Pretransplant donor biopsy (PTDB)‐based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the ...highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 median KDPI: 87; interquartile range (IQR): 78–94 and 62 with a score = 4 median KDPI: 87; IQR: 76–93; 102 dual transplants median KDPI: 93; IQR: 86–96) and 248 single standard transplant controls (median KDPI: 36; IQR: 18–51). PTDB‐based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80–90 and of 37% for kidneys with a KDPI of 91–100. Although 1‐year estimated GFRs were significantly lower in recipients of marginal kidneys (−9.3, −17.9 and −18.8 mL/min, for dual transplants, single kidneys with PTDB score <4 and =4, respectively; p < 0.001), graft survival (median follow‐up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 95% confidence interval: 0.80–1.79; p = 0.38). In conclusion, PTDB‐based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.
This study shows that the standardized assessment of formalin‐fixed pretransplant biopsies helps recover donors with KDPI in the highest range that would be otherwise discarded, and by providing the expected graft outcomes based on KDPI and pretransplant biopsy, it guides the clinician facing the difficult decision whether to accept or reject these organs. See editorial by Gupta et al on page 2444.
Abstract Introduction Delayed graft function (DGF) is a common complication in kidney transplantation. We sought to evaluate possible correlates for DGF including intraoperative parameters, focusing ...on fluid replacement and central venous pressure (CVP) values among patients undergoing kidney transplantation at our center. Methods One hundred fifty-five cadaveric donor transplantations performed at our center between 2001 and 2005 were selected for the study. We compared intraoperative parameters together with 15 other clinical and socio-demographic recipient and donor variables among patients experiencing DGF (n = 58) versus those with immediate graft function (IGF; n = 97). All significant variables at P < .05 upon univariate analysis were entered into a multivariate logistic regression model to identify risk factors for DGF. Results CVP at awakening of ≤8 mm Hg (odds ratio OR = 3.53; 95% confidence interval CI, 1.63–7.63), fluid input during surgery ≤2.250 mL (OR = 2.12; 95% CI, 1.00–4.51), and recipient age ≥50 years (OR = 2.72; 95% CI, 1.11–6.68) were the strongest correlates of DGF. Conclusions Our data suggested that reduced intraoperative perfusion as measured using CVP monitoring might increase DGF risk. This study provides the rationale to further investigate the optimal CVP target during this surgery.
Abstract Background Few solid-organ–transplanted patients (TP) perform regular sport activity. Poor data are available on the safety of intense and prolonged physical exercise on this population. The ...aim of the study was to evaluate kidney function parameters in a group of TP in comparison with healthy volunteers (HV) involved in a long-distance road cycling race: length 130 km and total uphill gradient, 1871 m. Methods Nineteen TP were recruited: 10 renal, 8 liver, and 1 heart and compared with 35 HV. Renal function parameters, namely, creatinine, estimated glomerular filtration rate (eGFR), urea, uric acid, urine specific gravity, microalbuminuria, and proteinuria were collected and their values were compared the day before the race (T1), immediately after crossing the finish line (T2), and 18 to 24 hours after the competition (T3). Results No adverse events were recorded. At baseline, TP showed lower values of eGFR (69 ± 22 versus 87 ± 13 mL/min/1.73 m2 ), lower urine specific gravity (1015 ± 4 versus 1019 ± 6), and higher microalbuminuria (56 ± 74 versus 8 ± 15) and proteinuria values (166 ± 99 versus 74 ± 44) (in mg/L). At T2 in both groups, renal function parameters showed the same trends: decline of eGFR (54 ± 19 versus 69 ± 15 mL/min/1.73 m2 ) and rise in protein excretion. At T3, functional parameters returned to baseline, except for urine specific gravity values remaining stable in TP (1018 ± 6) and growing higher in HV (1028 ± 4). Conclusions Selected and well-trained organ-transplanted patients can perform an intensive exercise, displaying temporary modifications on kidney function parameters comparable to healthy subjects, despite differences related to baseline clinical conditions and pharmacological therapies.
Abstract Background Organ transplant recipients frequently have chronic inflammation, with a weighty impact on cardiovascular risk. These patients can benefit from exercise, although the role of ...intense training is unclear. We evaluated the effect of a 130-km cycling race on inflammatory cytokines and adiponectin levels in transplant recipients. Methods Circulating interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and adiponectin were assayed in 35 healthy subjects vs 19 transplant recipients (10 kidney, 8 liver, 1 heart), matched for sex, age, body mass index, and preparation workout. The determinations were performed before the race, at the end, and after 18 to 24 hours. Baseline values of 32 sedentary transplant recipients also were evaluated to explore the possible chronic impact of lifestyle. Results All cyclists had 6- to 8-fold increased IL-6 levels after the race that decreased, without returning to baseline, the day after. Conversely, serum TNF-α and IFN-γ showed a progressive increase starting during physical performance and enduring for the next 18 to 24 hours in healthy subjects, whereas they were unchanged over time in cyclists with transplants. In transplant recipients who did not perform exercise, all of the analytes were significantly higher in comparison to basal levels of physically active subjects. Conclusions Our data suggest that clinically stable and properly trained transplant recipients can safely perform and progressively benefit from exercise, even at a competitive level. The changes in inflammation parameters were temporary and parallel with those of the healthy subjects. The comparison with sedentary transplant recipients revealed an overall amelioration of inflammatory indexes as a possible effect of regular physical activity on systemic inflammation.
