Vitamin D and subclinical cardiac damage in a cohort of kidney transplanted patients: a retrospective observational study.

In 178-kidney transplanted patients (KTxp), the prevalence of hypovitaminosis-D, the presence and novel development of left ventricular hypertrophy(LVH) and the correlations between native Vitamin-D (25OHD) and LVH were evaluated during the 1st year of transplantation (KTx). Clinical and instrumental data were recorded at pre-KTx and at one (T1) and 12 (T12) months after KTx. 25OHD levels were considered sufficient (s25OHD, ≥ 30 ng/dL) or insufficient (i25OHD, < 30 ng/dL). 25OHD correlated at T1 with parathormone(PTH), and at T12 with 25OHD-T1 and PTH-(T1,T12). At T12, s25OHD (15%) had higher 25OH and alkaline phosphatase (ALP), lower Ca, at T1, and lower PTH-(T1, T12) than i25OH-T12. At T1, KTxp with LVH (LVH-T1pos, 42%) were older and with longer dialysis vintage than LVH-T1neg. At T12, KTxp with LVH (LVH-T12pos, 53%) were older, with higher systolic blood pressure (SBP) at T12 than LVH-T12neg. No relation between 25OHD and LVH were found. Novel LVH was found in 14% of KTxp. They were older, had higher SBP-T12 and lower serum albumin-T12 than the others. LVH-modifications and 25OHD were not correlated. Hypovitaminosis-D is highly prevalent in KTxp. LVH correlates with different risk factors according to the time elapsed from KTx. However, during the 1st year of KTx, no relationship between LVH and 25OHD was observed.

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.

Novel markers of graft outcome in a cohort of kidney transplanted patients: a cohort observational study.

Renal biopsy (RBx) informs about kidney transplantation (KTx) prognosis. In our observational study the prevalence of histological anomalies and the prognostic role of CD45, vimentin (VIM) and periostin (POSTN) in KTx-RBx have been evaluated. One hundred forty-six KTx-RBx (2009-2012) were analysed for general histology and in immunohistochemistry for CD45, VIM and POSTN. Clinical data of the 146-KTx patients were collected at the RBx time (T0), 6 and 12 months before and after RBx. Follow-up time was 21 ± 14 months. Glomerulosclerosis was 20% glomeruli/biopsy. Tubular atrophy (TA), Interstitial infiltrate (I-Inf) and interstitial fibrosis (IF) were slight in 21-18% and 25%, moderate in 22-30% and 26% and severe in 30-18% and 28% of patients. Fifty-eight percent of patients had lesions compatible with IF-TA. CD45, VIM and POSTN correlated to each-other and to TA, I-Inf and IF. VIM and POSTN correlated to GS. CD45 and VIM correlated directly to renal function (RF) and 25(OH)VitD, while POSTN inversely to 25(OH)VitD. Thirty patients restarted dialysis (HD+). HD+ had lower T0-eGFR, and higher CD45, VIM and POSTN than HD-. POSTN resulted the strongest in discriminate for HD+ . CD45, VIM and POSTN correlate to each-other and predict graft outcome. POSTN was the strongest in discriminate for HD+. 25(OH)VitD might influence inflammation and fibrosis in KTx.

Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy characterized by hemolysis, platelet consumption, and renal injury. Eculizumab, a mAb that blocks complement activity, has been successfully used in aHUS. OBJECTIVES: To optimize eculizumab therapy in aHUS patients by monitoring complement functional tests and markers of disease activity. PATIENTS/METHODS: We studied 18 patients with aHUS (10 males; eight females; age range, 2-40 years) treated with eculizumab to induce and/or maintain disease remission. Patients were followed up for a cumulative observation period of 160 months, during which blood samples were obtained at various time intervals to measure complement activity (Wieslab for the classical, alternative and mannose-binding lectin complement pathways) and the parameters of disease activity (haptoglobin and lactate dehydrogenase serum levels, and platelet count). The intravenous eculizumab doses of 12-33 mg kg(-1) were initially administered every week, with the interval between doses being gradually extended to 2 weeks, 3 weeks and 4 weeks on the basis of strict laboratory and clinical control. RESULTS: Complement activity was normal before eculizumab treatment, regardless of the state of the disease (activity or remission). It was completely suppressed 1 week, 2 weeks and 3 weeks after the last eculizumab infusion (mean values ± standard deviation: 1% ± 1% to 3% ± 5% for both the classical and alternative pathways; P = 0.0001 vs. baseline), and partially suppressed after 4 weeks (22% ± 26% and 16% ± 27%; P = 0.0001 vs. baseline). The increase in the time interval between eculizumab infusions did not change disease activity markers. CONCLUSIONS: Monitoring complement tests can allow a safe reduction in the frequency of eculizumab administration in aHUS while keeping the disease in remission.

