Effect of VDRA on survival in incident hemodialysis patients: results of the FARO-2 observational study.

BACKGROUND: Mortality rate among patients with stage five chronic kidney disease (CKD) maintained on hemodialysis (HD) is high. Although evidence suggests that use of Vitamin D Receptor Activators (VDRA) in CKD patients increases survival, few studies have examined the effect of VDRA in incident HD patients. The FARO-2 study evaluated the clinical outcome of VDRA therapy on mortality in incident HD patients. METHODS: FARO-2 was a longitudinal epidemiological study performed on 568 incident HD patients followed prospectively from 26 dialysis centers over a 3-year period. Data were collected every 6 months using a questionnaire, obtaining clinical, biochemical and therapeutic parameters. Kaplan-Meier curves and Cox proportional hazard regression models were used to determine cumulative probability of time-to-death and adjusted hazard ratios. RESULTS: 568 patients (68% male) with an average age of 65.5 years were followed up. Mean dialysis duration at study entry was 3 months. VDRA use increased from 46% at 6 months to 54.7% at 36 months of follow-up (p = 0.08). No difference was observed in the presence of comorbid diseases at baseline in patients with and without VDRA therapy. Cumulative probability of survival at 24 months was 74.5% (95% CI: 70.2-78.3). Patients receiving VDRA therapy showed a significant increase in survival at 24 months (80.7%; 95% CI: 75.7-84.8) compared to those without (63.3%; 95% CI: 54.8-70.7, p <0.01). The presence of vascular disease, decreased hemoglobin, increased P and lack of VDRA treatment were significantly associated with an increased risk of mortality. Lack of VDRA treatment still remained significant as a predictor of mortality after adjusting for levels of PTH, P and Ca (HR = 2.16, 95% CI: 1.09-4.30, p = 0.03). CONCLUSIONS: Findings from FARO-2 indicate that in incident HD patients VDRA therapy was associated with increased survival.

Achievement of NKF/K-DOQI recommended target values for bone and mineral metabolism in incident hemodialysis patients: results of the FARO-2 cohort.

BACKGROUND: Mineral Bone Disorders (MBD) is prevalent in hemodialysis (HD) patients and associated with increased cardiovascular mortality. The FARO-2 study evaluated the achievement of the NKF/K-DOQI guidelines on recommended target values for serum calcium (Ca), phosphorous (P) and intact parathyroid hormone (PTH) levels on survival in incident HD patients. METHODS: Data were collected by questionnaire from 568 incident HD patients followed prospectively over a 3-year period from 26 Italian dialysis units. The cumulative probability of time-to-death for CKD-MBD treatment characteristics was determined by the Kaplan-Meier curves. RESULTS: Serum PTH levels (median values at 6 months vs. 36 months; 225 vs. 254 pg/ml), Ca (8.8 vs. 8.9 g/dl) and P (5.1 vs. 4.8 mg/dl) were not significantly different at 6 months versus follow-up. The majority of incident HD patients (60-70%) who were followed up for 36 months did not achieve the NKF/K-DOQI recommended target values. Survival rates were higher in patients on target for three parameters versus patients off target (survival at 24 months: at target 95.7% (95% CI: 84.0-98.9) versus not on target 71.1% (95% CI: 66.3-75.4, p < 0.01)). The 30.1% of patients on target for three MBD parameters at least once during the follow-up period had better survival rates compared to those not reaching these targets (survival at 24 months: at least once 88.0% (95% CI: 81.9-92.1); 67.7% (95% CI: 61.9-72.8, p < 0.01)). CONCLUSION: Our findings indicate that incident HD patients who achieved target levels (for three MBD parameters) for at least one visit have a lower risk of mortality.

Voice hearing in refugees survivors of traumatic events.

The term voice hearing (VH) refers to the experience of hearing voices in the absence of corresponding external stimuli and is considered a hallucinatory experience. According to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5; American Psychiatric Association [APA], 2013), hallucinations are perception-like experiences that occur without an external stimulus. They are vivid and clear, with the full force and impact of normal perceptions, and not under voluntary control. Specifically, auditory hallucinations involve the perception of sound, most frequently of voices (i.e., auditory verbal hallucinations- AVHs) but sometimes of clicks or other noises, that are not restricted to the period of awakening or the onset of sleep. AVHs are usually experienced as voices, whether familiar or unfamiliar, that are perceived as distinct from the individual's own thoughts.

