Abstract Background The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in clinical practice, but current management of hyponatremia and ...outcomes in patients with SIADH are not well understood. The objective of the Hyponatremia Registry was to assess the current state of management of hyponatremia due to SIADH in diverse hospital settings, specifically: which diagnostic and treatment modalities are currently employed and how rapidly and reliably they result in an increase in serum Na+ . A secondary objective was to determine whether treatment choices and outcomes differ across the United States (US) and the European Union (EU). Methods The HN Registry recorded selected diagnostic measures and utilization, efficacy, and outcomes of therapy for euvolemic HN diagnosed clinically as SIADH in 1,524 adult patients with serum sodium concentration (Na+ ) ≤130 mEq/L (1,034 from 146 US and 490 from 79 EU sites). A subgroup of patients with more rigorously defined SIADH via measurement of relevant laboratory parameters was also analyzed. Results The most common monotherapy treatments for hyponatremia in SIADH were fluid restriction (48%), isotonic (27%) or hypertonic (6%) saline, and tolvaptan (13%); 11% received no active agent. The mean rate of Na+ change (mEq/L/d) was greater for all active therapies than no active treatment. Hypertonic saline and tolvaptan produced the greatest mean rate of Na+ change (IQR both 3.0(6.0) mEq/L/d), compared to lower IQR rates of Na+ change for isotonic saline (1.5(3.0) mEq/L/d) and fluid restriction (1.0(2.3) mEq/L/d). The general pattern of responses was similar in both the US and EU cohorts. At discharge, Na+ was <135 mEq/L in 75% of patients and ≤130 mEq/L in 43%. Overly rapid correction occurred in 10.2%. Conclusions 1) Current treatment of hyponatremia in SIADH often employs therapies with limited efficacy; the most commonly chosen monotherapy treatments, fluid restriction and isotonic saline, failed to increase the serum Na+ by ≥5 mEq/L in 55% and 64% of monotherapy treatment episodes, respectively. 2) Appropriate laboratory tests to diagnose SIADH were obtained in <50% of patients; success rates in correcting hyponatremia were significantly higher when such tests were obtained. 3) Few outcome differences were found between the US and EU. A notable exception was hospital length of stay; use of tolvaptan was associated with significantly shorter length of stay in the EU but not the US. 4) Despite the availability of effective therapies, most patients with SIADH were discharged from the hospital still hyponatremic.
In this study, we investigated if the therapeutic potential of peripheral blood mononuclear cell (PBMC) therapy in a murine model of ischemic AKI is related with the survival pattern of ...monocyte/macrophages in tissue. CD-1 mice were subjected to bilateral renal ischemia followed by reperfusion to induce AKI. M2-polarized PBMCs isolated from CD-1 mice were administered intravenously at different time points post-injury. Our results demonstrate that early administration of PBMC therapy attenuates renal tissue damage, reduces tissue cell death and prevents fibrosis development. Reduction of tissue pyroptosis was observed by reduction on NLRP3 inflammasome activation and decreasing IL-1beta and Caspase-1 expression in the kidney. Furthermore, the therapy was shown to mitigate ferroptosis by inducing GPX4 overexpression. Early administration of PBMCs increased the survival pattern of renal tissue-macrophages, promoting a “pro-survival phenotype” resulting in decreased pyroptotic marker NLRP3, IL-1beta and Caspase 1 and increased anti-ferroptotic gene GPX4. Conversely, delayed administration of PBMC therapy exhibits diminished efficacy in preventing cell death and fibrosis in tissue and provoked a decrease in the pro-survival phenotype of both monocyte /macrophages in tissue. Our findings highlight the therapeutic potential of PBMC therapy in mitigating AKI and preventing CKD progression by modulating tissue-resident macrophage survival and reducing their cell death pathways. The fact that the effectiveness of the therapy depends on the time of administration after the injury underscores the importance of early intervention in AKI management.
Display omitted
•M2-polarized PBMC protects from pyroptosis and ferroptosis derived AKI.•M2-polarized PBMC reduces inflammation and fibrosis associated to AKI.•M2-polarized PBMC therapy enhanced the survival pattern of renal monocytes/macrophages if therapy were performed in early ischemia/ reperfusion.•M2-polarized PBMC therapy decreased the survival pattern of renal monocytes/macrophages if therapy were performed in late ischemia/ reperfusion.•Monocyte/macrophage survival phenotypes in tissue depends on tissue microenvironment.
