Vascular access for haemodialysis in patients with central vein thrombosis.

OBJECTIVES: Dialysis-dependent patients often have central venous drainage complications. In patients with functioning arm arteriovenous fistula, this may result in venous hypertension, arm oedema and vascular access failure. Percutaneous angioplasty and stent implantation might be inadequate to resolve these issues. In these cases, new access can potentially be created with anastomosis to the subclavian vein, iliac vein or vena cava or by making a veno-venous graft to bypass the thrombosis. The aim of this study was to assess the utility of unusual bypasses in vascular access in patients with the central vein thrombosis. MATERIALS: A total of 49 patients were treated. The mean number of previous vascular access surgery procedures was 7.6 (3-17). We performed 19 axillo-iliac, 14 axillo-axillary bypasses and 16 conduits from the arm fistula to the jugular (nine conduits) or subclavian (seven conduits) vein for haemodialysis purposes. RESULTS: All fistulas except one were used for haemodialysis. One patient died before the first use of the fistula. At 12 months, the primary, primary assisted and secondary patency rates were 85.4%, 89.6% and 95.8%, respectively. The follow-up period ranged from 1 to 84 months. CONCLUSION: Unusual grafts are an efficient option as a permanent vascular access for haemodialysis purposes in patients with central vein occlusion.

Therapeutic Problems and Pregnancy in a Patient With Infantile Nephropathic Cystinosis: A Case Report.

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the abnormal accumulation of cystine in the lysosomes of various tissues and organs leading to their dysfunction. The most common type is the infantile nephropathic cystinosis which without treatment leads to renal failure and before the introduction of cysteamine was the cause of death before puberty. CASE PRESENTATION: A 27-year-old female patient with infantile cystinosis developed end-stage renal disease at the age of 10. The first kidney transplantation from patient's father was carried out at the age of 12. The recurrent urinary tract infections led to the graft failure after 6 years. Following the removal of right appendages due to the ovarian tumor, the patient underwent the second kidney transplantation from her mother at the age of 19. After the transplantation, the cysteamine treatment was irregular due to limited availability of the medicine. When it became regular in 2017 the patient did not tolerate full doses. Despite elevated blood levels of cystine and the removal of right appendages, the patient naturally became pregnant in August 2017. Except for recurrent urinary tract infections, the renal parameters remained normal throughout the entire pregnancy. However, in the 32nd week of gestation, due to preeclampsia a caesarean section was performed. A healthy daughter was born, 1400/41 and with a 9 point Apgar score. CONCLUSIONS: Due to the possibility of treatment with cysteamine and kidney transplantations, patients with cystinosis live longer and their quality of life improves. These female patients can even naturally become pregnant and give birth to healthy children.

Long-term Outcomes in Simultaneous Pancreas-Kidney Transplant Recipients: Single-center Experience From Poland.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with end-stage renal disease (ESRD) due to type 1 diabetes mellitus (DM1). Since the 1980s, pancreas transplantation has become the most effective strategy to restore normoglycemia in patients with DM1. The aim of this study was to present long-term outcomes data for SPKT. METHODS: We performed a retrospective analysis of 73 SPKT recipients followed in our outpatient center who underwent transplantation between 1988 and 2015. RESULTS: A total of 50.7% of the patients were male. At the time of surgery, patients' mean age was 37.38 ± 7.44 years. Patients were diagnosed with DM1 at an average of 25 ± 6.08 years before SPKT. For 21.9% of patients, the transplant was done preemptively. Most (91.8%) had enteric drainage. All patients received induction of immunosuppression (either polyclonal immunoglobulins anti-thymocyte globulin or thymoglobulin [64.4%] or monoclonal globulins daclizumab or basiliximab [35.6%]). Patient survival at 1, 5, 10, 15 years was 99%, 97%, 89%, and 75%; kidney survival was 99%, 96%, 84%, and 67%; and pancreas survival was 95%, 92%, 84%, and 64%, respectively. There was a notable tendency toward increased creatinine level (from 1.18 at 1 year to 1.78 at 15 years) and decreased hemoglobin level (from 13.84 at 1 year to 12.65 at 15 years). CONCLUSION: Diabetic patients with ESRD have a poor prognosis without transplantation. SPKT provides marked prolongation of the patient's life and freedom from insulin injections. Enteric drainage is currently the surgical technique of choice. SPKT should remain as the treatment of choice in this patient population.

