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In the late 1970s, calcitriol was introduced into clinical practice for the management of secondary renal hyperparathyroidism in chronic kidney disease (CKD). Since then, the use of calcifediol or other native forms of vitamin D was largely ignored until the publication of the 2009 Kidney Disease Improving Global Outcomes (KDIGO) recommendations. The guidelines suggested that measurement of circulating levels of 25(OH)D (calcifediol) and its supplementation were to be performed on the same basis as for the general population. This indication was based on the fact that the precursors of active vitamin D had provided to CKD patients considerable benefits in survival, mainly due to their pleiotropic effects on the cardiovascular system. However, despite the long-term use of various classes of vitamin D in CKD, a clear definition is still lacking concerning the most appropriate time for initiation of therapy, the best compound to prescribe (active metabolites or analogs), the proper dosage, and the most suitable duration of therapy. The aim of this position statement is to provide and critically appraise the current plentiful evidence on vitamin D in different clinical settings related to CKD, particularly focusing on outcomes, monitoring and treatment-associated risks. However, it should be taken in account that position statements are meant to provide guidance; therefore, they are not to be considered prescriptive for all patients and, importantly, they cannot replace the judgment of clinicians.

Background: Cardiac valve calcifications are present in dialysis patients and regarded as dependent on a deranged mineral metabolism. Few data are available for patients with chronic kidney disease (CKD) not on dialysis. This study evaluates the potential association between the extent of cardiac valve calcification and levels of intact parathyroid hormone (i-PTH), phosphorus, calcium, 25-OH vitamin D, fibroblast growth factor 23 (FGF-23), Klotho and C-reactive protein (CRP) simultaneously measured in patients with mild to moderate CKD., Methods: Consecutive non-hospitalized patients referring to five nephrology units were evaluated. Inclusion criteria were age >18 years, CKD Stages 3-4, and the presence of aortic and/or mitral valve calcification assessed by echocardiography as routinely clinical evaluation. Patients underwent clinical examination and routine biochemistry. Baseline i-PTH, phosphorus, calcium, 25-OH vitamin D, FGF-23, Klotho and CRP were simultaneously ascertained., Results: Extent of aortic valve calcification (n = 100 patients) was moderate in 68 patients and mild in the remaining patients. Mitral valve calcification (n = 96 patients) score was 1, 2 and 3 in 61, 34 and 1 patients, respectively. In univariate analysis, no association was found between extent of mitral valve calcification and markers of mineral metabolism and CRP; aortic valve extent of calcification was positively associated with i-PTH (r(2) = 0.212; P = 0.03) and FGF-23 (r(2) = 0.272; P = 0.01), and negatively with Klotho (r(2) = -0.208; P = 0.04). In multivariable analysis, extent of aortic valve calcification was associated with FGF-23 (P = 0.01) and PTH (P = 0.01) levels., Conclusions: Extent of aortic valve calcification is associated to FGF-23 and PTH in naïve CKD patients with mild to moderate CKD. Further studies should examine whether FGF-23 assay should be included in routine clinical evaluation of CKD as part of cardiovascular risk stratification.

Background/aims: High BMI increases the risk of cardiovascular events (CVEs) in the general population. Conflicting results have been reported on the role of BMI on CVEs and on decline of renal function in patients with chronic kidney disease not on dialysis (CKD). This study evaluates the impact of BMI on CVEs, dialysis initiation, and coronary artery calcification (CAC) in CKD patients., Methods: CKD patients were divided in normal-BMI and high-BMI patients. CVEs, initiation of dialysis, and extent and progression of CAC were assessed. Univariate and multivariable analysis were performed (adjustment variables: age, diabetes, hypertension, gender, CKD stage, serum concentration of hemoglobin, parathyroid hormone, calcium, phosphorus, albumin, C-reactive protein, LDL-cholesterol, total calcium score, 24-hour proteinuria). Patients were followed to the first event (CVE, dialysis) or for 2 years., Results: 471 patients were evaluated. A CVE occurred in 13.5 and 21.3% (p < 0.05) of normal-BMI and high-BMI patients, respectively. High BMI did not increase the risk for CVEs in univariate (HR: 1.86; 95% CI: 0.97-3.54; p = 0.06) or multivariable analysis (HR: 1.36; 95% CI: 0.57-3.14; p = 0.50). High BMI did not increase the risk for initiation of dialysis in univariate (HR: 0.96; 95% CI: 0.58-1.60; p = 0.9) or multivariable analysis (HR: 1.77; 95% CI: 0.82-3.81; p = 0.14). Adding the interaction term (between BMI and glomerular filtration rate) to other variables, the risk of dialysis initiation significantly increased (HR: 3.06; 95% CI: 1.31-7.18; p = 0.01) in high-BMI patients. High BMI was not a predictor of CAC extent or progression., Conclusions: High BMI was not a predictor of CVEs. High BMI increased the risk for dialysis initiation, but high BMI was not associated to CAC extent and progression. The presence of confounders may underestimate the impact of high BMI on dialysis initiation., (© 2014 S. Karger AG, Basel.)

