Renal transplants from older deceased donors: Is pre-implantation biopsy useful? A monocentric observational clinical study.

AIM: To compare survival of kidney transplants from deceased extended criteria donors (ECD) according to: (1) donor graft histological score; and (2) allocation of high score grafts either to single (SKT) or dual (DKT) transplant. METHODS: Renal biopsy was performed as part of either a newly adopted DKT protocol, or of surveillance protocol in the past. A total 185 ECD graft recipients were categorized according to pre-implantation graft biopsy into 3 groups: SKT with graft score 1 to 4 [SKT(1-4), n = 102]; SKT with donor graft score 5 to 8 [SKT(> 4), n = 30]; DKT with donor graft score 5 to 7 (DKT, n = 53). Graft and patient survival were analyzed by Kaplan-Meier curves and compared by log-rank test. Mean number of functioning graft years by transplant reference, and mean number of dialysis-free life years by donor reference in recipients were also calculated at 1, 3 and 6 years from transplantation. RESULTS: There were no statistically significant differences in graft and patient survival between SKT(1-4) and SKT(> 4), and between SKT(> 4) and DKT. Recipient renal function (plasma creatinine and creatinine clearance) at 1 years did not differ in SKT(1-4) and SKT(> 4) (plasma creatinine 1.71 ± 0.69 and 1.69 ± 0.63 mg/dL; creatinine clearance 49.6 + 18.5 and 52.6 + 18.8 mL/min, respectively); DKT showed statistically lower plasma creatinine (1.46 ± 0.57, P < 0.04) but not different creatinine clearance (55.4 + 20.4). Due to older donor age in the DKT group, comparisons were repeated in transplants from donors older than 70 years, and equal graft and patient survival in SKT and DKT were confirmed. Total mean number of functioning graft years by transplant reference at 1, 3 and 6 post-transplant years were equal between the groups, but mean number of dialysis-free life years by donor reference were significantly higher in SKT (mean difference compared to DKT at 6 years: 292 [IQR 260-318] years/100 donors in SKT(1-4) and 292.5 [(IQR 247.8-331.6) in SKT(> 4)]. CONCLUSION: In transplants from clinically suitable ECD donors, graft survival was similar irrespective of pre-implantation biopsy score and of allocation to SKT or DKT. These results suggest use of caution in the use of histology as the only decision criteria for ECD organ allocation.

Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication.

BACKGROUND: Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. METHODS: A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKTpre) on clinical grounds alone (before Dec 2010, pre-DKT era, n = 170) or according to a clinical-histological protocol (after Dec 2010, DKT era, n = 132) to DKT (n = 48), SKT biopsy-based protocol ("high-risk", SKThr, n = 51), or SKT clinically based protocol ("low-risk", SKTlr, n = 33). Graft and patient survival were compared between the two periods and between different transplant categories. RESULTS: Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60-69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKThr showed worst graft and overall survival in the 60-69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. CONCLUSIONS: Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time.

Phosphate and Calcium Control in Short Frequent Hemodialysis with the NxStage System One Cycler: Mass Balance Studies and Comparison with Standard Thrice-Weekly Bicarbonate Dialysis.

BACKGROUND: Short frequent dialysis with NxStage System One cycler (NSO) has become increasingly popular as home hemodialysis prescription. Short dialysis sessions with NSO might not allow adequate phosphate (P) removal. METHODS: Single-session and weekly balances of P and calcium (Ca) were compared in 14 patients treated with NSO (6 sessions/week) and in 14 patients on standard bicarbonate dialysis (BHD). RESULTS: NSO and BHD showed similar plasma P fall, with end-dialysis plasma P slightly lower in BHD (2.2 ± 0.5 vs. 2.7 ± 0.8 mg/dL, p < 0.02). Single-session P removal was lower in NSO, but weekly removal was higher (3,488 ± 1,181 mg vs. 2,634 ± 878, p < 0.003). Plasma Ca increase was lower in NSO, with similar PTH fall. Ca balance varied according to start plasma Ca, dialysate to blood Ca gradient and net ultrafiltration. CONCLUSIONS: short, frequent home hemodialysis with NSO, on a 6/week-based prescription, allows higher weekly P removal than BHD. With the dialysate Ca concentration in use (6 mg/dL), total plasma Ca and iCa concentration increase is lower in NSO.

[Immunosuppression in kidney transplantation: a way between efficacy and toxicity].