Analysis of Hospitalizations in Simultaneous Pancreas-Kidney Transplant Recipients: A Single-center Experience in Poland.

BACKGROUND: End-stage renal disease due to type 1 diabetes mellitus appears to be a regular indication for simultaneous pancreas and kidney transplantation (SPKT). Although transplantation improves a patient's health condition, it does not mean that all complications will be eliminated. METHODS: We performed a retrospective analysis of 73 patients who underwent SPKT and follow-up between 1988 and 2015 at our institute. The number, duration, and reasons for hospitalization at 1, 5, 10, and 15 years after SPKT were analyzed. RESULTS: The average number of hospitalizations at 1, 5, 10, 15 years after SPKT were 1.66, 0.39, 0.36, and 0.33, respectively. The main reason for hospitalization over the 15-year period was infections, at 32.4% (SD, 6.8%). Within the first year after SPKT, 6.8% of hospital admissions were caused by cytomegalovirus (CMV) infection. Over time, the percentage of hospitalizations for cardiovascular complications increased from 0.6% at 1 year to 29% at 12-15 years. Incidence of hospitalization due to cardiovascular complications correlated with a longer period of dialysis and a diagnosis of ischemic heart disease before transplant (r = 0.56, P = .004; r = 0.54, P < .0001, respectively). At 12-15 years after transplantation, 18.2% of hospitalizations were caused by secondary complications of diabetes. CONCLUSION: The most common reason for hospitalization after SPKT is infectious complications. In the first year posttransplant, there is a high percentage of CMV infections. Hospitalization associated with cardiovascular complications was found to be most common in the latter follow-up period and showed a correlation with longer dialysis period.

Posttransplant Lymphoproliferative Disorder in Kidney and Liver Transplant Recipients: A Single-Center Experience.

INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid malignant neoplasms arising after solid organ transplantation or hematopoietic stem cell transplantation. The current World Health Organization classification identified 4 basic histologic types of PTLD: early, polymorphic variant, monomorphic variant, and classical Hodgkin lymphoma-type lesions. METHODS: Data of 12 PTLD cases of was retrospectively analyzed in terms of the transplanted organs, time to diagnosis of PTLD, type of immunosuppressive treatment in regard to the induction treatment and acute transplant rejection, and long-term survival. RESULTS: Most of the analyzed cases of PTLD occurred in men (n = 8, 67%); 83% of patients were renal transplant recipients and 17% were liver transplant recipients. Of the kidney recipients, 8% received induction of antithymocyte globulin and 17% received daclizumab. An episode of acute rejection occurred in 6 (50%) patients. All patients were treated with pulses of methylprednisolone and received triple immunosuppressive regimen. Histopathologic examination revealed polymorphic form of PTLD in 5 (42%) patients and classical Hodgkin lymphoma in 3 (25%) cases. Diffuse large B-cell lymphoma was diagnosed in 3 (25%) patients, and diffuse large B-cell lymphoma rich in T lymphocytes and histiocytes was diagnosed in 1 (8%) patient. ALK4- anaplastic lymphoma was diagnosed in 1 (8%) recipient. Four (25%) patients died as a result of PTLD progression (including all 3 patients with central nervous system involvement), and 8 survived with stable graft function. CONCLUSIONS: PTLD is a heterogeneous group of lymphoproliferative disorders occurring in organ recipients. The unusual location changes (especially central nervous system or intestine) can impede the proper diagnosis.

Evaluation of the Relationship Between Concentrations of Tacrolimus Metabolites, 13-O-Demethyl Tacrolimus and 15-O-Demethyl Tacrolimus, and Clinical and Biochemical Parameters in Kidney Transplant Recipients.

