The cardiorenal syndrome in heart failure

The frequently occurring condition of renal failure in heart failure (HF) has been termed the cardiorenal syndrome. However, the importance of renal insufficiency in HF has only been embraced in the last decade, and therefore, the pathophysiology of cardiorenal failure is still poorly understood. The main driving force of renal failure in HF is probably hemodynamic derangement, with both reduced renal perfusion and increased venous pressure as the most important driving forces. Different cardiorenal connectors may modulate this relationship. Furthermore, renal failure is not only limited to reduced filtration but also includes glomerular hypertension and tubulointerstitial hypoxia, leading to loss of glomerular integrity and tubular damage. Recognition of these key pathophysiologic pathways in the concept of the cardiorenal syndrome is needed to value the interrelationship and incremental contribution of different risk markers and possible new treatments to improve renal function and outcome in this complex and bidirectional interplay between the heart and the kidney.     

Cardiorenal Interactions in Acute Decompensated Heart Failure: Contemporary Concepts Facing Emerging Controversies

Simultaneous dysfunction of the heart and the kidney represents a distinct spectrum of disease states composed of complex clinical scenarios with adverse outcomes. Worsening renal function (WRF) in the setting of acute decompensated heart failure (ADHF) is one such clinical setup for which the underlying mechanisms are poorly understood. Apparent discrepancies exist between the emerging data on the cardiorenal interactions of patients with ADHF and contemporary concepts such as the low forward flow or the high backward pressure hypotheses. The findings of recent retrospective studies also suggest that apparent “improvement in renal function” might be yet another risk factor for untoward outcomes in this patient population, further challenging our current understanding of the cardiorenal interactions. Besides, these data do not seem to fully support our conventional thinking about other aspects of these interactions such as the independent adverse impact of WRF on the outcomes of patients with ADHF, pointing to congestion as a possibly overlooked factor. In this article, we provide an overview of these emerging controversial issues with the goal of identifying the areas where clinical research could be most helpful, because it is of paramount importance to characterize the pathways leading to WRF in ADHF to develop a mechanistically relevant management strategy. Although the paucity of data coupled with the complexity of this field precludes any firm conclusion, these discussions are meant to prompt clinicians and researchers to revisit a number of long-believed concepts surrounding the cardiorenal interactions in ADHF.     

Combined exposure to heavy metals in PM2.5 and pediatric asthma

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Hepatic and extra-hepatic metabolic pathways involved in flubendazole biotransformation in sheep

Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic compound used in pigs, poultry and humans. Its potential for parasite control in ruminant species is under investigation. The objective of the work described here was to identify the main enzymatic pathways involved in the hepatic and extra-hepatic biotransformation of FLBZ in sheep. Microsomal and cytosolic fractions obtained from sheep liver and duodenal mucosa metabolised FLBZ into a reduced FLBZ metabolite (red-FLBZ). The keto-reduction of FLBZ led to the prevalent (approximately 98%) stereospecific formation of one enantiomeric form of red-FLBZ. The amounts of red-FLBZ formed in liver subcellular fractions were 3-4-fold higher (P<0.05) compared to those observed in duodenal subcellular fractions. This observation correlates with the higher (P<0.05) carbonyl reductase (CBR) activities measured in the liver compared to the duodenal mucosa. No metabolic conversion was observed following FLBZ or red-FLBZ incubation with sheep ruminal fluid. Sheep liver microsomes failed to convert red-FLBZ into FLBZ. However, this metabolic reaction occurred in liver microsomes prepared from phenobarbital-induced rats, which may indicate a cytochrome P450-mediated oxidation of red-FLBZ. A NADPH-dependent CBR is proposed as the main enzymatic system involved in the keto-reduction of FLBZ in sheep. CBR substrates such as menadione and mebendazole (a non-fluoride analogue of FLBZ), inhibited this liver microsomal enzymatic reaction, which may confirm the involvement of a CBR enzyme in FLBZ metabolism in sheep. This research is a further contribution to the understanding of the metabolic fate of a promissory alternative compound for antiparasitic control in ruminant species.     

Proenkephalin,Renal Dysfunction,and Prognosis in Patients With Acute Heart Failure: A GREAT Network Study

Background

Proenkephalin A (PENK) and its receptors are widely distributed. Enkephalins are cardiodepressive and difficult to measure directly. PENK is a stable surrogate analyte of labile enkephalins that is correlated inversely with renal function. Cardiorenal syndrome is common in acute heart failure (HF) and portends poor prognosis.