Giovanni Tripepi

• Biostatistician, MSc, PhD
• Head of Department at Italian National Research Council

Background/Objectives: Recent studies have highlighted the Triglyceride–Glucose Index (TYG) as a significant risk factor for mortality and co-morbidities in various populations, including those with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. However, its prognostic role in obese individuals remains less clear. Methods: Utilizing d...

Background Daratumumab-refractory multiple myeloma (Dara-R MM) presents a significant treatment challenge. This study aimed to evaluate the efficacy and survival outcomes of elotuzumab, pomalidomide, and dexamethasone (EloPd) in a large, real-world cohort of patients with Dara-R MM, with particular focus on progression-free survival (PFS) and overa...

Introduction: Acute pulmonary edema (APE) due to fluid overload is considered the most feared complication in hemodialysis patients. Various diagnostic tests have been proposed to assess the fluid status in patients with end-stage kidney failure (ESKF); among these, lung ultrasound (measuring the number of B-lines) is emerging as a promising tool t...

Abstract: Mendelian Randomization (MR) studies have emerged as a powerful tool for investigating causal relationships between modifiable risk factors and clinical outcomes, using genetic variants as instrumental variables. In the context of vitamin D research, MR is a promising approach to elucidate the effects of vitamin D on various health outcom...

Background: This real-life study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after autologous stem cell transplantation (auto-SCT). Methods: Sixty consecutive NDMM patients received four cycles of induction therapy with D-VTd. The conditioning regimen consisted of melphalan 200 mg/m2. These pa...

Background/Objectives: Phosphate is a macro-element involved in all cellular energetic processes. As about 90% of the phosphate filtered by the glomerulus is excreted by kidneys, the impairment of renal function and the consequent over-secretion of parathyroid hormone and fibroblast growth factor 23 results in the increase in the serum phosphate le...

Background Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no me...

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key...

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of Vitamin D, there has been a progressive advancement in analytical technologies for its determination, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelin...

Background: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no m...

Background and Aims Vascular calcifications (VCs) are prevalent in chronic kidney disease (CKD) and mineral disorders, associated with aortic calcification and increased bone fracture risk. The complex pathogenesis involves factors like calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key inhibitors, vitamin K-dependent pro...

Background and Aims Isolated diastolic hypertension (IDH) is relatively rare in the general population (prevalence about 6.5%, Front Cardiovasc Med. 2021;8:810105) and of uncertain etiologic implications. The prevalence of this alteration in the hemodialysis (HD) population and the etiologic implications of IDH have not been studied. Method We inv...

Background and Aims Advanced stages of chronic kidney disease (CKD) are constantly characterized by a mineral and bone disorders (MBD) syndrome concerning a complex systemic condition that includes laboratory abnormalities of bone and mineral metabolism involving calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; abnormalities in bone tu...

Background and Aims Altered BP control during the night (non-dipping, reverse dipping and nocturnal hypertension) is recognized as a powerful risk factor for death and CV events in the hemodialysis (HD) population. However, these alterations have been described in relatively small studies and the epidemiology and risk factors for subtypes non-dippi...

Background and Aims Kidney transplantation represents the optimal treatment for end-stage renal disease patients. Benefits and disadvantages of different pre-transplant dialysis modalities and the effects on post-transplant outcomes remain unclear, but many authors identify peritoneal dialysis (PD) such a “bridge” versus renal transplantation. Met...

Introduction Diabetic kidney disease (DKD) is a major complication in patients with diabetes and the main contributor to the chronic kidney disease (CKD) global burden. Oxidative stress is a crucial factor in DKD pathogenesis but the role of the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) and its molecular regulators has been poo...

Background Atrial Fibrillation (AF) and chronic kidney disease (CKD) frequently coexist in elderly patient. Previous evidence showed that vitamin K antagonists (VKAs) may be associated with an accelerated decrease of estimated glomerular filtration rate (eGFR) compared to direct oral anticoagulants (DOACs). However, there is little evidence on DOAC...

Background and Aims Alterations of bone metabolism are a hallmark of chronic kidney disease (CKD) patients and do not completely ameliorate after kidney transplantation. In the setting of a secondary analysis of a RCT, we evaluated changes of bone turnover biomarkers (BTM) and their associations with changes of bone mineral density (BMD) as assesse...

Background and Aims Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces the expression of genes coding for antioxidant proteins and phase II detoxifying enzymes. Repressor molecule Kelch-like ECH-associated protein 1 (Keap1) and several microRNAs (miRNA) negatively regulate Nrf2 gene expression at post-transcri...

Background and Aims Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that regulates various physiological processes in both the central and peripheral nervous systems, including cardiovascular and metabolic control. We showed that high plasma NPY predicts CKD progression (NDT 2018;33:1805-1812) in a cohort of 735 patients with stage G2-5 CKD. W...

