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Papers by Paolo Monardo

Research paper thumbnail of Left Ventricular Mass Index Predicts Renal Function Decline in Patients with Chronic Kidney Disease

Medicina-lithuania, Jan 9, 2024

Research paper thumbnail of Therapeutic Management of Children with Vesicoureteral Reflux

Journal of Clinical Medicine, Dec 30, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Salivary Phosphorus and Phosphate Content of Beverages: Implications for the Treatment of Uremic Hyperphosphatemia

Journal of Renal Nutrition, 2009

Background: Hyperphosphatemia provides relevant and dangerous evidence of end-stage renal disease... more Background: Hyperphosphatemia provides relevant and dangerous evidence of end-stage renal disease (ESRD) in patients undergoing periodic hemodialysis. The relationship between hyperphosphatemia and cardiovascular calcification, with the consequences of high morbidity and mortality after cardiovascular events, is well-defined. Hyperphosphatemia is treated by dietary limitation of phosphorus ingestion and by phosphate binders, but only half of ESRD patients fall within the range of K/DOQI guidelines. Objective and Methods: We summarize the results of our studies on salivary phosphate secretion in hemodialysis (HD) and chronic kidney disease (CKD) patients, and on the habit of HD patients to drink beverages with a high or low phosphate content. We also examine the correlation between hyperphosphoremia and the phosphate content of common beverages consumed by HD patients. Results and Conclusions: Higher levels of salivary phosphate secretion were found in HD and in CKD patients, along with a relationship between serum phosphorus levels and a high phosphate content of beverages in HD patients.

Research paper thumbnail of Rene e Sport

Giornale di clinica nefrologica e dialisi, Oct 1, 1993

Research paper thumbnail of #5542 the Italian Registry of Polycystic Kidney Disease (Rirp): Design, Patient Characteristics and Initial Results

Nephrology Dialysis Transplantation, Jun 1, 2023

Background and Aims: In a population-based study, mainly constituted of unknown nephropathies (co... more Background and Aims: In a population-based study, mainly constituted of unknown nephropathies (cohort Sorbonne University, Paris, France N = 1197 patients), beyond reporting the diagnostic yield of nuclear genes, we also investigated the incidence of the mtDNA pathogenic variant MT-TL1 m.3243A>G. This variation was systematically searched from whole exome sequencing (WES) data. In retrospect, we described the renal phenotype and studied the heteroplasmy level of the mtDNA variation in urine or kidney tissues compared to its blood fraction. The prevalence of m.3243A>G has been estimated ranging from 0.08% to up to 0.25%. Method: From September 2018, to February 2023, WES has been prospectively performed, as a first exploration of adult's nephropathies of unknown origin or when a genetic renal disease was clinically suggested. As off-target result, we retrieved m.3243A>G variation in blood DNA and then determined the mtDNA heteroplasmic level respective from urine sample or kidney tissue when available with an orthogonal method. Results: We report a molecular diagnosis in 294 over 1197 adult patients sequenced (diagnostic yield: 24%, Age 43 y/o in average). Among these 294 patients with molecular diagnoses, 48 were distinct monogenic disorders, out of which 8 accounted for 52% of the genetic diagnoses. MT-TL1 m.3243A>G pathogenic variant was detected in 1,7% of the patients (20 patients over 1197 patients). An orthogonal method confirmed the presence of m.3243A>G variant in 10 patients supporting the possibility to diagnose from blood DNA analysed by WES. In all cases, the presence of m.3243A>G had major clinical implications for the patients and their families: living related donor aborted for two patients, a molecular diagnosis in three patients with unknown nephropathies and in three patients with histological diagnosis of focal segmental glomerulosclerosis. Other mitochondrial diseases appeared less likely involved in our adult cohort (only one patient with COQ2 pathogenic variants). Conclusion: This population-based study reinforces the place of WES as first-tier exploration for adult patients with chronic kidney disease in whom phenotypes are often poor and/or atypical. The mitochondrial genome analysis with the same assay allowed the detection of yet unsuspected MT-TL1 m.3243A>G variant in 1,7% of patients suggesting enrichment compared to current prevalence observed in other population. Our data suggest that the entity "mitochondrial nephropathy" can represent a significant part of adult unknown nephropathies.