BACKGROUND: Tacrolimus (Tac), an essential component of immunosuppressive therapy after solid-organ transplantation, has a narrow therapeutic index and requires therapeutic drug monitoring. Monitoring of Tac predose blood concentrations seems to be not always sufficient to avoid adverse effects. The aim of the study was to evaluate the levels of main Tac metabolites, 13-O-demethyl tacrolimus (13-DMT), 31-O-demethyl tacrolimus (31-DMT), and 15-O-demethyl tacrolimus (15-DMT), in kidney transplant recipients and to link them to clinical and biochemical parameters. METHODS: In 63 kidney transplant patients, concentrations of 13-DMT, 31-DMT, and 15-DMT were quantified using liquid chromatography combined with tandem mass spectrometry (LC/MS/MS). RESULTS: None of the patients had detectable 31-DMT blood levels. There was a positive correlation between 13-DMT/Tac and alanine aminotransferase (ALAT) (r = 0.29, P = .046) and a negative correlation between 13-DMT/Tac and hemoglobin (r = -0.33, P = .008). Tac level did not correlate with ALAT nor with hemoglobin. There was no relationship between 13-DMT/Tac or 15-DMT/Tac and other biochemical or hematologic parameters or data, such as age, body mass index, arterial pressure, or time posttransplant. We observed significantly higher Tac concentrations in patients with hypercholesterolemia or hypertriglyceridemia compared with those without these comorbidities (6.45 ± 2.32 vs 5.16 ± 2.12 ng/mL, P = .043; 6.60 ± 2.30 vs 5.34 ± 2.20 ng/mL, P = .033, respectively). CONCLUSION: Our data may reflect 13-DMT accumulation in liver dysfunction and higher Tac clearance in anemia. However, these results may suggest that 13-DMT/Tac ratio is a marker of myelotoxicity and hepatotoxicity. Further studies should be carried out to determine whether monitoring of 13-DMT could be beneficial in minimizing the adverse effects.

Effect of Thrombophilic Factors on Renal Graft Function: A Single-Center Experience.

BACKGROUND: Optimization of immunosuppressive therapy reduced the incidence of acute rejection, and therefore vascular complications, including graft thrombosis, which have emerged as the main cause of graft loss in the early post-transplant period. A thrombophilic condition may lead to renal graft loss. The aim of the study was to assess renal graft function in thrombophilic renal recipients receiving anticoagulation treatment. METHODS: This is a retrospective study including 29 renal recipients (ktx group) with a history of thrombosis and confirmed thrombophilic factor. Graft function was evaluated by median serum creatinine concentration at the third month after ktx (SCr1) and at the end of the observation (SCr2) with respect to hypercoagulability (factor V Leiden [FVL], mutation G20210A, antiphospholipid antibodies, deficiency of protein S [PS] or C [PC], factor VIII >200%). RESULTS: Recipients underwent retransplantation because of graft thrombosis (P < .001). They more often underwent urgent transplantation (P = .008), received induction therapy (P = .021), underwent an indication other than protocol biopsy (P = .001), or experienced acute rejection (P = .042). Differences in graft function (SCr2) were found at the end of observation (ktx group vs controls 1.9 mg/dL vs 1.3 mg/dL, respectively, P = .014). Multivariate analysis revealed inferior thrombophilic graft function in the model with SCr1 <2 mg/dL (odds ratio 0.07, 95% confidence interval 0.01-0.57, P = .014) and in the model with SCr2 <2 mg/dL (odds ratio 0.15; 95% confidence interval 0.04-0.54, P = .004). The incidence of antiphospholipid syndrome was 31%; FVIII, 31%; FVL, 24.1%; and PC/PS, 13.8%. After anticoagulation was introduced no thromboembolic events or bleeding complications occurred. CONCLUSION: Hypercoagulability is not a contraindication to ktx but may worsen graft function. Post-transplant care in thrombophilic recipients is demanding (retransplantation, immunization, protocol biopsy, anticoagulation), but is the only means by which to maintain a graft.

Cardiovascular Disease in Kidney Transplantation and Its Association With Blood Concentrations of Cyclosporine and Cyclosporine Metabolites.