Background and Aims Follow-up studies in CKD patients showed an inverse relationship between serum bicarbonate and CKD progression, but only sparse longitudinal observations testing this relationship exist. Bicarbonate supplementation slowed the progression rate of CKD in 5 trials, but no such effect was registered in six trials. All these trials h...

Background and Aims Male sex is considered a major risk factor for cardiovascular (CV) disease in the general population, but the role of this factor in the high risk for CV disease in the pre-dialysis CKD population is still debated. Methods We tested the relationship between sex and fatal and non-fatal major CV events (myocardial infarction, hea...

Increased arterial hypertension represents a prevalent condition in peritoneal dialysis patients that is often related to volume expansion. Pulse pressure is a robust predictor of mortality in dialysis patients, but its association with mortality is unknown in peritoneal patients. We investigated the relationship between home pulse pressure and sur...

Background and aims: Obesity without metabolic alterations (Metabolically Healthy Obesity, MHO) is a condition with a risk of death and cardiovascular disease lower than that of obesity associated with metabolic alterations (Metabolically Unhealthy Obesity, MUO) and similar to that of healthy non obese individuals. Inflammation is considered as a...

Endothelial dysfunction (ED) starts early in chronic kidney disease (CKD) and is the hallmark of atherosclerosis in these patients. During recent years, numerous markers have emerged, aiming to predict the onset of ED in CKD patients. Therefore, there is a need to evaluate and assess the discriminatory ability (or diagnostic accuracy) of such a mar...

Introduction: The evaluation of renal function is computed using the estimated glomerular filtration rate methods or the measured glomerular filtration rate. Cystatin C has been well studied as marker of renal function compared to serum creatinine, but only few studies compare Glomerular Filtration Rates estimated including both creatinine and cyst...

BACKGROUND AND AIMS The EXCITE trial (JASN 28: 1259–1268, 2017) in dialysis patients showed that a 6-month home walking exercise program increases the walking distance covered during the 6 min walking test (6MWT), improves the response to the 5 times sit-to-stand test (5STS) and the cognitive function and quality of social interaction scores of the...

BACKGROUND AND AIMS Ambulatory blood pressure monitoring (ABPM), extended to 44h or 48h for the diagnosis of hypertension in end-stage kidney disease (ESKD) patients, is recommended by Consensus Documents of the American Society of Nephrology and the European Renal Association. About 10%–20% of individuals in the general population report sleeping...

BACKGROUND AND AIMS Vascular calcifications (VCs), a known risk factor for cardiovascular disease and mortality, are strongly linked to vertebral fractures (VFs) [1]. The coronary calcium score from computer tomography (CT) is the gold standard to measure VCs [2], but this implies high radiation doses and costs. Although, several calcifications sco...

BACKGROUND AND AIMS Though the current dialysis population is characterized by a better survival, there is a greater burden of cardiovascular comorbidities. These two factors together expose patients to a greater number of diagnostic and therapeutic contrast tests. The European Society of Urogenital Radiology (ESUR) Guidelines on Contrast Agents 10...

BACKGROUND AND AIMS Amplified early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk in the general population. The early morning changes in these parameters have not been investigated in the haemodialysis population. METHOD In a pilot, single centre, study including a...

Background Vascular calcification and fragility fractures are common age-related disorders, associated with high morbidity and mortality especially in end-stage renal disease. Skeletal disorders occur in dialysis patients. Few studies have provided data on the prevalence of vertebral fractures (VF) and their association with large artery calcificat...

Fractures and vascular calcifications (VCs) are common in patients with chronic kidney disease (CKD). They are related to abnormalities in vitamin D metabolism, calcium, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23)/Klotho that occur with CKD. Impaired vitamin D metabolism and abnormal levels of calcium, phosphate, parath...

Background and Aims In patients with Chronic Kidney Disease (CKD) mineral, bone, and calcific cardiovascular abnormalities are associated to adverse clinical outcomes, including fractures, cardiovascular events and mortality. Vitamin D hormonal system along with alteration levels that occur in calcium, phosphate, PTH, FGF23/Klotho are the main resp...

Background and Aims Analyses in a large clinical trial in hypertensive patients (SPRINT) and in the Cardiovascular Health study cohort coherently showed that the difference between the GFR as estimated by serum cystatin and creatine (eGFRDiff) associates with frailty and predicts a lower risks for adverse outcomes including frailty, falls, cardiova...

Background and Aims Biomarkers of the Chronic Kidney Disease – Bone Mineral Disorder (CKD-BMD)-including serum phosphate, calcium, PTH, 1,25 vitamin D, alkaline phosphatase and FGF23- have been implicated in CKD progression in follow up studies focusing on single measurements made at baseline only. The relationship between the time trend of these b...