Research paper thumbnail of Ztráta denního rytmu sekrece fosfátů slinami u hemodialyzovaných pacientů. Důsledky pro hyperfosfatémii

Research paper thumbnail of Phosphate binders and management of hyperphosphataemia in end-stage renal disease

Nephrology Dialysis Transplantation, Jun 9, 2006

Research paper thumbnail of Endocrine-metabolic hypertension

Child nephrology and urology, 1992

Research paper thumbnail of Acute Kidney Injury, Renal Replacement Therapy, and Sepsis after Cardiac Surgery: The Roles of TIMP2*IGBP7 and Mid-Regional Pro-Adrenomedullin

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR... more Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Research paper thumbnail of Febrile Urinary Tract Infections in Children: The Role of High Mobility Group Box-1

Children (Basel), Dec 26, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of HMGB-1 and TGFβ-1 highlight immuno-inflammatory and fibrotic processes before proteinuria onset in pediatric patients with Alport syndrome

Journal of Nephrology, 2021

Alport syndrome (ALP) is a rare genetic condition characterized by progressive involvement of the... more Alport syndrome (ALP) is a rare genetic condition characterized by progressive involvement of the basal membranes and renal dysfunction. The purpose of the study was to evaluate urinary (u) and serum (s) levels of tumor growth factor (TGF)-beta(β) and high mobility group box (HMGB)-1 in ALP patients with normal renal function, albuminuria and proteinuria. A prospective, single-center study was performed with a follow-up period of 12 months, enrolling 11 pediatric ALP patients and 10 healthy subjects (HS). Normal values of serum creatinine, albuminuria and proteinuria, as well as unaltered estimated glomerular filtration rate (eGFR) were required at enrollment. ALP patients had significantly higher levels of serum and urinary HMGB1 compared to HS. The same trend was observed for TGF-β1, with higher values in ALP patients than in HS. HMGB1 and TGF-β1 correlated with each other and with markers of renal function and damage. Urinary biomarkers did not correlate with eGFR, whereas sHMGB1 and sTGF-β1 were negatively related to filtration rate (r: − 0.66; p = 0.02, r: − 0.96; p < 0.0001, respectively). Using proteinuria as a dependent variable in a multiple regression model, only the association with sTGF-β1 (β = 0.91, p < 0.0001) remained significant. High levels of HMGB1 and TGF-β1 characterized ALP patients with normal renal function, highlighting the subclinical pro-fibrotic and inflammatory mechanisms triggered before the onset of proteinuria. Further studies are needed to evaluate the role of HMGB1 and TGFβ-1 in ALP patients.

Research paper thumbnail of Contents Vol. 79, 2007

Urologia Internationalis, 2007

Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/uin_issues 92 Multiple Metastases of Prostatic Adenocarcinoma to the Urethra after Radical Prostatectomy

Research paper thumbnail of Acute Kidney Injury and Sepsis after Cardiac Surgery: The Roles of Tissue Inhibitor Metalloproteinase-2, Insulin-like Growth Factor Binding Protein-7, and Mid-Regional Pro-Adrenomedullin

Journal of Clinical Medicine

Background: Identifying a panel of markers detecting kidney injury before the glomerular filtrati... more Background: Identifying a panel of markers detecting kidney injury before the glomerular filtration rate reduction is a challenge to improving the diagnosis and management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase-2, insulin growth factor binding protein-7 (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in patients with AKI. Patients and Methods: This study was prospectively conducted in an intensive care unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 h of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7–36.5) hours after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 h in AKI patients (1.1 ± 0.4 mg/L vs. 0.08 ± 0.02 mg/L; p < 0.001). Its concentration > 2 mg/L increases AKI risk within the following 24 h, clearly identifying the population at high risk of renal repla...

