171 research outputs found
The pleiotropic effects of paricalcitol: Beyond bone-mineral metabolism
Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic
kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels
and a series of bone-mineral metabolism anomalies. In patients with SHPT, treatment with
paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels
with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is
that of a mediator in mineral and bone homeostasis. However, recent studies have suggested
that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance,
it has a positive effect on cardiovascular disease and survival. The objective of this study
is to review the most significant studies on the so-called pleiotropic effects of paricalcitol
treatment in patients with CK
Vitamin D, vitamin D receptor and the importance of its activation in patients with chronic kidney disease
El déficit de vitamina D se asocia a distintas patologÃas, siendo
especialmente significativa con la morbimortalidad en pacientes
con enfermedad renal crónica (ERC). La pérdida progresiva de la
función renal conduce a una reducción de calcitriol y alteración
de la homeostasis de calcio, fósforo, FGF-23 y PTH, entre otros,
los cuales influyen a su vez sobre la activación del receptor de
vitamina D (RVD) y el desarrollo de hiperparatiroidismo secundario
(HPS). El RVD media las acciones biológicas tanto de la vitamina
D como de sus análogos sintéticos, actuando sobre distintos
genes; existe una estrecha asociación entre niveles bajos de calcitriol
y la prevalencia del HPS. AsÃ, la activación de los RVD y la
restricción de fósforo, entre otros, desempeñan un papel importante
en el tratamiento de la «alteración óseo-mineral asociada
a la ERC». La Sociedad Española de NefrologÃa, dada la uniforme
e importante asociación con mortalidad y niveles altos de fósforo,
aconseja su normalización, asà como la de los niveles de calcidiol.
Igualmente considera que, aparte de la utilización de activadores
selectivos/no selectivos de RVD para la prevención y tratamiento
del HPS, se podrÃa asegurar la activación de los RVD en pacientes
en diálisis, con vitamina D nativa o incluso bajas dosis de
paricalcitol, independientemente de la PTH, dado que algunos
estudios de cohortes y un metaanálisis reciente han observado
una asociación entre el tratamiento con vitamina D activa y la
disminución de la mortalidad en pacientes con ERC. En general,
se considera que es razonable utilizar toda esta información para
individualizar la toma de decisionesVitamin D deficiency has been linked to many different pathologies,
especially with morbimortality in patients with chronic kidney
disease. The progressive loss of renal function leads to calcitriol
deficiency and homeostatic changes in calcium, phosphorus, FGF-
23 and PTH, among others. All these changes can also influence
vitamin D receptor (VDR) activation and the development of
secondary hyperparathyroidism (SHPT). The biologic actions of
both vitamin D and its synthetic analogues are mediated by
binding to the same VDR, acting on different genes. There is a
narrow relationship between low levels of calcitriol and SHPT. The
combined approach of VDR activation and phosphate restriction,
among others, plays an important role in the early treatment of
the chronic kidney disease-mineral and bone disorder (CKD-MBD).
The Spanish Society of Nephrology, in order to reduce the uniform
and significant association with CKD-associated mortality, calcidiol
and high phosphate levels suggests normalization of phosphate as
well as calcidiol levels in both CKD and dialysis patients. Moreover,
it considers that, in addition to selective/non selective activation
of VDR for the prevention and treatment of SHPT, VDR could
be activated in dialysis patients by native vitamin D or even low
paricalcitol doses, independently of PTH levels, as some cohort
studies and a recent metaanalysis have found an association
between treatment with active vitamin D and decreased mortality
in patients with CKD. In general it is considered reasonable to use
all this information to individualise decision makin
Actualización en sÃndrome hemolÃtico urémico atÃpico: diagnóstico y tratamiento. Documento de consenso
Trobareu una actualització (2015) d'aquest document a: http://hdl.handle.net/2445/99427Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Atypical HUS (aHUS) is a sub-type of HUS in which the TMA phenomena are the consequence of decreased regulation of the alternative complement pathway on cell surfaces due to a genetic cause. aHUS is an extremely rare disease that, despite the administration of standard treatment with plasma therapy, often progresses to terminal chronic renal failure with a high associated rate of mortality. In recent years, research has established the key role that the complement system plays in the induction of endothelial damage in patients with aHUS, through the characterisation of multiple mutations and polymorphisms in the genes that code for certain complement factors. Eculizumab is a monoclonal antibody that inhibits the terminal fraction of the complement protein, blocking the formation of a cell membrane attack complex. In prospective studies in patients with aHUS, administering eculizumab produces a rapid and sustained interruption in the TMA process, with significant improvements in long-term renal function and an important decrease in the need for dialysis or plasma therapy. In this document, we review and bring up to date the important aspects of this disease, with special emphasis on how recent advancements in diagnostic and therapeutic processes can modify the treatment of patients with aHUS
Mechanisms of cardiovascular disorders in patients with chronic kidney disease: a process related to accelerated senescence
Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is a systemic condition affecting approximately 10% of the general population. The prevalence of CKD has increased over the past decades because of the aging of the population worldwide. Indeed, CVDs in patients with CKD constitute a premature form of CVD observed in the general population. Multiple studies indicate that patients with renal disease undergo accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age. In this review, we discuss several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence. Uremiaassociated aging is linked with numerous changes at the cellular and molecular level. These changes are similar to those observed in the normal process of physiologic aging. We also discuss new perspectives in the study of CKD-associated CVDs and epigenetic alterations in intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), which promote vascular damage and subsequent development of CVD. Understanding the processes and factors involved in accelerated senescence and other abnormal intercellular signaling will identify new therapeutic targets and lead to improved methods of diagnosis and monitoring for patients with CKD-associated CVDs
Haematuria increases progression of advanced proteinuric kidney disease
Background
Haematuria has been traditionally considered as a benign hallmark of some glomerular diseases;
however new studies show that haematuria may decrease renal function.