Cyclosporine A (CsA) is the first calcineurin inhibitor used as immunosuppressive agent. Its administration is associated with multiple adverse effects including cardiovascular diseases (CVDs), but their mechanisms have not been fully elucidated. Cyclosporine metabolites are not well studied in this context. This study was aimed at analysis of the incidence of CVDs and their association with concentrations of cyclosporine and its metabolites. Sixty patients after kidney transplantation (KTX) taking an immunosuppressive regimen including CsA participated in the study. There were 22 women (36.67%) and 38 men (63.33%), mean age 51.73 years, mean 109.38 months after KTX. We observed a correlation between mean diastolic blood pressure and concentrations of metabolite to parent drug ratios of AM1-CsA/CsA (r = 0.35, P = .006), dihydroxy-CsA/CsA (r = 0.42, P = .001), trihydroxy-CsA/CsA (r = 0.42; P = .003) and desmethyl-carboxy-CsA/CsA (r = 0.65, P = .003). There were no significant associations of other CsA metabolites' parameters with CVDs (coronary disease, hypertension, stroke, arrhythmia, diabetes mellitus, obesity). Study results suggest that blood pressure increases associated with CsA therapy could be caused by CsA metabolites that influence mainly diastolic blood pressure levels. A lack of such differences in relation with other CVDs may suggest that more complex mechanisms are involved in the development of cardiovascular injury and disease after kidney transplantation.

Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity.

Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.

Use of drotrecogin alpha (recombinant human activated protein C, rhAPC) in the treatment of severe sepsis induced by graft pancreatitis after simultaneous pancreas and kidney transplantation: a case report.

We present our experience with recombinant human activated protein C (rhAPC) to treat a 40-year-old preemptive simultaneous pancreas-kidney transplant (spktx) recipient who developed septic shock due to graft pancreatitis. We diagnosed intra-abdominal septic complications with septicemia induced by multiple pathogens and cardiopulmonary insufficiency. Until the 59th posttransplant day, 21 peritoneal lavages were performed to treat peritonitis and intra-abdominal abscesses. On the 53rd day when septic shock was diagnosed, rhAPC was administered, after which the patient improved, vasoconstrictive agents were reduced, and respiratory insufficiency resolved. The Physiologic and Operative Severity Score for enumeration of Mortality and Morbidity (POSSUM) scale showed a decrease in predicted mortality from 93% to 17% on day 7 after rhAPC initiation. The patient was discharged at 128 days after spktx with good function of both grafts. Administration of rhAPC limited systemic inflammatory response syndrome (SIRS) and may be considered when faced with the dilemma of stopping immunosuppression to save a recipient's life but at the cost of rejection of a functioning graft.

Influence of pancreas and kidney transplant function on recipient survival.

The aim of this study was to evaluate long-term survival after simultaneous pancreas and kidney (SPK) transplantation in relation to function of both grafts. Among 67 recipients who received SPK transplants between 1988 and 2004, 35 had follow-up longer than 18 months, and were divided into: group I (n = 20), recipients with good function of both grafts; group II (n = 7), patients who had lost transplanted pancreas but had still good kidney graft function; group III (n = 8), patients who had lost both grafts. Comparison of survival rates and analysis of the reason of mortality among groups was performed. The cumulative survival rate was significantly higher in group I than in group III (after 3, 5, 10 years: 100%, 100%, 80% vs 75%, 50%, 37%, respectively). Cumulative survival rate for group II after 3, 5, 10 years was 100%, 100%, 33%, respectively. There were no significant differences in survival rates between groups I and II and between groups II and III. In group I deaths for cardiovascular event and for leukemia were noted. In group II deaths due to cardiovascular event and sepsis were observed. In group III all patients died due to cardiovascular events and the mean time from loss of pancreas and kidney graft function to death was: 75 +/- 51 months (range from 19 to 142), and 49 +/- 26 months (range 19 to 99), respectively. Good pancreas and kidney graft functions prevent death due to cardiovascular event.

A solution to organ shortage: vascular reconstructions for pancreas transplantation.

Multiorgan harvesting (MOH) accounts for approximately 40% of all organ procurements in Poland. Simultaneous procurement of the pancreas and liver necessitates division of the vessels supplying both organs. Therefore, reconstruction of the pancreas vasculature is mandatory for proper function of the transplanted organ. The aim of this study was to present various methods of vascular reconstruction to prepare the pancreas for transplantation. Between January 1999 and April 2005, among 42 whole pancreas transplantations, 35 came from MOH necessitating arterial reconstruction. In 32 cases, the splenic artery (SA) and superior mesenteric artery (SMA) were sewn into a single trunk using the common iliac arterial bifurcation. Occasionally, the iliac Y-graft was unsuitable for vascular reconstruction due to atherosclerosis or iatrogenic injury. Therefore, the SA was anastomosed to the side of the SMA in two cases. In one case we utilized the brachiocephalic trunk bifurcation. Portal vein elongation employed an external iliac vein procured from the donor in all 35 cases. Good perfusion was achieved in all transplanted pancreata. During the early follow-up period, two venous and one arterial thromboses were noted. No negative effects of pancreatic vessel reconstruction were observed in postoperative graft function. Reconstruction of the pancreas vasculature did not affect the long-term function of the allograft while significantly increasing the available donor organ pool.

