Prevalence and Risk Factors of Abnormal Glucose Metabolism and New-Onset Diabetes Mellitus after Kidney Transplantation: A Single-Center Retrospective Observational Cohort Study.

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.

Impact of hepatitis C virus and direct acting antivirals on kidney recipients: a retrospective study.

Hepatitis C virus (HCV) in kidney transplanted patients (KTx-p) carries a high risk for a worse outcome. This retrospective study evaluates the impact of HCV and of the new direct acting antivirals (DAAs) on patient and graft outcomes in KTx patients. Forty (6.5%) of the 616 KTx-p, who received a kidney transplantation (KTx) in our Centre had antibodies against HCV: 13 were positive for HCV RNA and received DAAs (Group A); 11 were HCV RNA positive and did not receive any treatment (Group B; n = 11); 16 were negative for HCV RNA (Group C). All Group A patients had HCV RNA negativity after 12 weeks of treatment, and 12 (92.30%) achieved a sustained virological response (SVR). Only two patients, who had proteinuria greater than 500 mg/day showed a worsening of proteinuria after antiviral therapy in Group A. Liver enzyme elevation and death were significantly more frequent in Group B than other groups. Our results support the notion that active HCV infection negatively affects kidney recipients and that DAA have a high safety and efficacy profile after KTx with no significant negative effect on allograft function, particularly in well-functioning renal grafts.

Kidney transplantation in patients with ANCA-associated vasculitis is associated with a high incidence of post-transplant cancer.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease with limited data on outcomes after transplantation. METHODS: In this single-center retrospective cohort study, we describe the outcomes of kidney transplant patients with AAV transplanted at our institute from February 2006 to January 2022. RESULTS: We identified 9 patients among 1026 with a pre-transplant diagnosis of AAV; all patients had received previous treatment with cyclophosphamide. Maintenance immunosuppression after transplantation was tacrolimus-based in 89% of the patients. At the end of a mean follow-up of 132 ± 61.1 months after transplantation, only one case of extrarenal vasculitis relapse was observed. The relapse rate was 0.01 per patient per year, which is comparable to that reported in the literature. However, seven patients were diagnosed with cancer after a mean follow-up of 81.4 months after transplantation; six had skin cancer and three had renal cell carcinoma (RCC) of the native kidneys (cumulative incidence of 78%). One patient died from metastatic squamous cell carcinoma. CONCLUSION: In this study, we found a noticeable decrease in disease relapse (1 relapse in the present cohort vs 7 relapses in 19 patients in the previous cohort) in kidney transplant patients with AAV compared with previous data from our group (December 1987-January 2006). Conversely, we found a high incidence of post-transplant cancer. This result could be attributed to reduced immunosurveillance due to immunosuppression therapy before and after transplantation. Therefore, constant cancer early diagnosis and prevention is mandatory during the post-transplant follow-up of AAV patients.

Optimizing utilization of kidneys from deceased donors over 60 years: five-year outcomes after implementation of a combined clinical and histological allocation algorithm.

This 5 year observational multicentre study conducted in the Nord Italian Transplant programme area evaluated outcomes in patients receiving kidneys from donors over 60 years allocated according to a combined clinical and histological algorithm. Low-risk donors 60-69 years without risk factors were allocated to single kidney transplant (LR-SKT) based on clinical criteria. Biopsy was performed in donors over 70 years or 60-69 years with risk factors, allocated to Single (HR-SKT) or Dual kidney transplant (HR-DKT) according to the severity of histological damage. Forty HR-DKTs, 41 HR-SKTs and 234 LR-SKTs were evaluated. Baseline differences generally reflected stratification and allocation criteria. Patient and graft (death censored) survival were 90% and 92% for HR-DKT, 85% and 89% for HR-SKT, 88% and 87% for LR-SKT. The algorithm appeared user-friendly in daily practice and was safe and efficient, as demonstrated by satisfactory outcomes in all groups at 5 years. Clinical criteria performed well in low-risk donors. The excellent outcomes observed in DKTs call for fine-tuning of cut-off scores for allocation to DKT or SKT in high-risk patients.

Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients.

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.

Outcomes of Patients Receiving a Kidney Transplant or Remaining on the Transplant Waiting List at the Epicentre of the COVID-19 Pandemic in Europe: An Observational Comparative Study.

Since the declaration of the COVID-19 pandemic, the number of kidney transplants (KT) performed worldwide has plummeted. Besides the generalised healthcare crisis, this unprecedented drop has multiple explanations such as the risk of viral transmission through the allograft, the perceived increase in SARS-CoV-2-related morbidity and mortality in immunocompromised hosts, and the virtual "safety" of dialysis while awaiting effective antiviral prophylaxis or treatment. Our institution, operating at the epicentre of the COVID-19 pandemic in Italy, has continued the KT programme without pre-set limitations. In this single-centre retrospective observational study with one-year follow-up, we assessed the outcomes of patients who had undergone KT (KTR) or remained on the transplant waiting list (TWL), before (Pre-COV) or during (COV) the pandemic. The main demographic and clinical characteristics of the patients on the TWL or receiving a KT were very similar in the two periods. The pandemic did not affect post-transplant recipient and allograft loss rates. On the contrary, there was a trend toward higher mortality among COV-TWL patients compared to Pre-COV-TWL subjects. Such a discrepancy was primarily due to SARS-CoV-2 infections. Chronic exposure to immunosuppression, incidence of delayed allograft function, and rejection rates were comparable. However, after one year, COV-KTR showed significantly higher median serum creatinine than Pre-COV-KTR. Our data confirm that KT practice could be safely maintained during the COVID-19 pandemic, with excellent patient- and allograft-related outcomes. Strict infection control strategies, aggressive follow-up monitoring, and preservation of dedicated personnel and resources are key factors for the optimisation of the results in case of future pandemics.

How Vaccinations Changed the Outcome of COVID-19 Infections in Kidney Transplant Patients: Single-Center Experience.

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.

The role for T cell repertoire/antigen-specific interactions in experimental kidney ischemia reperfusion injury.

T cells have been implicated in the early pathogenesis of ischemia reperfusion injury (IRI) of kidney, liver, lung, and brain. It is not known whether Ag-TCR engagement followed by Ag-specific T cell activation participates in IRI. T cell-deficient nu/nu mice are moderately resistant to renal IRI, which can be reversed upon reconstitution with syngeneic T cells. In this study, we found that nu/nu mice reconstituted with DO11.10 T cells, limited in their TCR repertoire, have significantly less kidney dysfunction and tubular injury after renal IRI compared with that in nu/nu mice reconstituted with wild-type T cells having a diverse TCR repertoire. CD4(+) T cells infiltrating ischemic kidneys of nu/nu mice reconstituted with DO11.10 T cells exhibited lower IFN-gamma production than that of wild-type controls. Frequency of regulatory T cells in kidneys of these mice was similar in both DO11.10 T cells and wild-type T cell recipient groups. DO11.10 mice immunized with OVA-CFA had significantly worse kidney function at 24 h after ischemia than those immunized with CFA alone. Thus, without T cell activation, diverse TCR repertoire was important for renal IRI in naive mice. However, once T cells were activated in an Ag-specific manner through TCR in DO11.10 mice, a restricted TCR repertoire no longer limited the extent of kidney injury. Thus, both TCR repertoire-dependent and -independent factors mediate T cell functions in kidney IRI.

B cells limit repair after ischemic acute kidney injury.

