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Introduction: Chronic kidney disease (CKD) of non-inherited etiology is one of the main causes of renal replacement therapy in our setting. Previous studies in other territories suggest that hereditary diseases could be one of the potential causes of this pathology, especially in younger patients. The GENSEN study will evaluate the presence of pathogenic genetic variants in subjects who have developed CKD category G5 before the age of 46 years, of non-inherited etiology., Methods: Observational, prospective, multicenter study, which evaluates the diagnostic utility of massive high-throughput sequencing (HTS) directed to a set of genes, in the identification of the cause of CKD. Patients from all over Spain will be included, from whom a blood or saliva sample will be taken and a panel of 529 genes associated with hereditary kidney disease will be analyzed. This publication communicates the study protocol., Conclusion: The GENSEN study will make it possible to evaluate the diagnostic performance of the gene panel study in young subjects in our setting with the development of CKD category G5 without a clear cause. An etiological diagnosis would offer potential benefits for patients and relatives (targeted therapies, clinical trials, detection of extrarenal manifestations, evaluation of relatives for live donation, estimation of the risk of recurrence in the renal graft, genetic counseling, among others) and would allow to apply this genetic study to the nephrology of our country., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: We compared hair cortisol (HC) with classic tests of the hypothalamic-pituitary-adrenal (HPA) axis in chronic kidney disease (CKD) and assessed its association with kidney and cardiometabolic status., Design and Methods: A cross-sectional study of 48 patients with CKD stages I-IV, matched by age, sex, and BMI with 24 healthy controls (CTR) was performed. Metabolic comorbidities, body composition, and HPA axis function were studied., Results: A total of 72 subjects (age 52.9 ± 12.2 years, 50% women, BMI 26.2 ± 4.1 kg/m 2 ) were included. Metabolic syndrome features (hypertension, dyslipidaemia, glucose, HOMA-IR, triglycerides, waist circumference) and 24-h urinary proteins increased progressively with worsening kidney function (p < 0.05 for all). Reduced cortisol suppression after 1-mg dexamethasone suppression (DST) (p < 0.001), a higher noon (12:00 h pm) salivary cortisol (p = 0.042), and salivary cortisol AUC (p = 0.008) were seen in CKD. 24-h urinary-free cortisol (24-h UFC) decreased in CKD stages III-IV compared with I-II (p < 0.001); higher midnight salivary cortisol (p = 0.015) and lower suppressibility after 1-mg DST were observed with declining kidney function (p < 0.001). Cortisol-after-DST cortisol was >2 mcg/dL in 23% of CKD patients (12.5% in stage III and 56.3% in stage IV); 45% of them had cortisol >2 mcg/dL after low-dose 2-day DST, all in stage IV (p < 0.001 for all). Cortisol-after-DST was lineally inversely correlated with eGFR (p < 0.001). Cortisol-after-DST (OR 14.9, 95% CI 1.7-103, p = 0.015) and glucose (OR 1.3, 95% CI 1.1-1.5, p = 0.003) were independently associated with eGFR <30 mL/min/m 2 ). HC was independently correlated with visceral adipose tissue (VAT) (p = 0.016). Cortisol-after-DST (p = 0.032) and VAT (p < 0.001) were independently correlated with BMI., Conclusion: Cortisol-after-DST and salivary cortisol rhythm present progressive alterations in CKD patients. Changes in cortisol excretion and HPA dynamics in CKD are not accompanied by significant changes in long-term exposure to cortisol evaluated by HC. The clinical significance and pathophysiological mechanisms explaining the associations between HPA parameters, body composition, and kidney damage warrant further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Boswell, Vega-Beyhart, Blasco, Quintana, Rodríguez, Díaz-Catalán, Vilardell, Claro, Mora, Amor, Casals and Hanzu.)