Comparison of 1-year patient and graft survival rates between preemptive and dialysed simultaneous pancreas and kidney transplant recipients.

It is well known that the main decrease in graft and recipient survival rates is observed during the first 12 months after transplantation. Improving results during this period seems to be crucial for the late outcome. The aim of this study was to compare 1-year survival rates of dialyzed and preemptive pancreas and renal graft recipients and their graft function. From November 1999 to January 2005, 42 whole simultaneous pancreas and kidney transplantations (spktx) were stratified into group I (n = 13): recipients who received a preemptive pancreas and kidney transplant versus group II (n = 29): previously dialyzed spktx recipients. The mean time of dialysis for group II was 39 +/- 16.5 months. We assessed 1-year cumulative survival rates for recipients and grafts for each group. The 1-year cumulative survival rate for preemptive graft recipients was significantly higher than that for dialyzed patients before spktx (100% vs 69%; P = .05). For groups I and II 1-year cumulative graft survival rates for kidney grafts were 100% and 89%, respectively, and for pancreatic grafts 84% and 65.5%, respectively. There was a significant improvement in the 1-year survival rate of preemptive spktx recipients compared with patients dialyzed before spktx. However, 1-year pancreas and kidney graft function did not differ significantly between the groups.

Proinsulinemia in simultaneous pancreas and kidney transplant recipients.

It has been shown that lipid profiles do not differ between pancreas recipients with systemic and portal venous anastomosis. However, it is unclear whether venous drainage from the transplanted pancreas has an impact on recipient atherogenesis and if other factors should be considered. Increased concentration of proinsulin correlates with tachycardia and other risk factors for ischemic heart disease. The aim of this study was to compare proinsulin levels in different types of pancreatic graft venous drainage. Twenty-four simultaneous pancreas and kidney transplantation (SPK) recipients with systemic venous drainage (group S, n = 12) and portal venous drainage (group P, n = 12) under identical immunosuppressive treatment were prospectively observed during 24 months. Following transplantation, only recipients with normoglycemia, normal HbA1c, and normal serum creatine were evaluated. Proinsulin was assessed in fasting state; after glucagon stimulation (Delta-proinsulin), and during oral 75-g glucose tolerance test twice: between 3 and 6 months and 12 to 24 months posttransplantation. All SPK patients had higher proinsulin concentration in fasting state compared with age-matched healthy controls. After stimulation, proinsulin level did not significantly differ between groups; the type of the pancreas venous anastomosis did not change the release of proinsulin and should not have impact on cardiovascular risk factors.

Duodenal patch and sphincterotomy: modification of an old technique to prevent graft pancreatitis.

The aim of this study was to preliminarily evaluate the duodenal patch technique combined with open sphincterotomy in terms of prevention of graft pancreatitis. From April 2003 to March 2005, 17 simultaneous pancreas and kidney transplantations were performed using this technique. All recipients are alive with good renal transplant function. Directly after sphincterotomy in 16 pancreatic grafts a good outflow of clear pancreatic juice and a lessening of graft tenseness were observed during surgery. In two transplants an additional sphincterotomy of the Santorini duct sphincter was necessary. In one recipient no pancreatic juice secretion was observed and insulin independence was not obtained. This graft was explanted shortly afterward. In 13 recipients no graft pancreatic or peripancreatic fluid collection requiring intervention was observed. Of the three recipients who developed graft pancreatitis, two required graft pancreatectomy. In conclusion, Sphincterotomy facilitates pancreatic juice outflow by reducing intraoperative graft edema, which could lead to subsequent inflammation. Further studies on the factors inducing graft pancreatitis are necessary to eliminate this severe complication.

Does the Parathyroidectomy Endanger the Transplanted Kidney?