Background and Aims The knowledge of the impact of peritoneal dialysis (PD) program in terms of hospitalization rate can provide solid guidance for nephrologists for management purpose. In a historical cohort of adult PD patients, we examined the hospitalization rates and causes of hospital admissions. Method One hundred ninety-one consecutive PD...

Background and Aims Lung ultrasound (US) is a reliable method for the identification of patients with lung congestion in the hemodialysis population (JACC Cardiovascular Imaging 2010;3:586-94) and a high number of US-B lines (an equivalent of B lines in the chest X-ray) is a powerful predictor of death and cardiovascular events in this population (...

Background and Aims Hypertension resistant to drug treatment is common among CKD patients. However, the phenotype of resistant hypertension in the CKD population is still loosely defined and scarcely characterized. Method In a cohort of 759 stage 2-5 CKD patients, we identified a subgroup of 647 patients with >4 longitudinal visits (range 4-7 visi...

Background During the last twenty years many tools, based on mathematical models, have been developed to predict ESKD at the time of kidney biopsy in patients with IgAN. The main limitation of these tools is the time frame to reach the ESKD. Recently, we have developed a Clinical Decision Support System (CDSS) (KI 2020) which includes 6 variables a...

Background and Aims Effective outpatient organization is essential in the management of patients with chronic kidney disease. Although peritoneal dialysis (PD) has many advantages it is still not popular. Method The aim of this study was to evaluate patient and center-related factors that affect the final choice of peritoneal dialysis (PD) versus...

Background and Aims Although physical activity has been documented to be effective in many categories of high-risk patients and more recently also in dialysis patients, there are no studies specifically focused on Peritoneal Dialysis (PD) patients. The peculiarity of this treatment modality for uremia is that it is carried out at the patient's home...

Background and Aims Developing risk predictive models in high-risk populations, such as patients with type 2 diabetes (T2DM), might provide an individualized risk prediction. During the past decade, the studies assessing carotid intima media thickness (cIMT) as a novel risk factor for cardiovascular (CV) disease, produced controversial results. In...

Background and objectivesEnd stage renal disease (ESRD) patients are exposed to the risk of ionizing radiation during repeated imaging studies. The variability in diagnostic imaging policies and the accompanying radiation doses across various renal units is still unknown. We studied this variability at the centre level and quantified the associated...

Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated...

The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylate...

Background and Aims Sevelamer (S) is a phosphate binding drug used to treat hyperphosphatemia in patients with CKD. Our aim was to evaluate the hypothesis that the use of (S) could interfere with Vitamin K absorption in hemodialysis (HD) patients of VIKI study. Method We tested this hypothesis in VIKI, a cross-sectional study of 387 hemodialysis p...

Background and Aims Measuring QoL in CKD patients is fundamental to estimate the human cost of chronic diseases and to assess the effect of treatments. Non-medical factors play an important role in CKD progression and QoL. However, there is very limited information on the evolution of QoL over time in CKD patients and it remains unclear whether tra...

Background and Aims In the post-hoc analyses of the SUSTAIN and ASSURE trials (Kidney Blood Press Res. 2018;43:449-457), Apabetalone, an epigenetic modulator which lowers serum alkaline phosphatase (AlkPhos), stabilized the GFR in patients with cardiovascular disease and a GFR <60/ml/min/1.73m2. Analyzing the relationship between AlkPhos and renal...

Background and Aims Tunneled central venous catheter (T CVC) use is rising among patients undergoing chronic hemodialysis (HD) and non-tunneled (NT) CVCs are often used for HD initiation in late referral chronic kidney disease (CKD) or acute kidney injury (AKI). Catheter-related bloodstream infections (CRBSI) are a major complication of CVC use. Th...

Background and Aims Cardiovascular deaths cluster in the early morning hours and studies in the general population documented that an exaggeration of the early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk. The circadian profile of BP and HR in hemodialysis patients i...

Background and Aims Lung Ultrasound (US) reliably estimates lung water and it is increasingly applied in clinical practice in dialysis patients. Lung water is currently measured by applying a semi-quantitative US score summing up the US-B lines (an equivalent of B lines in standard X-rays of the thorax) detected in 28 lung intercostal spaces (LIS)...

Background and Aims The natural history of ADPKD has been defined in numerous studies in various countries and in various genetic and environmental contexts but the problem has not yet been studied in sufficiently large studies in the Italian population. We have studied the evolution of ADPKD in a cohort of 445 incident patients enrolled in a time...

Background and Aims Two Vitamin K-dependent proteins (VDKPs) link bone and vasculature in CKD-MBD: Bone Gla Protein (BGP) and Matrix Gla Protein (MGP). In ESKD, Vitamin K deficiency is highly prevalent and leads to increased levels of inactive VKDPs (undercaboxylated (ucBGP and dephosphorylated (dp)-uMGP), which are linked to greater risk of fractu...