VDRA therapy is associated with improved survival in dialysis patients with serum intact PTH ≤ 150 pg/mL: results of the Italian FARO Survey.

BACKGROUND: Chronic kidney disease (CKD) patients affected by mineral bone disorders (MBD) have higher rates of all-cause and cardiovascular-related mortality. Approximately, one-third of dialysis patients have low serum parathyroid hormone (PTH) levels (≤ 150 pg/mL). However, the reason why these patients have higher mortality compared to patients with normal PTH levels has not yet been fully elucidated. METHODS: The FARO study was performed on 2453 Italian patients followed prospectively from 28 dialysis centres over a 2-year period. Data were collected every 6 months and end points included time-to-death cumulative probability in patients with serum intact PTH (iPTH) ≤ 150 pg/mL and the effect of vitamin D receptor activation (VDRA) therapy. Kaplan-Meier curves and proportional hazards regression models stratified by PTH levels (i.e. ≤ 150 and >150 pg/mL) were used to determine cumulative probability of time-to-death and adjusted hazard ratios (HRs) for demographic, clinical and CKD-MBD treatment characteristics. RESULTS: The cumulative probability of death was higher (P < 0.01) for patients with serum iPTH levels ≤ 150 pg/mL [25.1%, 95% confidence interval (CI): 22.1-28.5 at 18 months] versus those with serum iPTH levels within the normal range (18.0%, 95% CI: 16.1-20.1). In a model with time-dependent covariates restricted to time periods when patients had iPTH levels ≤ 150 pg/mL, lower mortality was observed in patients treated with VDRA [i.e. HR = 0.62, 95% CI: 0.42-0.92 for oral or intravenous (IV) calcitriol; HR = 0.18, 95% CI: 0.04-0.8 for IV paricalcitol] versus those not receiving any VDRA (P < 0.01) independently of other variables. Patients who received IV paricalcitol, compared with either oral or IV calcitriol, showed reduced mortality, but this was not statistically significant (HR = 0.3, 95% CI: 0.07-1.31, P = 0.11). CONCLUSION: Results from this observational study suggest that VDRA therapy was associated with improved survival in dialysis patients, even with low serum iPTH levels.

[Hypocomplementemic tubulointerstitial nephritis in IgG4-related disease]. / Nefrite tubulo-interstiziale ipocomplementemica in IgG4-related disease.

A novel lymphoproliferative disorder producing plasma cell expansion in the affected organ with fibrotic or sclerosing changes, known as ''IgG4-related disease'', was defined in Japan by Umehara's group in 2010. We present the first case reported in Italy. In 2007, a 63-year-old man presented with epigastric pain and elevated serum lipase levels. Computed tomography of the abdomen revealed a Kuttner's tumor of the pancreas. The patient underwent a biliary-enteric anastomosis, and biopsy of the pancreas revealed massive infiltration of lymphocytes and plasma cells. The patient was diagnosed with chronic sclerosing pancreatitis. After one year, he began to show signs of sicca syndrome and at the same time developed progressive renal failure. Immunological tests revealed hypocomplementemia, and the renal biopsy specimen showed diffuse interstitial inflammation. The infiltrate was composed of lymphocytes, while infiltrating plasma cells showed immunoreactivity to IgG-4. Sialography using a radioisotope revealed severe involvement of the salivary glands, and Schirmer's test gave a positive result. This led us to diagnose hypocomplementemic tubulointerstitial nephritis in IgG4-related disease. Corticosteroid treatment resulted in rapid improvement including disappearance of the sicca syndrome and progressive amelioration of renal function. After six months, we discontinued steroid administration and started mycophenolate mofetil to maintain a low degree of immunosuppression. Follow-up after two years showed that this therapy continued to be quite effective in our patient.

Is left ventricular hypertrophy a powerful predictor of progression to dialysis in chronic kidney disease?

