Efficacy and safety of continuous local infusion of ropivacaine after retroperitoneoscopic live donor nephrectomy.

Morphine-based analgesia is effective but can compromise donor safety. We investigated whether continuous infusion of local anesthetics (CILA) can provide sufficient pain control and reduce morbidity related to opiate analgesics after hand-assisted retroperitoneoscopic (HARS) live donor nephrectomy. Forty consecutive live kidney donors underwent HARS and were treated with the ON-Q system providing CILA with 0.5% ropivacaine through two SilvaGard catheters placed in the retroperitoneal cavity and the rectus sheath, respectively. The case control group consisted of 40 donors matched with regard to sex, age, BMI and surgical technique. All donors were maintained on standardized multimodal analgesia combining nurse-controlled oxycodone treatment and acetaminophen. CILA donors had lower median cumulative consumption of morphine equivalents (CCME) (7 mg [0-56] vs. 42 mg [15-127]; p < 0.0000001), lower incidence of nausea (18 [45%] vs. 35 [87.5%] donors; p < 0.001), shorter time in postoperative care unit (160 vs. 242.5 min; p < 0.001) and shorter hospital stay (4 [4-7] vs. 6 [4-11] days; p < 0.001). In 32.5% of CILA donors the CCME was 0 mg (0% in matched control group, p < 0.001). CILA with 0.5% ropivacaine provides effective postoperative pain relief, reduces the need for opioid treatment and promotes postoperative recovery.

Factors influencing outcome of simultaneous kidney and pancreas transplantation: a 23-year single-center clinical experience.

INTRODUCTION: Simultaneous kidney and pancreas transplantation (SKPT) has become an effective treatment for patients who have diabetes mellitus type I with advanced nephropathy. This study assesses the progress of the SKPT program at Uppsala University Hospital, Sweden, and evaluates prognostic factors for graft survival. MATERIALS AND METHODS: Between February 1986 and September 2009, we performed 113 SKPT. The immunosuppression protocols changed over time and are defined as era 1, cyclosporine (CyA), atzathioprine (AZA) and steroids (C/A/S); era 2, C/A/S with antithymocyte globulin (ATG) induction (C/A/S/A); era 3, CyA, mycophenolate mofetic (MMF), steroids and ATG induction (C/M/S/A); era 4, tacrolimus (TAC), MMF, steroid, and ATG induction (T/M/S/A) and era 5, TAC, MMF, steroids and basiliximab induction (T/M/S/B). We analyzed donor/recipient/operative and postoperative variables to assess their influence on pancreas graft and patient survivals. RESULTS: The overall 1-, 5-, and 10-year patient survivals were 95.5%, 84.1%, and 65.5%, respectively. The 1-, 5-, and 10-year overall pancreas graft survivals were 77.6%, 58.4%, and 48.4%. The 1-, 5-, and 10-year pancreas graft survivals in SKPT patients transplanted between October 1997 and September 2009. (T/M/S/A and T/M/S/B; eras 4 and 5) were 95.3%, 72.7%, and 63.1%, respectively, which was significantly better than those of patients transplanted between February 1986 and September 1997 (era, 1 through 3) (P < 0.01, P < 0.0001, respectively). The quadruple regimen with TAC and MMF (eras 4 and 5) decreased the incidence of acute rejection episodes compared with eras 1 through 3 (P < 0.0001). Basiliximab induction (T/M/S/B; era 5) reduced the CMV infection rate compared with eras 1 through 4 (P < 0.01). Multivariate analysis revealed that donor age (younger than 40 years), immunosuppressive regimen with TAC and MMF (eras 4 and 5), and absence of acute rejection episodes independently affected pancreas graft survival. CONCLUSIONS: We demonstrate a superiority of the quadruple protocol with T/M/S/B for graft and patient survival with a decreased incidence of CMV infection after SKPT.

Outcome after percutaneous transluminal angioplasty of arterial stenosis in renal transplant patients.