Abstract Kidney transplantations combined with other solid organs are progressively increasing in number. There are no guidelines regarding the nephrologic indications for combined transplantations, ...namely liver–kidney (LKT), or heart–kidney (HKT), in preemptive patients with chronic kidney failure who are not on regular dialysis therapy. The objective of this study was to assess the functional contribution of the native kidneys after preemptive kidney transplantation combined with other solid organs. From 2004, 9 patients (aged 50.3 ± 8.5 years) with chronic kidney failure (creatinine 2.5 ± 1.0 mg/dL) caused by polycystic kidney disease ( n = 4), vascular nephropathy ( n = 2), interstitial nephropathy ( n = 1), glomerulonephritis ( n = 1), or end-stage kidney disease ( n = 1), underwent combined transplantations (8 LKT, 1 HKT). A scintigraphic functional study (Tc-99DMSA or Tc-99mMAG3), was performed at 4 ± 3 months after transplantation to evaluate the functional contribution of both the native kidneys and the graft. All patients were given immunosuppressive drugs, including a calcineurin inhibitor (tacrolimus/or cyclosporine). At the time of scintigraphy, renal function in all patients was 1.3 ± 0.3 mg/dL. The functional contribution of the transplanted kidneys was on average 77 ± 18%. Only in 1 patient was the contribution of the graft <50%. At follow-up after 36 months, patient and kidney survivals were 100%. The study confirmed a high risk of loss of native kidney function in the presence of organic nephropathy. In light of our experience, a creatinine clearance <30 mL/min in an appropriate cutoff for a combined transplantation. Close clinical and instrumental assessment pretransplant is essential before proceeding with a combined transplant program to exclude functional forms and to optimize the use of organs.
Abstract Immunological evaluation by panel-reactive antibody (PRA) and determination of anti-HLA specificity are important phases in the evaluation of patients awaiting kidney transplantation. The ...main causes of immunization are previous solid organ transplantation, hemotransfusion, and pregnancy. It is also possible that immunogenicity can be triggered by vascularized tissue grafts. Immune induction by cryopreserved bone prostheses is not yet understood. A 19-year-old patient with osteosarcoma had undergone resection of the left proximal tibia with reconstruction using human bone in 1997. The donor HLA typing was as follows: A3, A29 (19); B44 (12), Bw4; DR13 (6), DR7, DR52, DR53. The patient was subsequently enrolled onto the waiting list for cadaveric donor kidney transplantation due to chronic kidney failure caused by cisplatin toxicity. Pretransplantation immunological screening using the complement-dependent cytotoxicity (CDC) technique revealed a PRA of 63%. IgG antibody specificities were detected against class I and class II donor antigens, specifically anti-A3, B44, DR7 antibodies, using flow cytometry (Tepnel Luminex). Further immunological studies using single HLA specificity analysis (LSA Class I°–II°, Tepnel-Luminex) showed direct antibodies against all donor antigen specificities. This case showed immune induction after the implantation of bone prosthesis in a kidney transplant candidate, underlining the importance of the availability of HLA typing data of donors of a human prosthesis.
Chronic allograft nephropathy (CAN) is characterized by progressive renal dysfunction leading in many cases to graft loss. The pathogenesis of CAN involves both immune and nonimmune factors. ...Concerning immune factors, one of the most remarkable predictors of CAN is acute rejection, which is associated with a worse prognosis if there are multiple episodes or when late onset occurs. Delayed graft function is also a major risk factor for CAN because of a correlation between late restoration of renal function after transplantation and long-term decreased graft survival. High creatinine levels at 6 months and 1 year after transplantation, proteinuria, viral infections, and cardiovascular risk factors are additional significant parameters for the development of CAN. Recent findings suggest that a high renal segmental arterial resistance index measured by Doppler ultrasonography in intrarenal vessels is associated with poor allograft function. Moreover, the study of patient genetic profile represents a new approach to identify predictive factors for CAN.
Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by paraesthesia, dysaesthesia and the irresistible urge to move the legs especially at night. Its prevalence is much ...higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. Here, we investigated the association between RLS and cardiovascular events risk and laboratory parameters in end-stage kidney disease (ESKD) patients on dialysis.
One hundred ESKD patients undergoing haemodialysis were enrolled in an 18-month prospective observational study. The main outcomes were the associations of RLS with new cardiovascular events and cardiovascular mortality.
RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual diuresis, lower albumin (P = 0.039) and inflammation, but not the dialysis parameters Kt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P = 0.019). New cardiovascular events increased with severity of RLS intermittent (I-RLS) vs continuous (C-RLS). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P = 0.04). In patients with I-RLS, mortality was 23.8% compared to 55.6% in patients with C-RLS (P = 0.014). Multivariate analysis confirmed the relationship between RLS and mortality.
This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.
In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation ...(LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR ≤ 30 to 35 mL/min may be an indication for LKT, but we need more experience.