Research paper thumbnail of The Switch from Ferric Gluconate to Ferric Carboxymaltose in Hemodialysis Patients Acts on Iron Metabolism, Erythropoietin, and Costs: A Retrospective Analysis

Medicina

Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialys... more Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialysis (HD). Available intravenous iron agents, such as ferric gluconate (FG) and ferric carboxymaltose (FCM), vary in dosing regimens and safety profiles. The aim of the present study was to analyze the modification of the iron status, the correction of anemia, and the economic implications after the shift from FG to FCM therapy in chronic HD patients. We evaluated, during the study, the variations in iron metabolism, assessing ferritin and transferrin saturation, erythropoietin-stimulating agent (ESA) doses and the number of administrations, the effects on anemic status, and consequent costs. Materials and Methods: A retrospective study was performed with a follow-up period of 24 months, enrolling forty-two HD patients. The enrolment phase started in January 2015, when patients were treated with iv FG, and continued until December 2015, when FG was discontinued, and, after a wash-out perio...

Research paper thumbnail of New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study

Ndt Plus, Jan 12, 2022

Background. Anemia is a common complication of chronic kidney disease (CKD), but its incidence in... more Background. Anemia is a common complication of chronic kidney disease (CKD), but its incidence in nephrology settings is poorly investigated. Similarly, the risks of adverse outcomes associated with new-onset anemia are not known. Methods. We performed a pooled analysis of three observational cohort studies including 1031 non-anemic CKD patients with eGFR <60 mL/min/1.73 m 2 regularly followed in renal clinics. We estimated the incidence of mild anemia (hemoglobin 11-12 g/dL in women and 11-13 g/dL in men) and severe anemia (hemoglobin <11 g/dL or use of erythropoiesis-stimulating agents) during a 3-year follow-up period. Thereafter we estimated the risk of end-stage kidney disease (ESKD) and all-cause death associated with new-onset mild and severe anemia. Results. The mean age was 63 ± 14 years, 60% were men and 20% had diabetes. The mean estimated glomerular filtration rate (eGFR) was 37 ± 13 mL/min/1.73 m 2 and the median proteinuria was 0.4 g/day [interquartile range (IQR) 0.1-1.1]. The incidence of mild and severe anemia was 13.7/100 patients-year and 6.2/100 patients-year, respectively. Basal predictors of either mild or severe anemia were diabetes, lower hemoglobin, higher serum phosphate, eGFR <30 mL/min/1.73 m 2 and proteinuria >0.50 g/day. Male sex, moderate CKD (eGFR 30-44 mL/min/1.73 m 2) and moderate proteinuria (0.15-0.50 g/day) predicted only mild anemia. The incidence of anemia increased progressively with CKD stages (from 8.77 to 76.59/100 patients-year) and the proteinuria category (from 13.99 to 25.02/100 patients-year). During a median follow-up of 3.1 years, 232 patients reached ESKD and 135 died. Compared with non-anemic patients, mild anemia was associated with a higher adjusted risk of ESKD {hazard ratio [HR] 1.42 [95% confidence interval (CI) 1.02-1.98]} and all-cause death [HR 1.55 (95% CI 1.04-2.32)]. Severe anemia was associated with an even higher risk of ESKD [HR 1.73 (95% CI 1.20-2.51)] and death [HR 1.83 (95% CI 1.05-3.19)].

