Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis.

Acute kidney injury (AKI) is one of the main conditions responsible for chronic kidney disease (CKD), including end-stage renal disease (ESRD) as a long-term complication. Besides short-term complications, such as electrolyte and acid-base disorders, fluid overload, bleeding complications or immune dysfunctions, AKI can develop chronic injuries and subsequent CKD through renal fibrosis pathways. Kidney fibrosis is a pathological process defined by excessive extracellular matrix (ECM) deposition, evidenced in chronic kidney injuries with maladaptive architecture restoration. So far, cited maladaptive kidney processes responsible for AKI to CKD transition were epithelial, endothelial, pericyte, macrophage and fibroblast transition to myofibroblasts. These are responsible for smooth muscle actin (SMA) synthesis and abnormal renal architecture. Recently, AKI progress to CKD or ESRD gained a lot of interest, with impressive progression in discovering the mechanisms involved in renal fibrosis, including cellular and molecular pathways. Risk factors mentioned in AKI progression to CKD are frequency and severity of kidney injury, chronic diseases such as uncontrolled hypertension, diabetes mellitus, obesity and unmodifiable risk factors (i.e., genetics, older age or gender). To provide a better understanding of AKI transition to CKD, we have selected relevant and updated information regarding the risk factors responsible for AKIs unfavorable long-term evolution and mechanisms incriminated in the progression to a chronic state, along with possible therapeutic approaches in preventing or delaying CKD from AKI.

Uric Acid and Oxidative Stress-Relationship with Cardiovascular, Metabolic, and Renal Impairment.

BACKGROUND: The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin-angiotensin-aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus. CONCLUSIONS: Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients' long-term prognosis and their quality of life.

Burn-Induced Acute Kidney Injury-Two-Lane Road: From Molecular to Clinical Aspects.

Severe burn injuries lead to acute kidney injury (AKI) development, increasing the mortality risk up to 28-100%. In addition, there is an increase in hospitalization days and complications appearance. Various factors are responsible for acute or late AKI debut, like hypovolemia, important inflammatory response, excessive load of denatured proteins, sepsis, and severe organic dysfunction. The main measure to improve the prognosis of these patients is rapidly recognizing this condition and reversing the underlying events. For this reason, different renal biomarkers have been studied over the years for early identification of burn-induced AKI, like neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), interleukin-18 (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP7). The fundamental purpose of these studies is to find a way to recognize and prevent acute renal injury progression early in order to decrease the risk of mortality and chronic kidney disease (CKD) onset.

The Relationship between Advanced Oxidation Protein Products, Vascular Calcifications and Arterial Stiffness in Predialysis Chronic Kidney Disease Patients.

Background and Objectives: Cardiovascular morbidity and mortality are increased in patients with chronic kidney disease (CKD). It is likely that the accumulation of uremic toxins resulting in increased oxidative stress (OS) is a major contributing factor, but no clear link has been identified. The purpose of this research is to establish if advanced oxidation protein product (AOPP) levels in the serum of predialysis patients are a contributing factor to vascular calcification and increased arterial stiffness. Materials and Methods: After obtaining the informed consent, 46 predialysis patients (CKD stages G3-G5) were included in the study. In order to identify vascular calcifications, hand and pelvic radiographs were performed. Valvular calcifications were identified using cardiac ultrasound. AOPP were measured using a commercially available ELISA kit. The relationships between serum AOPP values and biochemical parameters relevant in the evaluation of CKD patients were analyzed. In addition to identifying the differences in AOPP levels between patients with/without vascular or valvular calcifications, the research focused on describing the relationship between OS and arterial stiffness assessed by oscillometric pulse-wave velocity (PWV) measurement. Results: No significant relationship between serum AOPP and vascular or valvular calcifications was highlighted, but significant correlations of AOPP with C-reactive protein (p = 0.025), HDL-cholesterol levels (p = 0.04), HbA1c (p = 0.05) and PWV values (p = 0.02) were identified. Conclusions: The usefulness of (OS) measurement in clinical practice remains debatable; however, the relationship between AOPP and arterial stiffness could be valuable in improving cardiovascular risk assessment of patients with CKD.

Corrigendum to "Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes".

[This corrects the article DOI: 10.1155/2015/604208.].

Very low protein diets supplemented with keto-analogues in ESRD predialysis patients and its effect on vascular stiffness and AVF Maturation.

