[Atherosclerosis, chronic inflammation and oxidative stress in CKD].

Chronic low-grade inflammation is emerging as the pathophysiological mechanism underlying of the several chronic degenerative diseases. Atherosclerosis, inflammation and oxidative stress are some of the issues that arise from the general context of chronic inflammation. In this manuscript we analyzed the role of the immune system, metabolism and inflammation's molecular mediators in order to show an overview about only apparently different problems. Finally, we proposed some possible solutions to improve the survival and quality of life of patient with chronic kidney disease.

Left Ventricular Hypertrophy in Chronic Kidney Disease Patients: From Pathophysiology to Treatment.

Cardiovascular diseases represent the main causes of morbidity and mortality in patients with chronic kidney disease (CKD). According to a well-established classification, cardiovascular involvement in CKD can be set in the context of cardiorenal syndrome type 4. Left ventricular hypertrophy (LVH) represents a key feature to provide an accurate picture of systolic-diastolic left heart involvement in CKD patients. Cardiovascular involvement is present in about 80% of prevalent hemodialysis patients, and it is evident in CKD patients since stage IIIb-IV renal disease (according to the K/DOQI CKD classification). According to the definition of cardiorenal syndrome type 4, kidney disease is detected before the development of heart failure, although timing of the diagnosis is not always possible. The evaluation of LVH is a bit heterogeneous, and few standard imaging methods can provide the accuracy of either CT- or MRI-derived left ventricular mass. Key principles in the treatment of LVH in CKD patients are mainly based on anemia and blood pressure control, together with the management of secondary hyperparathyroidism and sudden cardiac death prevention. This review is mainly focused on the clinical aspects of CKD-related LVH to provide practical guidelines both for cardiologists and nephrologists in the daily clinical approach to CKD patients.

Fibroblast growth factor 23 and parathyroid hormone predict extent of aortic valve calcifications in patients with mild to moderate chronic kidney disease.

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.

Chronic kidney disease and cardiovascular complications.

Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias and sudden cardiac death represent main causes of morbidity and mortality in patients with chronic kidney disease (CKD). Pathogenesis includes close linkage between heart and kidneys and involves traditional and non-traditional cardiovascular risk factors. According to a well-established classification of cardiorenal syndrome, cardiovascular involvement in CKD is known as "type-4 cardiorenal syndrome" (chronic renocardiac). The following review makes an overview about epidemiology, pathophysiology, diagnosis and treatment of cardiovascular complications in CKD patients.

[Chronic kidney disease and sudden death]. / Malattia renale cronica e morte cardiaca improvvisa: dati epidemiologici, fisiopatologia e strategie d'intervento.

Cardiovascular disease represents the major cause of death in chronic kidney disease patients accounting for about 43% of all mortality causes among hemodialysis patients. Sudden cardiac death (SCD) is one of the most frequent and dangerous clinical syndrome occurring in end stage renal disease (ESRD) patients. Hemodialysis patients present a great number of non traditional risk factors for cardiovascular disease such as left ventricular hypertrophy, coronary artery disease, rapid electrolyte shifts, QT dispersion, sympathetic hyperactivity and hyperphosphatemia. The aim of the following review is to summarize epidemiological aspects and pathophysiological pathways of SCD in CKD patients, defining prevention and treatment guidelines.

Penile calciphylaxis in end stage renal disease.

Calciphylaxis, better described as "Calcific uremic arteriolopathy" (CUA), involves about 1-4% of hemodialysis patients all around the world with high mortality rates. We describe a rare clinical case of CUA in peritoneal dialysis patient associated with urological disease. Penile calciphylaxis represents rare clinical complication, and an early diagnosis and multidisciplinary approach are requested. Pathogenesis is still unclear, and therapeutic approaches need more long-term clinical trials to test their efficacy and safety.

Clinical management of nondialysis patients with chronic kidney disease: a retrospective observational study. Data from the SONDA study (Survey Of Non-Dialysis outpAtients).

