Papers by Matias Trillini
Infective endocarditis mimics ANCA associated glomerulonephritis
PubMed, 2012
Background: Sub-acute bacterial endocarditis (SBE) rarely presents with features of a small vesse... more Background: Sub-acute bacterial endocarditis (SBE) rarely presents with features of a small vessel vasculitis. Patients with SBE can also develop multiple serological abnormalities including ANCA. In this report, we present a case of infective endocarditis mimicked ANCA associated glomerulonephritis. Case presentation: A 57-year old male with a clinical picture of rapidly progressive renal failure (RPGN) and positive seology for PR3-ANCA (C-ANCA) was referred to our hospital. The renal histology findings were compatible with focal and segmental glomerular necrosis. After receiving corticosteroid therapy, the patient became febrile and his general condition worsened. Cardiac ultrasound echocardiographic study disclosed multiple large vegetations on the aortic valve. After appropriate antibiotic therapy and valvular surgery, the patient's condition improved and his serum creatinine reached 1.7 mg/d. Conclusion: Misdiagnosis of SBE as ANCA-associated vasculitis and an inappropriate immunosuppressive therapy can have catastrophic consequences.
Nephron, May 25, 2023
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited dis... more Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the diseasecausing variants observed in ADPKD patients are in two genes: PKD1 and PKD2. Methods: 237 patients from 198 families with a clinical diagnosis of ADPKD were screened for PKD1 and PKD2 genetic variants using Sanger sequencing and multiple ligation-dependent probe amplification analysis. Results: Disease-causing (diagnostic) variants were identified in 173 families (211 patients), 156 on PKD1 and 17 on PKD2. Variants of unknown significance were detected in 6 additional families, while no mutations were found in the remaining 19 families. Among the diagnostic variants detected, 51 were novel. In ten families, seven large rearrangements were found and the molecular breakpoints of 3 rearrangements were identified. Renal survival was significantly worse for PKD1-mutated patients, particularly those carrying truncating mutations. In patients with PKD1 truncating (PKD1-T) mutations, disease onset was significantly earlier than in patients with PKD1 non-truncating variants or PKD2-mutated patients. Conclusions: Comprehensive genetic testing confirms its utility in diagnosing patients with ADPKD and contributes to explaining the clinical heterogeneity observed in this disease. Moreover, the genotype-phenotype correlation can allow for a more accurate disease prognosis.
Epidemiology of End-Stage Renal Failure
Elsevier eBooks, 2017
Abstract Chronic kidney disease (CKD) is a key determinant of poor health outcomes for major nonc... more Abstract Chronic kidney disease (CKD) is a key determinant of poor health outcomes for major noncommunicable diseases, which are the leading cause of death in the world. Most chronic nephropathies progress relentlessly to end-stage renal disease (ESRD). The number of patients with ESRD now receiving renal replacement therapy worldwide is approximately 2 million. However, although CKD is a global threat to public health, the size of the problem is not fully appreciated. Efforts to prevent or halt renal disease progression are of utmost importance to reduce the clinical and economic consequences of CKD.
Infective Endocarditis Mimics Anca Associated Glomerulonephritis; Case Report
Diffusion magnetic resonance imaging for kidney cyst volume quantification and non-cystic tissue characterisation in ADPKD
European Radiology
International Journal of Molecular Sciences, Apr 22, 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
Nephron
Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited dis... more Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are in two genes: PKD1 and PKD2. Methods: 237 patients from 198 families with a clinical diagnosis of ADPKD were screened for PKD1 and PKD2 genetic variants using Sanger sequencing and multiple ligation-dependent probe amplification analysis. Results: Disease-causing (diagnostic) variants were identified in 173 families (211 patients), 156 on PKD1 and 17 on PKD2. Variants of unknown significance were detected in 6 additional families, while no mutations were found in the remaining 19 families. Among the diagnostic variants detected, 51 were novel. In ten families, seven large rearrangements were found and the molecular breakpoints of 3 rearrangements were identified. Renal survival was significantly worse for PKD1-mutated pati...
