Kidney Transplant from the Same Donor without Maintenance Immunosuppression after Previous Hematopoietic Stem Cell Transplant

In January 2005, an 18‐year‐old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end‐stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 μmol/L, 268 μmol/L on day 2 after KT, 88 μM on day 38 and 89 μmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation‐related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.     

Anaesthesia for renal transplant surgery

Renal transplantation is the preferred therapeutic option for patients with end-stage renal disease. Survival rates are much higher in patients who receive a transplant. Patients with renal failure have significant concomitant medical conditions, such as cardiovascular disease. This article provides an overview of the important issues to be considered in patients undergoing renal transplant, and discusses the anaesthetic management of these patients.     

Comparison of outcomes of peritoneal dialysis between patients after failed kidney transplant and transplant-naïve patients: a meta-analysis of observational studies

PurposeThe influence of prior failed kidney transplants on outcomes of peritoneal dialysis (PD) is unclear. Thus, we conducted a systematic review and meta-analysis to compare the outcomes of patients initiating PD after a failed kidney transplant with those initiating PD without a prior history of kidney transplantation.MethodsWe searched PubMed, Embase, CENTRAL, and Google Scholar databases from inception until 25 November 2020. Our meta-analysis considered the absolute number of events of mortality, technical failures, and patients with peritonitis, and we also pooled multi-variable adjusted hazard ratios (HR).ResultsWe included 12 retrospective studies. For absolute number of events, our analysis indicated no statistically significant difference in technique failure [RR, 1.14; 95% CI, 0.80–1.61; I²=52%; p = 0.48], number of patients with peritonitis [RR, 1.13; 95% CI, 0.97–1.32; I²=5%; p = 0.11] and mortality [RR, 1.00; 95% CI, 0.67–1.50; I²=63%; p = 0.99] between the study groups. The pooled analysis of adjusted HRs indicated no statistically significant difference in the risk of technique failure [HR, 1.25; 95% CI, 0.88–1.78; I²=79%; p = 0.22], peritonitis [HR, 1.04; 95% CI, 0.72–1.50; I²=76%; p = 0.85] and mortality [HR, 1.24; 95% CI, 0.77–2.00; I²=66%; p = 0.38] between the study groups.ConclusionPatients with kidney transplant failure initiating PD do not have an increased risk of mortality, technique failure, or peritonitis as compared to transplant-naïve patients initiating PD. Further studies are needed to evaluate the impact of prior and ongoing immunosuppression on PD outcomes.     

Transvenous Renal Transplant Biopsy via a Transfemoral Approach

Percutaneous renal biopsy (PRB) of kidney transplants might be prevented by an elevated risk of bleeding or limited access to the allograft. In the following, we describe our initial experience with 71 transvenous renal transplant biopsies in 53 consecutive patients with unexplained reduced graft function who were considered unsuitable candidates for PRB (4.2% of all renal transplant biopsies at our institution). Biopsies were performed via the ipsilateral femoral vein with a renal biopsy set designed for transjugular renal biopsy (TJRB) of native kidneys. Positioning of the biopsy system within the transplant vein was achievable in 58 of 71 (81.7%) procedures. The specimen contained a median of 10 glomeruli (range 0–38). Tissue was considered as adequate for diagnosis in 56 of 57 (98.2%) biopsies. With respect to BANFF 50.9% of the specimen were adequate (>10 glomeruli), 47.4% marginally adequate (1–9 glomeruli) and 1.8% inadequate (no glomeruli). After implementation of real‐time assessment all specimen contained glomeruli. One of the fifty‐eight (1.8%) procedure‐related major complications occurred (hydronephrosis requiring nephrostomy due to gross hematuria). Transfemoral renal transplant biopsy (TFRTB) is feasible and appears to be safe compared to PRB. It offers a useful new alternative for histological evaluation of graft dysfunction in selected patients with contraindications to PRB.     