Background & Aims The Acute Kidney Injury Network (AKIN) criteria are widely used in nephrology, but information on cirrhosis is limited. We aimed at evaluating the AKIN criteria and their ...relationship with the cause of kidney impairment and survival. Methods We performed a prospective study of 375 consecutive patients hospitalized for complications of cirrhosis. One-hundred and seventy-seven (47%) patients fulfilled the criteria of Acute Kidney Injury (AKI) during hospitalization, the causes being hypovolemia, infections, hepatorenal syndrome (HRS), nephrotoxicity, and miscellaneous (62, 54, 32, 8, and 21 cases, respectively). Results At diagnosis, most patients had AKI stage 1 (77%). Both the occurrence of AKI and its stage were associated with 3-month survival. However, survival difference between stages 2 and 3 was not statistically significant. Moreover, if stage 1 patients were categorized into 2 groups according to the level of serum creatinine used in the classical definition of kidney impairment (1.5 mg/dl), the two groups had a significantly different outcome. Combining AKIN criteria and maximum serum creatinine, 3 risk groups were identified: (A) patients with AKI stage 1 with peak creatinine ⩽1.5 mg/dl; (B) patients with stage 1 with peak creatinine >1.5 mg/dl; and (C) patients with stages 2–3 (survival 84%, 68%, and 36%, respectively; p <0.001). Survival was independently related to the cause of kidney impairment, patients with HRS or infection-related having the worst prognosis. Conclusions A classification that combines the AKIN criteria and classical criteria of kidney failure in cirrhosis provides a better risk stratification than AKIN criteria alone. The cause of impairment in kidney function is key in assessing prognosis in cirrhosis.
We propose the use of a peripheral blood mononuclear cell therapy based on cell NGAL release to be used in the clinical setting for acute kidney injury (AKI) and the derived fibrosis. First, we ...designed a procedure whereby PBMC overexpress NGAL and anti-inflammatory agents when subjected to repetitive anoxia/reoxygenation (PBMC (A/R)). Using an in vivo AKI model, we observed that PBMC(A/R) reduces BUN and creatinine levels in blood and inflammation, enhances anti-inflammation, induces proliferation of tubular epithelial cells and reduces AKI-induced fibrosis. Flow cytometry analysis evidenced that monocytes are the only cells accumulated in the injured kidney and phenotype analysis of freshly isolated kidney macrophages, revealed that the healing phenotype is maintained the time needed for recovery. NGAL release from PBMC(A/R) determines the beneficial effect of the therapy since administration of a NGAL antibody previous to the therapy or injection of PBMC(A/R) obtained from NGAL KO animals abolished the beneficial effects. CD11b–NGAL positive cells were enhanced in tissue after PBMC (A/R) therapy and were produced by the injected monocytes. In an in vitro model with tubular epithelial cells (NRK52e) we proved that NGAL release by PBMC(A/R) induced epithelial proliferation and activation of PI3K/Akt pathway.
Display omitted
•PBMC polarized by repetitive anoxia/ reoxygenation overexpress NGAL.•NGAL release from polarized PBMC induces antiinflammation and proliferation.•Therapy with PBMC polarized induces kidney repair and antiinflammation.•Therapy with PBMC polarized prevents kidney fibrosis associated to acute kidney injury.
In an overwhelming demand scenario, such as the SARS-CoV-2 pandemic, pressure over health systems may outburst their predicted capacity to deal with such extreme situations. Therefore, in order to ...successfully face a health emergency, scientific evidence and validated models are needed to provide real-time information that could be applied by any health center, especially for high-risk populations, such as transplant recipients. We have developed a hybrid prediction model whose accuracy relative to several alternative configurations has been validated through a battery of clustering techniques. Using hospital admission data from a cohort of hospitalized transplant patients, our hybrid Data Envelopment Analysis (DEA)—Artificial Neural Network (ANN) model extrapolates the progression towards severe COVID-19 disease with an accuracy of 96.3%, outperforming any competing model, such as logistic regression (65.5%) and random forest (44.8%). In this regard, DEA-ANN allows us to categorize the evolution of patients through the values of the analyses performed at hospital admission. Our prediction model may help guiding COVID-19 management through the identification of key predictors that permit a sustainable management of resources in a patient-centered model.
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, ...probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC).
Highlights
Following a positive screening test, no further studies are needed for diagnosis of PA if a plasma aldosterone concentration (PAC) > 20 ng/dL and a low circulating direct renin or plasma renin activity (PRA) are detected in a patient with spontaneous hypokalemia.
In all other patients, one (or more) of four different tests is (are) currently recommended: the fludrocortisone suppression test, the oral salt loading test, the intravenous saline test, and/or the captopril challenge test.
In all cases, hypokalemia must be corrected prior to testing.
Interfering medication must be progressively withdrawn before testing, while introducing alpha-1 adrenergic blockers, long-acting non-dihydropyridine calcium antagonists, and/or hydralazine as needed for control of hypertension.
All but the captopril challenge test run the risk of inducing hypokalemia, fluid overload, and a worsening of hypertension.