The link between serum parathyroid hormone (iPTH) and cardiovascular (CVS) mortality has not been fully elucidated. The EVOLVE Study was designed to test whether a drug such as cinacalcet, aimed at lowering iPTH, could reduce the astonishingly high cardiovascular risk in patients on maintenance dialysis (CKD-5D). Accordingly, the primary outcome of the study was the combined endpoint of time to death or hospitalization due to CVS factors or from any cause. Time to bone fracture and parathyroidectomy were regarded as secondary endpoints. At study completion, the Intention-To-Treat analysis documented a non- significant 7% (Hazard Ratio: 0.93; 95% Confidence interval: 0.85-1.02; P = 0.11) reduction of the primary composite endpoint. However, the intention to treat analysis does not take into account adherence to drug regimens or control for factors that may potentially jeopardize the conduction of the study. In particular, in spite of a careful pre-planned study sample calculation, the final power of the EVOLVE study was 54% instead of the assumed 90%, greatly reducing the reliability of study results. Furthermore, the pre-planned multivariable adjustment of the primary endpoint suggests a nominally significant reduction of the risk of the primary composite endpoint when age is entered into the statistical model. The sensitivity analysis further corroborates this result. The Lag Time Censoring Analysis (LTCA) evidenced a nominally significant 15% risk reduction of the composite endpoint among patients allocated to cinacalcet if the patients follow-up was terminated 6 months after the study drug discontinuation, as pre-planned in the protocol. It is interesting that the LTCA suggests that the effect of cinacalcet weakened over time and became insignificant after about 1 year from drug discontinuation. Although authors could not detect any effect of cinacalcet on bone fracture associated with cinacalcet use, the secondary analyses of the EVOLVE trial suggest a nominally significant 60-70% risk reduction of parathyroidectomy and a reassuring safety profile of prolonged exposure to cinacalcet. In summary, the EVOLVE study adds to the list of inconclusive randomized clinical trials in Nephrology. However, the preplanned exploratory and sensitivity analyses suggest that when imbalances of patients characteristics at study entry (i.e. age) or study drug discontinuation are considered, a 'nominally' significant risk reduction in CVS and parathyroidectomy associated with cinacalcet treatment is noted.

Background/aims: Presence and progression of coronary artery calcification (CAC) indicate severe atherosclerosis and predict cardiovascular events (CVE) in dialysis (ESRD patients) and nondialysis patients (CKD patients). This study aimed at evaluating the prevalence and progression of CAC and CVE in CKD patients with diabetes in whom atherosclerosis of coronary arteries is the leading cause of CVE., Methods: This was a retrospective study conducted in both out- and in-patients with chronic kidney disease, stage 2-5. CAC were assessed by the total calcium (TC) score. CT scans were performed at the entry and at the end of the study., Results: Patients (n = 341) were divided into nondiabetic (n = 281) and diabetic patients (n = 60). CAC prevalence and TC score were higher in diabetics and associated with age, diabetes mellitus and pulse pressure. Diabetics with CKD presented a higher percentage of CAC progression and CVE., Conclusion: Prevalence, extent, progression of CAC and CVE are higher in diabetics with concomitant CKD. These findings may promote a more aggressive protocol of screening and care in type 2 diabetics with concomitant CKD., (Copyright © 2013 S. Karger AG, Basel.)

Introduction: Serum concentrations of potassium (K) and calcium (Ca) influence ionic currents and play an important role in the duration of ventricular action potential. Further, the influence of alkalosis in reducing ionized calcium has been well known for a long time. The aim of this study was to assess the effects of different dialysate electrolytes and bicarbonate concentrations on changes of QTc interval in patients on chronic hemodialysis., Methods: The study hemodialysis sessions were performed in 22 patients, with different electrolyte and bicarbonate concentrations in dialysate. Tested dialysate concentrations were K of 2 and 3 mmol/L; Ca 1.25, 1.5 and 1.75 mmol/L; and bicarbonate 30 and 34 mmol/L. An electrocardiogram (ECG) was recorded 1 hour before, at the end and every hour for 4 hours after each study dialysis session. QTc interval was measured from the beginning of the QRS complex to the end of a T wave on a 12-lead ECG. Blood was collected and K, total Ca, ionic Ca and pH evaluated., Results: At the end of the study hemodialysis session with dialysate containing low K (2 mmol/L), low Ca (1.25 mmol/L) and high bicarbonate concentration (34 mmol), mean QTc interval was significantly prolonged compared with that recorded with dialysate containing high K (3 mmol/L), high Ca (1.75 mmol/L) and bicarbonate (30 mmol) (40 ± 10 milliseconds vs. 2 ± 2 milliseconds; p<0.01). Dialysate with low concentration of low Ca, K and high concentration of bicarbonate was an independent predictor of QTc; the combination of low Ca and K and high bicarbonate strongly increased the risk of prolonged QTc interval., Conclusion: The present pilot study shows that changes in QTc interval during hemodialysis depend on both electrolyte and bicarbonate concentrations in dialysate.