BACKGROUND: The role of cardiovascular factors in predicting renal outcome has not been extensively elucidated. Herein, we report a prospective evaluation of the impact of left ventricular hypertrophy (LVH) on outcome in non-diabetic patients with chronic kidney disease (CKD). METHODS: We studied 144 patients (99 men; age 62±14 years) with stage 3-4 CKD, with baseline assessment of left ventricular mass index (LVMi) by echocardiography, estimated glomerular filtration rate (eGFR) by MDRD equation, 24-h blood pressure profile and 24-h proteinuria. Combined end point was progression to ESRD requiring dialysis, or death within 5 years. RESULTS: Forty-nine patients (34%) progressed to dialysis, 24 (17%) died, 57 (39%) were dialysis-free after 5 years and 14 were lost to follow-up. Multivariate Cox proportional hazards analysis showed that increased LVMi (HR 1.28, 95% CI 1.17-1.40 for each 10-g/m2 increase, P<0.0001) and reduced eGFR (5% risk increase for each 1-mL/min reduction, P=0.027) were the significant predictors of the combined end point in stage 3 CKD patients, whereas LVMi proved to be the only significant predictor of the combined end point in patients with stage 4 CKD (HR 1.19, 95% CI 1.09-1.31, P<0.0001). The same analysis showed that LVMi was the only significant predictor of progression to dialysis in stage 3 CKD patients (HR 1.42, 95% CI 1.23-1.64 for each 10-g/m2 increase, P<0.0001), while a 20% increase in the risk of progression to ESRD was observed for each 10-g/m2 increase in LVMi (P<0.0001), and a 10% increase for each 1-mL/min reduction in eGFR (P=0.046) in patients with stage 4 CKD. When evaluating the predictive role of LVMi on outcome using AUC-ROC curves, the overall performance of the model including LVMi (AUC 0.877, 95% CI 0.8-0.954) was superior to the model including eGFR (AUC 0.737, 95% CI 0.656-0.817) for the end point of progression to dialysis (P=0.026, Hanley test). CONCLUSIONS: LVH proved to be the strongest predictor of the risk of progression to dialysis in non-diabetic CKD, especially among patients with less advanced renal dysfunction. Regardless of whether it is a simple marker or a pathogenetic factor, LVH encompasses all factors possibly affecting renal and general outcome in CKD patients.

Secondary hyperparathyroidism in chronic dialysis patients: results of the Italian FARO survey on treatment and mortality.

INTRODUCTION: Vitamin D receptor activator (VDRA) therapy has been shown to be associated with reduced mortality rates in chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT). However, differences between VDRAs in their ability to reduce both all-cause and cardiovascular-related mortality rates are not yet fully elucidated. METHODS: The objective of the current analysis was to determine the effect of VDRA therapy on mortality in an Italian dialysis population, observed prospectively every 6 months for 18 months. Patients were investigated for all-cause and cardiovascular-related mortality risk adjusted for various demographic, clinical, and/or SHPT treatment variables. RESULTS: The cumulative probabilities of all-cause and cardiovascular-related mortality were lower for patients who received any VDRA treatment compared with those who did not (p < 0.001) regardless of all measured variables. Additionally, patients who received paricalcitol and/or cinacalcet (with or without VDRAs) compared with calcitriol showed a significant improvement in both all-cause and cardiovascular-related mortality (p < 0.001). Cinacalcet with or without VDRAs was not associated with a further decrease of mortality hazard ratios compared with paricalcitol monotherapy. CONCLUSIONS: VDRA therapy (associated or not with cinacalcet) was associated with improved survival in dialysis patients, independent of demographic and clinical variables.

Patterns and predictors of PTSD in treatment-seeking African refugees and asylum seekers: A latent class analysis.