BACKGROUND: Some investigators maintain that a parathyroidectomy (PTX) performed for tertiary hyperparathyroidism may potentially cause graft malfunction or even loss of the transplanted kidney after the operation. The goal of this study was to determine if parathyroidectomy affects transplanted kidney function. METHODS: The study group consisted of 48 renal graft recipients who underwent operation due to tertiary hyperparathyroidism. Thirty-nine subtotal parathyroidectomies and 9 more selective, less than subtotal parathyroidectomies were performed. The estimated glomerular filtration rate (eGFR) was calculated retrospectively on days 2 to 3 and 4 to 5 and at 1, 3, 6, 12, 24, and 36 months after PTX; these findings were compared with preoperative values. The cumulative graft survival rate in the postoperative period was assessed. RESULTS: In the follow-up period, 4 of 48 patients returned to hemodialysis (after 1, 7, 22, and 57 months after PTX). In the first case, the patient had stopped taking the immunosuppressive drugs 1 month after PTX. Cumulative graft survival rate after PTX was 98.0% after 6 months, 96% after 12 months, and 93% after 2 and 3 years. The mean preoperative eGFR was 52 ± 17.15 mL/min/1.73 m(2), and the median was 48.28 mL/min/1.73 m(2). Overall and in the subtotal parathyroidectomy group, eGFR was significantly lower (P < .001) only on days 2 to 3. There were no differences between preoperative and postoperative eGFR values in the other follow-up periods. In the more selective, less than subtotal parathyroidectomy group, the decrease in eGFR values was nonsignificant compared with preoperative findings in the early postoperative period as well as in all follow-up periods. CONCLUSIONS: In this study, PTX did not significantly impair transplanted kidney function, but in the early postoperative period, transient reductions in graft function did occur.

Human Pooled Immunoglobulin as Treatment of Active Antibody-Mediated Rejection of Transplanted Kidney.

BACKGROUND: Antibody-mediated rejection (ABMR) has emerged as the leading cause of renal graft loss. The optimal treatment protocol in ABMR remains unknown. This study aimed to assess the efficacy of intravenous immunoglobulin (IVIG) for treatment of ABMR in renal recipients. METHODS: Thirty-nine ABO-compatible cross-match-negative renal recipients with biopsy-proven ABMR composed the study group. Pulses of methylprednisolone (MP) and appropriate enhancement of net state of immunosuppression were applied in all individuals; 17/39 recipients were administered IVIG (IVIG group); the remaining 22/39 patients, identified to be nonadherent or unsatisfactorily immunosuppressed, were kept on the initial treatment (MP group). Serum creatinine concentration was obtained at each of 10 intended visits, and glomerular filtration rate (GFR) was estimated with the use of the standard Modification of Diet in Renal Disease (MDRD) formula. Generalized linear mixed model was used for statistical analysis. RESULTS: Renal function (modeled as linear slope of MDRD-based GFR change over time, separately for the pre- and post-intervention periods) improved significantly in IVIG-treated recipients. Pre-intervention slopes were -0.72 and -0.46 mL/min/mo for IVIG and MP groups, respectively (P = NS), whereas post-intervention the slopes changed to -0.03 and -0.47 mL/min/mo (IVIG and MP, respectively; P < .005). Within-group changes of slopes at the time of intervention were 0.69 and -0.01 mL/min/mo in IVIG (P < .01) and MP (P = NS) groups, respectively. The relative slope change (pre- to post-intervention) was 0.7 mL/min/mo in favor of the IVIG group (P < .033). None of the classic immunologic or nonimmunologic graft function predictors influenced GFR during 12 months of follow-up. CONCLUSIONS: IVIG improved graft function in renal recipients diagnosed with ABMR.

Tacrolimus Metabolite M-III May Have Nephrotoxic and Myelotoxic Effects and Increase the Incidence of Infections in Kidney Transplant Recipients.