Elevated uric acid levels are a common finding in patients with metabolic syndrome and in those with cardiovascular and renal disease, but the meaning of this elevation is still unclear. In patients with chronic kidney diseases, it could merely reflect the reduction in glomerular filtration rate: but uric acid levels are known to be elevated in people, also in younger ones, prior to the development of hypertension or renal disease, independently of several risk factors. Multiple potential mechanisms suggest a causative role for uric acid in vascular disease. Uric acid has been shown to be involved in metabolic pathways that lead to oxidative stress, endothelial disfunction, and to a vascular and systemic inflammatory response. Moreover, the elevation in uric acid levels observed after fructose ingestion, with a consequent reduction in nitric oxide, may lead to a reduced glucose uptake in the skeletal muscle, hyperinsulinemia, and insulin resistance. Besides these bench research data, also clinical studies showed the beneficial effects of lowering uric acid therapies on several markers of cardiovascular and renal disease. To date, however, there is no evidence indicating that such therapies, that are not free of risk, may reduce cardiovascular events; so that to manage our prescriptions, we need larger, prospective, interventional data.

We have already demonstrated that in chronic hemodialysis (HD) patients, the cyclic variations in both hydration status and blood pressure are responsible for changes in pulse wave velocity (PWV). The aim of this study is to verify whether the cyclic variation of PWV influences mortality in dialysis patients. We studied 167 oligoanuric (urinary output <500 mL/day) patients on chronic standard bicarbonate HD for at least 6 months. They performed 3 HD sessions of 4 hours per week. Patients were classified into 3 groups: normal PWV before and after dialysis (LL); high PWV before and normal PWV after dialysis (HL); and high PWV before and after dialysis (HH). The carotid-femoral PWV was measured with an automated system using the foot-to-foot method. Analysis of variance was used to compare the different groups. The outcome event studied was all-cause mortality and cardiovascular mortality. The PWV values observed were LL in 44 patients (26.3%); HL in 53 patients (31.8%); and HH in 70 patients (41.9%). The 3 groups of patients are homogenous for sex, age, and blood pressure. The HH group had a higher prevalence of (P<0.001) ASCVD. It is interesting that the distribution of patients in the 3 groups is correlated with the basal value of PWV. In fact, when the basal measure of PWV is elevated, there is a higher probability that an HD session cannot reduce PWV (<12 ms). A total of 53 patients (31.7%) died during the follow-up of 2 years: 5 patients in the LL group (11.4%); 16 in the HL group (30.2%); and 32 in the HH group (50.7%) (LL vs. HL, P=0.047; LL vs. HH, P<0.00001; HL vs. HH, P=0.034). We evidence for the first time that different behaviors of PWV in dialysis subjects determine differences in mortality., (© 2011 The Authors. Hemodialysis International © 2011 International Society for Hemodialysis.)

KDIGO (KIDNEY DISEASE: Improving Global Outcomes) is an international nonprofit organization devoted to "improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines." The mineral and bone disorder (MBD) in patients with chronic kidney disease (CKD) has been the first area of interest of KDIGO international initiative. KDIGO guidelines on CKD-MBD were published in 2009 with the intent to modify the previous KDOQI guidelines that had failed to consistently change the global outcome of CKD patients. After the publication of KDOQI guidelines for bone metabolism and disease in 2003, a large number of observational data emerged in literature linking disordered mineral metabolism with adverse clinical outcomes. Notwithstanding this large body of observational data, a paucity of evidence from high-quality clinical trials was available for the development of KDIGO guidelines. Herein, a summary will be provided of the most important findings of KDIGO guidelines regarding the diagnostic workup and clinical monitoring of CKD-MBD patients.

Background: Haemodialysis patients are ageing and have with a high rate of comorbidities. The impact of this novel clinical setting on intact parathyroid hormone (iPTH) is not well established., Methods: For this observational, prospective multicentre cohort study, incident haemodialysis patients were recruited in 40 Italian centres and followed up for a mean period of 18 +/- 6.7 months. Clinical characteristics and biochemistry were recorded at baseline. Comorbid conditions were scored by the Charlson comorbidity index (CCI)., Results: Data of 411 patients (mean age: 66.5 +/- 14.8 years; 17.3% >80 years old) were recorded. The mean CCI was 4.17 +/- 2.8. In patients with CCI >0, an inverse correlation was observed between CCI (excluding age) and iPTH (P = 0.00002). Independently of CCI, patients with iPTH <150 pg/ml had 76% as high as the risk of all-cause mortality. After multivariable adjustment, the combination of the first tertile of iPTH with second and third tertiles of CCI was significantly associated with all-cause mortality (RR = 3.83, P = 0.02; RR = 3.79, P = 0.01, respectively)., Conclusions: Incident haemodialysis patients suffer from a high rate of clinical complications. In these patients, low iPTH and high CCI are often associated and very likely responsible for an adverse outcome.