BACKGROUND: Despite the empirical and clinical relevance of understanding posttraumatic stress disorder (PTSD) heterogeneity in refugees and asylum-seekers, very few studies have examined the manner in which PTSD symptoms manifest in such populations. AIMS: This study sought to investigate patterns and predictors of DSM-5 PTSD in a treatment-seeking sample of African refugees. METHODS: Participants were 122 African refugees and asylum-seekers living in Italy who completed measures of trauma exposure and PTSD symptoms. Latent class analysis (LCA) was used to identify PTSD symptom profiles, and predictors of class membership were identified via multinomial logistic regression. RESULTS: Among participants, 79.5% had a probable diagnosis of PTSD. Three PTSD classes were identified by LCA: Pervasive (32.0%) with high probabilities of all symptoms, high-Threat (45.9%) with higher probabilities of intrusions and avoidance symptoms, moderate-Avoidance (22.1%) with high probability of thoughts/feelings avoidance. None of the examined variables (legal status, gender, age, education, months spent in Italy, number of traumatic events, employment) significantly predicted class membership with the relevant exception of reception conditions. Specifically, living in large reception centres (over 1,000 people) significantly predicted Pervasive PTSD class membership compared to high/Threat PTSD class and to moderate/Avoidance class. CONCLUSION: This study provides evidence for distinct patterns of PTSD symptomatology in refugees and asylum seekers. We identified three classes which present both qualitative and quantitative differences in symptoms: Pervasive class, high-Threat class and a new moderate class, characterised by avoidance symptoms. Reception conditions contributed to the emergence of the Pervasive PTSD profile characterised by the symptoms highest severity. These findings highlight that stressors in the post-migration environment, as inadequate reception conditions in large facilities, may have detrimental effect on refugees' mental health. We emphasise the importance for host countries to implement reception models that provide effective protection and integration to this vulnerable population.

Kidney graft loss associated with JC polyomavirus nephropathy.

This is the first case of documented treatment failure of JCV nephritis, despite a reduction of immunosuppressive agents and the use of antiviral therapy. We consistently detected high levels of JCV viremia, which correlated with the progressive deterioration of the graft and caused the final loss of the kidney, suggesting that JCV plays an etiological role in the onset of severe nephropathy in kidney transplant patients.

Effect of sirolimus on left ventricular hypertrophy in kidney transplant recipients: a 1-year nonrandomized controlled trial.

BACKGROUND: Left ventricular hypertrophy (LVH) after renal transplantation may be affected by immunosuppressive therapy. STUDY DESIGN: Nonrandomized controlled trial evaluating the effect of sirolimus (SRL) on LVH of renal transplant recipients (RTRs). SETTING & PARTICIPANTS: 13 RTRs without diabetes who had received a single-kidney transplant from a deceased donor with chronic allograft dysfunction and biopsy-proven allograft nephropathy who were converted from calcineurin-inhibitor (CNI) to SRL treatment; 26 controls matched for age and year of transplantation who were not converted from CNI to SRL treatment. INTERVENTION: Conversion from CNI to SRL therapy. OUTCOMES & MEASUREMENTS: Left ventricular mass determination by using echocardiography at baseline and again 1 year later. Blood pressure (BP), hemoglobin level, serum creatinine level, uric acid level, lipid levels, trough levels of immunosuppressive drugs, and daily proteinuria were assessed at least twice monthly. Conventional antihypertensive therapy was used to achieve BP of 130/80 mm Hg or less. RESULTS: The study population included 26 men and 13 women (age, 25 to 66 years). Changes in BP were similar in the 2 groups (between-group difference, -4 +/- 5 mm Hg; P = 0.5 for systolic BP; -2 +/- 3; P = 0.6 for diastolic BP), whereas left ventricular mass significantly decreased in the SRL group alone (between-group difference, 8.6 +/- 2.4 g/m(2.7); P < 0.001) because of a decrease in both the interventricular septum and left ventricular posterior wall. LVH regressed in 12 of 13 patients on SRL therapy and 10 of 26 controls (P = 0.002). LIMITATIONS: Nonrandomized design. Single-center study with small sample size. CONCLUSIONS: Conversion from CNI to SRL therapy may regress LVH in RTRs regardless of BP changes, mainly by decreasing left ventricular wall thickness, thus suggesting nonhemodynamic-effect mechanisms of SRL on left ventricular mass.

Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients.

BACKGROUND: Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. METHODS: This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. RESULTS: Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (p< 0.001). The adjusted difference in mean hemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. CONCLUSIONS: This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.

ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial.