There is no established modality to repair kidney damage resulting from ischemia-reperfusion injury (IRI). Early responses to IRI involve lymphocytes, but the role of B cells in tissue repair after IRI is unknown. Here, we examined B cell trafficking into postischemic mouse kidneys and compared the repair response between control (wild-type) and muMT (B cell-deficient) mice with and without adoptive transfer of B cells. B cells infiltrated postischemic kidneys and subsequently activated and differentiated to plasma cells during the repair phase. Plasma cells expressing CD126 increased and B-1 B cells trafficked into postischemic kidneys with distinct kinetics. An increase in B lymphocyte chemoattractant in the kidney preceded B cell trafficking. Postischemic kidneys of muMT mice expressed higher IL-10 and vascular endothelial growth factor and exhibited more tubular proliferation and less tubular atrophy. Adoptive transfer of B cells into muMT mice reduced tubular proliferation and increased tubular atrophy. Treatment with anti-CD126 antibody increased tubular proliferation and reduced tubular atrophy in the late repair phase. These results demonstrate that B cells may limit the repair process after kidney IRI. Targeting B cells could have therapeutic potential to improve repair after IRI.

COVID-19 Infection in Kidney Transplant Patients: An Italian One Year Single Centre Experience.

COVID-19 is a life-threatening infection among elderly patients, comorbid patients, or transplanted patients. Lombardy (region of Italy), accounts for 786,324 cases as of 21 April 2021. We retrospectively describe our single Centre experience in 82 adult kidney-transplant patients with COVID-19 infection during two pandemic outbreaks: 27 (first outbreak) and 65 (second outbreak). Thirty-seven patients were hospitalized (HP) and sixty-five were home managed (HM). Infection presented with fever (80%), cough (51%), and dyspnea (33%). HP were older (60 ± 11 vs. 50 ± 14 years, p = 0.001), had more severe respiratory symptoms (dyspnea 62.1%, p < 0.0001-cough 67% p = 0.008), and a longer length of disease (30 ± 28 vs. 21 ± 10, p = 0.04). The incidence of acute kidney injury (AKI) was 29.7% (p < 0.0001). Steroid dosage was increased in 66% of patients (p = 0.0003), while calcineurin inhibitors were reduced by up to one third in 45% of cases, p < 0.0001. Eleven patients died (13%). HM patients recovered completely without sequelae. In the overall cohort, AKI development (p = 0.006 OR 50.4 CI 95% 3.0-836) and age (p = 0.04 OR 1.1 CI 95% 1.0-1.2) were the most important factors influencing the probability of death during the infection. Although we report a relatively low incidence of infection (5.1%) the incidence of death is almost four times higher than it is in the general population.

Bone Effect and Safety of One-Year Denosumab Therapy in a Cohort of Renal Transplanted Patients: An Observational Monocentric Study.

In 32-kidney transplanted patients (KTxps), the safety and the effects on BMD and mineral metabolism (MM) of one-year treatment with denosumab (DB) were studied. Femoral and vertebral BMD and T-score, FRAX score and vertebral fractures (sVF) before (T0) and after 12 months (T12) of treatment were measured. MM, renal parameters, hypocalcemic episodes (HpCa), urinary tract infections (UTI), major graft and KTxps outcomes were monitored. The cohort was composed mainly of females, n = 21. We had 29 KTxps on steroid therapy and 22 KTxps on vitamin D supplementation. At T0, 25 and 7 KTxps had femoral osteoporosis (F-OPS) and osteopenia (F-OPS), respectively. Twenty-three and six KTxps had vertebral osteoporosis (V-OPS) and osteopenia (V-OPS), respectively. Seventeen KTxps had sVF. At T12, T-score increased at femoral and vertebral sites (p = 0.05, p = 0.008). The prevalence of F-OPS and V-OPS reduced from 78% to 69% and from 72% to 50%, respectively. Twenty-five KTxps ameliorated FRAX score and two KTxps had novel sVF. At T12, a slight reduction of Ca was present, without HpCa. Four KTxps had UTI. No graft rejections, loss of graft or deaths were reported. Our preliminary results show a good efficacy and safety of DB in KTxps. Longer and randomized studies involving more KTxps might elucidate the possible primary role of DB in the treatment of bone disorders in KTxps.

