Introduction: The underdiagnosis of chronic kidney disease (CKD) remains a significant public health concern. The Early chroNic kiDney disease pOint of caRe Screening (ENDORSE) project aimed to evaluate the clinical and economic implications of a targeted training intervention for general practitioners (GPs) to enhance CKD awareness and early diagnosis. Methods: Data on estimated Glomerular Filtration Rate (eGFR) and Urinary Albumin-Creatinine Ratio (uACR) were collected by 53 Italian GPs from 112,178 patients at baseline and after six months. The intervention involved six months of hybrid training provided by 11 nephrologists, which included formal lectures, instant messaging support, and joint visits for complex cases. Results: The results demonstrated a substantial increase in the use of eGFR (+44.7%) and uACR (+95.2%) tests. This led to a 128.9% rise in the number of individuals screened for CKD using the KDIGO classification, resulting in a 62% increase in CKD diagnoses. The intervention's impact was particularly notable in high-risk groups, including patients with type 2 diabetes, hypertension, and heart failure. Discussion: A budget impact analysis projected cumulative five-year savings of € 1.7 million for the study cohort. When these findings were extrapolated to the entire Italian CKD population, potential savings were estimated at € 106.6 million, highlighting significant cost savings for the national health service. The clinical simulation assumed that early diagnosed CKD patients would be treated according to current indications for dapagliflozin, which slows disease progression. Conclusion: The ENDORSE model demonstrated that targeted training for GPs can significantly improve early CKD detection, leading to better patient outcomes and considerable economic benefits. This approach shows promise for broader implementation to address the underdiagnosis of CKD on a national and potentially international scale. Keywords: eGFR, uACR, awareness, chronic kidney disease, general practice, economic impact, training intervention, early diagnosis
Acute Kidney Injury (AKI) following radical nephrectomy (RN) is associated with an increased risk of morbidity and mortality due to the prolonged hospitalization for renal impairment, heart failure and sepsis. Several studies have identified, as possible risk factors, age, gender, comorbidities, and basal eGFR. However, in clinical practice does not exist a clear protocol able to stratify patients upon risk of AKI after surgery. Aim of our study was to investigate the most prominent risk factors for AKI among clinical features, in order to better tailor the medical approach before and after operation.
Background Although vegan–vegetarian diets are increasingly popular, no recent systematic reviews on vegan–vegetarian diets in pregnancy exist. Objectives To review the literature on vegan–vegetarian diets and pregnancy outcomes. Search strategy PubMed, Embase, and the Cochrane library were searched from inception to September 2013 for pregnancy and vegan or vegetarian Medical Subject Headings (MeSH) and free-text terms. Selection criteria Vegan or vegetarian diets in healthy pregnant women. We excluded case reports and papers analysing vegan–vegetarian diets in poverty and malnutrition. Searching, paper selection, and data extraction were performed in duplicate. Data collection and analysis The high heterogeneity of the studies led to a narrative review. Main results We obtained 262 full texts from 2329 references; 22 selected papers reporting maternal–fetal outcomes (13) and dietary deficiencies (nine) met the inclusion criteria. None of the studies reported an increase in severe adverse outcomes or in major malformations, except one report of increased hypospadias in infants of vegetarian mothers. Five studies reported vegetarian mothers had lower birthweight babies, yet two studies reported higher birthweights. The duration of pregnancy was available in six studies and was similar between vegan–vegetarians and omnivores. The nine heterogeneous studies on microelements and vitamins suggest vegan–vegetarian women may be at risk of vitamin B12 and iron deficiencies. Author's conclusions The evidence on vegan–vegetarian diets in pregnancy is heterogeneous and scant. The lack of randomised studies prevents us from distinguishing the effects of diet from confounding factors. Within these limits, vegan–vegetarian diets may be considered safe in pregnancy, provided that attention is paid to vitamin and trace element requirements.