BACKGROUND: Interventional studies of left ventricular hypertrophy (LVH) in renal transplant recipients are scarce and to date evaluated only patients immediately after renal transplantation. STUDY DESIGN: Randomized controlled trial that assessed the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in regressing persistent LVH after successful transplantation. SETTING & PARTICIPANTS: 70 renal transplant recipients (47 men; age, 30 to 68 years) without diabetes previously randomly assigned to either cyclosporine or tacrolimus therapy, with LVH persisting 3 to 6 months after transplantation. INTERVENTION: Subjects were randomly assigned to either lisinopril (ACE-inhibitor group; 36 patients) or no therapy (control group; 34 subjects). OUTCOMES: Main outcome was change in left ventricular mass index (LVMi) at month 18. RESULTS: A consistent decrease in both systolic (SBP) and diastolic blood pressure (DBP) was observed in both groups (between-group differences, -1.7 +/- 3.3 mm Hg; 95% confidence interval [CI], -4.8 to 8.2; P = 0.6 for SBP; 0.3 +/- 2.2 mm Hg; 95% CI, -4.8 to 4.1; P = 0.9 for DBP), whereas LVMi regressed more in the ACE-inhibitor group (between-group difference, 10.1 +/- 16.3 g/m(2.7); 95% CI, 4.2 to 16.1; P < 0.01). A significant interaction of ACE inhibitors with cyclosporine in affecting LVMi change was shown by means of post hoc multiple regression analysis (P < 0.01; differences between cyclosporine and tacrolimus group, 13.3 +/- 3.9 g/m(2.7); 95% CI, 5.3 to 21.2; P < 0.01 in the ACE-inhibitor group; 3.7 +/- 4.2 g/m(2.7); 95% CI, -4.7 to 12.2; P = 0.4 in the control group). LIMITATIONS: Single-center study with small sample size. Interaction of ACE inhibitors with cyclosporine treatment emerged from post hoc analysis. CONCLUSION: A prolonged course of ACE-inhibitor therapy is effective in regressing the persistent LVH of renal transplant recipients by mechanisms independent of effects on BP. This regression seems to be at least in part the effect of an interaction between ACE inhibitors and cyclosporine.

Bone disease in long-term renal transplant recipients with severe osteopenia: a cross-sectional study.

BACKGROUND: Fracture is a disabling clinical outcome after transplantation, but there is little histopathological information on long-term renal recipients with severe osteopenia. METHODS: Twenty kidney recipients (8.3+/-1.9 years after transplantation), 13 males and 7 females (five postmenopausal) with nearly normal renal function, affected by severe osteopenia (T-score: males= -4.9+/-0.28; females= -5.08+/-0.47) underwent bone biopsy and morphometric X-ray absorptiometry to evaluate vertebral fractures. RESULTS: Histopathological diagnosis was osteoporosis-osteopenia in seven patients, osteitis fibrosa in six, prevalent osteomalacic lesion in six, and "normal" bone in one patient. Significant increases in osteoid volume (OV/BV), osteoid surface, osteoblastic surface (ObS/BS) and osteoid thickness were observed. OV/BV and Obs/BS ratios were inversely correlated to cumulative doses of MPRED (r2=0.85 P<.0001 for both ratios), whereas age, sex, time after transplantation, iPTH levels, and cumulative cyclosporine A dose were not related to osteoblastic indices. Osteoclast surface was slightly increased. Widened mineralization lag times were observed, with normalcy of the bone formation rate. Half of the patients showed fractured vertebrae. No differences in T scores were found when patients were subdivided into groups "with" or "without" vertebral fractures. A higher prevalence of fractures was observed in patients with osteoporosis-osteopenia compared to other osteopathies (P<0.02). No relationships between bone volume versus T-scores were observed. CONCLUSIONS: In long-term renal transplant recipients, severe osteopenia does not predict osteoporosis alone. The main abnormality we found was an increase in osteoblastic activity with a slight mineralization defect. The heterogeneous bone illness we observed would suggest performing bone biopsy in these patients.

Therapy of secondary hyperparathyroidism to date: vitamin D analogs, calcimimetics or both?

