Search

PurposeWe studied the association between parathormone (PTH) levels and long-term graft loss in RTx patients (RTx-p).MethodsWe retrospectively evaluated 871 RTx-p, transplanted in our unit from Jan-2004 to Dec-2020 assessing renal function and mineral metabolism parameters at 1, 6, and 12 months after RTx. Graft loss and death with functioning graft during follow-up (FU, 8.3[5.4–11.4] years) were checked.ResultsAt month-1, 79% had HPT, of which 63% with secondary HPT (SHPT) and 16% tertiary HPT (THPT); at month-6, HPT prevalence was 80% of which SHPT 64% and THPT 16%; at month-12 HPT prevalence was 77% of which SHPT 62% and THPT 15%. A strong significant correlation was found between HPT type, PTH levels and graft loss at every time point. Mean PTH exposure remained strongly and independently associated to long term graft loss (OR 3.1 [1.4–7.1], p = 0.008). THPT was independently associated with graft loss at month-1 when compared to HPT absence and at every time point when compared to SHPT. No correlation was found with RTx-p death. Discriminatory analyses identified the best mean PTH cut-off to predict long-term graft loss to be between 88.6 and 89.9 pg/mL (AUC = 0.658). Cox regression analyses highlighted that THPT was strongly associated with shorter long-term graft survival at every time-point considered.ConclusionHigh PTH levels during 1st year of RTx seem to be associated with long term graft loss.

The wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has greatly reduced the incidence of relapsing atypical hemolytic uremic syndrome (aHUS) after kidney transplantation (KT). However, the optimal management of aHUS transplant candidates with anti-Complement Factor H (CFH) antibodies remains debated. In these patients, the benefits of chronic eculizumab administration should be weighed against the risk of fatal infections, repeated hospital admissions, and excessive costs. We report the case of a 45-year-old female patient with CFHR1/CFHR3 homozygous deletion-associated aHUS who underwent deceased-donor KT despite persistently elevated anti-CFH antibody titers. As induction and aHUS prophylaxis, she received a combination of eculizumab and obinutuzumab, a humanized type 2 anti-CD20 moAb. The post-operative course was uneventful. After 1-year of follow-up, she is doing well with excellent allograft function, undetectable anti-CFH antibodies, sustained B-cell depletion, and no signs of aHUS activity. A brief review summarizing current literature on the topic is also included. Although anecdotal, our experience suggests that peri-operative obinutuzumab administration can block anti-CFH antibodies production safely and effectively, thus ensuring long-lasting protection from post-transplant aHUS relapse, at a reasonable cost. For the first time, we have demonstrated in vivo that obinutuzumab B-cell depleting properties are not significantly affected by eculizumab-induced complement inhibition.

Background and objectives: New-onset diabetes after transplantation (NODAT) represents a primary cause of morbidity and allograft loss. We assessed prevalence and risk factors for NODAT in a population of Italian kidney transplant (KT) recipients. Methods: Data from 522 KT performed between January 2004 and December 2014 were analyzed. Participants underwent clinical examination; blood and urine laboratory tests were obtained at baseline, one, six, and 12-month of follow-up to detect glucose homeostasis abnormalities and associated metabolic disorders. An oral glucose tolerance test (OGTT) was performed at six months in 303 subjects. Results: Most patients were Caucasian (82.4%) with a mean age of 48 ± 12 years. The prevalence of abnormal glucose metabolism (AGM) and NODAT was 12.6% and 10.7%, respectively. Comparing characteristics of patients with normal glucose metabolism (NGM) to those with NODAT, we found a significant difference in living donation (16.6% vs. 6.1%; p = 0.03) and age at transplant (46 ± 12 vs. 56 ± 9 years; p = 0.0001). Also, we observed that patients developing NODAT had received higher cumulative steroid doses (1-month: 1165 ± 593 mg vs. 904 ± 427 mg; p = 0.002; 6-month:2194 ± 1159 mg vs. 1940 ± 744 mg; p = 0.002). The NODAT group showed inferior allograft function compared to patients with NGM (1-year eGFR: 50.1 ± 16.5 vs. 57 ± 20 mL/min/1.73 m2; p = 0.02). NODAT patients were more likely to exhibit elevated systolic blood pressure and higher total cholesterol and triglyceride levels than controls. Conclusions: The prevalence of NODAT in our cohort was relatively high. Patient age and early post-transplant events such as steroid abuse are associated with NODAT development.

Kidney transplant recipients are a vulnerable population at risk of a life-threatening COVID-19 infection with an incidence of death four-times higher than in the general population. The availability of mRNA COVID-19 vaccines has dramatically changed the fate of this infection also within this fragile population. Transplanted patients have an impaired immunological response also to mRNA vaccines. In March 2021, however, we started a vaccination campaign. These preliminary results show that both the incidence of death and of hospitalization dropped from 13% to 2.4% and from 45% to 12.5% compared to the previous outbreaks reported by our group. In univariate analysis, two variables were associated with an increased risk of hospitalization: older age and dyspnea (p = 0.023, p < 0.0001, respectively). In multivariate analysis, dyspnea (p < 0.0001) and mycophenolate therapy (p = 0.003) were independently associated with the risk of hospitalization. The association was even stronger when the two variables were combined (p < 0.0001). Vaccinations did not reduce the incidence of COVID-19 infections among our transplanted patients, but provided certain protection that was associated with a significantly better outcome for this infection.

Background: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). Methods: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV−). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). Results: 25(OH)D levels were lower in COV+ than in controls [19(12–26) vs. 23(17–31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5–0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP− [17(8–25) vs. 20(15–26) ng/mL, p = 0.19] and between D+ and D− [14(6–23) vs. 20(14–26) ng/mL, p = 0.22] and had no significant correlation with disease length. Conclusions: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.