Background: Coronary calcification (CAC) is found in early stages of CKD. Pulse pressure (PP) predicts CAC in dialysis patients. This study evaluates the accuracy of PP in predicting CAC in patients not yet on dialysis (CKD patients)., Methods: CKD patients (n = 388) underwent coronary calcium score (CAC score) and abdominal x-ray (n = 128) for estimating aorta calcification (AAC). Biochemistry and PP were measured every 3 and 6 months in patients with stage 4 to 5 and 2 to 3 CKD, respectively. The accuracy of PP and AAC was assessed by receiver operating characteristics analysis., Results: PP correlated with CAC score in the whole cohort and in patients with stages 2 to 3 and stages 4 to 5 CKD. PP >60 mmHg predicted CAC score >0 (OR: 2.14; P < 0.001), > or =100 (OR: 2.92; P < 0.001), > or =400 (OR: 6.17; P < 0.001) after multivariable adjustment. Area under the curve (AUC) was 0.626 for CAC score >0, 0.676 for score >100, and 0.746 for score >400. PP >60 mmHg reduced the rate of event-free survival. AAC was found in 58% of patients and correlated with CAC score. AUC was 0.628 for CAC score >0, 0.652 for score >100, 0.831 for score >400., Conclusion: PP may identify CKD patients with subclinical CAC who need further evaluation. Accuracy of PP and AAC is nearly similar in predicting CAC. High PP indicates vessel wall alterations leading to adverse outcome.

Background: Although several registries collecting data of patients with kidney diseases exist, there are only a few registries which specifically collect data relating to renal biopsy; one such registry is the Italian Registry of Renal Biopsies (IRRB). The aim of this study was to report on the relative frequency of nephropathies according to gender, age at time of biopsy, clinical presentation and renal function, based on the histologic diagnosis during the years 1996 to 2000., Methods: We evaluated data relating to 14607 renal biopsies, provided by 128 renal units in Italy. Data entry was performed by using the Internet-based database directly (URL http://www.irrb.net). Clinical presentation was defined as urinary abnormalities (UA), nephrotic syndrome (NS), acute nephritic syndrome (ANS). Renal diseases were divided in four major categories: (1) primary glomerulonephritides (GN); (2) secondary GN; (3) tubulointerstitial nephropathies (TIN); and (4) vascular nephropathies (VN)., Results: Primary GN, TIN, and VN were more frequent in males compared to females while secondary GN was more frequent in females. Diseases whose frequency was higher in males were IgA nephropathy (IgAN), benign nephroangiosclerosis (BNA), and acute tubular necrosis (ATN). A significantly higher frequency of immune-mediated secondary GN, as well as primary GN, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and mesangiocapillary GN (MCGN), was shown in females. Primary and secondary GN, TIN, and VN were more frequent in the range 15 to 65 years of age. At the time of biopsy 77% of primary GN and 61% of secondary GN presented with normal renal function. Acute renal failure (ACR) was more present in TIN (52%), while chronic renal failure (CRF) was more frequent in VN (47%)., Conclusion: We believe collection of data relating to renal biopsies in a national registry is a useful tool for nephrologists in that it meets one of the current challenges facing the clinical research enterprise. The availability of these data will allow epidemiologic studies in health care to answer the several open questions in both prevention and treatment of renal diseases.

Aim: The Cockcroft and Gault formula is a quick and reliable method for calculating creatinine clearance without a 24-hour urine collection (CG-cl). In obese subjects an excess of fat mass provokes a reduction in daily creatinine urine excretion per body kilo weight and is responsible for overestimated renal function when calculated by CG-cl. The aim of this study was to devise a simple correction method which could also make use of CG-cl in obese subjects., Patients and Methods: In 52 subjects with a body mass index (BMI) > 25, renal function was assessed by simultaneously determining creatinine clearance using 24-hour urine collection (Cr-cl) and the CG-cl. The percentage difference between the 2 clearances (delta %) was correlated with BMI for each patient using simple linear regression analysis. The estimated regression model (delta% = 1.217 BMI-- 24.81) provided the following CG-cl correction formula for obese subjects: Corrected CG-cl = CG-cl (1.25 - 0.012 BMI). Its validity was evaluated in another group of 20 subjects with BMI > 25 by comparing the results obtained with Corrected CG-cl to those obtained by CG-cl and MDRD formula (MDRD-cl) using the clearance of 51Cr-EDTA (5 Cr-EDTA-cl) as the GFR measurement gold standard., Results and Conclusion: Linear regression analysis of CG-cl, MDRD-cl and Corrected CG-cl compared to 5tCr-EDTA-cl (considered as the independent variable) resulted in the following determination coefficients (R2): 0.687; 0.818; 0.947, respectively. In conclusion, this formula can be considered a quick and reliable method for CG-cl correction in obese subjects.