Research paper thumbnail of Free Light Chains, High Mobility Group Box 1, and Mortality in Hemodialysis Patients

Journal of Clinical Medicine

Background: Uremic toxins are associated with immune dysfunction and inflammation. The inadequate... more Background: Uremic toxins are associated with immune dysfunction and inflammation. The inadequate removal by hemodialysis (HD) of serum free light chains (FLCs) determines their accumulation. This study evaluated FLCs in HD patients, analyzing their relations with other biomarkers, such as serum high mobility group box 1 (HMGB1). Methods: FLC and HMGB1 were evaluated in a cohort of 119 HD patients. κFLC and λFLC were summated to give a combined (c) FLC concentration. Patients were followed prospectively until the end of the observation period of four years, or until the endpoint: the patient’s death. Results: cFLC values in HD patients were 244.4 (197.9–273.5) mg/L. We detected a significant reduction in CD8+ cells and a decreased CD4+/CD8+ ratio. HMGB1 levels were 94.5 (55–302) pg/mL. After multivariate analysis, cFLCs correlated with β2-microglobulin and the CD4+/CD8+ ratio. Subjects with cFLC values above 263 mg/L and with sHMGB1 values < 80 pg/mL experienced a significantly f...

Research paper thumbnail of Tolvaptan resistance is related with a short-term poor prognosis in patients with lung cancer and syndrome of inappropriate anti-diuresis

Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia, Feb 27, 2023

Research paper thumbnail of Influence of Losartan Therapy on Tubular Sodium Kinetics in Mild to Moderate Hypertension

International Journal of Immunopathology and Pharmacology, 1998

Losartan is a selective antagonist of angiotensin II and it is useful in the therapy of tubular s... more Losartan is a selective antagonist of angiotensin II and it is useful in the therapy of tubular sodium kinetics in mild to moderate hypertension. In this study 30 subjects with mild to moderate hypertension were treated for 2 months with Losartan and were compared to control group of 30 normotensive subjects. Inulin and para aminohippuric acid (PAH) were administered intravenously to both groups, and blood and urine samples were collected every 30 minutes to determine baseline levels of inulin, PAH, lithium, sodium and potassium. A protein meal was given without salt, cereals nor vegetables. After 4 clearance periods were determined. Glomerular filtration rate data from treated and control subjects were not statistically significant. However, lithium clearance, fractional excretion, absolute distal reabsorption of sodium, as well as filtration fraction from Losartan treated and untreated subjects were highly significant at all minutes studied (30-60-90-120, and 180). In this paper w...

Research paper thumbnail of Acute Kidney Injury: Advances in Clinical Management

Journal of Clinical Medicine

Acute kidney injury (AKI), closely related to increased mortality, involved 15–20% of hospitalize... more Acute kidney injury (AKI), closely related to increased mortality, involved 15–20% of hospitalized patients with higher incidence, with about 50% in the intensive care unit (ICU) [...]

Research paper thumbnail of Acute and chronic kidney disease after pediatric liver transplantation: An underestimated problem

Clinical Transplantation

Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), bu... more Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), but whereas renal dysfunction in adult transplant patients is well documented, little is known about its prevalence in childhood. It is a challenge to accurately evaluate renal function in patients with liver disease, due to several confounding factors. Creatinine-based equations estimating glomerular filtration rate, validated in nephropathic patients without hepatic issues, are frequently inaccurate in end-stage liver disease, underestimating the real impact of renal disease. Moreover, whereas renal issues observed within 1 year from LTx were often related to acute injuries, kidney damage observed after 5-7 years from LTx, is due to chronic, irreversible mechanisms. Most immunosuppression protocols are based on calcineurin inhibitors (CNI) and corticosteroids, but mycophenolate mofetil or sirolimus could play significant roles, also in children. Early diagnosis and personalized treatment represent the bases of kidney disease management, in order to minimize its close relation with increased mortality. This review analyzed acute and chronic kidney damage after pediatric LTx, also discussing the impact of pre-existent renal disease. The main immunosuppressant strategies have been reviewed, highlighting their impact on kidney function. Different methods assessing renal function were reported, with the potential application of new renal biomarkers.

