Densitometria ossea: una breve guida per il nefrologo:

DXA: a beginner's guideStudies in patients with chronic kidney disease have definitively shown that "dual-energy X-ray absorptiometry" (DXA) may be helpful in assessing fracture risk. Moreover, it is essential to diagnose osteoporosis and evaluate response to treatment. In order to obtain the best utility from DXA, nephrologists need to know the fundamentals of this technique, its indications in clinical practice, and the potential pitfalls in the interpretation of its results. This review will provide an overview of the fundamentals, methodology, and current clinical applications of DXA with special focus on the nephrologist's perspective

Determinants of inappropriate setting allocation in the care of patients with type 2 diabetes: A population-based study in Reggio Emilia province

The study aims to describe the distribution of patients with type 2 diabetes (T2D) by care plan and to highlight determinants of underuse and overuse of integrated care (IC). This cross-sectional study included all T2D patients resident in Reggio Emilia on 31/12/2015 based on the population-based diabetes registry. Eligibility for IC requires good glycaemic control, no rapid insulin, no kidney failure and no diabetes complications. We calculated the proportion of IC underuse and overuse and adjusted prevalence estimate using multivariate logistic regression. Determinants were age, sex, citizenship, district of residence and time since diagnosis. Of 29,776 patients, 15,364 (51.6%) were in diabetes clinic plan, 9851 (33.1%) in IC plan and 4561 (15.3%) not in any care plan (i.e., in Other group). There were 10,906 (36.6%) patients eligible for IC, of whom 1000 in Other group. When we adjusted for all covariates and restricted the analysis to patients included in care plans, the proportion of those eligible for IC plan but cared for in diabetes clinic plan (i.e. underuse of IC) was 28% (n = 3028/9906; 95%CI 27–29). Similarly, the proportion of those not eligible for IC but cared for in IC plan (i.e. overuse of IC) was 11% (n = 1720/11,896; 95%CI 10–11).The main determinant of both IC underuse and overuse was the district of residence. Foreign status was associated with underuse (37%; 95%CI 33–43), while old age (≥80 years) with both underuse (36%; 95%CI 0.33–0.38) and overuse (23%; 95%CI 22–25). The criterion for suspension of IC plan most frequently found was renal failure, followed by hospitalization for diabetes-related complications. Patients are more often allocated to more specialized settings than not. Healthcare provider-related factors are the main determinants of inappropriate setting allocation

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)

Le sfide dell\u2019insufficienza renale cronica nei pazienti fragili: due progetti che affrontano l\u2019impatto dell\u2019invecchiamento e del cancro

