Long-term evaluation of coronary artery calcifications in kidney transplanted patients : a follow up of 5 years

Coronary artery calcifications(CACs), are related to the increased cardiovascular mortality during kidney transplantation(KTx). Using coronary-CT performed at 1 month(T0) and 5 years(T5) after KTx we evaluated: (1) the prevalence of CACs; (2) the clinical and biochemical factors related to CACs; 3) the factors implicated with CACs progression. We evaluated 67-pts selected from the 103-pts transplanted in our unit between 2007 and 2008. Clinical and biochemical parameters were recorded at the time of pre-KTx evaluation and for five years after KTx. Coronary-CT for the Agatson score (AS) evaluation was performed at T0 and at T5, and CACs progression was determined. At baseline AS was 45 [0-233]. At T5 AS was 119 [1-413]. At T0, 69% of patients had CACs. Age and dialytic vintage were the main independent variables related to CACs. At T5, CACs were present in 76% of patients. Age was the only independent factor in determining CACs. A progression of CACs was observed in 74% of patients. They were older, had higher CACs-T0 and higher SBP throughout the 5-years. The presence of CACs at T0 and age were the only independent factors in determining the CACs-progression. CACs-T0 had the best discriminative power for CACs progression. CACs prevalence is quite high in KTx patients; Age is strictly related to CACs; Age and the presence of CACs at baseline were the two major factors associated with the progression of CACs during the five years of follow up. CACs-T0 had the best discriminative power for progression of CACs

Rituximab therapy for primary glomerulonephritis: Report on two cases

The evidence in the medical literature on the efficacy and safety of rituximab therapy for primary glomerulonephritis is limited and controversial. We describe two male Caucasian patients with rapidly progressive kidney failure due to primary proliferative glomerulonephritis. Both of them received high-dose intravenous corticosteroids and oral cyclophosphamide with limited benefit. The first patient (hepatitis C virus-negative mixed cryoglobulinemia) underwent plasma-exchange with intravenous immunoglobulins; he showed significant benefit on kidney function (he became dialysis independent with serum creatinine going back to 1.6 mg/dL) after one rituximab pulse even if urinary abnormalities were still present. No improvement in renal function or urinary changes occurred in the second patient. Both these individuals developed sepsis over the follow-up, the first patient died two months after rituximab therapy. This report is in keeping with the occurrence of severe infections after rituximab therapy in patients with renal impairment at baseline and concomitant high-dose steroids

Remission of HCV-associated glomerulonephritis with pegylated ifn and ribavirin therapy after liver transplantation: case report and literature review

Background: Hepatitis C virus infection is associated with a variety of extrahepatic disorders such as membrano-proliferative glomerulonephritis, which is generally due to cryoglobulinemia. Setting: We describe the case of one liver transplant recipient who received antiviral therapy (subcutaneous administration of peg-IFN-alpha-2a 180 mcg weekly and oral ribavirin 200 mg thrice a day) for HCV-related membrano-proliferative glomerulonephritis. He presented normal kidney function, non-nephrotic proteinuria (2 g/24 h) and mild hematuria. Results: Urinary abnormalities disappeared within a few weeks after the initiation of antiviral therapy; however, combination antiviral therapy was not able to obtain viral clearance. After 11 months, IFN-therapy was interrupted and the patient continued low-dose ribavirin monotherapy (200 mg once per day) for one additional year-remission of proteinuria (< 0.3 g/24 h) and hematuria persisted with intact kidney function. Although other mechanisms cannot be excluded, we suggest that ribavirin therapy was critically implicated in the remission of urinary abnormalities in our patient. The existing literature on the association between HCV-associated glomerulonephritis and therapy with ribavirin is reviewed. Conclusions: Antiviral therapy may be effective in patients with HCV-induced glomerulonephritis. Further evidence is needed to evaluate efficacy and safety of ribavirin monotherapy for HCV-related glomerulonephritis

Laser capture microdissection on formalin-fixed and paraffin-embedded renal transplanted biopsies: Technical perspectives for clinical practice application

Renal biopsy (RBx) is an essential tool in the diagnostic and therapeutic process of most native kidney diseases and in the renal transplanted graft. Laser capture microdissection (LCM), combined with molecular biology, might improve the diagnostic power of RBx. However, the limited amount of available renal tissue is often an obstacle for achieving a satisfactory qualitative and quantitative analysis. In our work we present a method which allows us to obtain good quality and quantity of RNA from formalin-fixed and paraffin-embedded (FFPE) renal tissue derived from RBx performed in transplanted patients. Histology, immunohistochemistry, LCM, pre-amplify system and qRT-PCR of biomarkers related to tubular damage, inflammation and fibrosis on FFPE RBx were performed. Glomeruli, tubules and interstitium of three RBx (RB-A: no alteration; RB-B and -C: the progressive rise of creatinine) were compared. The method proposed, could well be useful in future clinical practice. It is quick, easy to perform and allows the analyses of many biomarkers. In addition, it could be extended to all types of RBx without any limitation on the sample amount. Nevertheless, the need for a higher number of well-trained technicians might represent some limitation, counterbalanced by the opportunity to elaborate more accurate diagnosis and, consequently, more targeted therapies