Research paper thumbnail of Left Ventricular Mass Index Predicts Renal Function Decline in Patients with Chronic Kidney Disease

Medicina-lithuania, Jan 9, 2024

Research paper thumbnail of Therapeutic Management of Children with Vesicoureteral Reflux

Journal of Clinical Medicine, Dec 30, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Salivary Phosphorus and Phosphate Content of Beverages: Implications for the Treatment of Uremic Hyperphosphatemia

Journal of Renal Nutrition, 2009

Background: Hyperphosphatemia provides relevant and dangerous evidence of end-stage renal disease... more Background: Hyperphosphatemia provides relevant and dangerous evidence of end-stage renal disease (ESRD) in patients undergoing periodic hemodialysis. The relationship between hyperphosphatemia and cardiovascular calcification, with the consequences of high morbidity and mortality after cardiovascular events, is well-defined. Hyperphosphatemia is treated by dietary limitation of phosphorus ingestion and by phosphate binders, but only half of ESRD patients fall within the range of K/DOQI guidelines. Objective and Methods: We summarize the results of our studies on salivary phosphate secretion in hemodialysis (HD) and chronic kidney disease (CKD) patients, and on the habit of HD patients to drink beverages with a high or low phosphate content. We also examine the correlation between hyperphosphoremia and the phosphate content of common beverages consumed by HD patients. Results and Conclusions: Higher levels of salivary phosphate secretion were found in HD and in CKD patients, along with a relationship between serum phosphorus levels and a high phosphate content of beverages in HD patients.

Research paper thumbnail of Rene e Sport

Giornale di clinica nefrologica e dialisi, Oct 1, 1993

Research paper thumbnail of #5542 the Italian Registry of Polycystic Kidney Disease (Rirp): Design, Patient Characteristics and Initial Results

Nephrology Dialysis Transplantation, Jun 1, 2023

Background and Aims: In a population-based study, mainly constituted of unknown nephropathies (co... more Background and Aims: In a population-based study, mainly constituted of unknown nephropathies (cohort Sorbonne University, Paris, France N = 1197 patients), beyond reporting the diagnostic yield of nuclear genes, we also investigated the incidence of the mtDNA pathogenic variant MT-TL1 m.3243A>G. This variation was systematically searched from whole exome sequencing (WES) data. In retrospect, we described the renal phenotype and studied the heteroplasmy level of the mtDNA variation in urine or kidney tissues compared to its blood fraction. The prevalence of m.3243A>G has been estimated ranging from 0.08% to up to 0.25%. Method: From September 2018, to February 2023, WES has been prospectively performed, as a first exploration of adult's nephropathies of unknown origin or when a genetic renal disease was clinically suggested. As off-target result, we retrieved m.3243A>G variation in blood DNA and then determined the mtDNA heteroplasmic level respective from urine sample or kidney tissue when available with an orthogonal method. Results: We report a molecular diagnosis in 294 over 1197 adult patients sequenced (diagnostic yield: 24%, Age 43 y/o in average). Among these 294 patients with molecular diagnoses, 48 were distinct monogenic disorders, out of which 8 accounted for 52% of the genetic diagnoses. MT-TL1 m.3243A>G pathogenic variant was detected in 1,7% of the patients (20 patients over 1197 patients). An orthogonal method confirmed the presence of m.3243A>G variant in 10 patients supporting the possibility to diagnose from blood DNA analysed by WES. In all cases, the presence of m.3243A>G had major clinical implications for the patients and their families: living related donor aborted for two patients, a molecular diagnosis in three patients with unknown nephropathies and in three patients with histological diagnosis of focal segmental glomerulosclerosis. Other mitochondrial diseases appeared less likely involved in our adult cohort (only one patient with COQ2 pathogenic variants). Conclusion: This population-based study reinforces the place of WES as first-tier exploration for adult patients with chronic kidney disease in whom phenotypes are often poor and/or atypical. The mitochondrial genome analysis with the same assay allowed the detection of yet unsuspected MT-TL1 m.3243A>G variant in 1,7% of patients suggesting enrichment compared to current prevalence observed in other population. Our data suggest that the entity "mitochondrial nephropathy" can represent a significant part of adult unknown nephropathies.