Therapy with i.v. calcitriol (CLT), that had been the mainstay of the cure of severe secondary hyperparathyroidism (SHPT) for many years, is often hindered by the occurrence of hypercalcemia, that requires discontinuation of the drug with consequent rebounding of the parathyroid hormone (PTH) oversecretion. To circumvent this shortcoming, CLT-analogs with less calcemic effects with respect to CLT have been developed. One of these analogs, paracalcitol (PCLT), proved to be at least as powerful as CLT in decreasing serum PTH, but it still remains endowed with some calcemic effect as the parent compound. Meanwhile, calcimimetics (CaMs) drugs targeting the calcium-sensing receptors on the PTG, have been marketed woldwide. Cinacalcet (CNC) is a CaM endowed with the unique prerogative to significantly decrease serum PTH while also decreasing serum calcium. Thus, one may attempt to speculate that CaMs may completely replace vitamin D derivatives from the therapeutic arena. Uremic patients, however, suffer from severe deprivation of biological vitamin D effects, that puts them in need of highly dosed vitamin D in order to both ameliorate their bone status and to preserve their general and cardiovascular health. Thus, a combination therapy with PCLT, which has a significant patient-survival advantage over CLT, and CNC seems to be more appropriate than only-one-drug based therapy for SHPT. Such a combination will hopefully result in a better control of SHPT, avoidance of cumbersome hypercalcemia and higher life expectancy for uremic patients than ever before.

Relationship between arterial hypertension and renal damage in chronic kidney disease: insights from ABPM.

BACKGROUND: To date, few studies have used ambulatory pressure monitoring (ABPM) in patients with chronic kidney disease (CKD) before the start of dialysis treatment. The aim of this study was therefore to ascertain the correlates of arterial hypertension assessed by ABPM in CKD patients at their first referral to a nephrologist. METHODS: We studied 244 (164 men; mean age 63 years) nondiabetic patients with CKD. Each patient had blood pres-sure (BP) measured by 24-hour ABPM, creatinine clearance (CrCl) estimated according to the Cockcroft-Gault formula, and Hgb concentration, serum lipids, iPTH, daily urinary protein (Uprot) and sodium (UNa) excretion assessed using routine methods. RESULTS: According to ABPM data analysis, 81 patients were normotensives, 78 were stable hypertensives, 26 had day-time hypertension and 59 had nocturnal hypertension. ANOVA showed both lower CrCl (p=0.0033), and higher Uprot (p<0.0001) in stable and nighttime hypertensives as compared with normotensives and daytime hypertensives. In the whole group each set of both systolic (SBP) and pulse pressure (PP) readings was directly associated with both age and Uprot (p<0.05), and inversely with both CrCl and Hgb (p<0.05). In multivariate analysis, however, Uprot emerged among modifiable risk factors, as the most significant predictor of both SBP and PP; the strength of this association was in the order nighttime PP > nighttime SBP > 24-hour PP > daytime PP > daytime SBP > 24-hour SBP. CONCLUSION: In CKD patients, proteinuria is the strongest correlate of arterial hypertension and particularly of increased nocturnal PP, possibly as an expression of vascular damage. On the basis of these results, ABPM appears to be the most reliable tool for detecting the associations between raised BP (particularly nighttime hypertension) and renal damage in CKD patients not yet on renal replacement therapy (RRT).

Left ventricular hypertrophy in nondiabetic predialysis CKD.

BACKGROUND: Although left ventricular hypertrophy (LVH) is a strong predictor of mortality in patients with end-stage renal disease, few studies are available before the start of dialysis treatment. The purpose of this study is to evaluate the prevalence and clinical correlates of LVH in nondiabetic patients with chronic kidney disease (CKD) not yet undergoing renal replacement therapy. METHODS: We investigated 244 nondiabetic patients with CKD; 57 patients (42 men; age, 20 to 78 years) had stages 1 to 2 CKD and 187 patients (122 men; age, 18 to 77 years) had stages 3 to 5 CKD. Fifty-two normotensive healthy subjects served as controls. Each patient had blood pressure (BP) measured by means of 24-hour ambulatory BP monitoring and left ventricular mass index (LVMi) assessed by means of M-mode echocardiography. Creatinine clearance was estimated by means of the Cockcroft-Gault formula, and hemoglobin, serum lipid, and intact parathyroid hormone concentrations and daily urinary protein excretion were assessed by using routine methods. RESULTS: In the overall group, prevalences of arterial hypertension and LVH were 66% and 74%, respectively. LVMi was 160 +/- 50 g/m2 body surface area and associated directly with age (P = 0.0013), duration of arterial hypertension (P = 0.0075), 24-hour systolic BP (P = 0.0113), pulse pressure (P = 0.0003), daytime (P = 0.0206) and nighttime systolic BP (P = 0.0059), and urinary protein excretion (P < 0.05) and inversely with creatinine clearance (P = 0.0103) and hemoglobin level (P = 0.0276). In patients with CKD stages 1 to 2 (LVH prevalence, 51%), age, duration of arterial hypertension, pulse pressure, and urinary protein excretion were significant predictors of LVMi (P < 0.00002) by using stepwise regression analysis, whereas in those with CKD stages 3 to 5 (LVH prevalence, 78%), pulse pressure emerged as the sole predictor of LVMi (P = 0.0011). CONCLUSION: The prevalence of LVH in nondiabetic predialysis patients with CKD is greater than previously reported, and there is evidence that LVH already is present in the early stages of renal disease. Arterial hypertension is associated with LVH in patients with CKD, and the strong relationship between elevated pulse pressure and LVH in those with more advanced CKD suggests that increased arterial stiffness might have a role for LVH well before the start of dialysis therapy.