We present the case of a 55-year-old patient who underwent total parathyroidectomy for severe hyperparathyroidism unresponsive to medical therapy, 4 years after having started hemodialysis treatment. It was decided to perform total parathyroidectomy because at macroscopic evaluation the parathyroid glands appeared completely compromised. After surgery, the patient developed hungry bone disease, characterized by severe hypocalcemia and hypophosphatemia. After parathyroidectomy, serial measurements were made for the long-term monitoring of the calcemia, phosphatemia and the serum levels of intact parathormone and bone alkaline phosphatase, a marker of bone turnover that mainly expresses bone formation. There was initially a slight decrease in the circulating levels of bone alkaline phosphatase as the calcemia dropped dramatically, then a new increase that anticipated the subsequent calcemia increase and finally, 6 months later, a decrease to very low values. We believe that the calcemia and blood bone alkaline phosphatase could be useful for the laboratory monitoring of the hungry bone state, providing information which may be useful to avoid excessive calcium administration and the dangerous consequences such as soft-tissue calcification.

Central diabetes insipidus (CDI) arising in the puerperal period has been attributed mainly to Sheehan's syndrome or to lymphocytic infundibulo-neurohypophysitis. We report the case of a 24-year-old woman who came to our observation for the appearance, 3 weeks after a normal delivery, of a polyuric-polydipsic syndrome. Measurements of urinary volumes, plasma osmolality and urinary osmolality, in conditions of free water intake, water deprivation and a water deprivation-vasopressin administration test, demonstrated CDI. Brain magnetic resonance imaging showed a normal morphology of the adenohypophysis and total absence of the neurohypophysis. Assays of the pituitary hormones were found to be within normal limits. These results, incompatible with a diagnosis of Sheehan's syndrome and lymphocytic infundibulo-neurohypophysis, excluded all the other known causes of acquired CDI. Our diagnosis was therefore of post-gravid idiopathic CDI. Thus, it is possible that in the puerperal period other diseases of the posterior hypophysis may develop, of unknown etiopathogenesis but equally responsible for CDI.

Antihypertensive drugs may have an important effect on glomerular haemodynamics. In chronic nephropathy patients, we compared the effect on glomerular haemodynamics of two second-generation dihydropyridinic agents, nitrendipine and amlodipine, with a first generation dihydropyridinic agent and an ACE-inhibitor, enalapril. In all, 32 patients (pts), divided into four groups, received the different drugs: ENA (enalapril, eight pts), NIF (nifedipine, eight pts), NIT (nitrendipine, eight pts) AML (amlodipine, eight pts). The study assessed the effect on glomerular haemodynamics of a single administration of the test drug in baseline conditions and in glomerular hyperfiltration experimentally induced by amino-acid infusion. The glomerular filtration rate (GFR, measured by inulin clearance), effective renal plasma flow (ERPF, measured by p-aminohippurate clearance), renal vascular resistances (RVR) and filtration fraction (FF) were assessed. Administration of AML and NIT test dose reduced FF, as did ENA, but not NIF, in both baseline (AML: P=0.005; NIT: P=0.02; ENA: P=0.007) and glomerular hyperfiltration conditions (AML: P=0.0003; NIT: P=0.03; ENA: P=0.00006). In baseline conditions, only ENA resulted in a significant drop in the GFR (P=0.008), while NIF, NIT and AML induced a significant increase (P=0.003, 0.03, 0.0001, respectively). However, in hyperfiltration conditions, NIT (0.08) and AML (0.00003) caused a decrease in the GFR, as did ENA (0.0003) but not NIF. In all the experimental conditions, a RVR reduction and an ERPF increase were observed. Single dose of NIT and AML were effective in attenuating the effect of amino-acid infusion on glomerular filtration, similar to ENA; this effect of NIT and AML on the glomerular filtration rate is not observed under basal conditions.