Research paper thumbnail of Ztráta denního rytmu sekrece fosfátů slinami u hemodialyzovaných pacientů. Důsledky pro hyperfosfatémii

Research paper thumbnail of Phosphate binders and management of hyperphosphataemia in end-stage renal disease

Nephrology Dialysis Transplantation, Jun 9, 2006

Research paper thumbnail of Endocrine-metabolic hypertension

Child nephrology and urology, 1992

Research paper thumbnail of Acute Kidney Injury, Renal Replacement Therapy, and Sepsis after Cardiac Surgery: The Roles of TIMP2*IGBP7 and Mid-Regional Pro-Adrenomedullin

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR... more Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p &lt; 0.001). Its concentration &gt;2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values &gt;5.1 nmol/l and urine TIMP2*IGBP7 levels &gt; 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Research paper thumbnail of Febrile Urinary Tract Infections in Children: The Role of High Mobility Group Box-1

Children (Basel), Dec 26, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of HMGB-1 and TGFβ-1 highlight immuno-inflammatory and fibrotic processes before proteinuria onset in pediatric patients with Alport syndrome

Journal of Nephrology, 2021

Alport syndrome (ALP) is a rare genetic condition characterized by progressive involvement of the... more Alport syndrome (ALP) is a rare genetic condition characterized by progressive involvement of the basal membranes and renal dysfunction. The purpose of the study was to evaluate urinary (u) and serum (s) levels of tumor growth factor (TGF)-beta(β) and high mobility group box (HMGB)-1 in ALP patients with normal renal function, albuminuria and proteinuria. A prospective, single-center study was performed with a follow-up period of 12 months, enrolling 11 pediatric ALP patients and 10 healthy subjects (HS). Normal values of serum creatinine, albuminuria and proteinuria, as well as unaltered estimated glomerular filtration rate (eGFR) were required at enrollment. ALP patients had significantly higher levels of serum and urinary HMGB1 compared to HS. The same trend was observed for TGF-β1, with higher values in ALP patients than in HS. HMGB1 and TGF-β1 correlated with each other and with markers of renal function and damage. Urinary biomarkers did not correlate with eGFR, whereas sHMGB1 and sTGF-β1 were negatively related to filtration rate (r: − 0.66; p = 0.02, r: − 0.96; p < 0.0001, respectively). Using proteinuria as a dependent variable in a multiple regression model, only the association with sTGF-β1 (β = 0.91, p < 0.0001) remained significant. High levels of HMGB1 and TGF-β1 characterized ALP patients with normal renal function, highlighting the subclinical pro-fibrotic and inflammatory mechanisms triggered before the onset of proteinuria. Further studies are needed to evaluate the role of HMGB1 and TGFβ-1 in ALP patients.

Research paper thumbnail of Contents Vol. 79, 2007

Urologia Internationalis, 2007

Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/uin_issues 92 Multiple Metastases of Prostatic Adenocarcinoma to the Urethra after Radical Prostatectomy

Research paper thumbnail of Acute Kidney Injury and Sepsis after Cardiac Surgery: The Roles of Tissue Inhibitor Metalloproteinase-2, Insulin-like Growth Factor Binding Protein-7, and Mid-Regional Pro-Adrenomedullin

Journal of Clinical Medicine

Background: Identifying a panel of markers detecting kidney injury before the glomerular filtrati... more Background: Identifying a panel of markers detecting kidney injury before the glomerular filtration rate reduction is a challenge to improving the diagnosis and management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase-2, insulin growth factor binding protein-7 (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in patients with AKI. Patients and Methods: This study was prospectively conducted in an intensive care unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 h of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7–36.5) hours after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 h in AKI patients (1.1 ± 0.4 mg/L vs. 0.08 ± 0.02 mg/L; p < 0.001). Its concentration > 2 mg/L increases AKI risk within the following 24 h, clearly identifying the population at high risk of renal repla...