Prevalence of fasting hypercalciuria associated with increased citraturia in the ambulatory evaluation of nephrolithiasis.

BACKGROUND: Nephrolithiasis is a common, high costing pathology of the urinary tract. The most common urinary abnormalities are fasting hypercalciuria, hypercalciuria and hypocitraturia. This study aimed to identify the principal urinary abnormalities in our patients. METHODS: Ninety-eight patients (pts) (43 females, 55 males) with recurrent calcium nephrolithiasis underwent metabolic evaluation. In two 24-hr urine collections the following parameters were evaluated: calcium, phosphate, sodium, potassium, chloride, magnesium, citrate, oxalate, uric acid, creatinine (Cr), urea, ammonium and pH; blood measurement of calcium, phosphate, sodium, potassium, chloride, magnesium, uric acid, Cr, urea, acid-base balance ionized calcium and intact parathyroid hormone (iPTH) were also performed. A first morning voided urine sample was collected for measuring the urinary cross-links and fasting calciuria. The tubular threshold of phosphate (TmP) was calculated according to Walton and Bijovet. Metabolic evaluation was repeated in 63/98 pts after 7 days on a low calcium diet. RESULTS: The most common urinary abnormalities were fasting hypercalciuria in 51/96 pts (53.1%), hypercalciuria in 33/97 pts (34%) and hypocitraturia in 29/98 pts (29%); 24/33 pts (73%) with hypercalciuria had fasting hypercalciuria. Hypercalciuria was partially corrected on the calcium-restricted diet, while fasting hypercalciuria was not. Urine citrate levels were significantly higher in patients with fasting hypercalciuria. CONCLUSIONS: Fasting hypercalciuria was the most frequent urinary abnormality and it was not corrected with a calcium-restricted diet. In fasting hypercalciuric patients, increased bone resorption activity could be responsible for higher citraturia levels.

Incidence of cancer after kidney transplant: results from the North Italy transplant program.

BACKGROUND: Patients undergoing kidney transplantation demonstrate a higher risk of developing cancer as the result of immunosuppressive treatment and concurrent infections. METHODS: The incidence of cancer in a cohort of patients who underwent kidney transplantation between 1990 and 2000, and who survived the acute phase (10 days), was analyzed as part of the North Italy Transplant program. RESULTS: A total of 3,521 patients underwent transplantation during a 10-year period in 10 of 13 participating centers; the length of follow-up after kidney transplant was 67.7+/-36.0 months. During the follow-up, 172 patients developed cancer (39 with Kaposi sarcoma, 38 with lymphoproliferative diseases, and 95 with carcinomas [17 kidney, 11 non-basal cell carcinoma of the skin, 10 colorectal, 8 breast, 7 gastric, 7 lung, 6 bladder, and 3 mesothelioma]). The average time to cancer development after transplant was 40.1+/-33.4 months (range 0-134 months). Twenty-four patients developed cancer within 6 months from the transplant (10 with carcinomas, 7 with Kaposi sarcoma, and 7 with lymphoproliferative diseases). Three patients demonstrated a second primary cancer. The average cancer incidence was 4.9%. The incidence of cancer was 0.01 per year. Independent determinants of cancer development were age, gender, and immunosuppressive protocol including induction. Ten-year mortality was significantly higher in patients with cancer (33.1%) than among patients without cancer (5.3%). The relative risk of death in subjects with cancer was 5.5 (confidence interval 4.1-7.4). CONCLUSIONS: These preliminary data underline the importance of long-term surveillance of transplant recipients, choice of immunosuppressive treatment, and careful donor selection.