BACKGROUND: Tacrolimus (Tac) is one of the most commonly used immunosuppressive drugs after solid organ transplantation. Eight Tac metabolites have been described, but their clinical importance remains unclear. The aim of this study was quantification of the 2 major Tac metabolites, 13-O-demethyl (M-I) and 15-O-demethyl (M-III), in kidney transplant recipients and to link them with parameters of kidney and liver function, peripheral blood cell counts, and infection incidence. METHODS: In 81 kidney transplant recipients, concentrations of Tac, M-I, and M-III were measured with the use of liquid chromatography combined with tandem mass spectrometry (LC-MS-MS). RESULTS: There was a negative correlation between M-III levels and estimated glomerular filtration rate (eGFR; r = -0.244; P < .05). Also, a negative correlation between M-III concentrations and red blood cell count (RBC) was found (r = -0.349; P < .05). Neither concentrations of Tac nor of M-I correlated with eGFR or RBC. M-I, M-III, and Tac were not related to alanine aminotransferase activity. Significantly higher Tac and M-III concentrations in the group with all types of infections in comparison with the group without infections were observed (6.95 ± 2.09 ng/mL vs 5.73 ± 2.43 ng/mL [P = .03] and 0.27 ± 0.17 ng/mL vs 0.20 ± 0.11 ng/mL [P = .04], respectively). CONCLUSIONS: The results suggest that higher concentrations of M-III may have a nephrotoxic or myelotoxic effect and result in higher incidence of infections. Further studies are needed to confirm if monitoring of M-III could minimalize adverse effects such as nephrotoxicity or infections.

Usefulness of Modified Dindo-Clavien Scale to Evaluate the Correlation Between the Severity of Surgical Complications and Complications Related to the Renal and Pancreatic Grafts After Simultaneous Kidney and Pancreas Transplantation.

OBJECTIVE: Simultaneous pancreas and kidney transplantation (spktx) is the multiorgan transplantation. Thus various complications originated from transplanted organs and the complications that are not directly related to pancreatic or renal grafts could be developed at the same recipient. AIM: The aim of this study is to explore whether there is a correlation between the severity of complications originated from transplanted pancreas, transplanted kidney and general surgical complication developed at the same spktx recipient. METHODS: Complications which developed among 112 spktx recipients were divided into three groups: related to the pancreatic graft (PTXc), to the renal graft (KTXc) and the general surgical complication (GNc). Severity of postoperative complications using modified Dindo-Clavien scale recipients was evaluated for each group. The correlation of severity of coexisting complications from different complication groups was analyzed. RESULTS: There were 22 recipients who developed the coexistence of complication between different complication groups. Complication originated from two and three complication groups developed 15 (68.2%) and 7 (31.8%) patients, respectively. There was not found correlation of the complication severity between: KTXc and GNc group, GNc and PTXc group, KTXc and PTXc group. The correlation (r = 0.84) of complication severity in recipients who developed concurrently complication from transplanted kidney, transplanted pancreas and general surgery complication was found. CONCLUSION: The modified Dindo-Clavien scale is an useful methodology for the correlation description of complication severity in complex multiorgan transplantation such is spktx, especially when the complications originated from different, potentially independent from the pathophysiological point of view, sources.

Surgical Complications Not Related to the Renal and Pancreatic Grafts After Simultaneous Kidney and Pancreas Transplantation.

BACKGROUND: Simultaneous pancreas and kidney transplantation (SPKTx) is the most commonly performed multiorgan transplantation procedure worldwide. Transplanted organs are the main source of complication; however, some postoperative complications are not directly related to the pancreatic or renal grafts. The goal of this study was to evaluate the prevalence, type, and severity of postoperative complications not related to transplanted kidney or pancreas among SPKTx recipients. METHODS: Complications unrelated to transplanted pancreas and kidneys among 112 SPKTx recipients were analyzed. The cumulative freedom from general surgical complications was assessed, and it was compared with cumulative freedom from complications related to kidney and pancreatic grafts. Severity of complications was classified according to a modified Clavien-Dindo scale. RESULTS: The general surgery complication rate was 22.2%. Cumulative freedom from general surgical complications at days 60 and 90 after transplantation was 0.89 and 0.87, respectively. Cumulative freedom from general surgical complications was comparable with cumulative freedom from complications related to kidney grafts but significantly higher than cumulative freedom from complications related to pancreatic grafts (log-rank test, P < .001). The rates for grades of severity II, IIIa, IIIb, and IVb were 19.4%, 9.7%, 64.5%, and 6.4%, respectively. The most frequent cause of complications was intra-abdominal hematoma or abscess (25.8%). CONCLUSIONS: The general surgical complication rate was comparable to the rate of complications originating from the renal grafts but significantly lower than the complication rate related to the transplanted pancreas. The incidence of general surgical complications could be defined as moderate, and the severity of this type of complication was low.