BACKGROUND: Ensuring graft survival in renal transplant patients is of paramount importance. Early detection and treatment of complications such as transplant renal artery stenosis (TRAS) are essential. PURPOSE: To evaluate the technical and clinical success rate of renal transplant patients with stenosis in the transplant renal artery or in the iliac artery after percutaneous transluminal angioplasty (PTA). MATERIAL AND METHODS: PTA was carried out on 24 patients with TRAS or iliac artery stenosis. Altogether, 28 stenoses were treated with PTA. The immediate technical result and the clinical outcomes after 1 and 3 months were assessed as well as clinical adverse events. A reduction in serum creatinine and/or a reduction in the number of antihypertensive drugs were criteria for clinical success. RESULTS: The immediate technical success rate after PTA was 93%. The clinical success rate after 1 month was 58%, increasing to 75% after 3 months. CONCLUSION: The technical success rate is not equivalent to the clinical success rate when treating TRAS with PTA. Furthermore, there is a delay in clinical response, sometimes of 3 months, after a technically successful PTA.

Decentralized glomerular filtration rate (GFR) estimates in healthy kidney donors show poor correlation and demonstrate the need for improvement in quality and standardization of GFR measurements in Sweden.

OBJECTIVE: Glomerular filtration rate (GFR) is generally accepted as the best overall index of renal function. Thus, all potential live kidney donors are tested to ensure that they have a normal GFR before they are eligible for kidney transplantation. The choice of GFR test is very much dependent on local traditions and may include iohexol, 51Cr-EDTA, inulin, or creatinine clearance based on urine collection, and creatinine clearance calculated from the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) equation as well as cystatin C. The aim of this study was to compare the results of GFR measurements performed in all actual live kidney donors who have undergone live donor nephrectomy at the University Hospital in Uppsala, Sweden, between the years 2000 and 2004. MATERIAL AND METHODS: The patients were selected from all parts of Sweden and the measurements were performed at their local hospital. RESULTS: We found large discrepancies between repeated iohexol measurements in these presumably healthy individuals. There was also a poor correlation between iohexol clearance and calculated creatinine clearance using the Cockcroft-Gault (R2=0.046) or MDRD formula (R2=0.045). CONCLUSIONS: The study shows that the standardization and quality of GFR measurements in Sweden have to be improved.

Introduction of hand-assisted retroperitoneoscopic living donor nephrectomy at Karolinska University Hospital Huddinge.

Living donor kidney transplantation accounts for about 50% of the total number of renal transplantations at our center. From 1999 through 2005, 75 out of 220 living donor nephrectomies were performed with a laparoscopic technique (LLDN). In June 2005, we introduced the technique of hand-assisted retroperitoneoscopic nephrectomy (HARS) for living donors. Since the introduction until the end of 2005, 11 out of 18 living donor nephrectomies (LDN) were performed with HARS. Reduced operation time was observed for the HARS group (mean, 166 minutes) compared with the LLDN (mean, 244 minutes). Two grafts showed delayed function, one in the LLND group and one in the HARS group. No major perioperative or postoperative complications were observed in the HARS group, whereas one patient who underwent LLDN developed severe pancreatitis. So far in our hands HARS is a fast and safe procedure with results comparable with open LDN. Compared to LLDN, we experienced reduced operation time together with the advantage of retroperitoneal access.

Split renal function in patients with suspected renal artery stenosis: a comparison between gamma camera renography and two methods of measurement with computed tomography.

PURPOSE: To validate a method for calculating split renal function from computed tomography (CT) compared with gamma camera renography, and to test a new method for the measurement based on a volume-rendering technique. MATERIAL AND METHODS: Thirty-eight patients, aged 65.7 +/- 11.6 (range 37.8-82.1) years, who had undergone both CT angiography and gamma camera renography for a suspected renal artery stenosis were included in this study. Split renal function was calculated from the CT examinations by measuring area and mean attenuation in the image slices of the kidneys, and also by measuring volume and mean attenuation from a 3D reconstruction of the kidneys. Gamma camera renography with 99mTc-MAG3 with or without captopril enhancement was used as a reference. RESULTS: The 2D CT method had good correlation with renography (r=0.93). Mean difference was 4.7 +/- 3.6 (0-12) percentage points per kidney. There was also excellent correlation between the two CT methods (r=1.00). CONCLUSION: CT is equivalent to renography in determining split renal function, and the measurement from the CT examination can be made more quickly and equally accurately with a 3D technique.

Three-dimensional rotational angiography of transplanted renal arteries: influence of an extended angle of rotation on beam-hardening artifacts.