INTRODUZIONE E SCOPI: Il miglioramento dei tassi di sopravvivenza dei pazienti neoplastici per effetto dei nuovi agenti chemioterapici, inclusi i farmaci biologici, ha determinato un aumento di coloro che sviluppano malattia renale conseguente alla neoplasia. L\u2019incidenza complessiva e la prevalenza dell\u2019insufficienza renale cronica (IRC) nei pazienti affetti da tumore sono tuttavia ancora incerte, ma molte evidenze suggeriscono che il rischio sia elevato e in aumento. Lo studio ROCK ha come obiettivi principali quelli di stimare la prevalenza e l\u2019incidenza dell\u2019IRC ne pazienti inclusi nel Registro Tumori della provincia di Reggio Emilia dall'1\ub0 Gennaio al 31 Dicembre 2016. METODI: Studio di coorte monocentrico, osservazionale, retrospettivo. I pazienti saranno caratterizzati per sesso, et\ue0, etnia, peso, creatinina sierica e relativo eGFR, numero e tipo di tumore, diagnosi di diabete mellito. Le principali sedi di tumore considerato sono state mammella, colon-retto, polmoni, pancreas, stomaco, prostata, leucemie e linfomi. Un valore di eGFR 65 60 ml/min1.73m2 \ue8 stato considerato indicativo di una condizione di normofunzione renale, mentre un filtrato glomerulare < 60 ml/min/1.73m2 come indicativo di un\u2019alterazione degli indici di funzione renale. Tutti i valori di eGFR sono stati inoltre ottenuti sia con la formula CKD-EPI, oggi riconosciuta come formula di riferimento per la stima dell\u2019eGFR nella popolazione generale, ma anche con l\u2019equazione di Wright che sembra fornire la stima migliore nel paziente oncologico. RISULTATI: sono stati identificati 4254 con diagnosi di cancro tra il 1\ub0 Gennaio e il 31 Dicembre 2016; di questi, 171 sono stati esclusi per mancanza di dati. Dei rimanenti 4083, 776 pazienti (19%) avevano almeno un valore di eGFR <60 mL/min/1.73m2 precedente alla diagnosi di cancro mentre 497 pazienti (11.7%) sono stati identificati come affetti da IRC. La prevalenza di IRC nei successivi 24 mesi dalla diagnosi di cancro \ue8 risultata essere di 4.4% (186 pazienti). Per entrambi le coorti (IRC pre-esistente e IRC di nuova diagnosi), sono state effettuate analisi relative a dati anagrafici e clinici. Facendo riferimento alla formula CKD-EPI, i pazienti con IRC pre-esistente (497), l'et\ue0 media \ue8 risultata essere di 81 anni, il 53.7% erano maschi, il 18.3% aveva una diagnosi di diabete mellito tipo 2, il 3.6% di questi pazienti aveva due o pi\uf9 diagnosi di tumore; il 44.3% risultavano in vita al termine del follow-up (31 Dicembre 2018). Usando la formula di Wright, sono stati identificati 504 pazienti con IRC gi\ue0 presente al momento della diagnosi di cancro; questi pazienti presentavano un'et\ue0 media di 82 anni, nel 55.4% dei casi erano maschi, il 18.8% era affetto da diabete mellito tipo 2 e il 3.8% aveva 2 o pi\uf9 diagnosi di tumore. CONCLUSIONI: Migliorare la conoscenza delle interazioni tra IRC e cancro sono di fondamentale importanza. La rapida evoluzione dei trattamenti e l\u2019anticipazione diagnostica che si \ue8 avuta in molte sedi, hanno cambiato in modo drastico i fattori di rischio e prognostici dell\u2019insufficienza renale nel paziente oncologico. L'applicazione di misure volte alla riduzione del rischio di progressione dell'IRC pu\uf2 pertanto migliorare gli outcomes clinici dei pazienti oncologici ad alto rischio.BACKGROUND AND AIMS: The improvement in the survival rates of cancer patients due to the new oncological and biological agents has led to an increase in those who develop kidney diseases. It is now well known that chronic kidney disease (CKD) and cancer are connected in several ways. However, the overall incidence and prevalence of CKD in cancer patients are still uncertain, but much evidence suggests that the risk is high and increasing. The purpose of the study is to provide data on the prevalence and incidence of CKD in patients included in the Cancer Registry of the province of Reggio Emilia from January 1st to December 31st 2016. METHODS: single-center, observational and retrospective study. For all patients included, data on sex, age, ethnicity, serum creatinine and related eGFR, type and number of tumors, diagnosis of diabetes mellitus were collected. The main cancer sites considered were breast, colorectal, lungs, pancreas, stomach, prostate, lymphomas and leukemias. An eGFR 65 60 ml/min1.73m2 was indicative of a normal kidney function, while an eGFR <60 ml/min/1.73m2 as kidney impairment. All the eGFR data were calculated not only with the CKD-EPI formula, now recognized as the reference formula for estimating eGFR in the general population, but also with the Wright formula which seems to provide the best evaluation in cancer patients. RESULTS: 4254 patients with a cancer diagnosis were identified between January 1st and December 31st 2016; of these, 171 patients were excluded due to lack of data. Of the remaining 4083 patients, 776 (19%) had at least an eGFR value <60 mL/min/1.73m2 prior to cancer diagnosis and 497 patients (11.7%) were identified as affected by CKD. The prevalence of CKD was 4.4% (186 patients) calculated in the following 24 months from cancer diagnosis. For both cohorts of patients (pre-existing CKD and CKD diagnosed at the time of cancer diagnosis), descriptive analyzes were conducted related to personal and clinical data. Referring to the CKD-EPI formula, in patients with pre-existing CKD (497 patients), the mean age was 81 years, 53.7% were men, 18.3% had a known diagnosis of type 2 diabetes mellitus, 3.6% of these patients had 2 or more cancer diagnosis in the study period. 44.3% were alive at the end of the follow-up (December 31st, 2018). Using Wright formula, 504 patients with CKD already present at the time of cancer diagnosis were identified; these patients had an average age of 82 years and in 55.4% of cases were men; 18.8% had type 2 diabetes mellitus and 3.8% had 2 or more cancer diagnosis. CONCLUSIONS: Knowledge of association between CKD and cancer is critically relevant information. Therefore, the rapid evolution of treatments and the diagnostic anticipation have changed the risk and prognostic factors of kidney diseases in cancer patients. Application of measures to reduce the risk progression of CKD could improve the clinical outcomes high risk cancer patients

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.

BACKGROUND: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS: We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS: We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10 CONCLUSIONS: We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN