Roberta Giraudi

BACKGROUND: The relative role of IgA anomalies and genetic factors in IgA nephropathy (IgAN) recurrence after transplantation has never been investigated in a single cohort. METHODS: Sixty-one transplanted patients who had IgAN as an original disease (30 with biopsy-proved early recurrence, median 2.9 yr post-transplant), and 120 controls, were investigated for aberrantly glycosylated IgA1, IgA binding to mesangial matrix, macromolecular IgA (IgA/fibronectin and uteroglobulin/IgA/fibronectin complexes), and polymorphisms of cytokines [tumor necrosis factor alpha (TNFalpha), interleukin 10 (IL-10), IL-6, interferon gamma and transforming growth factor beta 1] and renin-angiotensin system (angiotensinogen converting enzyme, angiotensin II receptor 1, and angiotensinogen) genes. RESULTS: At multivariate logistic regression analysis, recurrence showed a border-line association with aberrantly glycosylated IgA1 [odds ratio (OR) 8.172, p = 0.077], and was significantly less frequent in carriers of -308 AG/AA TNF-alpha"high producer" genotype (OR 0.125, p = 0.036) and -1082, -819, -592 ACC/ATA IL-10 "low producer" (OR 0.038, p = 0.009) genotypes. CONCLUSION: High levels of aberrantly glycosylated IgA1 do not appear to play a strong crucial role in recurrence of IgAN. Polymorphisms of TNFalpha and IL-10 known to condition Th1 prevalence were associated with protection from early recurrence of IgAN.

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation is associated with a high graft loss rate with standard treatments based on plasmapheresis with/without rituximab.We present 2 consecutive cases of nongenetic early severe recurrent FSGS refractory to rituximab and anti-interleukin 1 treatment and with a partial response to plasmapheresis.Case 1 was a 22-year-old man who was rescuetreated for recurrence 36 weeks after transplantation with obinutuzumab (1000 mg/1.73 m 2 , 1 dose) and daratumumab (18 mg/kg each dose, 8 doses), resulting in plasmapheresis discontinuation and a drop of proteinuria from 29 to 2.3 g/d.Proteinuria increased with circulating CD38 plasma cells and responded to an additional daratumumab dose.Currently, the proteinuria is 1.8 g/d, 14.5 months after discontinuing plasmapheresis and starting obinutuzumab and daratumumab therapy.Case 2 was a 15-year-old girl who was plasmapheresis dependent with 2 g/d proteinuria 82 weeks after transplantation, with a Tesio catheter in the right jugular vein as the only possible vascular access.After treatment

BACKGROUND: Pre-existing chronic hypotension affects a percentage of kidney transplanted patients (KTs). Although a relationship with delayed graft function (DGF) has been hypothesized, available data are still scarce and inconclusive. METHODS: A monocentric retrospective observational study was performed on 1127 consecutive KTs from brain death donors over 11 years (2003-2013), classified according to their pre-transplant Mean Blood Pressure (MBP) as hypotensive (MBP < 80 mmHg) or normal-hypertensive (MBP ≥ 80 mmHg, with or without effective antihypertensive therapy). RESULTS: Univariate analysis showed that a pre-existing hypotension is associated to DGF occurrence (p<0.01; OR for KTs with MBP < 80 mmHg, 4.5; 95% confidence interval [CI], 2.7 to 7.5). Chronic hypotension remained a major predictive factor for DGF development in the logistic regression model adjusted for all DGF determinants. Adjunctive evaluations on paired grafts performed in two different recipients (one hypotensive and the other one normal-hypertensive) confirmed this assumption. Although graft survival was only associated with DGF but not with chronic hypotension in the overall population, stratification according to donor age revealed that death-censored graft survival was significantly lower in hypotensive patients who received a KT from >50 years old donor. CONCLUSIONS: Our findings suggest that pre-existing recipient hypotension, and the subsequent hypotension-related DGF, could be considered a significant detrimental factor, especially when elderly donors are involved in the transplant procedure.

Abstract Despite type 2 diabetes mellitus (T2D) is commonly considered a detrimental factor in dialysis, its clear effect on morbidity and mortality on waitlisted patients for kidney transplant (KT) has never been completely elucidated. We performed a retrospective analysis on 714 patients admitted to wait-list (WL) for their first kidney transplant from 2005 to 2010. Clinical characteristics at registration in WL (age, body mass index -BMI-, duration and modality of dialysis, underlying nephropathy, coronary artery -CAD- and/or peripheral vascular disease), mortality rates, and effective time on WL were investigated and compared according to T2D status (presence/absence). Data about therapy and management of T2D were also considered. At the time of WL registration T2D patients (n = 86) were older than non-T2D (n = 628) (58.7 ± 8.6 years vs 51.3 ± 12.9) with higher BMI (26.2 ± 3.8 kg/m 2 vs 23.8 ± 3.6), more frequent history of CAD (33.3% vs 9.8%) and peripheral vascular disease (25.3% vs 5.8%) ( p &lt; 0.001 for all analyses). Considering overall population, T2D patients had reduced survival vs non-T2D ( p &lt; 0.001). Transplanted patients showed better survival in both T2D and non-T2D groups despite transplant rate are lower in T2D (75.6% vs 85.8%, p &lt; 0.001). T2D was also associated to similar waiting time but longer periods between dialysis start and registration in WL (1.6 years vs 1.2, p = 0.008), comorbidity-related suspension from WL (571 days vs 257, p = 0.002), and increased mortality rate (33.7% vs 13.9% in the overall population, p &lt; 0.001). In T2D patients admitted to WL, an history of vascular disease was significantly associated to low patient survival ( p = 0.019). In conclusion, T2D significantly affects survival also on waitlisted patients. Allocation policies in T2D patients may be adjusted according to increased risk of mortality and WL suspension due to comorbidities.