BACKGROUND: A lack of awareness of chronic kidney disease (CKD) often results in delayed diagnosis and inadequate treatment. PURPOSE: The objective of this study was to assess the therapeutic management and outcome of nondialysis CKD patients. METHODS: Three hundred ninety-seven patients (54.9% males aged 67.5 ± 14.6 years) were retrospectively screened at the Nephrology Department, GB Grassi Hospital, Rome, Italy. After a baseline visit, patient data were collected every 6 months for a total of 24 months. Clinical characteristics were measured at baseline, then the following outcomes were measured every 6 months: staging of CKD, presence of concomitant diseases, treatment and adherence to Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for anemia management. RESULTS: Three hundred sixty-eight (92.7%) patients attended at least one visit and 92 (23.2%) patients attended all four visits. Patients were mainly referred to a nephrologist for chronic renal failure (61.7%) or hypertension (42.8%). At baseline, 79.6% of patients had previous hospitalization and 79.1% were receiving antihypertensive medication. Serum creatinine and/or glomerular filtration rate was examined in >90% of patients, whereas parathyroid hormone was rarely examined (5.5%). Vitamin D supplementation was received by 6.5% of patients. The majority of patients were staged at 3 or 4 CKD (32% and 23.9%, respectively) and did not significantly change over time. The use of antithrombotic, antilipidemic and erythropoietin medication increased over the four surveys. The majority of patients (86.8%) achieved hemoglobin K/DOQI target levels. CONCLUSION: These findings demonstrate a current lack of attention of CKD and related disorders (mineral metabolism, electrolyte balance, and anemia) at the level of the general practitioner (GP) and non-nephrology specialist, which can result in both delayed referral and inadequate treatment. By increasing both awareness of CKD and the coordinated relationship between GPs and nephrologists, patient clinical and therapeutic outcome may be improved.

[Pathophysiology and diagnosis of cardio-renal syndrome: actual picture and future prospectives]. / Fisiopatologia e diagnosi della sindrome cardio-renale: stato dell'arte e prospettive future.

The cardiorenal syndrome (CRS) indicates how close the relationship is between heart and kidney during failure of these organs. At present, the classification of the syndrome includes five types of CRS: types I and II which are strictly related to initial heart failure (both acute and chronic), types III and IV which include initial kidney failure, and type V which includes several systemic diseases. Many pathophysiological pathways have been described illustrating how heart and kidney disease are involved in clinical conditions. The diagnosis of CRS is based on both blood tests and ultrasound imaging. Several biomarkers indicating levels of heart and kidney function have emerged over the last few decades which can be used to predict kidney failure in patients with acute or chronic heart disease. Kidney injury biomarkers have also to be tested, especially those indicating glomerular and tubular damage. Renal ultrasound and trans-thoracic echocardiography can provide further information on heart and kidney failure in patients with cardio-renal syndrome at any stage.

Antiproteinuric effect of add-on paricalcitol in CKD patients under maximal tolerated inhibition of renin-angiotensin system: a prospective observational study.

BACKGROUND: Whether paricalcitol (PCT) reduces proteinuria in the presence of intensified inhibition of Renin-Angiotensin-System (RAS) is poorly studied. We evaluated the antiproteinuric effect of PCT in non-dialysis chronic kidney disease (CKD) patients with proteinuria greater than 0.5 g/24 h persisting despite anti-RAS therapy titrated to minimize proteinuria in the absence of adverse effects. METHODS: Forty-eight CKD patients were studied in the first six months of add-on oral PCT (1 mcg/day) and three months after drug withdrawal. RESULTS: Males were 87.5%, age 63 ± 14 yrs, systolic/diastolic blood pressure (BP) 143 ± 22/78 ± 11 mmHg, eGFR 29.7 ± 14.5 mL/min/1.73 m(2), diabetes 40%, and cardiovascular disease 38%. At referral in the center (28 months prior to study baseline), proteinuria was 2.44 (95% CI 1.80-3.04) g/24 h with 6 patients not receiving any anti-RAS and 42 treated with a single agent, at low dosage in most cases. At study baseline, twenty patients were under 2-3 anti-RAS drugs while twenty-eight received 1 agent at full dose and proteinuria resulted to be reduced versus referral to 1.23 g/24 h (95%CI 1.00-1.51). Six months of add-on PCT significantly decreased proteinuria to 0.61 g/24 h (95%CI 0.40-0.93), with levels less than 0.5 g/24 h achieved in 37.5% patients, in the absence of changes of BP and GFR. Proteinuria recovered to basal value after drug withdrawal. The extent of antiproteinuric response to PCT was positively associated with diabetes, eGFR and daily Na excretion (R(2) = 0.459, P < 0.0001). PTH decreased from 201 (IQR 92-273) to 83 (IQR 50-189) pg/mL. CONCLUSIONS: In CKD patients, add-on PCT induces a significant reduction of proteinuria that is evident despite intensified anti-RAS therapy and larger in the presence of diabetes, higher GFR and unrestricted salt intake.

[Hepatitis B prevention measures in chronic kidney disease patients]. / Strategie di prevenzione dell'infezione HBV nel paziente nefropatico.

Hepatitis B virus infection is a major cause of morbidity and mortality among patients on dialysis, that are a target for vaccination. However, due to the poor immunogenicity of all types of vaccines in dialysis patients the collaboration between general practitioners, nephrologists and vaccination centers is essential to introduce the best preventive measures and to identify and immunize patients with chronic kidney disease before they enter dialysis.

Renal status in adult volunteers in central Italy: results from Family Abbott Renal Disease Monitoring Project (FARM) study.