Early exposure to germs modifies kidney damage and inflammation after experimental ischemia-reperfusion injury.

Kidney ischemia-reperfusion injury (IRI) is, in part, mediated by immune and inflammatory factors. Since microbial stimuli are known to alter immune and inflammatory responses, we hypothesized that differences in perinatal microbial status would modify renal injury following IRI. We performed bilateral renal IRI on 6-wk-old germ-free and control mice and studied the effects on kidney lymphocyte trafficking, cytokines, function, and structure. Compared with control mice, normal kidneys of germ-free mice exhibited more NKT cells and lower IL-4 levels. Postischemia, more CD8 T cells trafficked into postischemic kidneys of germ-free mice compared with control mice. Renal structural injury and functional decline following IRI were more severe in germ-free mice compared with control mice. When germ-free mice were conventionalized with the addition of bacteria to their diet, the extent of renal injury after IRI became equivalent to age-matched control mice, with similar numbers and phenotypes of T cells and NKT cells, as well as cytokine expression in both normal kidneys and postischemic kidneys of conventionalized germ-free mice and age-matched control mice. Thus microbial stimuli influence the phenotype of renal lymphocytes and the expression of cytokines of normal kidneys and also modulate the outcome of IRI.

Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury.

T lymphocytes modulate early ischemia-reperfusion injury in the kidney; however, their role during repair is unknown. We studied the role of TCRbeta(+)CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), known to blunt immune responses, in repair after ischemia-reperfusion injury to the kidney. Using a murine model of ischemic acute kidney injury we found that there was a significant trafficking of Tregs into the kidneys after 3 and 10 days. Post-ischemic kidneys had increased numbers of TCRbeta(+)CD4(+) and TCRbeta(+)CD8(+) T cells with enhanced pro-inflammatory cytokine production. Treg depletion starting 1 day after ischemic injury using anti-CD25 antibodies increased renal tubular damage, reduced tubular proliferation at both time points, enhanced infiltrating T lymphocyte cytokine production at 3 days and TNF-alpha generation by TCRbeta(+)CD4(+) T cells at 10 days. In separate mice, infusion of CD4(+)CD25(+) Tregs 1 day after initial injury reduced INF-gamma production by TCRbeta(+)CD4(+) T cells at 3 days, improved repair and reduced cytokine generation at 10 days. Treg manipulation had minimal effect on neutrophil and macrophage infiltration; Treg depletion worsened mortality and serum creatinine, while Treg infusion had a late beneficial effect on serum creatinine in bilateral ischemia. Our study demonstrates that Tregs infiltrate ischemic-reperfused kidneys during the healing process promoting repair, likely through modulation of pro-inflammatory cytokine production of other T cell subsets. Treg targeting could be a novel therapeutic approach to enhance recovery from ischemic acute kidney injury.

Androgen-mediated apoptosis of kidney tubule cells: role of c-Jun amino terminal kinase.

The incidence and the rate of progression of chronic kidney diseases (CKD) are for most diseases greater in men than in age-matched women. We have previously shown that testosterone (T) promotes the apoptosis of proximal tubule kidney cells. To better understand the downstream signaling process associated with T-induced apoptosis, we examined the involvement of c-Jun amino terminal kinase (JNK) in a human proximal tubule cell line (HK-2) exposed to T: JNK and its downstream effector c-Jun were rapidly phosphorylated. By blocking androgen receptor, JNK phosphorylation was reduced and 17beta-Estradiol treatment had no effect on it. Similarly, pre-treatment with the JNK inhibitor SP600125 prevented the T-induced apoptosis, the phosphorylation of c-Jun and the upregulation of the Fas/FADD pathway. These data show that the JNK/c-Jun pathway is directly regulated by androgens in vitro and highlight a potential mechanism explaining the reported gender differences in the progression of renal diseases.