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 +/- 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.

Effect of incremental doses of folate on homocysteine and metabolically related vitamin concentrations in nondiabetic patients on peritoneal dialysis.

The role of folate supplementation in reducing hyperhomocystinemia in patients on dialysis has been reported, but the optimal dose of folate is still unknown. The aim of the present study was to investigate whether greater than 5 mg/day folate supplementation provides any additional effect on plasma homocysteine (HCY) levels. The study was prospective, open, and had no control group. Of the 64 eligible nondiabetic patients on peritoneal dialysis with hyperhomocystinemia (>20 micromol/L), 56 were given oral folate (5 mg/day) for 3 months. When Hcy did not fall below 20 micromol/L, folate doses were increased by 5 mg every 3 months to up to 15 mg/day. With 5 mg/day supplementation, serum folate concentrations increased above the upper confidence limit in 23 patients and erythrocyte folate concentrations in 27 patients. Hcy levels decreased to less than 15 micromol/L in 6 cases and by more than 50% in 12 cases. Nineteen of the remaining patients were given 10 mg/day folate. After increasing the dose, serum and erythrocyte folate levels rose above the upper detection limit. In one patient, plasma Hcy concentrations decreased to less than 15 micromol/L. Ten patients were given 15 mg/day oral folate for an additional 3 months with no effect on homocystinemia. This study confirms that oral folate supplementation may improve hyperhomocystinemia even in patients on dialysis with normal serum or erythrocyte folate concentrations. In fact, serum and erythrocyte levels cannot predict the effect of supplementation on plasma Hcy levels. However, 5 mg/day folate supplementation normalized Hcy in 10% of cases and reduced Hcy levels in another 21%. Increasing the folate dose to greater than 5 mg/day had a minimal (10 mg/day) or no (15 mg/day) additional effect on Hcy concentrations. Despite the minimal effect of increasing folate doses, given the low cost, the absence of side effects, and the high cardiovascular risk for patients on peritoneal dialysis, a careful attempt to increase the dose of oral folate up to 10 mg/day might be suggested.

Cancer among patients on renal replacement therapy: a population-based survey in Lombardy, Italy.

Longer and better survival of End-Stage Renal Disease (ESRD) patients undergoing renal replacement therapy (RRT) is now associated with a higher prevalence of new elderly patients receiving renal replacement therapy (dialysis). In order to help clarify the association of cancer risk with RRT, the incidence of cancer in a population-based cohort of uraemic patients in the Region of Lombardy, northern Italy, was undertaken using data from the Lombardy Regional Dialysis and Renal Transplant Registry. A total of 479 cases of cancer of all sites was recorded in this population. There were statistically significantly elevated risks of primary liver cancer, kidney cancer, thyroid cancer, lymphoma and multiple myeloma. When the data were examined according to primary renal diseases, there did not appear to be any particular association between excess cancer risk and the underlying pathology. While some caution must be expressed in interpreting these data, due to the relatively small numbers of cases expected in many of the disease entities, the results indicate an excess of renal-cell and liver carcinomas and lymphomas in patients receiving RRT and highlight the necessity of careful follow-up and awareness of these associations, together with the need for early detection of such tumours.

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 asses 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 38-71, 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 micrograms 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 vs. 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 micrograms/dL in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Unilateral nephrectomy and progression of renal failure.