PURPOSE: To investigate whether three-dimensional rotational angiography (3D-RA) of the transplant renal artery performed with an extended angle of rotation can reduce beam-hardening artifacts in 3D reconstructed images without image quality being lost or side effects to the transplanted kidney being increased. MATERIAL AND METHODS: 3D-RA with a C-arm rotation of 180 degrees was performed consecutively in 12 renal transplanted patients with suspicion of renal artery stenosis. A 1.7-mm balloon occlusion catheter was placed using the crossover technique and this was compared to a protocol with 160 degrees rotation and a traditional 1.4-mm catheter in 10 patients. The occurrence of beam-hardening artifacts was registered and the effects of the reduced contrast load on image quality and of arterial occlusion on renal function were assessed. RESULTS: The extended angle of rotation, from 160 degrees to 180 degrees, reduced the beam-hardening artifacts. Artifacts were observed in 4/11 patients (36%) in the study group and in all 10 (100%) of the controls. There was no statistical difference regarding image quality between the two protocols. Renal function was equally affected in both protocols. CONCLUSION: 3D-RA with an extended C-arm rotation reduced the beam-hardening artifacts. Image quality was not reduced despite the reduced contrast medium load. The different protocols had no effect on patient outcome.

Measuring split renal function in renal donors: can computed tomography replace renography?

PURPOSE: To develop and evaluate a method of calculating split renal function from computed tomography (CT) images based on the assumption that the accumulation of contrast medium is proportional to the renal function, and to compare the results with the renogram. MATERIAL AND METHODS: The study comprised a retrospective analysis of CT images and renograms from previous donors. Twenty-seven potential renal donors were studied using a technique for measuring the area and mean attenuation of the separate CT slices, and for calculating the volume and total attenuation of the whole kidney. RESULTS: Correlation between CT and renography was moderate (r = 0.43), but the range of results was narrow. The ratio between the two kidneys was more even with CT (50 +/- 2.1%) than with the renogram (48 +/- 2.9%) (right kidney), and the mean difference between the two methods was 3 +/- 2.3 percentage points. CONCLUSION: The renogram can be replaced using calculations from the CT examination in estimating split renal function in potential renal donors.

3D rotational angiography of transplanted kidneys.

PURPOSE: To develop a protocol for 3D rotational angiography (3D-RA) of the transplant renal artery. MATERIAL AND METHODS: 3D-RA was consecutively performed in 39 renal transplanted patients with suspicion of renal artery stenosis. A series of images were acquired while the C-arm of the equipment rotated around the region of interest. Contrast media in different concentrations were given through a 1.4 mm catheter with different sites of injection in the ipsilateral iliac artery. The 3D reconstructions were done at a workstation. Suspected stenoses were in most cases verified with pressure measurement, and a systolic pressure gradient of 10 mm Hg or more was regarded as significant. RESULTS: 28 stenoses were found in 24/39 patients (62%); 21/28 (75%) were verified by pressure measurement. The 3D reconstructions gave a better description of the stenoses in 10 patients. CONCLUSION: 3D-RA is a helpful supplement in cases with complicated vascular anatomy, especially when intervention may be indicated. The best results were achieved with the catheter tip in the proximal iliac artery and 70-75 ml of a high concentration contrast medium at a flow rate of 8-10 ml/s.

Blood flow distribution during elevated intraperitoneal pressure in the rat.

AIM: Oliguria is seen during elevated intraperitoneal pressure, but the physiological mechanisms are not yet clarified. The purpose of the present study was to investigate the changes in renal function, cardiac output and distribution of systemic blood flow (BF) that occur in connection with an elevation of intra-abdominal pressure (IAP) in a rat model by isotope-labelled microsphere technique. METHODS: A 5 or 10 mmHg IAP was created by CO2 insufflation and maintained for 90 min in anaesthetized and mechanically ventilated rats. Rats with normal IAP served as controls. Blood flow and cardiac output measurements by injection of isotope-labelled microspheres were conducted at three time points. Acid-base balance, urine output, glomerular filtration rate (GFR) and urinary excretion products were also followed. RESULTS: Glomerular filtration rate decreased [0.7-0.1 mL min(-1) g(-1) kidney weight (KW)] with elevated IAP, as did urine output (8.5-0.6 microL min(-1) g(-1) KW). Dramatic decreases were seen in renal excretion of sodium (by 97%), potassium (by 94%) and osmotic active substances (by 93%). Cardiac output was diminished by 54% at 5 mmHg and by 65% at 10 mmHg intraperitoneal pressure and systemic vascular resistance (SVR) was elevated threefold. CONCLUSION: Cardiac output, measured by microsphere technique, decreased during elevated intraperitoneal pressure by CO2 in anaesthetized rats, while SVR was elevated and renal excretory functions were decreased to a large extent.

