Plasma glycocalyx pattern: a mirror of endothelial damage in chronic kidney disease.

Background: Endothelial damage and cardiovascular disease complicate chronic kidney disease (CKD). The increased atherogenicity observed in patients with CKD can be linked to microinflammation and endothelial damage. Circulating endothelial glycocalyx degradation products, such as perlecan and decorin, tend to be elevated in CKD. We aimed to explore the association between the plasma perlecan and decorin levels and this pro-inflammatory and atherogenic state by studying monocyte subpopulations and intracellular adhesion molecule (ICAM)-1 expression in patients with CKD. Methods: We studied 17 healthy controls, 23 patients with advanced CKD, 25 patients on haemodialysis, 23 patients on peritoneal dialysis and 20 patients who underwent kidney transplantation. Perlecan and decorin levels were evaluated using enzyme-linked immunosorbent assays, and the monocyte phenotype was analysed using direct immunofluorescence and flow cytometry. Results: The plasma perlecan levels were higher in patients with CKD than in the healthy controls. These levels were associated with a higher prevalence of ICAM-1+ monocytes. Conversely, patients with advanced CKD (pre-dialysis) had higher plasma decorin levels, which were associated with a reduced ICAM-1 expression per monocyte. Conclusions: Elevated perlecan levels in CKD may be associated with a higher prevalence of ICAM-1+ monocytes and a pro-inflammatory phenotype. Elevated decorin levels may act as a negative regulator of ICAM-1 expression in monocytes. Therefore, perlecan and decorin may be related to inflammation and monocyte activation in CKD and may act as potential markers of endothelial damage.

Effect of Kidney Transplantation on Accelerated Immunosenescence and Vascular Changes Induced by Chronic Kidney Disease.

Kidney transplantation is the best option for patients with end-stage renal disease. Despite the improvement in cardiovascular burden (leading cause of mortality among patients with chronic kidney disease), cardiovascular adverse outcomes related to the inflammatory process remain a problem. Thus, the aim of the present study was to characterize the immune profile and microvesicles of patients who underwent transplantation. We investigated the lymphocyte phenotype (CD3, CD4, CD8, CD19, and CD56) and monocyte phenotype (CD14, CD16, CD86, and CD54) in peripheral blood, and endothelium-derived microvesicles (annexin V+CD31+CD41-) in plasma of patients with advanced chronic kidney disease (n = 40), patients with transplantation (n = 40), and healthy subjects (n = 18) recruited from the University Hospital "12 de Octubre" (Madrid, Spain). Patients with kidney transplantation had B-cell lymphopenia, an impairment in co-stimulatory (CD86) and adhesion (CD54) molecules in monocytes, and a reduction in endothelium-derived microvesicles in plasma. The correlations between those parameters explained the modifications in the expression of co-stimulatory and adhesion molecules in monocytes caused by changes in lymphocyte populations, as well as the increase in the levels of endothelial-derived microvesicles in plasma caused by changes in lymphocyte and monocytes populations. Immunosuppressive treatment could directly or indirectly induce those changes. Nevertheless, the particular characteristics of these cells may partly explain the persistence of cardiovascular and renal alterations in patients who underwent transplantation, along with the decrease in arteriosclerotic events compared with advanced chronic kidney disease. In conclusion, the expression of adhesion molecules by monocytes and endothelial-derived microvesicles is related to lymphocyte alterations in patients with kidney transplantation.

The Forgotten Antiproteinuric Properties of Diuretics.

BACKGROUND: Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. SUMMARY: Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.

Beneficial long-term effect of aldosterone antagonist added to a traditional blockade of the renin–angiotensin–aldosterone system among patients with obesity and proteinuria / Efecto beneficioso a largo plazo de la incorporación de un antagonista de la aldosterona a un tradicional bloqueo del sistema renina-angiotensina-aldosterona en pacientes con obesidad y proteinuria

Introduction: Over the past decade, obesity has become a risk factor for developing chronic kidney disease. Proteinuria is known to be an independent determinant of the progression of chronic kidney disease, and adipose tissue is a recognized source of components of the renin–angiotensin–aldosterone system (RAAS). Recent studies have shown that plasma aldosterone levels are disproportionately higher in patients with obesity. Drugs that block the RAAS are unable to inhibit aldosterone in the long term. The aim of our study was to analyze the renoprotective effect of an aldosterone antagonist in combination with RAAS blockers in patients with obesity and proteinuric nephropathy. Material and methods: This study is a substudy of previously published study on the renoprotective effect of mineralocorticoid receptor blockers in patients with proteinuric nephropathies. Patients with proteinuria levels >1g/24h who were taking spironolactone and were being treated with other RAAS blockers were divided according to body mass index (BMI) into an obesity group (BMI ≥30kg/m2) and a control group. Results: Seventy-one patients were included in the study, with a mean age of 56.7±15.1 years. More than 50% of the patients in both groups had diabetes. Thirty-two patients were included in the obesity group and 39 were included in the control group. There were no significant differences in renal function, proteinuria, blood pressure, serum potassium levels and the percentage of RAAS blockers in both groups. After a follow-up of 28.9 (14–84) months, there was a 59.4% reduction in proteinuria in the obesity group (2.8±2.1 vs. 1.3±1.6g/24h, p<.05). The reduction in proteinuria was greater than 50% in 22 (68.8%) cases, and the mean blood pressure showed a significant decrease (from 100.6±9 to 92.1±7.4mm Hg, p<.05). The control group showed a 69.6% reduction in proteinuria (1.9±1.4 to 0.8±0.5, p<0.05). The reduction of proteinuria was higher than 50% in 22 (68.8%) cases in obese patients and in 33 (84.6%) cases in non-obese group. Renal function remained stable in both groups during the follow-up. Nine patients (28.1%) in the obesity group experienced gynecomastia. The incidence of hyperkalemia was similar for the 2 groups (6.3%). Conclusion: Aldosterone antagonist treatment in obese patients with proteinuric nephropathies induces a drastic and sustained reduction in proteinuria but not more than the non-obese group. There was a trend toward slowing progression of renal failure with few adverse events (AU)

Introducción: Durante la última década, la obesidad se ha convertido en un factor de riesgo para el desarrollo de la enfermedad renal crónica. La proteinuria está considerada un factor independiente de la progresión de la enfermedad renal crónica y el tejido adiposo se reconoce como una fuente de los componentes del sistema renina-angiotensina-aldosterona (SRAA). Estudios recientes han demostrado que los niveles de aldosterona plasmática son desproporcionadamente mayores en pacientes con obesidad. Los fármacos que bloquean el SRAA son incapaces de inhibir la aldosterona a largo plazo. El objetivo de nuestro estudio fue analizar el efecto protector a nivel renal de un antagonista de la aldosterona en combinación con bloqueadores del SRAA en pacientes con obesidad y nefropatía con proteinuria. Material y métodos: Este estudio es un subestudio del estudio publicado previamente sobre el efecto protector a nivel renal de los bloqueadores del receptor de mineralocorticoides en pacientes con nefropatías con proteinuria. Se dividió a los pacientes con niveles de proteinuria >1 g/24 h que estaban tomando espironolactona y se los trataba con otros bloqueadores del SRAA según el índice de masa corporal (IMC) en un grupo de obesidad (IMC ≥30 kg/m2) y un grupo de control. Resultados: Se incluyó a 71 pacientes en el estudio, con una media de edad de 56,7±15,1 años. Más del 50% de los pacientes en ambos grupos tenía diabetes. Se incluyó a 32 pacientes en el grupo de obesidad y a 39 en el grupo de control. No hubo diferencias significativas en la función renal, proteinuria, presión arterial, niveles de potasio sérico y el porcentaje de bloqueadores del SRAA en ambos grupos. Tras un seguimiento de 28,9 meses (14-84), hubo una reducción del 59,4% de la proteinuria en el grupo de obesidad (2,8±2,1 frente a 1,3±1,6 g/24 h, p<0,05). La reducción de la proteinuria fue superior al 50% en 22 casos (68,8%) y la presión arterial media experimentó una disminución significativa (de 100,6±9 a 92,1±7,4 mm Hg, p<0,05). El grupo de control experimentó una reducción del 69,6% de la proteinuria (de 1,9±1,4 a 0,8±0,5, p<0,05). La reducción de la proteinuria fue superior al 50% en 22 casos (68,8%) en pacientes obesos y en 33 casos (84,6%) en el grupo de no obesos. La función renal de ambos grupos permaneció estable durante el seguimiento. En 9 pacientes (28,1%) del grupo de obesidad se observó ginecomastia. La incidencia de hiperpotasemia fue similar en los 2 grupos (6,3%). Conclusión: El tratamiento con un antagonista de la aldosterona en pacientes obesos con nefropatías con proteinuria induce una reducción drástica y sostenida de la proteinuria, pero no superior a la del grupo de no obesos. La tendencia fue frenar la progresión de la insuficiencia renal con pocos eventos adversos (AU)

Beneficial long-term effect of aldosterone antagonist added to a traditional blockade of the renin-angiotensin-aldosterone system among patients with obesity and proteinuria.

INTRODUCTION: Over the past decade, obesity has become a risk factor for developing chronic kidney disease. Proteinuria is known to be an independent determinant of the progression of chronic kidney disease, and adipose tissue is a recognized source of components of the renin-angiotensin-aldosterone system (RAAS). Recent studies have shown that plasma aldosterone levels are disproportionately higher in patients with obesity. Drugs that block the RAAS are unable to inhibit aldosterone in the long term. The aim of our study was to analyze the renoprotective effect of an aldosterone antagonist in combination with RAAS blockers in patients with obesity and proteinuric nephropathy. MATERIAL AND METHODS: This study is a substudy of previously published study on the renoprotective effect of mineralocorticoid receptor blockers in patients with proteinuric nephropathies. Patients with proteinuria levels >1g/24h who were taking spironolactone and were being treated with other RAAS blockers were divided according to body mass index (BMI) into an obesity group (BMI ≥30kg/m2) and a control group. RESULTS: Seventy-one patients were included in the study, with a mean age of 56.7±15.1 years. More than 50% of the patients in both groups had diabetes. Thirty-two patients were included in the obesity group and 39 were included in the control group. There were no significant differences in renal function, proteinuria, blood pressure, serum potassium levels and the percentage of RAAS blockers in both groups. After a follow-up of 28.9 (14-84) months, there was a 59.4% reduction in proteinuria in the obesity group (2.8±2.1 vs. 1.3±1.6g/24h, p<.05). The reduction in proteinuria was greater than 50% in 22 (68.8%) cases, and the mean blood pressure showed a significant decrease (from 100.6±9 to 92.1±7.4mm Hg, p<.05). The control group showed a 69.6% reduction in proteinuria (1.9±1.4 to 0.8±0.5, p<0.05). The reduction of proteinuria was higher than 50% in 22 (68.8%) cases in obese patients and in 33 (84.6%) cases in non-obese group. Renal function remained stable in both groups during the follow-up. Nine patients (28.1%) in the obesity group experienced gynecomastia. The incidence of hyperkalemia was similar for the 2 groups (6.3%). CONCLUSION: Aldosterone antagonist treatment in obese patients with proteinuric nephropathies induces a drastic and sustained reduction in proteinuria but not more than the non-obese group. There was a trend toward slowing progression of renal failure with few adverse events.

Diverse diuretics regimens differentially enhance the antialbuminuric effect of renin-angiotensin blockers in patients with chronic kidney disease.

The addition of spironolactone or hydrochlorothiazide enhances the antialbuminuric effect of renin-angiotensin blockers. However, comparative studies on the effect of different diuretics are lacking. We conducted a prospective randomized crossover study to compare the effects of spironolactone (25 mg/day), hydrochlorothiazide (50 mg/day) without/with amiloride (5 mg/day) on top of enalapril treatment in 21 patients with CKD stages 1-3 and a urinary albumin-to-creatinine ratio (UACR) over 300 mg/g. Treatment periods lasted 4 weeks. The UACR showed a significant reduction with the diuretics: spironolactone, -34% or hydrochlorothiazide without/with amiloride -42% or -56%, respectively. Reduction of the UACR was significantly greater with hydrochlorothiazide without/with amiloride when compared with spironolactone. The percentage of patients who achieved UACR reductions greater than 30% and 50% was greater with hydrochlorothiazide without/with amiloride (81% and 57%, and 81% and 66%, respectively) when compared with spironolactone alone (57% and 28%, respectively). Glomerular filtration rate (GFR), blood pressure, and body weight decreased with the three diuretic regimens. A significant correlation was found between the UACR reduction and GFR and blood pressure changes. Thus, diverse diuretic regimens differentially enhance albuminuria reduction, an effect likely associated with the degree of GFR reduction.

Predictors of response and relapse in patients with idiopathic membranous nephropathy treated with tacrolimus.

BACKGROUND: Although tacrolimus is recommended by KDIGO Clinical Practice Guideline for Glomerulonephritis for the treatment of idiopathic membranous nephropathy (MN), little is known about factors that influence response and relapse of the disease after tacrolimus therapy. METHODS: Multicentre study that collected 122 MN patients with nephrotic syndrome and stable renal function treated with tacrolimus. Duration of treatment was 17.6 ± 7.2 months, including a full-dose and a tapering period. RESULTS: The percentage of remission was 60, 78 and 84% after 6, 12 and 18 months of treatment, respectively. The amount of proteinuria at baseline significantly predicted remission, the lower the baseline proteinuria the higher the probability of remission. Only 10 patients (8%) received concomitantly corticosteroids, and their rate of remission was similar (80% at 18 months). Among responders, 42% achieved complete remission (CR) and 58% partial remission (PR). Almost half (44%) of the responder patients relapsed. The amount of proteinuria at the onset of tacrolimus tapering was significantly higher in relapsing patients. By multivariable analysis, the presence of a PR versus CR at the onset of tacrolimus tapering and a shorter duration of the tapering period significantly predicted relapses. Tolerance was good and the number of adverse events low. CONCLUSIONS: Tacrolimus monotherapy is an effective and safe option for the treatment of MN with stable renal function. Relapses are frequent in patients with PR and can be partially prevented by a longer tapering period.

Ateroembolia de colesterol y tratamiento combinado con esteroides e iloprost / Cholesterol atheroembolism and combined treatment with steroids and iloprost

La ateroembolia de colesterol (AEC) es una enfermedad sistémica cuya incidencia ha aumentado en las últimas décadas y que presenta una elevada morbimortalidad. En el momento actual se desconocen cuáles son las alternativas terapéuticas más efectivas en esta entidad. En este artículo presentamos el caso de una paciente diagnosticada de AEC con afectación cutánea, intestinal y renal, que presentó una buena evolución tras el inicio de terapia combinada con esteroides y análogos de las prostaglandinas. A pesar de que no existen estudios concluyentes, sugerimos esta alternativa para el manejo de AEC con afectación orgánica (AU)

Cholesterol atheroembolism (CAE) is a systemic disorder whose incidence has increased in recent decades and that presents high morbidity and mortality. Although several therapeutic alternatives have been reported, there is no consensus about the best treatment for this disease. In this paper we report the case of a patient with CAE with skin, bowel and kidney involvement who presented a good response to combined therapy with steroids and prostaglandin analogues. Although there are no conclusive studies, we recommend this therapeutic alternative in the management of CAE with organic failure (AU)