There is clear clinical evidence that a drastic lowering of plasma LDL-Cholesterol (LDL) concentrations significantly reduces the rate of total and coronary mortality as well as the incidence of cardiovascular events in high risk hypercholesterolemic patients. We describe the case of a 51-year-old woman with coronary heart disease (CHD) who presented with increasing angina on exertion in 1995, at the age of 45. She suffered from a heterozygous familial hypercholesterolemia and in 1985 her total cholesterol (TCHO) was 328 +/- 62 mg/dl (mean value of ten analysis). After ten years of statins her mean values (20 analysis, 2 per year) were: TCHO 259 +/- 71, LDL 209 +/- 47, HDL 35 +/- 7 mg/dl. Coronary angiography (CA) performed in 1995 disclosed three vessel coronary heart disease with significant stenoses of the distal right coronary artery, multiple calcifications of the interventricularis artery and multiple plaques with significant stenoses in the ramus circumflexus. The woman underwent coronary by-pass surgery. Thereafter the patient was treated for six years with HELP in biweekly intervals, in combination with statins. TCHO, LDL, HDL and fibrinogen (fb) levels were measured before and after each treatment. Their mean values for an amount of 120 sessions were: TCHO pre 216 +/- 23, post 111 +/- 18 LDL pre 152 +/- 16 post 67 +/- 18, HDL pre 42 +/- 5 post 35 +/- 4 fb pre 306 +/- 48 post 125 +/- 31. In 2001 a new CA was performed. Calcifications disappeared and stenoses were identical to the previous CA or reduced. There were no further clinical manifestations of CHD. We trust that the clinical benefit of the HELP procedure will be substantial for those patients who have problems in clearing LDL from their plasma pool and who are at the same time sensitive to elevated LDL levels by the development of premature coronary sclerosis.

Over the last few years emerging evidence indicate the involvement of herpes viruses in the pathogenesis of several medical complications in transplanted patients. Herpes viruses are transmitted via inter-human contact and cause a primary infection, which commonly fails to give clinical signs and may persist even for years in a latent state in healthy subjects. In transplanted patients, herpes viruses may be transmitted through the transplanted organ or may be reactivated because of the use of powerful immunosuppressive drugs. Moreover, the persistence of immunosuppression greatly favours the clinical expression and severity of virus infection. Thus, herpes viruses seem to be involved in both acute and chronic deterioration of graft function, in the pathogenesis of post-transplant lymphoproliferative disorders and Kaposi sarcoma, and even in vessel atherosclerosis. This review will focus on relevant clinical aspects of herpes-virus infection, namely cytomegalovirus, EBV, herpes simplex 1 and 2, varicella zoster virus, HHV-6, HHV-7 and HHV-8, in kidney transplanted patients.

Background: Since tumor markers can be high in the course of many inflammatory diseases, the aim of this study is to verify if it also occurs in the course of rheumathologic chronic inflammatory diseases, and if there is any statistical correlation between tumor markers and inflammatory indices., Methods: Seventy-nine patients (51 females and 28 males) with rheumatologic chronic inflammatory diseases, aged 17-92 years, were studied, all of them took 4 mg of prednisone. alphaFP, CEA, TPA, CA19.9, CA15.3, CA72.4, CA125, ferritina, beta2 microglobuling, betaHCG, and free and total PSA in males, were evaluated as tumor markers; and VES, PCR and Fibrinogen, as inflammatory indices., Results: The results obtained showed that there is a significative correlation between ferritin, beta2 microglobulin, TPA and PCR, and between free and total PSA and Fibrinogen., Conclusions: PCR is a very good index of an active disease and it can be helpful, along with tumor markers, in the monitoring of chronic inflammatory diseases.

Brown tumors are unusual but serious complications of renal osteodystrophy, and can be successfully treated by parathyroidectomy or by pharmacological treatment of hyperparathyroidism. Brown tumors in patients with severe hyperparathyroidism (HPT) secondary to renal failure have been increasingly reported. We describe an unusual case of brown tumors at the maxillary bone and the seventh right rib, in a 57-year old man with a long history of hemodialysis. The maxillary lesion caused serious local discomfort due to its rapid growth. In this setting, surgical total parathyroidectomy was chosen as the most adequate therapeutic approach, given the previous unsatisfactory response to calcitriol. After successful parathyroidectomy, rapid healing was achieved with sclerosis of both brown tumors, as documented by serial computerized tomograms. In conclusion, although vitamin D therapy has been beneficial in several cases of secondary hyperparathyroidism complicated by brown tumors, we propose that whenever regression of the tumor bulk is urgently needed, as in our case, parathyroidectomy should be the first treatment choice.

