Precision medicine: "Point of Care Ultrasound" (PoCUS) in the diagnostic approach to the patient with hyponatremia.

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume (ECV). However, ECV determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (POCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's ECV status in combination with the other parameters.

High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation.

Introduction: We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management. Methods: Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n = 71) or MN diagnosed de novo after KT (n = 4). Results: Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P = 0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5-2.5) vs 0.3 (0.1-0.5) g/24 h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR < 30 ml/min: RR = 6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86 vs 1.18; P = 0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring. Conclusions: One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.

Association of severe preeclampsia and vascular damage assessed by noninvasive markers of arterial stiffness.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with high maternal and fetal morbidity and mortality and increased future risk of cardiovascular complications. OBJECTIVE: To analyze whether women who have had PE with severe features in their pregnancy have higher arterial stiffness (AS) parameters than those whose PE course was without signs of severity. METHODS: Sixty-five women who developed PE during their gestation were evaluated, divided into two groups: PE group without severe features or non-severe PE (n=30) and PE group with severe features or severe PE (n=35). Carotid-femoral pulse wave velocity (cfPWV), central augmentation index corrected to a heart rate of 75 beats per minute (AIxc75) and central augmentation pressure (cAP) were determined one month and six months postpartum. Comparison of proportions was carried out using the chi-square test, comparison of means between groups using the Student's t-test or the Mann-Whitney test, and comparison of means of the same group at different evolutionary moments, using the t-test or the Wilcoxon test. Correlation, with and between hemodynamic parameters, was carried out with Spearman's correlation coefficient and the association between demographic variables, personal history and hemodynamic parameters, and altered arterial stiffness parameters was carried out using linear and logistic regression models. RESULTS: Women with severe PE presented, both at 1 and 6 months postpartum, higher values of blood pressure, both central and peripheral, as well as AR and pulse amplification parameters, than those women whose PE was not severe. Central augmentation index (cAIx) values at 1 month and 6 months postpartum were higher, although not significantly, in the severe PE group compared to the non-severe PE group (24.0 (16.5-34.3) vs. 19.0% (14-29) and 24.0 (14.0-30.0) vs. 20.0% (12.3-26.8), respectively). Carotid-femoral pulse wave velocity (cfPWV) was significantly higher at both 1 and 6 months postpartum in the severe PE group compared to the non-severe PE group (10.2 (8.8-10.7) vs. 8.8m/s (8.3-9.6) and 10.0 (8.8-10.6) vs. 8.8m/s (8.3-9.3), respectively). Central systolic pressure and central pulse pressure amplification were also higher, although not significantly, in the severe PE group in comparison with the non-severe PE group. CONCLUSIONS: Women who have had severe PE have more pronounced arterial stiffness parameters than those in whom PE was not particularly severe. The determination of cAIx and cfPWV, as a strategy for the assessment of cardiovascular risk, should be evaluated among women who have had PE.

Growth Differentiation Factor 15: A Biomarker with High Clinical Potential in the Evaluation of Kidney Transplant Candidates.

Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. The median GDF-15 was 5331.3 (50.49-16242.3) pg/mL. After a mean of 90.6 ± 41.5 months of follow-up, 82 (20.8%) patients died. Patients with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (p = 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2-8.8), p = 0.021 and high risk tertiles HR 4.3 95%CI (1.65-11.54), p = 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09, p = 0.039) and 3-year mortality (ΔAUC = 0.11, p = 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates.

Immunosuppression with Calcineurin Inhibitor after Renal Transplant Failure Inhibits Allosensitization.

Immunosuppression withdrawal after graft failure seems to favor sensitization. A high percentage of calculated panel-reactive antibody (cPRA) and the development of de novo donor specific antibodies (dnDSA) indicate human leukocyte antigen (HLA) sensitization and may hinder the option of retransplantation. There are no established protocols on the immunosuppressive treatment that should be maintained after transplant failure. A retrospective analysis including 77 patients who lost their first renal graft between 1 January 2006-31 December 2015 was performed. Two sera were selected per patient, one immediately prior to graft loss and another one after graft failure. cPRA was calculated by Single Antigen in all patients. It was possible to analyze the development of dnDSA in 73 patients. By multivariate logistic regression analysis, the absence of calcineurin inhibitor (CNI) at 6 months after graft failure was related to cPRA > 75% (OR 4.8, CI 95% 1.5-15.0, p = 0.006). The absence of calcineurin inhibitor (CNI) at 6 months after graft loss was significantly associated with dnDSA development (OR 23.2, CI 95% 5.3-100.6, p < 0.001). Our results suggest that the absence of CNI at the sixth month after graft loss is a risk factor for sensitization. Therefore, maintenance of an immunosuppressive regimen based on CNI after transplant failure should be considered when a new transplant is planned, since it seems to prevent HLA allosensitization.