Effect of T cells on vascular permeability in early ischemic acute kidney injury in mice.

Although previous studies have demonstrated that microvascular dysfunction and inflammation occur in ischemia-reperfusion injury (IRI), the underlying mechanisms are poorly understood. We hypothesized that T cells could mediate renal vascular permeability (RVP) during IRI. We evaluated renal vascular permeability by extravasation of Evans blue dye from the kidney in CD3, CD4 or CD8 T cell deficient mice as well as in TNF receptor knock out mice in our mouse model of kidney ischemia-reperfusion injury. In wild type mice, RVP was significantly increased at 3 h, peaked at 6 h and declined by 24 h after ischemia. Immunohistochemistry revealed that CD3(+) T cells trafficked into ischemic kidney at 1 h and peaked at 6 h. Gene microarray analysis demonstrated that endothelial-related genes including TNF-alpha were up-regulated in ischemic kidney. The production of TNF-alpha and IFN-gamma protein was increased in CD3 and CD4 T cells from the blood and kidney after ischemia. The rise in RVP after ischemia in wild type mice was attenuated in CD3, CD4 or CD8 T cell deficient mice as well as in TNF receptor knock out mice. The attenuation of RVP in CD3 T-cell deficient mice after ischemia was restored by adoptive transfer of T cells from WT mice. Our data demonstrate that T cells directly contribute to the increased RVP after kidney ischemia-reperfusion, potentially through T cell cytokine production.

Oxalate deposits in biopsies from native and transplanted kidneys, and impact on graft function.

BACKGROUND: The purpose of this study was to examine the incidence of oxalate deposits in native and renal allograft biopsies, and its impact on graft function. METHODS: The renal biopsy files at The Johns Hopkins University between 2000 and 2006 were searched to identify biopsies with oxalate deposits, determine the density of oxalate deposits in renal graft biopsies, compare graft histology and function between allograft recipients with oxalate in the graft biopsies, and a control group of recipients without oxalate in the graft. RESULTS: Oxalate crystal deposits were observed in 61 of 5160 biopsies of native kidneys, and in 76 of 1621 renal allograft biopsies, with a frequency of 1 and 4%, respectively. Sixty-three (9%) of 680 transplant recipients showed oxalate in graft biopsies obtained within the first year from transplantation, with 1.3 +/- 1.2 average number of oxalate deposits per mm(2) of biopsy tissue. The high oxalate density and decreased renal function were correlated in the first 2 years post-transplant (P = 0.037-0.05). Compared with a control group of 70 kidney graft recipients, the renal function was significantly lower in the oxalate group at 1 year, but not at 2 years post-transplant. High tubulo-interstitial scarring (P < 0.0001) was noted in repeated biopsies in the oxalate group, and was significantly greater than that in the control group (P = 0.027). No significant difference in graft loss was observed between oxalate and control groups, and although mortality was higher in the oxalate group, the difference was not significant. CONCLUSIONS: In summary, this study defines the frequency of oxalate deposition in native and allograft kidney biopsies, and suggests its possible negative impact on graft function beyond the early post-transplant period.

Effects of uremia and inflammation on growth hormone resistance in patients with chronic kidney diseases.

Resistance to the anabolic action of growth hormone may contribute to the loss of strength and muscle mass in adult patients with chronic kidney disease. We tested this hypothesis by infusing growth hormone in patients to levels necessary to saturate hormone receptors. This led to a significant decrease of plasma potassium and amino acid levels in control and hyperkalemic patients with chronic kidney disease. These effects were completely or partially blunted in patients with elevated C-reactive protein levels. In forearm perfusion studies, growth hormone caused a further decrease in the negative potassium and protein balance of hemodialysis patients without inflammation but no effect was seen in patients with inflammation. Only IL-6 levels and age were found to be independent correlates in these growth hormone-induced variations in plasma potassium and blood amino acids. This shows that although a resistance to pharmacologic doses of growth hormone is not a general feature of patients with chronic kidney disease, there is a subgroup characterized by blunted growth hormone action. Our results support the hypothesis that uremia with inflammation, but not uremia per se, inhibits downstream growth hormone signaling contributing to muscle atrophy.