Chronic kidney disease (CKD) is an increasing cause of morbidity and mortality worldwide. Besides the higher prevalence of diabetes, hypertension and aging worldwide, immune mediated disorders remain an important cause of kidney disease and are especially prevalent in young adults. Regardless of the initial insult, final pathway to CKD and kidney failure is always the loss of normal tissue and fibrosis development, in which the dynamic equilibrium between extracellular matrix synthesis and degradation is disturbed, leading to excessive production and accumulation. During fibrosis, a multitude of cell types intervene at different levels, but myofibroblasts and inflammatory cells are considered critical in the process. They exert their effects through different molecular pathways, of which transforming growth factor β (TGF-β) has demonstrated to be of particular importance. Additionally, CKD itself promotes fibrosis due to the accumulation of toxins and hormonal changes, and proteinuria is simultaneously a manifestation of CKD and a specific driver of renal fibrosis. Pathways involved in renal fibrosis and CKD are closely interrelated, and although important advances have been made in our knowledge of them, it is still necessary to translate them into clinical practice. Given the complexity of this process, it is highly likely that its treatment will require a multi-target strategy to control the origin of the damage but also the mechanisms that perpetuate it. Fortunately, rapid technology development over the last years and new available drugs in the nephrologist's armamentarium give reasons for optimism that more personalized assistance for CKD and renal fibrosis will appear in the future., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acute kidney injury (AKI) increases early mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients and may accelerate chronic kidney disease (CKD) development. We analyzed prospective variables related to AKI and CKD in 422 allo-HCT recipients to establish risk factors of severe acute renal failure and CKD. Renal function and creatinine were periodically assessed from baseline till the last follow-up. Sixty-three patients (14%) developed severe AKI (AKI-3) at 100 days post transplant and 15% at 12 months. Variables associated with AKI-3 were age above 55 years [hazard ratio (HR): 2.4; p = 0.019], total body irradiation (TBI) (HR: 1.8; p = 0.044), high-risk cytomegalovirus reactivation (HR: 1.8; p = 0.041), and methotrexate as GVHD prophylaxis (HR: 2.1; p = 0.024). AKI-3 increased the mortality risk (HR: 2.5, 95% confidence interval: 1.9-3.4). The CKD prevalence in 161 living patients was 10.2% at the last follow-up and in most, CKD developed 1 year post HCT, independent of AKI. The CKD at 1 year post HCT was associated with increased mortality (HR: 3.54; p < 0.001). Interestingly, pretransplant CKD was associated with early mortality (HR: 5.6; p < 0.001). In fact, pre- and posttransplant CKD had independent unfavorable long-term outcomes. These pretransplant factors can potentially be targeted to improve allo-HCT outcomes.

Background: Monoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. However, its interpretation is altered in patients with chronic kidney disease (CKD). This study aims to evaluate the modification of the sFLC ratio reference range in patients with CKD, and propose an optimal range for patients with CKD., Methods: Serum FLC κ/λ ratio and estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 113 control patients (without hematologic disease), 63 patients with MM in complete remission and 347 patients with active MM. The three groups included patients with CKD (eGFR < 90)., Results: In the group of patients without active MM (n = 176), the sFLC ratio increased at different stages of CKD without pathological significance, with an increase in the number of false positives specially when eGFR is ≤55 ml/min. An optimal range was established for patients with eGFR ≤55 ml/min/1.73 m2: 0.82-3,6 with maximum sensitivity + specificity for that group with an improvement in the Area under the curve (AUC), 0.91 (0.84-0.97) compared with the current ranges proposed by Katzmann and Hutchinson., Conclusions: This study confirms the influence of eGFR on the interpretation of the sFLC ratio, showing a decreasing specificity in progressive CKD stages when using the reference sFLC range (Katzmann), especially in patients with eFGR ≤55. According to our results, we suggest a modified optimal range (0.82-3,6) for eGFR ≤55 ml/min/1.73 m2. It is necessary to validate this modified range in larger and prospective studies.

IgA nephropathy (IgAN), a frequent cause of chronic kidney disease worldwide, is characterized by mesangial deposition of galactose-deficient IgA1-containing immune complexes. Complement involvement in IgAN pathogenesis is suggested by the glomerular deposition of complement components and the strong protection from IgAN development conferred by the deletion of the CFHR3 and CFHR1 genes (Δ CFHR3-CFHR1 ). Here we searched for correlations between clinical progression and levels of factor H (FH) and FH-related protein 1 (FHR-1) using well-characterized patient cohorts consisting of 112 patients with IgAN, 46 with non-complement-related autosomal dominant polycystic kidney disease (ADPKD), and 76 control individuals. Patients with either IgAN or ADPKD presented normal FH but abnormally elevated FHR-1 levels and FHR-1/FH ratios compared to control individuals. Highest FHR-1 levels and FHR-1/FH ratios are found in patients with IgAN with disease progression and in patients with ADPKD who have reached chronic kidney disease, suggesting that renal function impairment elevates the FHR-1/FH ratio, which may increase FHR-1/FH competition for activated C3 fragments. Interestingly, Δ CFHR3-CFHR1 homozygotes are protected from IgAN, but not from ADPKD, and we found five IgAN patients with low FH carrying CFH or CFI pathogenic variants. These data support a decreased FH activity in IgAN due to increased FHR-1/FH competition or pathogenic CFH variants. They also suggest that alternative pathway complement activation in patients with IgAN, initially triggered by galactose-deficient IgA1-containing immune complexes, may exacerbate in a vicious circle as renal function deterioration increase FHR-1 levels. Thus, a role of FHR-1 in IgAN pathogenesis is to compete with complement regulation by FH., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Continuous ionic dialysance monitoring is a useful clinical tool to determine the dialysis dose in real time in each hemodialysis session. We followed up 49 patients for 16 months. Six patients with a Kt reduction of ≥20% in >3 consecutive hemodialysis sessions were identified. Fistulography demonstrated significant stenosis in all 6 patients. Angioplasty was performed in 5 with an excellent angiographic result and optimal Kt levels were restored. Unexplained and persistent Kt reduction in patients with stable chronic kidney disease under hemodialysis could represent, together with an accurate vascular access examination, a practical and additional indirect method for the early detection of vascular access dysfunction., (© 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.)