Research paper thumbnail of The Switch from Ferric Gluconate to Ferric Carboxymaltose in Hemodialysis Patients Acts on Iron Metabolism, Erythropoietin, and Costs: A Retrospective Analysis

Medicina

Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialys... more Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialysis (HD). Available intravenous iron agents, such as ferric gluconate (FG) and ferric carboxymaltose (FCM), vary in dosing regimens and safety profiles. The aim of the present study was to analyze the modification of the iron status, the correction of anemia, and the economic implications after the shift from FG to FCM therapy in chronic HD patients. We evaluated, during the study, the variations in iron metabolism, assessing ferritin and transferrin saturation, erythropoietin-stimulating agent (ESA) doses and the number of administrations, the effects on anemic status, and consequent costs. Materials and Methods: A retrospective study was performed with a follow-up period of 24 months, enrolling forty-two HD patients. The enrolment phase started in January 2015, when patients were treated with iv FG, and continued until December 2015, when FG was discontinued, and, after a wash-out perio...

Research paper thumbnail of New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study

Ndt Plus, Jan 12, 2022

Background. Anemia is a common complication of chronic kidney disease (CKD), but its incidence in... more Background. Anemia is a common complication of chronic kidney disease (CKD), but its incidence in nephrology settings is poorly investigated. Similarly, the risks of adverse outcomes associated with new-onset anemia are not known. Methods. We performed a pooled analysis of three observational cohort studies including 1031 non-anemic CKD patients with eGFR <60 mL/min/1.73 m 2 regularly followed in renal clinics. We estimated the incidence of mild anemia (hemoglobin 11-12 g/dL in women and 11-13 g/dL in men) and severe anemia (hemoglobin <11 g/dL or use of erythropoiesis-stimulating agents) during a 3-year follow-up period. Thereafter we estimated the risk of end-stage kidney disease (ESKD) and all-cause death associated with new-onset mild and severe anemia. Results. The mean age was 63 ± 14 years, 60% were men and 20% had diabetes. The mean estimated glomerular filtration rate (eGFR) was 37 ± 13 mL/min/1.73 m 2 and the median proteinuria was 0.4 g/day [interquartile range (IQR) 0.1-1.1]. The incidence of mild and severe anemia was 13.7/100 patients-year and 6.2/100 patients-year, respectively. Basal predictors of either mild or severe anemia were diabetes, lower hemoglobin, higher serum phosphate, eGFR <30 mL/min/1.73 m 2 and proteinuria >0.50 g/day. Male sex, moderate CKD (eGFR 30-44 mL/min/1.73 m 2) and moderate proteinuria (0.15-0.50 g/day) predicted only mild anemia. The incidence of anemia increased progressively with CKD stages (from 8.77 to 76.59/100 patients-year) and the proteinuria category (from 13.99 to 25.02/100 patients-year). During a median follow-up of 3.1 years, 232 patients reached ESKD and 135 died. Compared with non-anemic patients, mild anemia was associated with a higher adjusted risk of ESKD {hazard ratio [HR] 1.42 [95% confidence interval (CI) 1.02-1.98]} and all-cause death [HR 1.55 (95% CI 1.04-2.32)]. Severe anemia was associated with an even higher risk of ESKD [HR 1.73 (95% CI 1.20-2.51)] and death [HR 1.83 (95% CI 1.05-3.19)].