Epidemiology of End-Stage Renal Failure: The Burden of Kidney Diseases to Global Health
Chronic kidney disease (CKD) is a key determinant of poor health outcomes for major noncommunicab... more Chronic kidney disease (CKD) is a key determinant of poor health outcomes for major noncommunicable diseases, which are the leading cause of death in the world. Most chronic nephropathies progress relentlessly to end-stage renal disease (ESRD). The number of patients with ESRD now receiving renal replacement therapy worldwide is approximately 2 million. However, although CKD is a global threat to public health, the size of the problem is not fully appreciated. Efforts to prevent or halt renal disease progression are of utmost importance to reduce the clinical and economic consequences of CKD.
In type-2 diabetics with abdominal obesity, hyperfiltration is a risk factor for accelerated GFR decline and nephropathy. In this academic, single-center, parallel-group, Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) trial (ClinicalTRials.gov number: NCT01213212), consenting >18-year
1 IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Centro di Ricerche Cliniche per le Mal... more 1 IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Centro di Ricerche Cliniche per le Malattie Rare “Aldo e Cele Daccò”, Bergamo, Italy; 2 Unit of Nephrology, Azienda Socio Sanitaria Territoriale (ASST) Ospedale Papa Giovanni XXIII, Bergamo, Italy; 3 Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy; 4 Department of Clinical and Experimental Sciences, Brescia University Medical School, Brescia, Italy; 5 Department of Medicine, Washington University in St. Louis, MO, USA; 6 CEINGE Biotecnologie Avanzate, Napoli, Italy
BACKGROUND Sub-acute bacterial endocarditis (SBE) rarely presents with features of a small vessel... more BACKGROUND Sub-acute bacterial endocarditis (SBE) rarely presents with features of a small vessel vasculitis. Patients with SBE can also develop multiple serological abnormalities including ANCA. In this report, we present a case of infective endocarditis mimicked ANCA associated glomerulonephritis. CASE PRESENTATION A 57-year old male with a clinical picture of rapidly progressive renal failure (RPGN) and positive seology for PR3-ANCA (C-ANCA) was referred to our hospital. The renal histology findings were compatible with focal and segmental glomerular necrosis. After receiving corticosteroid therapy, the patient became febrile and his general condition worsened. Cardiac ultrasound echocardiographic study disclosed multiple large vegetations on the aortic valve. After appropriate antibiotic therapy and valvular surgery, the patient's condition improved and his serum creatinine reached 1.7 mg/d. CONCLUSION Misdiagnosis of SBE as ANCA-associated vasculitis and an inappropriate im...
Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis
Clinical Journal of the American Society of Nephrology
Background and objectivesRenin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidit... more Background and objectivesRenin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis.Design, setting, participants, & measurementsIn this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25–10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset o...
Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): a prospective observational study and embedded randomised placebo-controlled trial
The Lancet Diabetes & Endocrinology
PLOS Medicine
Background Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically ... more Background Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically determined renal disease. In affected patients, renal function may progressively decline up to end-stage renal disease (ESRD), and approximately 10% of those with ESRD are affected by ADPKD. The somatostatin analog octreotide long-acting release (octreotide-LAR) slows renal function deterioration in patients in early stages of the disease. We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD. Methods and findings We did an internally funded, parallel-group, double-blind, placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate (GFR) 15-40 ml/ min/1.73 m 2. Participants were randomized to receive 2 intramuscular injections of 20 mg octreotide-LAR (n = 51) or 0.9% sodium chloride solution (placebo; n = 49) every 28 days for 3 years. Central randomization was 1:1 using a computerized list stratified by center and
Effects of Sevelamer Carbonate in Patients With CKD and Proteinuria: The ANSWER Randomized Trial
American Journal of Kidney Diseases
Journal of the Endocrine Society, 2018
Acetyl-l-carnitine (ALC), a mitochondrial carrier involved in lipid oxidation and glucose metabol... more Acetyl-l-carnitine (ALC), a mitochondrial carrier involved in lipid oxidation and glucose metabolism, decreased systolic blood pressure (SBP), and ameliorated insulin sensitivity in hypertensive nondiabetic subjects at high cardiovascular risk. To assess the effects of ALC on SBP and glycemic and lipid control in patients with hypertension, type 2 diabetes mellitus (T2D), and dyslipidemia on background statin therapy. After 4-week run-in period and stratification according to previous statin therapy, patients were randomized to 6-month, double-blind treatment with ALC or placebo added-on simvastatin. Five diabetology units and one clinical research center in Italy. Two hundred twenty-nine patients with hypertension and dyslipidemic T2D >40 years with stable background antihypertensive, hypoglycemic, and statin therapy and serum creatinine <1.5 mg/dL. Oral ALC 1000 mg or placebo twice daily on top of stable simvastatin therapy. Primary outcome was SBP. Secondary outcomes includ...