Hand-assisted laparoscopic surgery (HALS) for live donor nephrectomy is more time- and cost-effective than standard laparoscopic nephrectomy.

BACKGROUND: Hand-assisted laparoscopy (HALS) was introduced to increase the safety of living donor nephrectomies. Herein we evaluate the first HALS living donor nephrectomies performed at our center. METHODS: Traditional laparoscopic nephrectomies (TLS) (n = 11) and HALS nephrectomies (n = 11) were included in the study. One patient from the TLS group was excluded because the operation was converted to open nephrectomy. We compared the operating times (OT) and warm ischemia times (WIT) for the two procedures and calculated the operating costs. RESULTS: Mean OT was 270 min in the TLS group and 197 min in the HALS group; thus, there was, a significant reduction of 27% with HALS. WIT was 297 sec for the TLS group and 214 sec for the HALS group, for a reduction of 28%. Costs were also lowered for HALS. CONCLUSION: In addition to shortening both OT and WIT, HALS enhances the safety margin of the procedure, especially during trocar placement. It is further helpful in preventing torsion of the kidney and controlling potential bleedings, as well as during vascular stapling and kidney removal.

Effect of fluvastatin on acute renal allograft rejection: a randomized multicenter trial.

BACKGROUND: Statin therapy has been reported to reduce the acute rejection rate following renal transplantation in a pilot study. The present study is the first randomized, double-blind and adequately powered study to examine the effect of statins on acute rejection of renal allografts. METHODS: A total of 364 patients were randomly assigned to receive either fluvastatin 40 mg or placebo in combination with conventional cyclosporine-based immunosuppressive therapy. The primary end point was treated first acute rejection. Secondary end points included biopsy-proven rejection, histological severity of rejection, occurrence of steroid-resistant rejection, and serum creatinine at three months following transplantation. RESULTS: Fluvastatin was well tolerated; no patients developed myositis or rhabdomyolysis. There was no difference in the acute rejection rate [86 (47.3%) fluvastatin vs. 87 (47.8%) placebo] and no significant difference in the severity of rejection, steroid resistant rejection or mean serum creatinine at three months (160 micromol/L vs. 160 micromol/L). Total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglyceride levels increased following renal transplantation. With the exception of the increase in HDL-C, which was augmented, the increases in lipid parameters were significantly reduced by fluvastatin (total cholesterol +17.5% vs. 35.7%; LDL-C +6.3% vs. 46.7%; HDL-C +43.3% vs. 38.1%; triglyceride +52.2% vs 77.6%). CONCLUSIONS: Contrary to the reported effects of statins, fluvastatin had no effect on the incidence or severity of acute rejection following renal transplantation. There were no increases in adverse events. A significant and potentially beneficial alteration in the lipid profile was observed in the early post transplant period. We conclude that fluvastatin may be used safely to correct dyslipidemia in patients with end-stage renal failure through the peri-transplant period.

Antibodies to human herpesvirus 8 latent and lytic antigens in blood donors and potential high-risk groups in Sweden: variable frequencies found in a multicenter serological study.