Objective
To determine the influence of haematuria on the rate of chronic kidney disease (CKD) progression
in 71 proteinuric patients with advanced CKD (baseline eGFR <30 mL/min) during
12 months of follow-up.
Results
The mean rate of decline in eGFR was higher in patients with both haematuria and proteinuria
(haemoproteinuria, HP, n=31) than in patients with proteinuria alone (P patients, n=40)
(-3.8±8.9 vs 0.9±9.5 mL/min/1.73m2/year, p<0.05, respectively). The deleterious effect of
haematuria on rate of decline in eGFR was observed in patients <65 years (-6.8±9.9 (HP)
vs. 0.1±11.7 (P) mL/min/1.73m2/year, p65 years (-1.2±6.8 (HP)
vs. 1.5±7.7 (P) mL/min/1.73m2/year). Furthermore, the harmful effect of haematuria on
eGFR slope was found patients with proteinuria >0.5 g/24 h (-5.8±6.4 (HP) vs. -1.37± 7.9
(P) mL/min/1.73m2/year, p<0.05), whereas no significant differences were found in patients
with proteinuria < 0.5 g/24 h (-0.62±7.4 (HP) vs. 3.4±11.1 (P) mL/min/1.73m2/year). Multivariate
analysis reported that presence of haematuria was significantly and independently
associated with eGFR deterioration after adjusting for traditional risk factors, including age,
serum phosphate, mean proteinuria and mean serum PTH (β=-4.316, p=0.025)
Conclusions
The presence of haematuria is closely associated with a faster decrease in renal function in
advanced proteinuric CKD patients, especially in younger CKD patients with high proteinuria
levels; therefore this high risk subgroup of patients would benefit of intensive medical
surveillance and treatmentThis work was supported by grants from
FIS (Programa Miguel Servet: CP10/00479, PI13/
00802 and PI14/00883) and Spanish Society of
Nephrology to Juan Antonio Moreno. Fundacion Lilly,
FRIAT (Fundación Renal Iñigo Alvarez de Toledo)
and ISCIII fund PI14/00386 to Jesus Egid
Aki associated with macroscopic glomerular hematuria: Clinical and pathophysiologic consequences
Hematuria is a common finding in various glomerular diseases. This article reviews the clinical data on glomerular
hematuria and kidney injury, as well as the pathophysiology of hematuria-associated renal damage. Although
glomerular hematuria has been considered a clinical manifestation of glomerular diseases without real
consequences on renal function and long-term prognosis, many studies performed have shown a relationship
between macroscopic glomerular hematuria and AKI and have suggested that macroscopic hematuria-associated
AKI is related to adverse long-term outcomes. Thus, up to 25% of patients with macroscopic hematuria–
associated AKI do not recover baseline renal function. Oral anticoagulation has been associated with glomerular
macrohematuria–related kidney injury. Several pathophysiologic mechanisms may account for the tubular injury
found on renal biopsy specimens. Mechanical obstruction by red blood cell casts was thought to play a role. More
recent evidence points to cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from
red blood cells. These mechanisms of injury may be shared with hemoglobinuria or myoglobinuria-induced AKI.
Heme oxygenase catalyzes the conversion of heme to biliverdin and is protective in animal models of heme
toxicity. CD163, the recently identified scavenger receptor for extracellular hemoglobin, promotes the activation
of anti-inflammatory pathways, opening the gates for novel therapeutic approachesThis work was supported by FIS (Programa Miguel Servet)
to J.A.M.; ISCIII and FEDER funds CP04/00060, PS09/00447,
Sociedad Espa~nola de Nefrologia, ISCIII-RETIC REDinREN/RD06/
0016, Comunidad de Madrid/FRACM/S-BIO0283/2006, Programa
Intensificación Actividad Investigadora (ISCIII/) to A.O.; FIS 10/
02668 and AITER (Asociación para el Estudio y Tratamiento de las
Enfermedades Renales) to E.G. and M.P.; and ISCIII-Redes
RECAVA (RD06/0014/0035) and ISCIII funds PI10/00072 and
Fundacion Lilly to J.E
High exposure to tacrolimus is associated to 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.12 página
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