Primary prevention for acute kidney injury in ambulatory patients

Acute kidney injury (AKI) is a heterogeneous group of conditions characterized by a sudden decrease in glomerular filtration rate (GFR), which usually induces the accumulation of nitrogenous-waste substances in the blood. It is expressed as an increase in serum creatinine levels (≥ 0.3 mg/dl within 48 hours or ≥1.5 times from baseline within the previous 7 days) or by a urine volume reduction of ˂0.5 ml/kg/h in 6 hours [1]. AKI is a relevant condition since it is usually associated with 1–7% and 30–50% of hospital and intensive care unit (ICU) admissions, respectively; showing a significant morbidity-mortality rate, and progression to chronic kidney disease (CKD) [1–7]. Even though many strategies have been proposed to achieve an early AKI diagnosis (e.g. novel biomarkers, informatics alarms), and an AKI effective treatment (e.g. renal protective drugs, biocompatible renal replacement therapies), both objectives remain unachieved; therefore, AKI prevention is currently the best ‘therapeutic’ strategy for this condition

Consecutive renal biopsy in a cohort of patients with lupus nephritis of the Colombian Caribbean

Background: Renal biopsy is the gold standard for the diagnosis and classification of lupus nephritis (LN). However, a consecutive biopsy can predict the clinical course and optimize the therapeutic strategies. Objectives: To compare the histopathological findings with clinical responses. Patients and Methods: Thirty patients with active LN were included. Renal biopsies were performed at the time of diagnosis and subsequently under clinical criteria according to consensus of Spanish Society of Nephrology. The response to treatment was defined as complete response, partial responder or non-responder. The histological change in second biopsy towards LN classes I, II or III/IV-C was defined as histological response (HR). Results: In initial renal biopsy, 28 (93%) patients showed proliferative LN; III-A or A/C (n; 7), IV-A or A/C (n: 19) and mixed; III+IV/V (n; 2). LN class V was presented in two cases. The clinical response was; complete response (10%), partial response (20%), and non-response (70%). HR was manifested in 37% and non-histologic response in 63% of patients. Around 33% of patients with complete response/partial response showed active lesions in the consecutive renal biopsy. Conclusions: In Colombian Caribbean, LN is aggressive and refractory to treatment. The consecutive renal biopsy allowed to demonstrate the persistence of the activity of the lesion in almost half of the patients, which may provide additional information to create better response criteria. The consecutive renal biopsy is a tool that allows improving the evaluation of the response to treatment in the LN

New Insights into the Evolution of Metazoan Tyrosinase Gene Family

Tyrosinases, widely distributed among animals, plants and fungi, are involved in the biosynthesis of melanin, a pigment that has been exploited, in the course of evolution, to serve different functions. We conducted a deep evolutionary analysis of tyrosinase family amongst metazoa, thanks to the availability of new sequenced genomes, assessing that tyrosinases (tyr) represent a distinctive feature of all the organisms included in our study and, interestingly, they show an independent expansion in most of the analyzed phyla. Tyrosinase-related proteins (tyrp), which derive from tyr but show distinct key residues in the catalytic domain, constitute an invention of chordate lineage. In addition we here reported a detailed study of the expression territories of the ascidian Ciona intestinalis tyr and tyrps. Furthermore, we put efforts in the identification of the regulatory sequences responsible for their expression in pigment cell lineage. Collectively, the results reported here enlarge our knowledge about the tyrosinase gene family as valuable resource for understanding the genetic components involved in pigment cells evolution and development

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Osmotic diuresis in chronic kidney disease: its significance and clinical utility

Introduction The kidneys contribute to maintain plasma osmolality in normal range by achieving the adequate daily osmolar urine excretion (DOUE). An equation has been described for estimating the expected daily urine volume necessary to excrete the osmolar load required to keep serum osmolality in normal range. According to this equation, a difference between real and expected daily osmolar diuresis (DOD) can be obtained, being normally this difference value zero (± 500 cc). However, a positive DOD difference signifies a reduced urine concentration capability, while a negative DOD difference signifies a reduced urine dilution capability. Therefore, we decided to originally investigate how DOUE, and DOD difference are modified through the different stages of CKD. Materials and methods 61 patients suffering from CKD (stages I–V) secondary to glomerulopathies were studied. Creatinine clearance (CrCl), DOUE, and difference between real and expected DOD were obtained from each patient. Besides, correlation (Spearman) between CrCl and DOUE, and between CrCl and real–expected DOD difference were also obtained. Results Spearman correlation between CrCl and DOUE was positive and significant (Spearman’s ρ = 0.63, p < 0.0001). In addition, CKD patients who were not able to achieve the minimal DOUE required (600 mOsm/day) were mostly those with CrCl < 40 mL/min. Spearman correlation between CrCl and real–expected DOD difference was negative and significant (Spearman’s ρ = − 0.4, p < 0.0013). Additionally, abnormal DOD difference (> 500 cc) was found in CKD patients with CrCl < 80 mL/min/1.73 m2. Conclusion Daily osmolar urine excretion, and difference between real and expected daily osmolar diuresis are simple and significant clinical parameter which can be useful to easily evaluate urine concentration–dilution capability (tubular function) in CKD patients

Alactic base excess (ABE): a novel internal milieu parameter—its concept and clinical importance

Inspired by the Stewart-Figge acid–base approach, Gattinoni et al. recently introduced a new internal milieu parameter known as alactic base excess (ABE). The authors defined ABE as the sum of lactate and standard base excess. In the context of sepsis, ABE has been proposed as a valuable marker to discern between metabolic acidosis resulting from the accumulation of lactate and the retention of fixed acids, which can occur in cases of renal failure. Multiple studies have demonstrated that a negative ABE value (<−3 mmol/L) represents an early marker of renal dysfunction, and significantly correlates with higher mortality rates in septic patients. In conclusion, ABE is a simple and useful parameter that can be used to better interpret a patient’s acid–base status, assess renal function, and general prognosis in sepsis. By incorporating ABE into clinical practice, healthcare professionals can enhance their understanding of the complex acid–base imbalances in their patients and tailor more individualized, effective treatment plans

Obesity and glomerular filtration rate

Obesity has received considerable attention in general medicine and nephrology over the last few years. This condition increases the risk of metabolic syndrome, diabetes mellitus, hypertension, and dyslipidemia, which are the main risk factors for developing chronic kidney disease (CKD). Kidney damage caused by obesity can be explained by many mechanisms, such as sympathetic nervous and renin-angiotensin-aldosterone systems activation, mechanical stress, hormonal unbalance, as well as inflammatory cytokines production. Even though creatinine-based glomerular filtration rate (GFR) equations in obese individuals have been validated (Salazar-Corcoran and CKD-MCQ), changes in body weight after bariatric surgery (BS) leads to changes in creatininemia, affecting its reliability. Thus, an average between creatine and cystatin-based GFR equations would be more appropriate in this setting. Bariatric surgery can reverse diabetes mellitus and improve hypertension, which are the main causes of CKD. Conclusion: GFR can be affected by obesity and BS, and its value should be cautiously evaluated in this setting