons. This study aims to define an optimal pass/fail cutoff value for the STRESS test score. METHODS: The STRESS machine consists of a dry glass model of the abdominal aorta and its tributaries with various stenotic lesions, elongations, and tortuosities. A camera and computer software are used to simulate plain fluoroscopy-mode. The test subjects are given two assignments after which two reviewers use a combination of the ICEPS and MRS to produce the final total score; 43 subjects were tested. According to previous endovascular experience, subjects were classified into four groups: novice-low (no experience, less than 11 performed procedures, less than 50 assisted procedures), novice-high (11-25 performed procedures, more than 50 assisted procedures), intermediate (1-10 performed and >11-25 assisted procedures, 11-25 performed and >1-10 assisted procedures or 25-50 performed procedures) and advanced (more than 50 performed procedures). RESULTS: Test-score and noted experience showed a correlation of 0.794. All intermediate and advanced test subjects scored more than 50 points compared to 4 out of 15 novices. CONCLUSION: We demonstrated that it is possible to determine an optimal cut-off value for competence testing with the STRESS machine.

Acute arterial occlusion after deployment of the Angio-Seal closure device: is it as uncommon as we think?

Angio-Seal is a frequently used vascular closure device after arterial catheterisation. Major complications are infrequently reported. We present four cases occurring within a 2-month period in our hospital with dislodgement of an Angio-Seal causing acute arterial occlusion, resulting in loss of limb in one case. Surgical intervention was necessary in all cases. Acute arterial occlusion after deployment of the Angio-Seal in patients with peripheral arterial disease might be less uncommon than the literature suggests.

Preservation for future use of the autologous saphenous vein during femoro-popliteal bypass surgery is inexpedient.

PURPOSE: To investigate the usefulness of greater saphenous vein preservation for future vascular reconstructions during femoro-popliteal bypass surgery. DESIGN: Post-hoc analysis of data acquired in a randomized multi-centre clinical trial comparing two different vascular prostheses (ClinicalTrials.gov ID: NCT 00523263). PATIENTS AND METHODS: The true frequency of ipsilateral saphenous vein use in subsequent femoro-popliteal and coronary bypass surgery was investigated through case-record analysis with a median follow-up of 60 months in 100 consecutive patients, that received a prosthetic femoro-popliteal bypass between 1996 and 2001. RESULTS: An ipsilateral secondary femoro-popliteal bypass was performed in 11 patients (11%) at a mean interval of 34 months (range 1-96). The ipsilateral saphenous vein was applied for these procedures in 8 cases (8%). The cumulative probability of receiving a subsequent bypass was 8% at 3 years and 10% at 5 years follow-up respectively. One patient (1%) underwent CABG at 8 years follow-up with the use of ipsilateral lower leg saphenous vein segments only. CONCLUSION: Preservation of the greater saphenous vein in supragenicular femoro-popliteal bypass surgery is not a valid argument for application of prosthetic material.

Human umbilical vein versus heparin-bonded polyester for femoro-popliteal bypass: 5-year results of a prospective randomized multicentre trial.

PURPOSE: To compare long-term patency of Heparin-Bonded Dacron (HBD) and Human Umbilical Vein (HUV) vascular prostheses in above-knee femoro-popliteal bypass surgery. DESIGN: A prospective randomized multi-centre clinical trial. PATIENTS AND METHODS: Femoro-popliteal bypasses were performed in 129 patients between 1996 and 2001. After randomization 70 patients received an HUV and 59 an HBD prosthesis. Patients were followed up every three months during the first postoperative year and yearly thereafter. The median follow-up was 60 months (range 3-96 months). Graft occlusions were detected by duplex scanning, angiography or surgical exploration. RESULTS: The cumulative primary patency rates were 79%, 66% and 58% at 1, 3 and 5 years postoperatively. Primary patency rates for HUV were 74%, 64% and 58% at 1, 3 and 5 years and 84%, 68% and 58% for HBD, respectively (log-rank test, p=0.745). Overall secondary patency rates were 82%, 72% and 61% at 1, 3 and 5 years postoperatively. The overall cumulative limb salvage at 5 years follow-up was 89% (CI 80%-91%) and was not dependent on graft type. Smoking (p=0.019), number of patent crural arteries (p=0.030) and previous cerebro-vascular events (p=0.030) were significant predictors of graft occlusion. CONCLUSION: There was no difference in long-term graft performance between HUV and HBD for above knee infrainguinal bypass.