Background and Aims Mortality risk is very high in the dialysis population and the Charlson Comorbidities Index (CCI) is considered as an useful risk stratification tool in these patients. The purpose of this study was to examine the accuracy of CCI for predicting mortality in peritoneal dialysis (PD) patients and to compare the prognostic power of...

The authors wish to make the following corrections to the previous publication [...]

Long-term treatment with Proton Pump Inhibitors (PPIs) is associated with an increased risk of fractures in the general population. PPIs are widely prescribed to dialysis patients but to date no study specifically tested, by state-of-art statistical methods, the relationship between PPIs use and fractures in this patient-population. This study aime...

Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide efficacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in “real world” setting that is different from randomized controlled trials (RCTs) to (1) evalu...

In the general population and in heart disease, pulmonary hypertension (PH) is a strong and independent risk factor for mortality and adverse cardiovascular outcomes. We performed a systematic review and meta‐analysis of longitudinal cohort studies of individuals with chronic kidney disease (CKD) of any‐stage (also including end‐stage kidney diseas...

Hypertensive patients with normal glucose tolerance (NGT) but 1-h post-load plasma glucose ≥ 155 mg/dl (1-h high), during an oral glucose tolerance test (OGTT), show higher insulin resistance and multiple target organ damages. Experimental and clinical studies demonstrate that silybin presents anti-inflammatory and metabolic effects, improving insu...

Hematopoietic Stem Cell Transplantation activity levels vary across European countries. No data are available on the homogeneity of access to the transplant procedure for patient with leukaemia, within any European country. We measured homogeneity of the rate of alternative donor search in patients affected by acute leukaemia resident in each Itali...

Background and aims: The nature of the link (causal vs non-causal) between low 1,25-OH vitamin D and insulin resistance (IR) in patients with chronic kidney disease (CKD) remains elusive. We have now made a post hoc analysis of the effect of vitamin D receptor activation by paricalcitol on IR in the complete dataset of a double-blind, randomized,...

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, and an emerging risk factor for atrial fibrillation (AF). CHADS2 and CHA2DS2-VASc scores are significantly associated with incident AF independently of other risk factors. The aim of this study was to demonstrate a possible interaction between C...

Background: Bone gamma-carboxyglutamic acid (Gla)-protein (BGP or osteocalcin) is a vitamin K-dependent protein involved in the regulation of bone mineralization. Smoking is a risk factor for osteoporosis. Methods: We carried out a secondary analysis of the vitamin K Italian (VIKI) study to investigate the association between cigarette smoking a...

The Inventory Déjà Vu Experiences Assessment (IDEA) is the only screening instrument proposed to evaluate the Déjà vu (DV) experience. Here, we intended to validate the Italian version of IDEA (I-IDEA) and at the same time to investigate the incidence and subjective qualities of the DV phenomenon in healthy Italian adult individuals on basis of an...

Background Renal denervation reduces blood pressure (BP) and sympathetic drive in experimental animal models, but the effect of this intervention on sympathetic activity in patients with treatment-resistant hypertension is still unclear. Methods In an incident series of 29 patients with treatment-resistant hypertension, we performed serial measure...

Impaired fasting glucose (IFG) and type 2 diabetes (T2D) represents adverse events in Chronic Myeloid Leukemia (CML) patients treated with the second-generation tyrosine kinase inhibitor (TKI) nilotinib. A genetic risk score (uGRS) for the prediction of insulin resistance, consisting of 10 multiple single-nucleotide polymorphisms (SNPs), has been p...

We here report final results of a phase II/III prospective study that evaluated in Multiple Myeloma the use of on-demand plerixafor (PLX) added to mobilizing chemotherapy for patients showing predictive signs of mobilization failure. A total of 111 patients with MM were registered, all received cyclophosphamide 4 g/m² and granulocyte colony-stimula...

We read the letter by dr. Schliet raising the problem of data integrity in our study. Overall the problem was only descriptive and due to computation mistakes related to the use of the SD of the geometric mean. The problem was absolutely immaterial for data interpretation and for the conclusions of our study. Problems of data integrity are a very s...

Sustained fluid overload (FO) is considered a major cause of hypertension, heart failure, and mortality in patients with ESRD on maintenance hemodialysis. However, there has not been a cohort study investigating the relationship between chronic exposure to FO and mortality in this population. We studied the relationship of baseline and cumulative F...

Background: Hyperuricemia is associated with incident cardiovascular events in different settings of patients. We tested whether the inclusion of uric acid (UA) in Cox models including standard risk factors allows to better stratify cardiovascular risk in a cohort of 1522 naïve hypertensives with preserved renal function. Methods: We used multip...