Artificial intelligence in chronic kidney diseases: methodology and potential applications.

Chronic kidney disease (CKD) represents a significant global health challenge, characterized by kidney damage and decreased function. Its prevalence has steadily increased, necessitating a comprehensive understanding of its epidemiology, risk factors, and management strategies. While traditional prognostic markers such as estimated glomerular filtration rate (eGFR) and albuminuria provide valuable insights, they may not fully capture the complexity of CKD progression and associated cardiovascular (CV) risks.This paper reviews the current state of renal and CV risk prediction in CKD, highlighting the limitations of traditional models and the potential for integrating artificial intelligence (AI) techniques. AI, particularly machine learning (ML) and deep learning (DL), offers a promising avenue for enhancing risk prediction by analyzing vast and diverse patient data, including genetic markers, biomarkers, and imaging. By identifying intricate patterns and relationships within datasets, AI algorithms can generate more comprehensive risk profiles, enabling personalized and nuanced risk assessments.Despite its potential, the integration of AI into clinical practice faces challenges such as the opacity of some algorithms and concerns regarding data quality, privacy, and bias. Efforts towards explainable AI (XAI) and rigorous data governance are essential to ensure transparency, interpretability, and trustworthiness in AI-driven predictions.

The Missense Variant in the Signal Peptide of α-GLA Gene, c.13 A/G, Promotes Endoplasmic Reticular Stress and the Related Pathway's Activation.

Anderson-Fabry disease (AFD) is an X-linked multisystemic disorder with a heterogeneous phenotype, resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and leading to globotriaosylceramide systemic accumulation. Lysosomal storage is not the unique player in organ failure and different mechanisms could drive tissue damage, including endoplasmic reticulum (ER) stress and its related signaling pathway's activation. We identified a new missense variant in the signal peptide of α-GLA gene, c.13 A/G, in a 55-year-old woman affected by chronic kidney disease, acroparesthesia, hypohidrosis, and deafness and exhibiting normal values of lysoGb3 and αGLA activity. The functional study of the new variant performed by its overexpression in HEK293T cells showed an increased protein expression of a key ER stress marker, GRP78, the pro-apoptotic BAX, the negative regulator of cell cycle p21, the pro-inflammatory cytokine, IL1ß, together with pNFkB, and the pro-fibrotic marker, N-cadherin. Transmission electron microscopy showed signs of ER injury and intra-lysosomal inclusions. The proband's PBMC exhibited higher expression of TGFß 1 and pNFkB compared to control. Our findings suggest that the new variant, although it did not affect enzymatic activity, could cause cellular damage by affecting ER homeostasis and promoting apoptosis, inflammation, and fibrosis. Further studies are needed to demonstrate the variant's contribution to cellular and tissue damage.

[Semaglutide in Chronic Kidney Disease: Great Enthusiasm. But How Does It Work?] / La Semaglutide nella Malattia Renale Cronica: tanto entusiasmo. Ma come funziona?

Chronic Kidney Disease (CKD) is a clinical condition characterized by the progressive loss of kidney function. 10% of the world's population is affected by this condition, which represents the fifth leading cause of death globally. Furthermore, CKD is associated with increased risk of fatal and non-fatal cardiovascular events, and progression to end-stage renal disease. Over the last twenty years, an exponential growth in its prevalence and incidence has been observed. For this reason, various drugs have been developed and implemented in clinical practice, with various mechanisms, with the aim of reducing and minimizing this dramatic "cardio-renal" risk. These include SGLT2 inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists. However, a large proportion of CKD patients do not respond sufficiently to these treatments. GLP-1 receptor agonists represent a class of antidiabetic and nephroprotective drugs that are very promising in improving the prognosis of patients with CKD, especially if associated with one of the above-mentioned classes. In this article, we discuss the direct and indirect mechanisms through which one of the GLP-1 agonists, semaglutide, ensures nephro- and cardioprotection in patients with CKD and type 2 diabetes.

Early subclinical rejection treated with low dose i.v. steroids is not associated to graft survival impairment: 13-years' experience at a single center.