[Peripheral artery disease: clinical and cost comparison between duplex ultrasonography and contrast-enhanced magnetic resonance angiography--a multicenter randomized trial]. / De kosten en de effecten van magnetischeresonantieangiografie en duplexechografie bij patiënten met perifeer arterieel vaatlijden: een multicentrische gerandomiseerde studie.

OBJECTIVE: To determine the clinical and economic consequences of replacing duplex ultrasonography (DUS) by contrast-enhanced magnetic resonance angiography (CE-MRA) for the initial diagnostic work-up of patients with peripheral artery disease (PAD). DESIGN: Randomised multicentre study. METHOD: In the period from January 2002 to August 2003, consecutive patients with PAD were randomly assigned to CE-MRA or DUS. The primary outcome measure was the costs. Secondary outcome measures included the confidence with which the specialist could take a therapeutic decision on the basis of the imaging study, the change in disease severity, and the change in quality of life (QOL) assessed during 6 months of follow-up. In addition, all costs of imaging, therapeutic interventions and outpatient visits were calculated. RESULTS: After 6 months of follow-up the data on 352 patients were analysed. Use of CE-MRA reduced the number of additional vascular-imaging procedures by 42% ((69-40)/69) and the specialists felt more confident about their therapeutic decisions. The diagnostic costs of all imaging studies taken together were Euro 167,- higher, on average, in the CE-MRA group (p < 0.001). However, after 6 months of follow-up, no statistically significant differences were found between the two groups with regard to the change in disease severity, the QOL, or the total costs (p > 0.05). CONCLUSION: Based on these findings, a specialist that replaces DUS by CE-MRA will feel more confident about taking a therapeutic decision and will feel less need for additional imaging. However, the diagnostic costs were higher with CE-MRA.

[Donor nephrectomy: less fatigue and better quality of life following laparoscopic kidney removal compared with an open procedure by mini-incision: blind randomised study]. / Donornefrectomie: minder vermoeidheid en meer kwaliteit van leven na een laparoscopische uitname dan na een open ingreep met een mini-incisie: geblindeerd, gerandomiseerd onderzoek.

OBJECTIVE: Determining possible differences in living donor nephrectomy procedures: laparoscopy against mini-incision concerning discomfort to the donor and the maintenance of good graft function. DESIGN: Blind randomized study. METHOD: In two university medical centres, one hundred living kidney donors were randomly assigned to either total laparoscopic donor nephrectomy or mini-incision muscle-splitting open donor nephrectomy. Primary outcome was physical fatigue measured with the 'Multidimensional Fatigue Inventory' (MFI-20) during one-year follow-up. Secondary outcomes were physical function measured with the 'Short form-36' questionnaire, postoperative hospital stay, amount of pain, operating times and graft and patient survival. RESULTS: Donors who underwent laparoscopy experienced less fatigue (difference: -1.3; 95% CI: -2.4 - (-0.1)) and physical function was better (difference: 6.2; 95% CI: 2.0-10.3) during one-year follow-up. Those donors who underwent laparoscopy required less morphine (16 mg versus 25 mg; p = 0.005) and the duration of hospital stay was shorter (3 versus 4 days; p = 0.003). The laparoscopic procedure resulted in a longer operation time (221 versus 164 min; p < 0.001) a longer first warm ischaemia time (6 versus 3 min; p < 0.001) and less blood loss (100 versus 240 ml; p < 0.001). Recipient renal function and one-year graft survival rates did not differ. The number of preoperative and postoperative complications did not differ significantly between both surgery techniques. Conversions did not occur. CONCLUSION: Donor nephrectomy through laparoscopy led to less fatigue and a better quality of life compared with the open procedure. The safety factors for donors and recipients were comparable for both techniques. Laparoscopic donor nephrectomy is therefore the better surgical choice for kidney donor programmes with living donors.

Long-term follow-up of polyneuropathy in diabetic kidney transplant recipients.