The prevalence of CKD and of renal failure vary worldwide, yet parallel increases in leading risk factors explain only part of the differential prevalence. We measured CKD prevalence and eGFR, and their relationship with traditional and additional risk factors, in a Sardinian founder population cohort. The eGFR was calculated using equations from the CKD Epidemiology Collaboration and Modification of Diet in Renal Disease studies. With use of the Kidney Disease Improving Global Outcomes guidelines, a cross-sectional analysis of 4842 individuals showed that CKD prevalence was 15.1%, including 3.6% of patients in the high-risk and 0.46% in the very-high-risk categories. Longitudinal analyses performed on 4074 of these individuals who completed three visits with an average follow-up of 7 years revealed that, consistent with other populations, average eGFR slope was −0.79 ml/min per 1.73 m2 per year, but 11.4% of the participants had an eGFR decline >2.3 ml/min per 1.73 m2 per year (fast decline). A genetic score was generated from 13 reported eGFR- and CKD-related loci, and univariable and multivariable analyses were applied to assess the relationship between clinical, ultrasonographic, and genetic variables with three outcomes: CKD, change in eGFR, and fast eGFR decline. Genetic risk score, older age, and female sex independently correlated with each outcome. Diabetes was associated with CKD prevalence, whereas hypertension and hyperuricemia correlated more strongly with fast eGFR decline. Diabetes, hypertension, hyperuricemia, and high baseline eGFR were associated with a decline of eGFR. Along with differential health practices, population variations in this spectrum of risk factors probably contributes to the variable CKD prevalence worldwide.
Monoclonal Gammopathies of Renal Significance (MGRS) are a complex group of disorders characterized by the production of aberrant monoclonal proteins that interact with kidney structures, causing tissue damage. Unlike neoplastic forms, kidney damage in MGRS does not correlate with clone mass or circulating monoclonal protein levels, conferring unique pre-neoplastic or non-neoplastic properties to the responsible clones. This manuscript explores the heterogeneity of monoclonal proteins involved, varying from full immunoglobulins to free light chains (FLC), and how they result in a spectrum of kidney lesions with differing prognoses. We also elaborate on diagnostic challenges, emphasizing the indispensable role of kidney biopsy, including advanced techniques like laser microdissection and mass spectrometry (LMD/MS) for deposit characterization, particularly in ambiguous or complex cases. Clinical management and treatment considerations, including the necessity for clone identification, are also discussed.
Abstract Background and Aims ADPKD is the most common form of inherited renal disease worldwide. ADPKD care has advanced over the past decade by the identification of several clinical/genetic risk factors of progression and approval of first disease-modifying drug. Further clinical outcomes research is needed to improve patient-centered clinical care; in addition new disease-modifying therapies are in pipeline, requiring a growing need for patient enrolment in clinical trials. To advance these goals, the Italian Society of Nephrology, supported by the Italian PKD Foundation (AIRP) established in 2020 the creation of a National web-based ADPKD Registry. Here we present the design of this Registry and the preliminary results. Method Adult patients with clinical or genetically confirmed diagnosis of ADPKD have been enrolled in the Registry, hosted by a secure online platform including both a clinical and genetic database. Databases have modular design collecting clinical features, including demographic data, type of diagnosis, e-GFR at onset and at time of first and last nephrological referral, age at onset of hypertension (HTN) and major urological complications (UC), Total Kidney Volume (hTKV) and Mayo Imaging Classification of ADPKD, age at ESRD, use of aspecific renal-protective and disease-modifying drugs, additional risk factors for CKD progression (smoke, diabetes, NSAID), extra-renal manifestations. Genetic data collected include type of PKD1/2 variant with ACMG classification and pathogenic prediction tools, testing method, results of segregation analysis. Statistics included estimation of eGFR slope using linear-mixed modelling. Results By January 2023, the Registry had recruited 985 ADPKD patients across 21 Italian Nephrology Unit; 513 (52,1%) were females; 967 (98,2%) Caucasians. Familiar