In the case of borderline results, the initial test employed can be repeated, or a second test performed. Patients with both a negative saline infusion and captopril challenge test appear to be at a low risk for harboring unilateral disease, whereas those positive for both are more likely to exhibit unilateral aldosterone secretion than when tests render conflicting results.
Patients showing a positive screening aldosterone to renin ratio (ARR) with normal/high PAC and a low renin/PRA, yet with negative diagnostic testing, presenting mild hyperaldosteronism, can benefit from targeted therapy of hypertension with mineralocorticoid receptor antagonists.
La vía de suplementación óptima (intravenosa vs. oral) de hierro en pacientes con enfermedad renal crónica (ERC) no en diálisis es controvertida. Recientemente se ha desarrollado una preparación oral ...(hierro liposomal, FeSu) con elevada biodisponibilidad y baja incidencia de efectos secundarios. El objetivo fue evaluar la eficacia del FeSu en pacientes con ERC estadio 3 y limitación digestiva a la ferroterapia oral convencional.
Estudio observacional prospectivo con pacientes con ERC estadio 3 estable e intolerancia digestiva a la ferroterapia oral convencional. Se administró una dosis de FeSu de 30mg/día oral durante 12 meses. El objetivo primario fue el aumento de la hemoglobina a los 6 y 12 meses. También se evaluó la adherencia terapéutica y efectos adversos.
Se incluyeron 37 pacientes de 72,6±14,7 años y un filtrado glomerular estimado de 42±10mL/min/1,73m2. Treinta y dos pacientes habían recibido tratamiento previo con formulaciones orales convencionales, manifestando el 73% intolerancia digestiva con una adherencia del 9,4%. Tras 6 meses con FeSu se objetivó un incremento de las cifras de hemoglobina respecto a la basal, manteniéndose a los 12 meses (0,49±0,19 y 0,36±0,19g/dL, respectivamente, p<0,05), y pese a un descenso significativo del filtrado glomerular estimado de 3,16±1,16 y 4,20±1,28mL/min/1,72 m2 a los 6 y 12 meses, respectivamente. Ningún paciente presentó reacciones adversas que obligaran a suspender el tratamiento. La adherencia fue del 100% en ambos momentos analizados.
El FeSu es eficaz en una cohorte de pacientes con ERC estadio 3 de características extrapolables a la población general de pacientes con ERC moderada, con una baja tasa de reacciones adversas y excelente tolerabilidad.
The optimal iron supplementation route of administration (intravenous vs oral) in patients with chronic kidney disease (CKD) not on dialysis is a hot topic of debate. An oral preparation (liposomal iron, FeSu) has recently been developed with high bioavailability and low incidence of side effects. The objective was to evaluate the efficacy of FeSu in patients with stage 3 CKD and gastrointestinal intolerance to conventional oral iron therapy.
Prospective observational study of patients with stable stage 3 CKD and gastrointestinal intolerance to conventional oral iron therapy. An oral 30mg/day dose of FeSu was administered for 12 months. The primary outcome measure was haemoglobin increase at 6 and 12 months. Treatment adherence and adverse effects were also evaluated.
37 patients aged 72.6±14.7 years and with an estimated glomerular filtration rate (eGFR) of 42±10ml/min/1.73m2 were included. 32 patients had received previous treatment with conventional oral formulations, 73% of which exhibited gastrointestinal intolerance with treatment adherence of 9.4%. After 6 months with FeSu, an increase in haemoglobin was observed versus baseline, which was sustained at 12 months (0.49±0.19 and 0.36±0.19g/dl, respectively, P<.05), despite a significant eGFR decrease of 3.16±1.16 and 4.20±1.28ml/min/1.73 m2 at 6 and 12 months, respectively. None of the patients experienced adverse reactions that required the treatment to be suspended. Adherence was 100% at both 6 and 12 months.
FeSu is effective in a cohort of patients with stage 3 CKD with similar characteristics to the general population of moderate CKD patients, with a low rate of adverse reactions and excellent tolerability.
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to ...provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC).
Keypoints
The treatment of choice for PA is medical therapy with mineralocorticoid receptor blockade for bilateral cases and unilateral adrenalectomy for unilateral PA.
The goals of PA treatment are to normalize blood pressure (BP) and excessive aldosterone production, with the final aim of improving associated comorbidities and reducing mortality.
Spironolactone is usually the mineralocorticoid receptor antagonist (MRA) of choice for medical treatment of PA. However, eplerenone has a similar efficacy to that of spironolactone when used in doses 2–3 times higher than the latter and administered 2–3 times a day.
Eplerenone has the advantage of not inducing the anti-androgenic side effects commonly seen with spironolactone.
Adrenalectomy is the gold standard procedure used to remove the aldosterone-hypersecreting adrenal tissue.
The Primary Aldosteronism Outcome (PASO) group criteria are recommended for defining the control objectives of biochemical and clinical response to treatment.
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.
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).
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.
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.
PDF