Taurine prevents apoptosis induced by high ambient glucose in human tubule renal cells.

BACKGROUND: Hyperglycemia selectively triggers apoptosis in tubule and endothelial cells. Taurine, a conditionally essential amino acid, is abundant in several tubule segments, but its role has not been defined fully. It can serve as an osmolyte or as an endogenous antioxidant. Taurine metabolism is altered in diabetes mellitus, with extracellular and intracellular pools reduced. It is still unknown whether taurine can play a role as a protective agent in apoptosis induced by high glucose in tubular cells. METHODS: Apoptosis (by annexin V binding and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling method), cellular reactive oxygen species (ROS) formation (by fluorescent probe 2'-7' dichlorofluorescin diacetate and FACScan flow cytometry), and Bcl-2 and Bax proteins (by immunostaining) were studied in a human proximal tubular cell line (HK-2) grown in a medium with physiologic (5.5 mM) or high (30 mM) glucose concentrations for 48 hours. In separate experiments, taurine (3-24 mM) was added to the media. RESULTS: The exposure of human tubule cells to 30 mM glucose for 48 hours resulted in a significant increase in apoptosis compared with 5.5 mM glucose (35 +/- 8% vs. 6 +/- 3%, p < 0.001). Thirty mM mannitol failed to induce the effects of high glucose. High glucose-mediated apoptosis was associated with a decrease in the expression of Bcl-2 (-87%) and a twofold increase in the expression of Bax protein. Taurine had a dose-dependent effect in preventing high-glucose-induced apoptosis (-78%, p < 0.001 at 24 mM). Moreover, with taurine, intracellular ROS decreased by 34% (p < 0.05), and changes in intracellular ROS formation induced by taurine at 24 hours predicted the variations in the apoptotic index at 48 hours (r = 0.87, p < 0.02). Other antioxidants, such as glutathione and N-acetylcysteine, also attenuated the high glucose-induced apoptosis. CONCLUSION: These results demonstrate that taurine attenuates hyperglycemia-induced apoptosis in human tubular cells via an inhibition of oxidative stress. Taurine might act as an endogenous antioxidant in tubule cells and could exert a beneficial effect in preventing tubulointerstitial injury in diabetic nephropathy.

Calcium and osteoprotegerin levels predict the progression of the abdominal aortic calcifications after kidney transplantation.

BACKGROUND: Vascular calcifications (VCs) are a cardiovascular risk factor in patients affected by chronic kidney disease and after kidney transplantation (KTx). We evaluated the prevalence of VCs at the abdominal aortic site in KTx patients at the time of transplantation and 1 year after KTx, exploring the possibly associated factors. METHODS: In 107 transplanted patients, the following parameters were evaluated at the first and twelfth month after KTx: the aortic calcification index (ACI), fibroblast growth factor 23, osteoprotegerin (OPG), fetuin A, and clinical and biochemical parameters. Patients were followed up for 2 years after KTx. RESULTS: At the time of KTx, 60% of patients had some degree of VC (ACI>0), whereas 40% had no VC. One year after KTx, VCs worsened in 26% of patients, whereas in 74%, VCs remained stable or improved. The progression of VC was observed almost exclusively in patients with a positive ACI score at the first month. At the multivariate analysis, serum calcium, OPG, and estimated glomerular filtration rate were the only variables independently associated with the progression of VC. CONCLUSIONS: VCs at the aortic site are frequent in KTx patients, and in a significant percentage of them, they tend to progress even in the short time. High levels of serum calcium and OPG are significantly associated with the progression of VCs. Whether these associations are based on a cause-effect relationship and their correction might impact on the calcification process could be ascertained by prospective interventional studies.

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.