Research paper thumbnail of Free Light Chains, High Mobility Group Box 1, and Mortality in Hemodialysis Patients

Journal of Clinical Medicine

Background: Uremic toxins are associated with immune dysfunction and inflammation. The inadequate... more Background: Uremic toxins are associated with immune dysfunction and inflammation. The inadequate removal by hemodialysis (HD) of serum free light chains (FLCs) determines their accumulation. This study evaluated FLCs in HD patients, analyzing their relations with other biomarkers, such as serum high mobility group box 1 (HMGB1). Methods: FLC and HMGB1 were evaluated in a cohort of 119 HD patients. κFLC and λFLC were summated to give a combined (c) FLC concentration. Patients were followed prospectively until the end of the observation period of four years, or until the endpoint: the patient’s death. Results: cFLC values in HD patients were 244.4 (197.9–273.5) mg/L. We detected a significant reduction in CD8+ cells and a decreased CD4+/CD8+ ratio. HMGB1 levels were 94.5 (55–302) pg/mL. After multivariate analysis, cFLCs correlated with β2-microglobulin and the CD4+/CD8+ ratio. Subjects with cFLC values above 263 mg/L and with sHMGB1 values < 80 pg/mL experienced a significantly f...

Research paper thumbnail of Tolvaptan resistance is related with a short-term poor prognosis in patients with lung cancer and syndrome of inappropriate anti-diuresis

Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia, Feb 27, 2023

Research paper thumbnail of Influence of Losartan Therapy on Tubular Sodium Kinetics in Mild to Moderate Hypertension

International Journal of Immunopathology and Pharmacology, 1998

Losartan is a selective antagonist of angiotensin II and it is useful in the therapy of tubular s... more Losartan is a selective antagonist of angiotensin II and it is useful in the therapy of tubular sodium kinetics in mild to moderate hypertension. In this study 30 subjects with mild to moderate hypertension were treated for 2 months with Losartan and were compared to control group of 30 normotensive subjects. Inulin and para aminohippuric acid (PAH) were administered intravenously to both groups, and blood and urine samples were collected every 30 minutes to determine baseline levels of inulin, PAH, lithium, sodium and potassium. A protein meal was given without salt, cereals nor vegetables. After 4 clearance periods were determined. Glomerular filtration rate data from treated and control subjects were not statistically significant. However, lithium clearance, fractional excretion, absolute distal reabsorption of sodium, as well as filtration fraction from Losartan treated and untreated subjects were highly significant at all minutes studied (30-60-90-120, and 180). In this paper w...

Research paper thumbnail of Acute Kidney Injury: Advances in Clinical Management

Journal of Clinical Medicine

Acute kidney injury (AKI), closely related to increased mortality, involved 15–20% of hospitalize... more Acute kidney injury (AKI), closely related to increased mortality, involved 15–20% of hospitalized patients with higher incidence, with about 50% in the intensive care unit (ICU) [...]

Research paper thumbnail of Acute and chronic kidney disease after pediatric liver transplantation: An underestimated problem

Clinical Transplantation

Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), bu... more Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), but whereas renal dysfunction in adult transplant patients is well documented, little is known about its prevalence in childhood. It is a challenge to accurately evaluate renal function in patients with liver disease, due to several confounding factors. Creatinine-based equations estimating glomerular filtration rate, validated in nephropathic patients without hepatic issues, are frequently inaccurate in end-stage liver disease, underestimating the real impact of renal disease. Moreover, whereas renal issues observed within 1 year from LTx were often related to acute injuries, kidney damage observed after 5-7 years from LTx, is due to chronic, irreversible mechanisms. Most immunosuppression protocols are based on calcineurin inhibitors (CNI) and corticosteroids, but mycophenolate mofetil or sirolimus could play significant roles, also in children. Early diagnosis and personalized treatment represent the bases of kidney disease management, in order to minimize its close relation with increased mortality. This review analyzed acute and chronic kidney damage after pediatric LTx, also discussing the impact of pre-existent renal disease. The main immunosuppressant strategies have been reviewed, highlighting their impact on kidney function. Different methods assessing renal function were reported, with the potential application of new renal biomarkers.