BACKGROUND: Chronic kidney disease (CKD) is a major worldwide problem. A lack of CKD awareness and knowledge of associated risk factors may delay diagnosis and treatment. The purpose of this epidemiological study was to assess the presence and awareness of CKD, in addition to evaluating associated clinical characteristics. METHODS: This cross-sectional observational study included 573 healthy volunteers (aged 21-62 years) based in central Italy. All participants underwent a nephrological visit, providing data on medical history, anamnesis and CKD awareness. Blood and urine samples were also collected. RESULTS: Estimated glomerular filtration rate (eGFR) calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) study formula revealed that 55% of participants had an eGFR of <90 ml/min per 1.73 m2 compared with 24.6% by the Cockcroft-Gault formula (C-G; p<0.0001). Approximately 45% of participants showed an awareness of CKD, these subjects also having a significantly lower Framingham score (p<0.046). Approximately half of participants (51%) had insufficient levels (<30 ng/mL) of serum 25-hydroxyvitamin D (25(OH)D), with a higher proportion observed in female (58.3%) than male participants (45.6%, p=0.0016). Levels of 25(OH)D were negatively correlated with eGFR, measured by either MDRD or C-G (r=-0.12, p=0.0039 and r=-0.09, p=0.029 respectively). Logistic regression analysis revealed that male sex and increased serum creatinine levels were predictors associated with study outcomes (clinical risk factors). CONCLUSIONS: This study suggests that screening for CKD in the general population by eGFR calculations (MDRD or C-G) is unreliable; therefore, the monitoring of serum creatinine and other risk factors may be more appropriate. The presence of vitamin D insufficiency in apparently healthy individuals warrants further investigation.

[Seroconversion and immune response after anti-HBV vaccination in patients on chronic hemodialysis: comparison of two vaccines]. / Sieroconversione e risposta immunitaria dopo vaccinazione anti-HBV in pazienti sottoposti a trattamento emodialitico cronico: confronto tra due diversi protocolli di vaccinazione.

ESRD patients on hemodialysis (HD) have a high risk of HBV infections. Primary prevention through vaccination is a first choice to reduce the morbidity from HBV. Prevention can be accomplished by two types of vaccines. The aim of this study was to evaluate the serological response to HBV vaccination in a population of HD patients who were randomized to Fendrix or Engerix B according to common administration protocols. Ninety-two HD patients were randomized to Fendrix or Engerix B immunization protocols. Patients in the Fendrix arm received four intramuscular administrations of 20 micron g, while patients in the Engerix arm received three intramuscular administrations of 40 micron g with an optional booster dose at two months from the last administration in nonresponders. The seroconversion rates were higher in the Fendrix group than the Engerix group, with faster responses, higher titers and longer duration of immune memory. Fendrix seems to be more effective than the older vaccine, Engerix, especially in patients at high infection risk like those making up our study population. Other crucial factors for good outcomes in patient immunization were biological and dialysis age. This underlines the importance of early immunization protocols such as already discussed by many nephrologists.

IPF-1/MODY4 gene missense mutation in an Italian family with type 2 and gestational diabetes.

Maturity-onset diabetes of the young (MODY) is a monogenic autosomal-dominant form of diabetes mellitus with onset before 25 years of age. Genetic variation in insulin promoter factor-1 (IPF1) (MODY4) is uncommon but may contribute to early- or late-onset diabetes as part of a polygenic background. IPF1 is a homeodomain transcription factor required for pancreas development. Our aim was to identify whether IPF1 gene mutations play a role in Italian early-onset type 2 diabetic (T2D) patients and what functional impact mutations may have in the beta cell. We screened 40 Italian early-onset type 2 diabetic probands for IPF1 mutations, performed oral glucose tolerance tests in the unaffected family members, and performed in vitro functional studies of the mutant variant. In an extended family (Italy-6) of 46 members with clinical phenotypes of gestational diabetes, MODY, and T2D, a single nucleotide change of CCT to ACT was identified at codon 33 resulting in a Pro to Thr substitution (P33T) in the IPF1 transactivation domain that also contributes to an altered metabolic status in the unaffected NM subjects. Of the 22 genotyped Italy-6 members, 9 carried the P33T allele (NM), of whom 5 have either T2D or elevated fasting glucose levels. Oral glucose tolerance tests showed higher glucose levels at 90 minutes in unaffected NM compared with unaffected NN subjects. Of the 5 female pregnant carriers of the IPF1 mutation, 4 had pregnancies complicated by reduced birth weights, miscarriages, or early postnatal deaths. In studies in vitro, the IPF1 mutant protein (P33T) showed a reduction in DNA-binding and transcriptional activation functions as compared to the wild-type IPF1 protein. Our findings suggest that the P33T IPF1 mutation may provide an increased susceptibility to the development of gestational diabetes and MODY4 in the Italy-6 pedigree.