Safety of Iohexol Administration to Measure Glomerular Filtration Rate in Different Patient Populations: A 25-Year Experience
Nephron, Jan 17, 2018
In clinical research setting, accurate and precise measurement of glomerular filtration rate (GFR... more In clinical research setting, accurate and precise measurement of glomerular filtration rate (GFR) is essential to overcome the limitations of GFR estimation with equations, which are often unreliable. In recent decades, a method for measuring GFR by plasma clearance of iohexol, a non-ionic radiocontrast agent, was developed. To evaluate the safety of the procedure, we aimed to review all immediate adverse reactions that could be related to iohexol administration in our group's 25 years worth of experience. We retrospectively reviewed all GFR investigations in 2,891 patients, between 1992 and 2016, as part of 37 clinical trials coordinated by our group. Subjects with disparate renal diseases, kidney transplant recipients, and living donors - all with different renal function categories - were included in the surveyed clinical trials. During 15,147 GFR measurements, only one treatment-related event of moderate intensity was identified. Flushing, urticaria, and itching were observ...
Conversion from Brand-Name Neoral to the Generic Ciqorin in Stable Renal Transplant Recipients
Nephron, 2016
Transplant physicians and patients are often reluctant to change to generic versions of immunosup... more Transplant physicians and patients are often reluctant to change to generic versions of immunosuppressive drugs with a narrow therapeutic index, such as ciclosporin (CsA). Thus, in routine follow-up for kidney transplant patients receiving CsA maintenance immunosuppressive therapy in our center, we evaluated the exchangeability of the brand name, Neoral, and the recently approved CsA generic formulation, Ciqorin. We assessed the complete 12-h CsA pharmacokinetic profile and direct measurement of glomerular filtration rate (mGFR) of 10 patients receiving stable doses of Neoral (138 ± 43 mg/day), at least 6 months after kidney transplantation (Neoral 1). The same evaluations were repeated 10 days after conversion to Ciqorin on a milligram-to-milligram basis and 10 days after reinstituting Neoral (Neoral 2). The mean CsA area under the concentration-time curve increased slightly after switching from Neoral to Ciqorin (p = 0.03), but did not change significantly after Neoral was reintroduced (Neoral 1: 2,234 ± 783, Ciqorin: 2,452 ± 767, Neoral 2: 2,472 ± 784 ng × h/mL). There were no appreciable differences between the 2 CsA formulations in trough levels, maximum concentrations, or time to reach maximum concentrations. In all patients, renal function remained stable throughout the monitoring period (mGFR, Neoral 1: 52.0 ± 16.2; Ciqorin: 55.0 ± 19.0; Neoral 2: 55.8 ± 18.9 mL/min/1.73 m2), as did urinary and hematochemical parameters. In stable kidney transplant recipients, switching from Neoral to Ciqorin resulted in similar pharmacokinetic parameters and did not change renal allograft function, reassuring physicians and patients regarding the exchangeability of reference and generic CsA formulations.
Caspian Journal of Internal Medicine, 2012
Background: Sub-acute bacterial endocarditis (SBE) rarely presents with features of a small vesse... more Background: Sub-acute bacterial endocarditis (SBE) rarely presents with features of a small vessel vasculitis. Patients with SBE can also develop multiple serological abnormalities including ANCA. In this report, we present a case of infective endocarditis mimicked ANCA associated glomerulonephritis. Case presentation: A 57-year old male with a clinical picture of rapidly progressive renal failure (RPGN) and positive seology for PR3-ANCA (C-ANCA) was referred to our hospital. The renal histology findings were compatible with focal and segmental glomerular necrosis. After receiving corticosteroid therapy, the patient became febrile and his general condition worsened. Cardiac ultrasound echocardiographic study disclosed multiple large vegetations on the aortic valve. After appropriate antibiotic therapy and valvular surgery, the patient’s condition improved and his serum creatinine reached 1.7 mg/d. Conclusion: Misdiagnosis of SBE as ANCA-associated vasculitis and an inappropriate immunosuppressive therapy can have catastrophic consequences.
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
Lancet (London, England), Jan 10, 2015
The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a s... more The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental...
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Papers by Matias Trillini