Subclinical rejection (SCR) has been variably associated with reduced graft survival, development and progression of interstitial fibrosis/tubular atrophy and chronic allograft nephropathy, but data are controversial concerning SCR treatment in terms of graft survival improvement. In this single-center retrospective study, we enrolled 174 adult kidney transplant recipients with a protocol biopsy performed at 30 days after transplantation to evaluate the incidence rate and risk factors for early SCR and its impact on 10-year graft survival. Five patients showed primary non function and were excluded. Among 159/169 (94.08 %) patients with stable graft function who underwent protocol biopsy, 17 (10.7 %) showed signs of SCR and were treated with low-dose intravenous (i.v.) steroids. Ten patients showed functional impairment, 8 (4.73 %) resulting as acute rejection. At multivariate analysis, donor age [odds ratio (OR) 1.04, 95 % confidence interval (CI) 1.01-1.09], and delayed graft function (DGF) (OR 1.08, 95 % CI 1.03-1.12) were significantly associated with SCR. The 10-year graft survival rate in the SCR group was similar to that in the normal-findings group (76.5 vs. 74.9 % respectively; p = 0.61). At multivariate Cox regression, acute [hazard ratio (HR) 5.22, 95 % CI 1.70-16.01], but not sub-clinical, rejection was independently associated with long-term graft failure. In conclusion, early protocol biopsy is a useful and safe tool to detect early SCR which seems not to affect the long-term survival. We suggest that this could be, probably, linked to early SCR treatment with low dose i.v. steroids.

Anthropometric measures can better predict high blood pressure in adolescents.

BACKGROUND: Among children, obesity and overweight may be predictors of cardiovascular (CV) risk. The purpose of this study was to examine whether body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR) were related to blood pressure (BP) among healthy southern Italian students enrolled in 3 different secondary schools. METHODS: Weight, height, BP and WC were measured; BMI and WHtR were calculated for 872 Italian students. Based on percentiles of BMI, the subjects were classified as underweight, normal weight, overweight or obese. Systolic BP or diastolic BP >95th percentile were considered as high BP values (according to the 2004 guidelines of the US National Heart, Lung, and Blood Institute). Central obesity was defined as WC >75th percentile or WHtR =0.5. RESULTS: Of the students, 8.7% were obese, 29% with WC >75th percentile and 29.5% with WHtR >0.5, while 4.6% showed high BP. Logistic regression showed a strong correlation between BMI and high BP (odds ratio [OR] = 1.030, p<0.0001), between WC and high BP (OR = 1.029, p<0.0001). Also WHtR (OR = 3.403, p<0.0001) was shown to be a predictor of high BP. In the male group, all of the variables considered showed a good capability to predict high BP, while in the females, only BMI (OR = 1.019, p<0.05) and WHtR (OR = 2.685, p<0.05) were associated with high BP. CONCLUSIONS: In this study, we found a different correlation between BMI, WC and BP in the 2 subgroups: males and females. Only WHtR showed a significant ability to predict high BP in both groups. WHtR might represent an easily measurable anthropometric index and a better predictor of CV risk in adolescents.

[Acute renal failure in the course of Hashimoto's thyroiditis]. / Insufficienza renale acuta in corso di tiroidite di Hashimoto.

Hashimoto's thyroiditis is the commonest form of autoimmune thyroiditis in the world. It occurs most frequently in women (female/male ratio, 6:1) in the age group between 30 and 60 years. Here we report the case of a 38-year-old Caucasian man who presented with a few days' history of upper limb paresthesias, widespread joint and muscle pain, and headaches. Laboratory findings showed increased CPK, myoglobin and plasma creatinine levels with acute renal failure. Low free T3 and T4 values associated with a high TSH value, the presence of antithyroid globulin and peroxidase autoantibodies pointed to a diagnosis of hypothyroidism with Hashimoto's thyroiditis. Treatment with levothyroxine was initiated and within 2 months normalization of renal function, myoglobin, CPK and thyroid hormone levels was observed.

Impact of body mass index on graft loss in normal and overweight patients: retrospective analysis of 206 renal transplants.