Minimally invasive salvage therapy for transplanted renal allografts

Abstract

Purpose: To evaluate the effectiveness of interventional therapy for complications of transplanted renal allografts. Materials and methods: Between January 2009 and March 2014, 14 patients underwent interventional therapy for complications of renal allografts. Complications included transplant renal artery stenosis (TRAS), TRAS combined with pseudoaneurysms, transplant renal venous kinking and ureteral obstruction (UO). Serum creatinine (S.Cr) levels were evaluated before and after procedure. The characteristics and procedure outcomes of these patients with vascular and nonvascular complications were also analyzed. Results: All primary procedures were successfully performed, which included percutaneous transluminal angioplasty (PTA) for TRAS (n?=?4), stenting and coil embolization for TRAS combined with pseudoaneurysms (n?=?1), stenting for renal vein kinking (n?=?2), and percutaneous nephrostomy (PCN) for UO (n?=?7) and secondary antegrade stent placement in six UO patients after 1 week of PCN. No major procedure related complications occurred. S.Cr level subsequently improved from 6.0?±?3.6 to 2.6?±?2.1?mg/dL (p?<?0.001), as well as patients’ clinical features within 1 week after procedure. In our study, the onset time of vascular complications was earlier (<6 months) than nonvascular complications with significant difference (p?<?0.001). During follow-up, the patient with TRAS and pseudoaneurysms suffered acute rejection 1 month after treatment and received transplant renal artery embolization. One patient with TRAS showed restenosis 4 months after procedure, and was retreated successfully with stenting. Thirteen cases reserved their transplanted renal allografts. Conclusion: Interventional therapy could be prior considered for transplanted renal allograft complications as its effectiveness and minimal invasiveness in saving the transplanted renal grafts.     

Sirolimus Versus Cyclosporine in Kidney Recipients Receiving Thymoglobulin®, Mycophenolate Mofetil and a 6-Month Course of Steroids

To evaluate the efficacy and tolerance of a calcineurin inhibitor (CNI)-free regimen, 145 renal recipients were prospectively randomized to receive either sirolimus (n = 71) or cyclosporine (CsA; n = 74). All patients received polyclonal antilymphocyte antibodies, mycophenolate mofetil (MMF) and steroids (6 months). The primary endpoint, estimated glomerular filtration rate (eGFR) was not significantly different at 12 months comparing sirolimus- and CsA-treated patients (60 +/- 27 vs. 57 +/- 21 mL/min). At 12 months, patient and graft survival, incidence of biopsy-proven rejection and rates of steroid withdrawal were not statistically different (97% vs. 97%; 90% vs. 93%; 14.3% vs. 8.6% and 82.8% vs. 84.1%, respectively). Delayed and slow graft function (SGF) was not significantly different (18.6% vs. 12.3% and 11.4% vs. 13.7%, respectively). In patients who remained on treatment according to protocol at 12 months, eGFR was significantly higher with sirolimus (69 +/- 19 vs. 60 +/- 14 mL/min, p = 0.01). Overall study drug discontinuation rates were 28.2% with sirolimus and 14.9% with CsA. Adverse events (wound complications, mouth ulcers, diarrhea, hypokalemia, bronchopneumonia) and proteinuria >0.5 g/24h (38.8% vs. 5.6%, p < 0.001) were significantly more frequent in sirolimus-treated patients. Cytomegalovirus (CMV) infections were significantly less frequent with sirolimus (6% vs. 23%, p < 0.01). A CNI-free regimen using sirolimus-MMF can achieve excellent renal function, but patients on sirolimus experienced a high rate of adverse events and study drug discontinuation.     

Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised Clustering

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Acute Humoral Rejection in an ABO Compatible Combined Liver–Kidney Transplant—The Kidney Is Not Always Protected

Combined liver–kidney transplantation has become a common practice for the treatment of patients with concurrent end-stage renal disease and end-stage liver disease. Liver transplantation in the setting of multiorgan transplantation is thought to have a protective effect against humoral rejection even when a positive crossmatch is obtained prior to surgery. In most centers, a pre liver–kidney transplant crossmatch is rarely performed because of the known immunoprotective effect of the liver allograft. In this report, a case of acute humoral rejection in the kidney allograft after a combined liver–kidney transplant is described. Although humoral rejection was treated using plasmapheresis, intravenous immunoglobulin and rituximab, the kidney required 3 months to recover function and finally progressed to chronic allograft nephropathy. A heightened index of suspicion for acute humoral rejection of the renal allograft is necessary when performing combined liver–kidney transplants to highly sensitized patients due to previous organ transplants.     