Human herpesvirus 8 (HHV-8) is a herpesvirus associated with Kaposi's sarcoma (KS). An immunofluorescence assay was used for detection of IgG, IgM, and IgA antibodies against lytic and latent HHV-8 antigens to analyse samples from KS patients (n = 8), healthy blood donors (n = 162), individuals with a high risk sexual behaviour (n = 114), and bone marrow transplant patients (with high risk for bloodborne infections) (n = 34) in Sweden. Of the KS patients, 88% had IgG antibodies to both lytic and latent antigens by immunofluorescence. In all other groups, antilatent antibodies were rare (0-2.6%). IgG antibodies to the lytic antigens were found, by immunofluorescence, in 20% of the blood donors, 31% of the high risk patients, and in 24 and 29% of the bone marrow transplant patients (pre- and post-transplant samples, respectively). For verification of the specificity of the anti-lytic antibodies, 170 of the samples were also tested blindly at different laboratories world-wide with five other assays shown previously to detect HHV-8 antibodies in most KS patients. By using two recombinant HHV-8 proteins (ORF65/vp17 and K8.1/gp 35-37) in ELISA, a whole-virion ELISA and two immunofluorescence assays confirmation of the reactivity against lytic viral antigens was sought. The comparison of the different methods suggested the K8.1 ELISA to be highly specific and also showed a good agreement between two of the immunofluorescence assays. However, generally there was a poor correlation for positive results, indicating the need of further methodological development.

Characterization of CMVpp65-specific CD8+ T lymphocytes using MHC tetramers in kidney transplant patients and healthy participants.

BACKGROUND: Cytomegalovirus (CMV) is a ubiquitous herpesvirus that infects 50-90% of individuals in different populations. After primary infection, the virus persists latently in myeloid cells under the control of specific T-cells. Reactivation of CMV infection may cause lethal organ dysfunction and is frequently seen in immunosuppressed individuals. CD8+ cytotoxic T-cells (CTL) have a primary role in suppressing CMV reactivation, and the dominating CTL response is directed against pp65. METHODS: MHC tetramers, that is, complexes between HLA class I (or class II) molecules and antigenic peptides conjugated to fluorochromes allow the direct visualization of antigen-specific receptor-carrying T-cells using flow cytometry. We constructed a novel MHC tetramer for identification of CMVpp65-specific CD8+ T-cells using HLA-A2 molecules folded with the immunodominant NLVPMVATV peptide. RESULTS: The A2/pp65 tetramer specifically stained CMV-directed T-cell lines, and sorted cells showed CMV-specific cytotoxicity. High proportions (0.1-9%) of the CD8+ T-cells were A2/pp65 tetramer+ in healthy HLA-A2+ CMV carriers and in immunosuppressed kidney transplant patients with latent infection. Patients with reactivated CMV infection exhibited up to 15% A2/pp65 tetramer+ cells, which seemed to correlate with CMV load over time. A2/pp65 tetramer+ cells expressed T-cell activation markers. CONCLUSIONS: The construction of a novel A2/pp65 MHC tetramer enabled the design of a rapid and precise flow cytometric method allowing quantitative and qualitative analysis of CMV-specific T-cells. The number of A2/pp65 tetramer binding CTLs in blood may prove to be clinically relevant in assessing the immune response to CMV.

[Laparoscopic living-donor nephrectomy. A small study shows positive results, but the procedure still lacks satisfactory evaluation]. / Laparoskopisk nefrektomi från levande givare. Liten studie visar positiva resultat, men tekniken ännu ej tillräckligt utvärderad.

Retrospective analysis and comparison of a small series of 12 laparoscopic live donor nephrectomy (LapLDN) procedures with 15 open live donor nephrectomies, all 27 performed in 1998, showed operating time to be significantly longer but sick leave shorter and hospital stay somewhat shorter in the LapLDN subgroup. One patient in the open procedure subgroup developed herniation and scar discomfort, and in one LapLDN procedure severe bleeding necessitated conversion to open nephrectomy. All kidneys in both subgroups manifested immediate resumption of function after transplantation. Though the LapLDN procedure has yet to be satisfactorily evaluated, the present findings were predominantly in its favour.

Serum erythropoietin and erythropoiesis during six years after kidney transplantation.

We have studied serum erythropoietin (EPO) levels during 6 years after kidney transplantation in 16 patients. There was a serum EPO peak around 50 mU/ml after 5 weeks. After 3 months the serum EPO level stabilized at around 30 mU/ml. Patients with good transplant function had significantly higher serum EPO levels and normalized their hemoglobin (Hb) after a mean of 3 months. If transplant function was good, Hb was normalized even if the serum EPO was only slightly elevated. Patients with poor transplant function had lower serum EPO and Hb levels. We concluded that a good transplant function is the key to a normal erythropoiesis and that small amounts of EPO are needed to improve Hb.