BACKGROUND: Excess body mass is increasingly prevalent in transplant recipients. Currently, most investigators consider body mass index (BMI) a categorical variable, which assumes that all risk factors and transplant outcomes will be similar in all patients within the same category. We investigated the effect of categorical and continuous BMI increments on renal transplant outcome in normal weight (NW: BMI 18.5-24.9) and overweight (OW: BMI 25-30) patients. METHODS: We retrospectively studied 206 patients. The mean BMI of our population was 24.3 ± 2.83 kg/m(2) . Patients of each group were similar regarding age, gender, time on dialysis, donor type, cold ischemia time, and number of HLA mismatches. The independent association of BMI with survival was determined using Cox multivariate regression. RESULTS: OW patients showed a higher prevalence of co-morbidities. In patients with graft loss, there was a higher incidence of delayed graft function, chronic allograft nephropathy, acute rejection, and hypertension. Graft survival was significantly lower in OW patients compared to NW patients upon Kaplan-Meier analysis (p = 0.008). In a multivariate Cox regression analysis, the initial BMI, evaluated as a continuous variable, remained an independent predictor of graft loss (hazard ratio 1.21, 95% CI 1.04-1.47). However, with patient stratification into World Health Organization BMI category and, further, into quartiles of initial BMI, no significant correlation between BMI category and graft loss was found. CONCLUSION: We suggest that increasing BMI value, although without categorical variation, may represent an independent risk factor for graft loss. Our retrospective analysis of a small sample population will require further studies to confirm these data.

Prospective study of BKV nephropathy in 117 renal transplant recipients.

Nephropathy caused by poliomavirus (BKVAN) in transplant recipients is responsible for the loss of the transplanted organ. In this study we suggest a non-invasive diagnostic protocol for the early identification of BKVAN during follow-up treatments. In 117 kidney transplant recipients follow-up was performed every three months during a two year period after transplantation and a positive screening result was confirmed and assessed by quantitative assays (BKV DNA load in plasma and urine). The definitive diagnosis of BKV requires allograft biopsy. Of the 117 patients 4 had BKVAN (3.4%), and the consequential reduction of immunosuppression improved kidney function and plasma clearance of the virus was achieved.

Antiendomysial antibodies in Berger's disease.

The finding of increased levels of immunoglobulin A (IgA) against food antigens in patients with IgA nephropathy prompted the hypothesis of an association between IgA nephropathy and celiac disease (CD). Attention was initially directed to antigliadin antibodies, then to IgA antiendomysial antibodies (IgA-EMA). IgG1-EMA have been found in patients with CD with IgA-EMA-negative results. The presence of IgA- and IgG1-EMA was investigated in 36 patients with IgA nephropathy, 15 patients with other primary glomerulonephritis, and 15 patients with lupus nephritis. IgA-EMA and IgG1-EMA were detected by indirect immunofluorescence analysis. At the time of renal biopsy, the following factors were evaluated: history of macroscopic hematuria, serum creatinine level, urinalysis, 24-hour proteinuria, blood pressure, and histological classification of IgA nephropathy. Sixteen of 36 patients with IgA nephropathy (44.4%) showed EMA positivity. Among patients with positive EMA, 12 patients (75%) were IgG1-EMA positive, 2 patients (12.5%) were IgA-EMA positive, and 2 patients (12.5%) were positive for both isotypes. No significant differences were observed between the two groups (EMA positive versus EMA negative) concerning age, serum creatinine level, macroscopic hematuria, blood pressure, 24-hour proteinuria, or degree of renal histological involvement. IgA- and IgG1-EMA were not detected in patients with other primary nephropathies or lupus nephritis. These results, based on the finding of IgG1-EMA, suggest a common pathogenetic pathway for CD and IgA nephropathy. On this basis, the presence of IgG1-EMA and/or IgA-EMA should be investigated in patients with IgA nephropathy. Furthermore, the role of a gluten-free diet in the natural history of IgA nephropathy, at least in EMA-positive patients, needs to be ascertained.