history of ADPKD was reported in 738 patients (79%). All CKD stages were represented and 105 (14,1%) patients reached ESRD (median age 57y ± 11,5). hTKV was available for 353 (35,9%) patients, with a median value of 1100 ± 996 ml/m; a Mayo class of 1C or higher was found in 221 (70,4%). PROPKD score was evaluated in 162 patients, and in 50% of them it was associated with low risk of progression. A total of 191 (21,6%) were receiving Tolvaptan. Demographic and clinical characteristics are summarized in Table 1. Genetic testing was performed in 288 patients; 111 (38,5%) had PKD1 truncating (T) variants; 67 (23,3%) PKD1 non truncating variants; 69 (24%) PKD2 variants. In 41 patients (14,2%) no pathogenic variants were detected. In our cohort deterioration of renal function over time, estimated using eGFR slope was significantly associated with Mayo Imaging classes, high-medium PROPKD score, PKD1-T variant, HTN onset before 35 yo (Figure) and early UC (−2,3 vs. −1,9 ml/min/1.73m2/y, p = 0.014). Conclusion The Italian ADPKD National Registry is an important research tool collecting clinical and genetic information. Our preliminary data confirm that in the Italian population genotype, early onset HTN or UC, Mayo Imaging classification and PROPKD score are able to predict deterioration of GFR in ADPKD. The future empowerment of the Registry will provide a comprehensive description of clinical features and genetic variants related to ADPKD in a large cohort of Italian patients, enabling us to better understand genotype-phenotype correlation. Furthermore, the Registry could be an opportunity to identify patients suitable for future clinical trials or observational studies concerning specific aspects of the disease.
Abstract Background and Aims Daprodustat (GSK1278863) is a hypoxia-inducible factor prolyl hydroxylase inhibitor under investigation for the treatment of anaemia of chronic kidney disease. Phase 3 studies in dialysis (ASCEND-D) and non-dialysis (ASCEND-ND) patients demonstrated the non-inferiority of daprodustat vs recombinant human erythropoietin (rhEPO) control (in ASCEND-D) or darbepoetin alfa (ASCEND-ND) control in terms of the mean change in haemoglobin levels between Weeks 28 and 52 versus baseline and the first occurrence of a composite major adverse cardiovascular (CV) event (MACE) [1, 2]. Post-hoc analyses were conducted to evaluate prespecified CV endpoints for patients enrolled in these studies from participating countries in Europe (EU patients) versus elsewhere (non-EU patients). Method Post-hoc time to the first adjudicated MACE (death from any cause, non-fatal myocardial infarction or non-fatal stroke), time to the first adjudicated MACE or thromboembolic event (TEE; deep vein thrombosis, pulmonary embolism or vascular access thrombosis), and time to the first adjudicated MACE or hospitalisation for heart failure (HHF) were analysed for EU (enrolled from Austria, Belgium, Bulgaria, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Romania, Spain, Sweden and the UK; not all countries participated in both studies) and non-EU (all other participating countries) patients. Hazard ratios (HRs) and associated 95% confidence intervals were calculated to evaluate the likelihood of CV events with daprodustat versus alternative therapy in both studies. HRs for EU and non-EU patients were compared for each endpoint in each study and p-values were calculated to assess the statistical significance of observed differences. Significance was defined at the 10% level (interaction p-value <0.1). Results ASCEND-D included 415 EU patients and 1072 non-EU patients randomised to daprodustat, and 440 EU and 1037 non-EU patients randomised to rhEPO. ASCEND-ND included 410 EU patients and 1527 non-EU patients randomised to daprodustat, and 407 EU and 1528 non-EU patients randomised to darbepoetin alfa. No significant heterogeneity was observed between EU and non-EU patients in terms of the prespecified CV endpoints (p≥0.1979). In ASCEND-D and ASCEND-ND, the results for MACE, MACE+TEE and MACE+HHF for the EU subgroup were consistent with the non-EU subgroup (Table), as well as with the co-primary analysis [1, 2]. Efficacy and additional safety data for EU versus non-EU patients are being explored and will be included in the subsequent presentation. Conclusion Non-inferiority in terms of the first occurrence of MACE was demonstrated for daprodustat versus rhEPO in ASCEND-D and versus darbepoetin alfa in ASCEND-ND.1,2 Results for EU and non-EU patients in the current analysis were consistent with the global outcomes from both studies.