Extensive ablation of renal mass in experimental animals leads to progressive glomerulosclerosis and chronic renal failure (CRF). Clinical studies are far from answering the question whether patients with reduced renal mass are at risk of developing progressive CRF. The aim of our study was to examine the morphological and functional aspects of the remnant kidney in a group of patients who underwent unilateral nephrectomy for renal tuberculosis: 313 patients (161 M, 152 F) mean age 57.2 +/- 10.7, were examined after a period ranging from 13.56 to 591.2 months. All patients were on ad libitum diet. Hypertension was found in 34.19% of the patients; SBP was 155.29 +/- 19.9 mmHg and DBP was 92.74 +/- 13.07 mmHg. Estimation of renal size performed by ultrasound scanner gave the following results: length 116.78 +/- 8.99 mm; width 58.24 +/- 7.21 mm; thickness 17.88 +/- 1.96 mm. Kidney function assessed by serum creatinine levels showed a mean level of 1.28 +/- 0.53 mg%. Forty-two patients (13.41%) had serum levels > 1.5 mg% but 18 of them had nonconcomitant systemic or renal involvement. Microalbuminuria determined by RIA assay was found in 50.5% of the patients. In our group of patients renal functional impairment was low and hyperfiltration expressed as microalbuminuria does not appear to be a primary factor in the progression of renal failure.

Kinetics of anti-Xa activity during combined defibrotide-heparin administration in hemodialysis.

Defibrotide, a polydesoxyribonucleotide derivative with antithrombotic and fibrinolytic activity, capable of inducing the release of PGI2 from vascular endothelia, was proposed as an alternative to standard heparin coverage during blood dialysis for patients at risk of bleeding. The original procedure featured the preliminary washing of the dialysis circuit with heparin, which was then recirculated and eliminated, and the two drugs, heparin and defibrotide, are known to interact with each other. The purpose of this present study was to explore the ex-vivo heparin activity (assessed as anti-Xa activity) in diverse hemodialysis models using defibrotide (800 mg intravenous, in 4 bolus injections) and various dosages of heparin. Anti-Xa activity is negligible in dialysis conducted with defibrotide alone. When the circuit was prewashed with heparin (5000 and 2500 IU), there was evident anti-Xa activity (0.3-0.5 U/ml) in the first 30-60 minutes of dialysis; continuous heparin infusion (500 U/hour) resulted in high anti-Xa activity levels at the end of dialysis. Thus the best hemodialysis procedure for patients at high risk of bleeding should be one utilizing only defibrotide, or defibrotide plus small amounts of calcium heparin infused at the rate of 500 U/hour for not more than two hours.

Effects of calcifediol treatment on the progression of renal osteodystrophy during continuous ambulatory peritoneal dialysis.

Mineral metabolism was studied in 31 patients with chronic renal failure on continuous ambulatory peritoneal dialysis (CAPD) for a year. After baseline observations, 1-year calcifediol treatment was started in all the patients (100 micrograms/day). After therapy, progressive normalization of calcium levels was found in all the patients, while plasma phosphate did not change. After therapy, plasma alkaline phosphatase and parathyroid hormone decreased significantly. 1,25-Dihydroxyvitamin D showed a slight increase, and 25-hydroxyvitamin D (extremely low at the start of the study) rose, reaching normal levels, after 1 year of treatment. Bone mineral density and bone biopsy indexes showed general improvement after calcifediol. In conclusion, calcifediol seems to act positively on the disorders of mineral metabolism in CAPD.

Failure of platelet markers to evaluate membrane biocompatibility during a combined hemodialysis-hemoperfusion treatment.

Plasma levels of the platelet markers beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) are among the most sophisticated indexes of biocompatibility available to evaluate new members for hemodialysis. This investigation was designed to determine the extent of platelet activation by measuring the alpha-granule release products, beta-TG and PF4; anticoagulation and thrombogenesis by monitoring plasma heparin; and fibrinopeptide A (FPA) and thromboxane B2 (TX B2) levels during treatment with a combined hemodialysis-hemoperfusion system. Both in vivo and in vitro results showed that the platelet markers had a pattern different from that generally observed during treatment with hemodialysis alone. This is due to the avidity of charcoal for the markers studied, which therefore cannot be used to evaluate the biocompatibility of the system.

Biofiltration and calcium-phosphate metabolism.

We evaluated the effect of one session of biofiltration on calcium-phosphate metabolism in four uremic patients and compared the results with those of a previous traditional hemodialysis (Cuprophane membrane) session, on the same subjects. The most noteworthy results were: both total and ionized plasma calcium rose less in biofiltration; phosphate clearance and parathyroid hormone clearance were higher in biofiltration; plasma 25-OH D did not change in either dialysis technique.