Left ventricular geometry and adverse cardiovascular events in chronic hemodialysis patients on prolonged therapy with ACE inhibitors.

BACKGROUND: In addition to the absolute magnitude of left ventricular (LV) mass (LVM), the geometric pattern of the left ventricle might help explain the different tendency toward LV hypertrophy (LVH) regression seen under effective therapy in chronic hemodialysis patients. METHODS: Forty-five hemodialyzed uremic subjects, 17 patients with concentric LVH and 28 patients with eccentric LVH, were followed up with yearly echocardiography over 3 years while on monotherapy with angiotensin-converting enzyme (ACE) inhibitors. Predialysis blood pressure (BP) and percentage of interdialytic weight gain recorded during the month the echocardiographic study was performed were retrieved and averaged. Any adverse cardiovascular events occurring during the 3-year follow-up period also were recorded. RESULTS: Significant regression of LVH (P = 0.0028) was observed in the group as a whole during the 3 years on ACE-inhibitor therapy, mainly accounted for by a reduction in pulse pressure (PP; r = 0.45; P = 0.0017). After subgrouping patients according to LV geometry, an LVM reduction was observed only in the 17 patients with concentric LVH (P = 0.0003), whereas no difference was detected in subjects with eccentric LVH despite the same degree of BP reduction and hemoglobin level and Kt/V increases in both groups. Moreover, a greater incidence of cardiovascular events was observed in patients with eccentric LVH than in those with concentric LVH during the 3-year follow-up period. CONCLUSION: The most important finding of this study is that eccentric LVH seems to be less responsive to ACE-inhibitor treatment and is associated with a greater incidence of adverse cardiovascular events compared with concentric LVH. Furthermore, the decrease in PP appears to be the main predictor of LVH regression in chronic hemodialysis patients on ACE-inhibitor therapy.

Effect of everolimus on left ventricular hypertrophy of de novo kidney transplant recipients: a 1 year, randomized, controlled trial.

BACKGROUND: Although conversion from calcineurin inhibitors to mammalian target of rapamycin inhibitors proved to be effective in regressing left ventricular hypertrophy (LVH) in renal transplant recipients (RTRs) with chronic allograft dysfunction, there are currently no reports of randomized trials on this issue involving de novo RTRs administered everolimus (EVL). METHODS: This randomized, open-label, controlled trial evaluated the effect of EVL on the left ventricular mass index (LVMi) of 30 nondiabetic RTRs (21 men; age 28-65 years). Ten were allocated to EVL plus reduced-exposure cyclosporine A (CsA), and 20 to standard dose CsA. LVMi was assessed by echocardiography both at baseline and 1 year later. Blood pressure (BP), hemoglobin, serum creatinine, lipids, trough levels of immunosuppressive drugs, and daily proteinuria were also evaluated twice monthly. Antihypertensive therapy that did not include renin-angiotensin system blockers was administered to achieve BP less than or equal to 130/80 mm Hg. RESULTS: Changes in BP were similar in the two groups (between group difference 1.2 ± 5.7 mm Hg, P=0.84 for systolic, and -1.5 ± 3.7, P=0.69, for diastolic BP), whereas LVMi significantly decreased in the EVL group alone (between group difference 9.2 ± 3.1 g/m(2.7), P=0.005), due to a reduction in both the interventricular septum and the left ventricular posterior wall thickness. EVL therapy together with baseline LVMi were the only significant predictors of LVH regression according to a multivariate model that explained 49% of the total LVMi variance (P=0.0015). CONCLUSIONS: An immunosuppressive regimen consisting of EVL plus reduced exposure CsA proved to be effective in regressing LVH in RTRs regardless of BP, mainly by reducing left ventricular wall thickness.