Renal transplantation is the best treatment for patients with end-stage renal disease. Over the last decades, the introduction of new immunosuppressive agents resulted into the reduction of the incidence of acute rejection and early graft loss. Despite this progress, there has been little improvement in the average life of the transplant. The main reasons of late failure are patient's death due to several complications (e.g. cancer, infectious or metabolic), and progressive deterioration of renal function caused by immunological and non-immunological factors. The immunosuppressive therapy can be distinguished into two components: the induction therapy and the maintenance therapy. The former has the aim to implement intense and immediate immunosuppression. This therapy is mostly useful in transplant with high immunological risk, although it is correlated with an increased risk of cytopenias and viral infections. The latter offers the rationale to prevent organ rejection and minimize drug toxicity. This is generally constituted by the association of two or three drugs with different mechanism of action. The most common application of this scheme includes a calcineurin inhibitor in combination with an antimetabolite and a minimum dose of steroids. Immunosuppressive therapy is also associated to an increased risk of infections and cancer development. For instance, each class of drugs is related to a different profile of toxicity. The choice of treatment protocol should take into account the clinical characteristics of the donor and recipient. Furthermore, this treatment may change anytime when clinical conditions result into complications.

Unraveling unidirectional threading of α-cyclodextrin in a [2]rotaxane through spin labeling approach.

We present here the results of a CW-ESR investigation of a double spin labeled α-cyclodextrin-based [2]rotaxane that is characterized by the presence of nitroxide labels both at the wheel and at the dumbbell. This was accomplished by synthesizing a spin labeled α-CD (the wheel) that was mechanically blocked on a thread containing a nitroxide unit by a Cu(I) catalyzed azide-alkyne cycloaddition (CuAAC). Both ESI-MS analysis and NMR spectroscopy were used to provide evidence of the threading processes. Because of the unsymmetrical structure of both the wheel and the axle, two different geometrical isomers could be predicted on the basis of the orientation of the CD along the thread. By combining molecular dynamic calculations and information extracted from the CW-ESR spectra, we were able to determine the geometrical nature of the isomer that was isolated as the only species. The ESR spectra showed J-coupling between the two mechanically connected nitroxide units and were analyzed by a model assuming three main molecular states. The intramolecular noncovalent nature of spin exchange was confirmed by reversibly switching the magnetic interaction on-off by changing the pH of the solution in the presence of a competing macrocyclic host.

End-to-end distance determination in a cucurbit[6]uril-based rotaxane by PELDOR spectroscopy.

Distance determination: The use of pulsed electron-electron double resonance (PELDOR/DEER) spectroscopy to determine the distances among the end units of a paramagnetic cucurbit[6]uril-based rotaxane is demonstrated.

Kinetic control of the direction of inclusion of nitroxide radicals into cyclodextrins.

N-benzyl-tert-butyl nitroxide derivatives substituted at the aromatic ring form host-guest inclusion complexes with ß-and γ-cyclodextrin. They were employed as probes to assess substituent effects on the geometry of the complex and on the kinetics of this complexation by combining EPR and (1)H NMR data.

Membranoproliferative glomerulonephritis type I in renal transplantation patients: a single-center study of a cohort of 68 renal transplants followed up for 11 years.

BACKGROUND: To evaluate the long-term outcome of renal transplant patients with membranoproliferative glomerulonephritis (MPGN) type I and the impact of recurrence. METHODS: The outcomes of 68 renal transplants performed between 1976 and 2009 in 63 patients with MPGN were compared with those of 136 controls matched for time of transplantation, sex, age, and source of donors. RESULTS: The mean posttransplant follow-up was 131.3±83.8 months for patients with MPGN and 139.21±88.7 months for controls. At 15 years, patient survival rates were 76.2% in patients with MPGN and 78.8% in controls (P=ns), whereas pure graft survival rates were 68% in MPGN and 67.9% in controls (P=ns). MPGN recurred in 16 patients (23.5%) 44±30.3 months after transplant (range, 3.5-105 months). Of recurrent grafts, nine were lost for recurrence within 116.5±51.36 months, three patients died with functioning kidney, the other 4 grafts are functioning 156.7±47.5 months after transplantation. Graft survival at 15 years was 73.5% in nonrecurrent and 40.4% in recurrent patients (P=0.02). Patients with recurrence were younger at diagnosis of MPGN (17.64±5.02 years vs. 22.9±9.6 years; P=0.037) and had low C3 more frequently than nonrecurrent patients (75% vs. 28.8%; P=0.01). Proteinuria was higher in recurrent patients who lost the graft in comparison with those with functioning graft (7.14±4.05 vs. 2.86±1.95; P=0.02). CONCLUSIONS: The long-term patient and graft survival were similar in patients with MPGN and in controls. Recurrence occurred in one-fourth of patients and caused graft loss in 56%. Younger age at diagnosis of MPGN and low C3 during transplantation seems to be predictive of recurrence.

Nitroxide biradicals as thread units in paramagnetic cucurbituril-based rotaxanes.

The first example of paramagnetic rotaxane containing cucurbit[6]urils has been reported and characterized both by ESR and NMR spectroscopy.