Nerve conduction and electromyography (EMG) of insulin-dependent (type 1) diabetic patients with end-stage nephropathy was studied before and up to 10 yr after kidney transplantation (KTx). A series of nondiabetic KTx patients served as a comparison group. Motor nerve conduction velocity (NCV) was measured in the ulnar, median, peroneal, and tibial nerves; sensory NCV was measured in the median nerve. EMG was performed in the first dorsal interosseus, flexor carpi radialis, anterior tibialis, and gastrocnemius muscles. In 68 pre-KTx diabetic patients, the mean NCV was below normal in all nerves, and the mean amplitudes of the evoked muscle action potential (MAP) were low normal in the upper extremity and below normal in the lower extremity. The values of the comparison group were within the normal range. At 1 (n = 57), 5 (n = 23), and 10 (n = 10) yr after KTx, the mean NCV of the diabetic patients remained essentially unchanged, but MAP amplitudes of all muscles had declined. EMG revealed progression of the denervation process, especially in muscles of the lower extremities. We conclude that diabetic neuropathy continues to progress by a progressive axonal loss after correction of uremia by KTx.

Vascular replacement using a layered elastin-collagen vascular graft in a porcine model: one week patency versus one month occlusion.

A persistent clinical demand exists for a suitable arterial prosthesis. In this study, a vascular conduit mimicking the native 3-layered artery, and constructed from the extracellular matrix proteins type I collagen and elastin, was evaluated for its performance as a blood vessel equivalent. A tubular 3-layered graft (elastin-collagen-collagen) was prepared using highly purified type I collagen fibrils and elastin fibers, resembling the 3-layered native blood vessel architecture. The vascular graft was crosslinked and heparinised (37 ± 4 µg heparin/mg graft), and evaluated as a vascular graft using a porcine bilateral iliac artery model. An intra-animal comparison with clinically-used heparinised ePTFE (Propaten®) was made. Analyses included biochemical characterization, duplex scanning, (immuno)histochemistry and scanning electron microscopy. The tubular graft was easy to handle with adequate suturability. Implantation resulted in pulsating grafts without leakage. One week after implantation, both ePTFE and the natural acellular graft had 100% patencies on duplex scanning. Grafts were partially endothelialised (Von Willebrand-positive endothelium with a laminin-positive basal membrane layer). After one month, layered thrombi were found in the natural (4/4) and ePTFE graft (1/4), resulting in occlusion which in case of the natural graft is likely due to the porosity of the inner elastin layer. In vivo application of a molecularly-defined tubular graft, based on nature's matrix proteins, for vascular surgery is feasible.

The effect of pancreas transplantation on diabetic polyneuropathy.

Neuromuscular function was evaluated in long-term type I diabetic patients who retained a functioning pancreas graft. A group of 34 patients was examined at 1 year and another group of 11 patients at 2 years after pancreas transplantation. In this report the clinical and electrophysiological course of motor features of polyneuropathy are described. Before pancreas transplantation, clinical evidence of polyneuropathy was present in all patients. The mean motor nerve conduction velocities (NCV) were below normal and the mean amplitude of the evoked muscle action potentials (MAP) were in the low normal range. The observed abnormalities of muscle strength and tendon reflexes had not progressed in these intervals. Motor NCV improved slightly and MAP amplitude was essentially unchanged. These preliminary results indicate that the progression of diabetic polyneuropathy may be halted by successful pancreas transplantation.

Ling Zhi-8: studies of a new immunomodulating agent.

Ling Zhi-8 (LZ-8) is a protein derived from the fungus Ganoderma lucidum and has immunomodulatory capacities. It was shown to be mitogenic toward mouse splenocytes in vitro and immunosuppressive in vivo by reducing antigen-induced antibody formation and by preventing completely the incidence of autoimmune diabetes in nonobese diabetic mice. In this study, the mitogenic effects of LZ-8 on human mononuclear cells are reported. In accordance to its mitogenic effect on mouse splenocytes, LZ-8 proved to be mitogenic for human PBMC. This mitogenic effect of LZ-8 apparently required the presence of monocytes. We also demonstrated it to be immunosuppressive in vitro in a human MLC performed in the absence of monocytes, using purified T cells and EBV-transformed allogeneic B cells. Furthermore, we tested LZ-8 for its possible suppressive effects in 2 different models of allogeneic tissue transplantation. LZ-8 proved to have a significant effect on cellular immunity, since its administration in an allografted mouse skin model resulted in an increased survival time. In a model of transplanted allogeneic pancreatic rat islets, LZ-8 was effective in delaying the rejection process of allografted islets. More frequent or continuous administration resulted in a further prolongation of survival time. No serious side effects of LZ-8 could be discerned in these experiments.