Background: In rodents, CsA has been shown to affect T-cell development, giving rise to an abnormal production of mature T cells and the absence of many T-cell subsets as well as to autoimmunity. Surprisingly, only a few studies investigated the effect of the immunosuppressive drug on the immune system of the human fetus., Methods: We examined six infants born to female kidney transplant recipients who had received cyclosporine and methylprednisolone throughout their pregnancies. Peripheral blood was obtained 1 day and 2, 4, 6, and 12 months after birth, and two-color flow cytometric immunophenotyping of lymphocytes was performed., Results: Total T cells, as well as CD4+ and CD8+ T cells, were low at birth, but normalized thereafter. Among T-cell activation markers, the expression of CD25, the alpha chain of the interleukin-2 receptor, was below the normal range or low range throughout the study period, and HLA-DR expression was extremely low at birth and failed to increase up to 12 months. The number of total B cells was lower than normal at birth, but steeply increased over time. In contrast, B-cell subset bearing CD5 antigen was severely depleted throughout the first year of life. Total IgG concentration was significantly lower than in controls at 2 months, mainly because of subnormal levels of IgG1 and IgG3 subclasses, which remained in the low range up to 6 months. Finally, infants showed normal numbers of true natural killer (NK) cells (CD3-CD16+CD56+), whereas the expression of CD57 antigen, defining non-MHC-restricted cytotoxic lymphocytes, was barely detectable at birth and failed to increase over time, in both CD8+ and CD8- subsets. Of note, none of the infants had clinical evidence of an immunodeficient state., Conclusions: continuous exposure to CsA in utero seemingly impairs T-, B-, and NK-cell development and/or maturation, and most of its effects are still apparent at 1 year, which might suggest that conventional vaccinations should be delayed in these infants.

Hyperlipoproteinemia has been reported to frequently occur in kidney transplanted patients, thus possibly explaining, at least in part, the increased incidence of cardiovascular disease in this population. To evaluate the impact of renal transplantation (Tx), and related immunosuppressive therapy, on plasma lipoprotein and Lp(a) profile, we selected a cohort of kidney transplanted patients (36 M/14 F; age 33.8 + 12.0 yr, range 13-62) lacking significant causes of hyperlipidemia. All patients received a triple immunosuppressive regimen and showed a stable renal function after Tx (plasma creatinine: 1.36 +/- 0.35 mg/dL). One year after Tx, we found a significant increase of total cholesterol (TC), LDL, HDL, ApoB and ApoA-I (p < 0.005), while plasma triglyceride levels remained unmodified. Lp(a) plasma levels after Tx were within the normal range and displayed a significant inverse relationship with apo(a) size. Noteworthy, LDL/HDL ratio and ApoB/ ApoA-I ratio in kidney transplanted patients were almost superimposable with those of normal controls. Specifically, LDL/HDL ratio significantly decreased in 64% of patients after Tx, due to a prevalent increase of HDL, and was associated with a moderate amelioration of plasma TG. In a multiple linear regression model, post-Tx HDL level was significantly related to recipient's age, gender, BMI and cyclosporine (CyA) trough levels (Adj-R2 = 0.35, p = 0.0002), with gender and CyA trough levels being the better predictors of HDL. In conclusion, immunosuppressive regimens, in themselves, do not appear to significantly increase the atherogenic risk related to lipoproteins. Rather, other factors can affect the lipoprotein profile and its vascular effects in renal transplant recipients.

Background: Recent data indicate that factors other than erythropoietin (EPO), such as insulin-like growth factor 1 (IGF-1), can promote erythropoiesis in vitro and correct the anemia of chronic renal failure in vivo. IGF-1 is produced by the liver under growth hormone control, as well as by other sources, including the kidney. The erythropoietic role of growth factors and cytokines and their possible modulation by angiotensin-converting enzyme inhibitors (ACEI) has never been explored., Methods: This study evaluated the serum levels of EPO, IGF-1, interleukin (IL)-2, IL-3, and granulocyte macrophage-colony-stimulating factor in 40 kidney transplanted patients with or without posttransplant erythrocytosis (PTE) and in 10 living kidney donors. Then, the effect of ACEI therapy on the above pattern was examined in patients with PTE., Results: EPO and IGF-1 serum levels were significantly higher in patients with PTE than in patients without PTE and in living kidney donor subjects. ACEI therapy significantly reduced hematocrit (Hct) as well as circulating IGF-1 and EPO levels. Of note, the decrease in IGF-1 was prominent mainly in those patients whose EPO levels were not significantly modified by ACEI therapy. In all of the patients Hct levels displayed a direct relationship with circulating IGF-1 levels, but not with EPO concentration. Growth hormone did not significantly differ among the groups examined, whereas it steeply increased under ACEI. Finally, no significant difference in IL-2, IL-3, and granulocyte macrophage-colony-stimulating factor serum levels was detected., Conclusions: IGF-1 seems to play a role in the ACEI-related decrease of Hct in patients with PTE, chiefly in patients without any modification of EPO serum levels.