Current indications to parathyroidectomy in CKD patients before and after renal transplantation

Secondary hyperparathyroidism (SHP) is one of the most challenging complications in the most advanced stages of end-stage renal disease. In the last decade, newly available medical tools have greatly increased the possibilities for controlling SHP. However, one of these tools, cinacalcet, has not yet been approved for its use in transplanted patients and the evidence for its safety in this clinical setting is still incomplete. For these reasons, many questions still remain open for the clinical nephrologist: when to consider a parathyroidectomy (PTX) in a patient on a waiting list for kidney transplant (KTx); when to recommend PTX after KTx; when could a regression of parathyroid hyperplasia be expected at any time after KTx. In the present paper, we will briefly deal with these questions in the light of an unusual clinical case

The impact of long-term hemodialysis on pituitary-adrenocortical function

The activity of the hypothalamic-pituitary-adrenal axis in hemodialyzed (HD) patients has been investigated, with conflicting results. Different results are reported concerning both basal ACTH and cortisol concentration and the responses to different stimulating agents, in chronic hemodialyzed patients. The present study was performed in order to assess whether the length of the hemodialytic treatment may affect the pituitary and adrenocortical response to stimulation with ovine CRH (oCRH) and with exogenous ACTH in a group of patients on chronic HD for more than 10 years. Ten uremic patients (aged 3871, 6 males and 4 females) on chronic hemodialysis for at least 10 years and 7 healthy subjects matched for age and sex were studied. The patients were tested on the day preceding dialysis session. Each subject received on different non-consecutive days oCRH (100 μg i.v. in bolus) and ACTH (Synacthen 0.25 mg i.v. in bolus), and blood samples were obtained at appropriate intervals. Basal ACTH and cortisol levels of HD patients were in the upper limit of normal range (ACTH 39.21 ± 11.11 pg/mL in HD patients vs. 26.88 ± 14.12 pg/mL in controls; cortisol 19.96 ± 5.07 in HD patients rs. 12.66 ± 4.44 in controls); however, the means were not significantly different compared with controls. Following oCRH administration a net increase of ACTH and cortisol was observed in every patient tested (ACTH peak 83.81 ±28.49 in HD vs. 78.73 ± 22.87 pg/mL in controls; cortisol peak 30.73 ± 19.31 in HD vs. 20.05 ± 3.19 μg/dL in controls). Comparing the ACTH and cortisol responses to oCRH obtained in HD pts and in controls, a mild delay in the maximum response peak of ACTH (peak at 60 min vs. 30 min) and a prolonged cortisol dismission was observed. Exogenous A CTH administration elicited a normal cortisol response in both HD patients and control groups. In conclusion, our results show that the responsiveness of the pituitary-adrenal axis is maintained in uremic patients, even after more than 10 years of chronic hemodialysis; the delayed ACTH response to oCRH might be considered a further manifestation of the disordered hypothalamic regulation described in uremia and/or it is probably due to a maladaptative response to chronic stress

Immediate graft function positively affects long-term outcome of renal allografts from older but not from younger donors

There is disagreement about the impact of delayed graft function (DGF) on renal allograft outcome. This may depend on several variables including the age of the donor. We evaluated whether DGF could have different effects in recipients of kidneys from donors aged more than 60 years versus well-matched recipients of younger kidney donors. Patients were retrospectively subdivided into 3 groups. Immediate graft function (IGF), DGF without dialysis (DGF-ND), DGF requiring dialysis (DGF-D). DGF-ND and DGF-D occurred more frequently among 198 older than 198 younger donors (P = .016 and P = .044, respectively). The 5-year patient (96% vs 93%) and pure graft (96% vs 89%) survivals were significantly better in younger recipients, while the incidence of acute rejection was similar. After a mean follow-up of 66 \ub1 44 months in older donor recipients, the graft survival was significantly better among IGF than patients in the DGF-ND (P = .046) or DGF-D (P = .003) groups. Instead, in younger recipients there was no difference in graft survival between IGD and DGF-ND. Only patients with DGF-D showed a significantly worse outcome. Upon multivariate analysis of older donors, their recipients, showed the pattern of graft function recovery to be the only variable associated with allograft outcome. Instead in younger donor recipients, acute rejection and time on dialysis were the main variables associated with a poor outcome. In older donor recipients, DGF was an independent variable associated with a poor graft outcome. In younger donor recipients, duration of dialysis and rejection were the most important predictors of poor graft outcomes