ABSTRACT
INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: 615 renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years.The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased.Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7±0.8, 2.1±1.2 and 1.8±1 mg/dl respectively (p<0.001).56.9% of the patients (N=350) were monitored for anti-HLA antibodies. 94% (N=329) had no anti-HLA changes, while 6% (N=21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N=9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.
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Background: In living kidney transplantation there are two different individuals, a healthy donor and a renal transplant recipient. This is an excellent human model to study factors that influence kidney function in the context of reduced renal mass and the adaptation of two comparable kidneys to different metabolic demands. Methods: We analyzed the changes in measured glomerular filtration rate (GFR, iohexol) from pretransplantation to 12 months after transplantation in 30 donor-recipient pairs. Each donor was compared with his/her recipient. We defined a priori three different groups based on GFR differences at 12 months: donor > recipient (Group A; 78 ± 8 versus 57 ± 8 mL/min), donor < recipient (Group B; 65 ± 11 versus 79 ± 11 mL/min) and donor ≈ recipient (Group C; 66 ± 7 versus 67 ± 7 mL/min). Other factors like donor/recipient mismatches in body mass index (BMI), surface area and gender were evaluated. Results: In Group A donors were mostly male and recipients were female (75% each). Donors had a higher baseline weight than their recipients. During follow-up, weight remained stable in donors but increased 7% in recipients. In Group B donors were mostly female (60%) and recipients male. At baseline, donors had a lower weight than recipients. At 12 months, weight was stable in donors but increased in recipients. In Group C donors were mostly (75%) female and recipients male. At baseline, donors had a higher BMI than their recipients. At 12 months, BMI was stable in donors but increased 14% in recipients. In multivariable analysis, higher GFR at 12 months was associated with higher baseline weight and GFR in donors and with male gender and higher baseline weight in recipients. Conclusions: Kidneys from living donors are more 'plastic' than originally thought and respond to metabolic demands and weight changes of their new host. These changes should be taken into account when assessing GFR outcomes in this population.
ABSTRACT
Background. New-onset diabetes after transplantation (NODAT) is associated with poorer outcomes in kidney transplantation (KT). Thus, identification of modifiable risk factors may be crucial for ameliorating the impact of this entity on transplant outcomes. We assessed the relationships between the weight, body mass index (BMI) and weight gain with NODAT.Methods. We retrospectively analysed 2168 KT performed in Spain during 1990, 1994, 1998 and 2002, with a functioning graft after the first year. At 1 year after KT, three groups were considered: (i) NODAT group (n = 215); (ii) impaired fasting glucose (IFG) group (n = 389); (iii) control group (n = 1564).Results. The incidence of NODAT was 10.8%, 9.9% and 10.0% at 3, 12 and 24 months post-transplantation, respectively. Older recipient age (P < 0.0001) and greater use of tacrolimus (P < 0.0001) were observed in NODAT group. Obesity was more frequent in NODAT group (P < 0.0001), but patients with NODAT had a lower weight gain during the first year after KT (P = 0.038). On multivariate analysis, independent risk factors associated with the development of NODAT were: recipient age [odds ratio (OR): 1.060, P = 0.0001], tacrolimus (OR: 1.611, P = 0.005), triglycerides (OR: 1.511, P = 0.018), positive hepatitis C virus (HCV) status (OR: 1.969, P = 0.001) and pre-transplant body mass index (BMI) (OR: 1.135, P = 0.0001), but not the weight gain.Conclusions. BMI, but not the weight gain at 1 year after transplant, is an independent risk factor for NODAT. Tailoring clinical strategies may minimize the impact of this complication.
ABSTRACT
BACKGROUND: Post-transplant diabetes mellitus (PTDM) is associated with poorer outcomes in kidney transplantation (KT) but little information exists about the evolution of traditional cardiovascular risk (CVR) factors under this disorder. METHODS: We retrospectively analysed CVR factors at 3, 12 and 24 months of follow-up and mortality at three yr in 3365 KT performed in Spain during the years 1990, 1994 and 1998 with a functioning graft after the first year. Three groups were considered: (i) (PTDM, n, 251), (ii) diabetes mellitus as primary disease (DM, n = 156) and (iii) the remaining patients (controls, n = 2958). RESULTS: Recipient age, weight and body mass index (BMI) were higher in PTDM than in the other groups (p < 0.0001), with a lower increase of body weight during follow-up (p < 0.003). PTDM patients showed higher total-cholesterol levels than controls at one (p < 0.01) and two yr (p < 0.0009), and higher triglyceride levels than the other groups during follow-up (p < 0.002). Compared with Controls, PTDM patients had significantly higher systolic blood pressure at one (p < 0.001) and two yr (p < 0.005). Diastolic blood pressure was higher in PTDM and controls (p < 0.001), while pulse pressure was higher in PTDM and DM patients (p < 0.0001) during follow-up. Using Cox proportional hazards analysis, PTDM correlated with total mortality (RR = 1.55; range 1.05-2.3; p < 0.02) but not with cardiovascular mortality. CONCLUSIONS: In Spanish KT recipients with graft function after one yr, PTDM is associated with a worse traditional CVR profile and a higher overall mortality. Although short-term cardiovascular mortality remains similar, better control of CVR factors is mandatory to prevent long-term cardiovascular mortality inherent to this population.