We report the use of excimer-laser angioplasty for the treatment of Wiktor and Gianturco-Roubin in-stent restenosis of in two patients. Case 1-a 48-year-old man presented unstable angina five months after Wiktor stent was deployed in right coronary artery. Cardiac catheterization revealed stenosis (95%) within the stent. Case 2-a 65-year-old man presented stable angina four months after Gianturco-Roubin stent was deployed in left anterior descending artery. Cardiac catheterization revealed stenosis (80%) within the stent. Excimer-laser angioplasty within the stent reduced the stenosis to 19% and 30%, respectively. The patients recovered and currently, six months post-procedure, are free of chest pain, and cardiac catheterization revealed stenosis to 30% and 35%, respectively, within the stent. Therefore, the procedure was an effective means of treating restenosis after coronary stent placement, and a prospective comparison of excimer-laser angioplasty and other management alternatives to in-stent restenosis is needed.

Purpose: To evaluate the immediate and long term results of percutaneous transluminal coronary balloon angioplasty (PTCA) in patients over 80 years old., Methods: From 1/1/89 to 6/31/95, 97 patients with 80 years of age or older were submitted to PTCA and were divided into three groups: group A (GrA)-30 patients with stable angina, mean age of 82.5 years, 24 (80%) men; group B(GrB)-40 patients with unstable angina, mean age 81.2 years, 31 (77.5%) men; group C (GrC)-27 patients with myocardial infarction (MI), mean age of 82 years, 16 (59.2%) men., Results: Early outcome-general success rate of 84.5% and mortality rate of 5.1%. The success and mortality rate were in GrA 83.3% and 3.3%, in GrB 85% and 5% and in GrC 85.2% and 7.4%, respectively. Late outcome-the number and percentage of patients with late follow-up and the clinic-angiographic and angiographic restenosis rates were for GrA 19(76%), 52.9%, 75%; GrB 30(88.2%), 30.8%, 61.5% and GrC 12(52.2%), 66.6%, 85.7%, respectively., Conclusion: PTCA can be considered an important revascularization alternative in octogenarian patients because of high early success rate, low mortality and acceptable long-term outcome.

Endomyocardial fibrosis is an endemic cardiac disease, characterized by the presence of fibrous tissue in the endocardium, eventually extending to the myocardium. Massive endocardial calcification of the left ventricle is a rare finding, with only a few cases reported in the literature. We reported a first case of biventricular massive endocardial calcification associated with endomyocardial fibrosis in a 22 year old woman.

The authors describe a rare case of circumflex coronary artery perforation during rotational coronary atherectomy complicated with cardiac tamponade and good outcome. The possible causes of perforation are discussed and the burr oversize (burr/artery ratio was 0.58) was refused. Shortening and artery plicature (accordeon effect) might have been the cause of this event. Quantitative measurement was made in order to strengthen this hypothesis. It is emphasized the importance of selecting lesions that should be submitted to rotational coronary atherectomy.

Two clinical cases of female patients with hepatic cirrhosis and autoimmune multisystemic involvement with infectious intercurrent are reported. Case 1 presented infective endocarditis and erysipelas on the left thigh. In the course of the clinical picture a cutaneous vasculitis developed in the same place together with autoimmune thrombocytopenia, leukopenia and pulmonary restrictive picture with inflammatory pattern. There are also elevate immune complexes and complement consumption. Case 2 presented erysipelas on the left thigh cutaneous vasculitis and complement consumption. In Case 1 the infective endocarditis was treated with antibiotic therapy during 4 weeks followed by 1 mg/kg corticoid (Prednisone) with thrombocytopenia and leukopenia reversion. Case 2 presented an improvement with antibiotic only. The relation between chronic liver diseases and systemic autoimmune phenomena is commented, special attention being paid to the cutaneous, hematological and pulmonary affection.

Fibrin deposition in kidney is a common event in some forms of human and experimental glomerulonephritis, and is thought to result from local activation of blood coagulation and/or impaired removal by the fibrinolytic system. We studied the urinary procoagulant and fibrinolytic activities in 46 patients with renal disease (26 with IgA nephritis, 13 with other forms of glomerulonephritis and 7 with non-inflammatory kidney disease) and in 15 matched healthy subjects, as possible indicators of the coagulation-fibrinolysis balance in kidney. Procoagulant activity was slightly but not significantly increased in patients with serum creatinine levels higher than 1.5 mg/dl (group II) as compared with patients with normal creatinine (group I) and controls. It was identified as tissue factor by biological criteria (dependence on factor VII). Fibrinolysis studies showed that both plasminogen activator activity and urokinase antigen were significantly lower in group II than in group I patients and controls (P less than 0.0005). Reduced fibrinolytic activity in patients' urine was due to decreased excretion of urokinase since no inhibitor was detected by both fibrin autography and functional assay. No differences were found between patients and controls in plasma fibrinolytic activity, plasminogen activator inhibitor, and procoagulant activity of blood monocytes. The urinary changes in severe renal disease may reflect an unbalance of the coagulation-fibrinolysis equilibrium in kidney and might be of pathogenetic and clinical relevance.