Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis—a proteomics study

We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n = 8 donors after brain death [DBD], n = 8 donors after circulatory death [DCD]) and three with UR (n = 2 DBD, n = 1 DCD), followed by quantitative analysis by mass spectrometry. Damage-associated molecular patterns (DAMPs) were decreased in kidney tissue after 6 hours NMP with URC, suggesting reduced inflammation. Vasoconstriction was also attenuated in kidneys with URC as angiotensinogen levels were reduced. Strikingly, kidneys became metabolically active during NMP, which could be enhanced and prolonged by URC. For instance, mitochondrial succinate dehydrogenase enzyme levels as well as carbonic anhydrase were enhanced with URC, contributing to pH stabilization. Levels of cytosolic and the mitochondrial phosphoenolpyruvate carboxykinase were elevated after 24 hours of NMP, more prevalent in DCD than DBD tissue. Key enzymes involved in glucose metabolism were also increased after 12 and 24 hours of NMP with URC, including mitochondrial malate dehydrogenase and glutamic-oxaloacetic transaminase, predominantly in DCD tissue. We conclude that NMP with URC permits prolonged preservation and revitalizes metabolism to possibly better cope with ischemia reperfusion injury in discarded kidneys.     

Low Mediterranean Diet scores are associated with reduced kidney function and health related quality of life but not other markers of cardiovascular risk in adults with diabetes and chronic kidney disease

Background and aimsHow Mediterranean-style diets impact cardiovascular and health outcomes in patients with diabetes and chronic kidney disease (CKD) is not well known. Our aim was to investigate the association between diet quality, using Mediterranean Diet Scores (MDS) and health outcomes.Methods and resultsThis is a post-hoc analysis of an RCT and longitudinal study investigating patients with diabetes and CKD. MDS was calculated annually. Scores were analyzed for correlation with lipids, HbA_1c, serum potassium, health-related quality of life (HRQOL) and depression. 178 diet records from 50 patients who attended two or more visits were included. Mean MDS was moderate (4.1 ± 1.6) and stable over time. Stage 1–2 vs 3–5 CKD had lower raw MDS (3.8 ± 1.5 vs 4.6 ± 1.5, p < 0.001). Having hyperkalemia was associated with a lower raw MDS scores (3.6 ± 1.6 vs 4.2 ± 1.5, p = 0.03) but not energy adjusted MDS. MDS was not associated with HbA_1c or lipids. High vs low MDS was associated with improved HRQOL (mental health 84.4 ± 14.3 vs 80.3 ± 17.1, p < 0.05; general health 62.6 ± 21.0 vs 56.3 ± 19.8, p < 0.001) and fewer depressive symptoms (9.1 ± 7.4 vs 11.7 ± 10.6, p = 0.01).ConclusionsLow MDS was associated with reduced kidney function and health related quality of life, but not other markers of cardiovascular risk. Further studies are needed to understand the nature and direction of the association between diet quality and disease outcomes in this population.     

Acute kidney injury and the critically ill

Acute renal failure is commonly encountered in the intensive care unit. It is associated with considerable morbidity and mortality. There are many possible aetiologies in the critically ill, including nephrotoxic agents, hypovolaemia and sepsis. While many classification systems for acute renal failure exist, the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria and the Acute Kidney Injury Network (AKIN) criteria are the most commonly utilized. Many supportive therapies are employed to minimize the degree of renal injury once recognized, such as fluid resuscitation, maintenance of an adequate mean arterial pressure (with the use of vasopressors in persistent hypotension despite fluid and treatment of the underlying aetiology). However, if renal failure becomes established, then renal replacement therapy (RRT) may be needed to maintain homeostasis. While there are no clear guidelines with respect to the ideal mode or timing of RRT, we will discuss pros and cons of the various options.     

Antioxidant treatment and outcome of cortinarius orellanus poisoning: a case series

Abstract

Objectives: To study the frequency, severity, and long-term outcome of renal injury in Cortinarius orellanus poisoning, to evaluate the association between the ingested amount of C. orellanus and outcome, and to evaluate the effect of N-acetylcysteine and corticosteroid treatment on outcome. Methods: Case series of eight patients. Diagnosis and severity of acute kidney injury (AKI) and chronic kidney disease (CKD) were classified according to current AKI and CKD definitions. N-acetylcysteine and corticosteroids were administered to six patients, former according to the standard for paracetamol poisoning. Main findings: All patients developed AKI, six in the most severe stage and four required renal replacement therapy (RRT). After 12 months, seven patients presented with CKD, of whom three required chronic RRT and further two were in advanced CKD. AKI and CKD severity highly correlated with the consumed amounts of Cortinarius orellanus (r?=?0.98, p?<?0.001 and r?=?0.78, p?=?0.02, respectively) but not with N-acetylcysteine and corticosteroid treatment. Conclusions: AKI and CKD by current definitions and classifications are frequent and severe after Cortinarius orellanus poisoning. The ingested amount of Cortinarius orellanus correlates with the severity of both AKI and CKD. N-acetylcysteine and corticosteroid treatment do not seem to have a beneficial effect on either AKI or CKD.     

Nutrient-restricted fetus and the cardio–renal connection in hypertensive offspring

A suboptimal intrauterine environment has a number of deleterious effects on fetal development and postpartum health outcomes. Epidemiological studies on several human populations have linked socioeconomic status and low birth weight to an increased incidence of diseases such as hypertension, diabetes, obesity and cardiovascular disease. A growing number of experimental studies in a variety of animal models demonstrate that maternal stressors, such as nutrition and reduced uterine perfusion, affect the intrauterine milieu and result in increased blood pressure in offspring. Several mechanisms appear to contribute to hypertension, including vascular dysfunction and increased peripheral resistance, altered cardio–renal structure and alterations in cardio–renal function. Although many studies have characterized models of developmentally generated hypertension, few have begun to seek therapeutic modalities to ameliorate its incidence. This review discusses recent work that refines hypotheses linking a suboptimal intrauterine environment to cardiovascular and renal phenotypes that have increased susceptibility to cardiovascular disease and hypertension.     

Immunosuppressive agents as risk factors for BK virus nephropathy: an overview and update

Important of the field: BK virus has emerged as an important cause of graft dysfunction and failure in renal transplant recipients. Risk factors for BK virus nephropathy (BKN) are not well established, but evidence suggests that it is the result of a complex interplay between multiple donor- and recipient-related factors.

Areas covered in this review: The purpose of this article is to review the current understanding on the effect of various immunosuppressive agents on BK viral replication and the results of different reported immunosuppression reduction protocols.

What the reader will gain: The intensity of overall immunosuppression has been accepted as a major risk factor for the development of BKN. We review the data regarding the contribution of different anti-rejection agents to the risk of BK virus-induced graft injury.

Take home message: Although reduction in immunosuppression on detection of BK viral replication appears to be the most successful means in preserving allograft function, data are emerging that support the stronger association of the disease with tacrolimus, in contrast to mycophenolate compounds. Therefore, initial dose reduction for tacrolimus may be more beneficial than this anti-metabolite preemptively or after diagnosis of BKN.