Altered expression of aquaporin-2 in human explants with chronic renal allograft dysfunction

OBJECTIVE: To investigate the distribution of aquaporins, a recently discovered family of transmembrane water channels, in human renal explants, with specific reference to chronic renal allograft dysfunction (CRAD). MATERIALS AND METHODS: Immunohistochemistry for aquaporin-1 and -2 was used in 11 explants, of which five had clinically and histologically confirmed CRAD. Controls were taken from the six explants unaffected by CRAD and from histologically normal areas of six kidneys excised for renal tumours. RESULTS: In the renal tumour control group, aquaporin-1 immunoreactivity was detected in the glomerular endothelium, Bowman's capsule, the proximal convoluted tubules and the thin limb of the loop of Henle, whereas immunoreactivity for aquaporin-2 was detected in the collecting ducts only. Of the explants without CRAD, where architecture was preserved, immunoreactivity for aquaporin-1 and -2 was the same as in the renal tumour controls. In the two explants with no CRAD and loss of collecting ducts, there was no aquaporin-2 immunoreactivity. In five explants with CRAD, immunoreactivity for aquaporin-2 was decreased or absent from the medulla to the cortex. The apparent decreased immunoreactivity of aquaporin-1 in this group was secondary to a decrease in the number of viable proximal tubules. CONCLUSION: There was less aquaporin-2 immunoreactivity in human renal explants diagnosed with CRAD, starting from the medullary region. In explants with no CRAD and viable collecting ducts, or in normal controls, aquaporin-2 immunoreactivity remained unchanged. Aquaporins might be useful as markers for CRAD.     

T Cell‐mediated Rejection of Kidney Transplants: A Personal Viewpoint

In kidney allografts, T cell mediated rejection (TCMR) is characterized by infiltration of the interstitium by T cells and macrophages, intense IFNG and TGFB effects, and epithelial deterioration. Recent experimental and clinical studies provide the basis for a provisional model for TCMR. The model proposes that the major unit of cognate recognition in TCMR is effector T cells engaging donor antigen on macrophages. This event creates the inflammatory compartment that recruits effector and effector memory CD4 and CD8 T cells, both cognate and noncognate, and macrophage precursors. Cognate T cells cross the donor microcirculation to enter the interstitium but spare the microcirculation. Local inflammation triggers dedifferentiation of the adjacent epithelium (e.g. loss of transporters and expression of embryonic genes) rather than cell death, via mechanisms that do not require known T‐cell cytotoxic mechanisms or direct contact of T cells with the epithelium. Local epithelial changes trigger a response of the entire nephron and a second wave of dedifferentiation. The dedifferentiated epithelium is unable to exclude T cells, which enter to produce tubulitis lesions. Thus TCMR is a cognate recognition‐based process that creates local inflammation and epithelial dedifferentiation, stereotyped nephron responses, and tubulitis, and if untreated causes irreversible nephron loss.     

Simultaneous Intestinal and Kidney Transplantation in Adults

Aim of the study: Intestinal transplantation (IT) is a life-saving procedure for carefully selected patients with intestinal failure. We evaluated patients who had undergone simultaneous intestinal and kidney transplantation (SIKT) to determine whether UK guidelines for inclusion of a renal allograft (dialysis dependent or estimated glomerular filtration rate ((eGFR)) < 45 ml/min/1.73 m²) are justified. Methods: A single centre analysis was undertaken of adults undergoing IT at the Cambridge Transplant Centre between December 2007 and January 2016. A prospectively maintained database was used to identify SIKT recipients and determine outcomes. Results: Over this period, 63 intestinal transplants were performed. Seven (11.1%) recipients received a SIKT. Five were pre-dialysis (median eGFR 29 ml/min/1.73 m², range 16–36 ml/min/1.73 m²). One recipient was on dialysis, and one needed bilateral nephrectomy at transplant. There were no primary kidney allograft failures and at three months, the median eGFR (55 ml/min/1.73 m² range 39–124) was similar to recipients of IT alone (median eGFR 56 ml/min/1.73 m² range 17–143 ml/min/1.73 m²). Two recipients required dialysis due to sepsis related kidney injury and died from multi-organ failure (20 and 63 months). Two died with a functioning renal transplant (10 and 15 months). The remaining three patients are alive at follow up (12–96 months) with an eGFR of 20–45 ml/min/1.73 m². Conclusion: Patients with significant renal impairment (eGFR <45 ml/min/1.73 m²), and receiving dialysis may benefit from SIKT. Patient survival and renal function are broadly comparable to those undergoing IT alone. Further studies are required to justify allocation of a kidney to this complex high risk group.     

Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts

Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000–2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P<0.001). In a multivariate Cox model, subclinical ABMR at 1 year was independently associated with a 3.5-fold increase in graft loss (95% confidence interval, 2.1 to 5.7) along with eGFR and proteinuria (P<0.001). Subclinical ABMR was associated with more rapid progression to transplant glomerulopathy. Of patients with subclinical TCMR at 1 year, only those who further developed de novo donor-specific antibodies and transplant glomerulopathy showed higher risk of graft loss compared with patients without rejection. Our findings suggest that subclinical TCMR and subclinical ABMR have distinct effects on long-term graft loss. Subclinical ABMR detected at the 1-year screening biopsy carries a prognostic value independent of initial donor-specific antibody status, previous immunologic events, current eGFR, and proteinuria.     

Impact of failed allograft nephrectomy on initial function and graft survival after kidney retransplantation

The management of an asymptomatic failed renal graft remains controversial. The aim of our study was to explore the effect of failed allograft nephrectomy on kidney retransplantation by comparing the outcome of recipients who underwent graft nephrectomy prior to retransplantation with those who did not. Retrospective comparison of patients undergoing kidney retransplantation with (group A, n = 121) and without (group B, n = 45) preliminary nephrectomy was performed, including subgroup analysis with reference to patients with multiple (≥2) retransplantations and patients of the European Senior Program (ESP). Nephrectomy leads to increased panel reactive antibody (PRA) levels prior to retransplantation and is associated with significantly increased rates of primary nonfunction (PNF; P = 0.05) and acute rejection (P = 0.04). Overall graft survival after retransplantation was significantly worse in group A compared with group B (P = 0.03). Among the subgroups especially ESP patients showed a shorter graft survival after previous allograft nephrectomy. On the multivariate analysis, pretransplant graft nephrectomy and PRA >70% were independent and significant risk factors associated with graft loss after kidney retransplantation. Nephrectomy of the failed allograft was not beneficial for retransplant outcome in our series. Patients with failed graft nephrectomy tended to have a higher risk of PNF and acute rejection after retransplantation. The possibility that the graft nephrectomy has a negative impact on graft function and survival after retransplantation is worth studying further.     

Emphysematous pyelonephritis in a renal allograft: successful treatment with percutaneous drainage and nephrostomy

Emphysematous pyelonephritis in renal transplant allograft occurs rarely. This is a case report on a 55-year-old man who had renal transplantation in 1983 and developed post-transplant diabetes mellitus in 1984. This patient suffered from fever and right low abdominal pain and was subsequently diagnosed as emphysematous pyelonephritis by computerized tomography. He was successfully treated with percutaneous drainage, percutaneous nephrostomy and parenteral antibiotics. Although the management of emphysematous pyelonephritis has been a subject of controversy, we recommend consideration of renal preservation in patients with few risk factors, especially in those patients presenting with chronic renal insufficiency, solitary kidney and transplant allograft.     

Prolonged cold ischemia accelerates cellular and humoral chronic rejection in a rat model of kidney allotransplantation

One of the leading causes of long-term kidney graft loss is chronic allograft injury (CAI), a pathological process triggered by alloantigen-dependent and alloantigen-independent factors. Alloantigen-independent factors, such as cold ischemia (CI) may amplify the recipient immune response against the graft. We investigated the impact of prolonged cold ischemia and the subsequent delayed graft function on CAI in a fully MHC-mismatched rat model of kidney allotransplantation. Prolonged CI was associated with anticipation of proteinuria onset and graft function deterioration (ischemia: 90d; no ischemia: 150d), more severe tubular atrophy, interstitial fibrosis, and glomerulosclerosis, and increased mortality rate (180d survival, ischemia: 0%; no ischemia: 67%). In ischemic allografts, T and B cells were detected very early and were organized in inflammatory clusters. Higher expression of BAFF-R and TACI within the ischemic allografts indicates that B cells are mature and activated. As a consequence of B cell activity, anti-donor antibodies, glomerular C4d and IgG deposition, important features of chronic humoral rejection, appeared earlier in ischemic than in non-ischemic allograft recipients. Thus, prolonged CI time plays a main role in CAI development by triggering acceleration of cellular and humoral reactions of chronic rejection. Limiting CI time should be considered as a main target in kidney transplantation.