Objective
This study was performed to examine the suitability of transplantation in kidney transplant recipients (KTRs) with a high body mass index (BMI).
Methods
In total, 370 consecutive KTRs ...stratified according to the World Health Organization BMI categories were retrospectively analysed. The estimated glomerular filtration rate (eGFR) was used to assess allograft function.
Results
The mean BMI was 26.2 kg/m2. Among all patients, 148 (40.0%) were pre-obese, 47 (12.7%) were class I obese, 11 (3.0%) were class II obese, and 9 (2.4%) were class III obese. A linear trend for male sex and younger age was observed from the normal BMI group through the progressively higher groups. Overweight and obese KTRs had a significantly higher incidence of pre-transplant diabetes, but there was no difference in post-transplant new-onset hyperglycaemia. Obesity was not a significant risk factor for a lower eGFR at the 1-year follow-up, but it became significant at the 2- and 3-year follow-ups. Graft loss occurred in 28 patients, and 25 patients died during follow-up. No difference in all-cause allograft loss was found among the different BMI groups during follow-up.
Conclusion
Obesity affects the eGFR in the long term. Allograft survival was lower, but not significantly.
There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4-12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal ...transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection.
Venous thromboembolism (VTE) occurs in 7%-40% of nephrotic patients. The risk of VTE depends on the severity and underlying cause of nephrotic syndrome. This study investigated the use of low-dose ...prophylactic anticoagulation to prevent VTE in patients with nephrotic syndrome caused by primary glomerulonephritis.
Since 2006, all patients presenting with nephrotic syndrome to Imperial College Kidney and Transplant Centre have been considered for treatment with a novel anticoagulation prophylaxis regimen. All cases of nephrotic syndrome secondary to primary membranous nephropathy, minimal-change disease, and FSGS over a 5-year period were retrospectively reviewed. Patients with serum albumin<2.0 g/dl received prophylactic-dose low-molecular-weight heparin or low-dose warfarin; patients with albumin levels of 2.0-3.0 g/dl received aspirin, 75 mg once daily. All thrombotic events and bleeding complications were recorded.
A total of 143 patients received the prophylactic anticoagulation regimen. Median follow-up was 154 weeks (range, 30-298 weeks). The cohort had features associated with a high risk of developing VTE; 40% of the cohort had an underlying diagnosis of membranous nephropathy, and the initial median serum albumin was 1.5 g/dl (range, 0.5-2.9 g/dl). No VTE occurred in patients established on prophylaxis for at least 1 week. VTE was diagnosed in 2 of 143 patients (1.39%) within the first week after presentation and starting prophylaxis. In both cases, it is unclear whether the thrombus had developed before or after the start of prophylaxis. One of 143 (0.69%) patients receiving prophylaxis was admitted urgently with gastrointestinal hemorrhage. Two of 143 patients (1.40%) had elective blood transfusions and procedures to manage occult gastrointestinal bleeding. No other bleeding events occurred in patients receiving prophylaxis.
This regimen of prophylactic antiplatelet or anticoagulant therapy appears effective in preventing VTE in nephrotic syndrome, with relatively few hemorrhagic complications.
ABOi transplantation is an accepted method of expanding the kidney donor pool but there is little analysis of the protocols used. We established an ABOi programme utilising leukocyte depletion, ...tacrolimus, TPE and IvIg. There are few reports in the literature on the success rates of antibody removal protocols or relating to patients in whom antibody removal fails. The purpose of this study was to define the likelihood of achieving transplantation depending on ABO antibody titers.
56 patients entered our ABOi program. Data were analysed to determine the likelihood of achieving transplantation, ABO antibody titre prior to antibody removal and amount of TPE required to achieve transplantation. The median antibody titer was 1:64 (Range 0-1:1024). Transplantation proceeded when the ABO titer reached ≤1:4.
51/56 (91%) patients achieved transplantation after 8.3±5 TPE. Five patients with high ABO titers were not transplanted despite extensive TPE. The number of TPE required to reach an ABO titer of ≤1:4 correlates best with pre-treatment IgG titers.
This is the first study to demonstrate a cut off titer for entry in to the ABO incompatible program using the relationship between ABO titer and amount of TPE required to reach transplantation. We now tailor the antibody removal protocol prior to transplantation and have introduced a cut-off entry titer to the program (≤1:256), because of the unacceptable risk of exposing patients with higher titers to long-lasting immunosuppression and costly, prolonged, courses of TPE without the guarantee of successful transplantation. Patients whose ABO titer exceeds the cut-off are counselled and offered alternative routes to transplantation.
Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the ...addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate.
Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy (n = 20) or TAC combined with MMF (n = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function.
16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group (p = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group (p = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group (p = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment.
Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN.
This trial is registered with EudraCTN2008-001009-41 . Trial registration date 2008-10-08.
Antibody-mediated rejection (AMR) is associated with allograft loss. Identification of factors associated with poor outcome has not been extensively studied.
We retrospectively studied 469 patients ...who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies DSAbs). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P = 0.0016, 0.001, and 0.012, respectively).
Allograft survival was inferior in the AMR group (70.2%) compared with the nonrejector group (97.0%) (P<0.001). Forty-two of 48 (87.5%) of patients with acute AMR had DSAbs. Patients with CII DSAbs at the time of AMR, whether alone or in combination with CI DSAbs had the worst allograft survival (P = 0.014). Both the mean cumulative and immunodominant mean fluorescence index were higher in those patients who subsequently lost their grafts (P<0.001). Patients with diffuse C4d staining had inferior allograft survival than those with focal C4d or no staining (P = 0.02). There was no significant difference in survival by histological grade but a trend to inferior outcomes in those with vascular involvement (P = 0.06). Those patients who met the full Banff criteria had worse survival than those with suspicion for AMR only (P = 0.04).
This study identifies patients at risk of graft failure from AMR. These patients may benefit from newer therapeutic strategies including the use of eculizumab or bortezomib.
Severe peritubular capillary basement membrane multilayering (PTCBML) is part of the Banff definition of chronic antibody-mediated rejection. We retrospectively investigated whether assessment of the ...mean number of layers of basement membrane (BM) around peritubular capillaries (PTC) can be used in a cohort of patients with de novo donor-specific antibodies (dnDSA) as an early marker to predict long-term antibody-mediated injury.
This is a retrospective cohort study with 151 electron microscopy samples from 54 patients with dnDSA, assessed at around 1 year after transplantation, for a mean number of BM layers around PTC and in serial biopsies. Graft survival and time to transplant glomerulopathy (TG) development were estimated in survival analyses.
We found that a mean PTCBML count greater than 2.5 layers assessed in a sample of 25 PTCs around 1 year after transplantation is indicative of the development of TG in patients with dnDSA (P = 0.001). In addition, in patients with serial biopsies available for electron microscopy analysis, we could distinguish 2 groups: patients with a mean PTCBML count of 2.5 or less on all biopsies, and patients who developed greater than 2.5 layers at any time after transplantation. The latter group reflected dnDSA patients at risk for TG development (P < 0.001). In patients with dnDSA, PTCBML score added significantly to the sensitivity and specificity of prediction of TG compared with microcirculation injury score alone.
Our results highlight the potential value of assessing the mean number of BM in PTC for early prediction of progression to chronic antibody-mediated injury.
The prevalence of overweight and obese kidney transplant recipients (KTR) has risen in parallel to the obesity epidemic that has affected the general population over the last two decades. At present, ...there is an ongoing debate regarding the suitability for transplantation of obese patients.
Data were prospectively collected on consecutive single organ KTR transplanted between January 2014 and March 2016. The patients were stratified according to their body mass index (BMI) using the World Health Organization classification. As a measure of allograft function Modification of Diet in Renal Disease, estimated glomerular filtration rate was used at 3, 6, and 12 months posttransplant.
We included 370 KTR: 126 of 370 women; median age, 52.7 years (range, 19-77 years), followed up for a median of 19.5 ± 8.6 months. In total, 155 (41.9%) KTR were underweight or of normal BMI at transplant, whereas 148 (40%) were overweight, and 67 (18.1%) were classified as obese (47 12.7% class 1, 11 3% class 2, 9 2.4% class 3). Overweight and obese KTR had a higher incidence of pretransplant diabetes (
= 0.021), but no difference was found in new-onset hyperglycemia posttransplant (
= 0.35). There was also no difference in posttransplant hospital length of stay (
= 0.386). Obese and overweight KTR had a significantly lower estimated glomerular filtration rate than underweight and normal BMI KTR at 3 and 6 months posttransplant, a finding that did not persist at 1 year follow-up. Overall, 23 patients lost their grafts, and 20 patients died during follow-up. Kaplan Meier analysis showed no difference in allograft loss between the different BMI groups (log rank
= 0.7).
In this single-center study, which used short-term data, overweight and obese patients were shown not to have inferior outcomes regarding renal function 1 year posttransplant.
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