BACKGROUND: Native arteriovenous fistula (AVF) is the most appropriate type of vascular access for chronic dialysis. Its patency rates depend on vascular wall characteristics. Ketoacid analogues of essential amino acids (KA/EAA) are prescribed in end-stage renal disease (ESRD) pre-dialysis patients to lower toxic metabolic products generation and improve nutritional status. We hypothesized that very-low protein diet (VLPD) supplemented with KA/EAA may influence arterial wall stiffness and affect AVF maturation rates and duration in pre-dialysis ESRD patients. METHODS: In a prospective, cohort, 3 years study we enrolled 67 consecutive non-diabetic early referral ESRD patients that underwent AVF creation in our hospital. Patients were divided in two groups based on their regimen 12 months prior to surgery: a VLPD supplemented with KA/EAA study group versus a low protein diet non-KA/EAA-supplemented control group. For each patient we performed serum analysis for the parameters of bone mineral disease, inflammation and nutritional status, one pulse wave velocity (PWV) measurement and one Doppler ultrasound (US) determination prior the surgery, followed by consequent Doppler US assessments at 4, 6, 8 and 12 weeks after it. Rates and duration of mature AVF achievement were noted. We used logistic regression to analyze the association between AVF maturation and KA/EAA administration, by comparing rates and durations between groups, unadjusted and adjusted for systolic blood pressure, C-reactive protein, PWV, phosphorus values. All parameters in the logistic model were transformed in binary variables. A p-value < α = 0.05 was considered significant; data were processed using SPSS 16 software and Excel. RESULTS: In the study group (n = 28, aged 57 ± 12.35, 13 females) we registered better serum phosphate (p = 0.022) and C-reactive protein control (p = 0.021), lower PWV (p = 0.007) and a higher percent of AVF creation success (33.3 % versus 17.8 %, p < 0.05). AVF maturation duration was lower in study group (5.91 versus 7.15 weeks, p < 0.001). CONCLUSIONS: VLPD supplemented with KA/EAA appear to improve the native AVF primary outcome, decreasing the initial vascular stiffness, possible by preserving vascular wall quality in CKD patients through a better serum phosphate levels control and the limitation of inflammatory response.

Giant Myxofibrosarcoma in the Lower Limb: An Overview of Diagnostic and Clinical Management.

Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, is one of the undifferentiated pleomorphic sarcomas; it has a low incidence, affecting people in the sixth to eighth decades of life. It usually involves the extremities and is painless with a slow-growing pattern. Based on the case of a 52-year-old female patient who presented with a painful, massive, rapid-growing, ulcerated tumor of the anterior surface of the left thigh, we performed a literature review regarding the current standard of care for patients with MFS. Computed tomography examination, followed by magnetic resonance imaging and surgical biopsy with histopathological examination, confirmed the diagnosis and the presence of lung and inguinal lymph node metastases. Due to the rapid-growing pattern and the local aggressiveness, our tumor board team recommended emergency excisional surgery, with subsequent reconstructive procedures followed by referral to an oncological center. This review emphasizes the importance of proper and rapid diagnosis, followed by multidisciplinary management, for MFS cases with atypical presentation and distal metastases to improve overall outcomes.

Magnesium-A More Important Role in CKD-MBD than We Thought.

Chronic kidney disease (CKD) is associated with different complications, including chronic kidney disease-mineral and bone disorder (CKD-MBD), which represents a systemic disorder that involves the presence of different mineral or bone structure abnormalities (i.e., modification of bone turnover, strength, volume, etc.), including even vascular calcification development. Even if, over the years, different pathophysiological theories have been developed to explain the onset and progression of CKD-MBD, the influence and importance of serum magnesium level on the evolution of CKD have only recently been highlighted. So far, data are inconclusive and conflicting; therefore, further studies are necessary to validate these findings, which could be useful in developing a better, more adequate, and personalized management of CKD patients.

Epidemiological Characteristics and Mortality Risk Factors Comparison in Dialysis and Non-Dialysis CKD Patients with COVID-19-A Single Center Experience.

(1) Background: Despite some controversies between studies, chronic kidney disease (CKD) has a negative impact on COVID-19 outcomes, with patients presenting a higher mortality risk than in the general population. Studies have shown an association between COVID-19 severe cases and different inflammatory biomarkers. The aim of this study was to emphasize the epidemiological characteristics of CKD patients diagnosed with COVID-19 and to determine if the risk of mortality, and the severity of this infection might be influenced by different parameters. (2) Methods: Our retrospective study included CKD patients with COVID-19­362 in the non-dialysis group and 132 in the dialysis group. (3) Results: There were significant statistical differences between our groups regarding age (p < 0.001), hemoglobin (p < 0.001), interleukin-6 (p < 0.001), serum albumin (p = 0.016), procalcitonin (p = 0.002), ferritin (p < 0.001), and of course serum creatinine (p < 0.001). Even if the risk of death was higher in the dialysis group (Exp(b) = 1.839), the survival proportions were similar in both groups. (4) Conclusions: High values of hemoglobin, serum creatinine, and LDH at admission, age, length of hospital stay ≤ 10 days, and a pulmonary impairment > 25% are responsible for an adverse outcome in non-dialysis and dialysis patients diagnosed with COVID-19.

Overview of Renal Replacement Therapy Use in a General Intensive Care Unit.

OBJECTIVES: Population-based studies regarding renal replacement therapy (RRT) used in critical care populations are useful to understand the trend and impact of medical care interventions. We describe the use of RRT and associated outcomes (mortality and length of intensive care stay) in a level 1 hospital. DESIGN: A retrospective descriptive observational study. PATIENTS: Critically ill patients admitted to the ICU from 1 January to 31 December 2018. INTERVENTIONS: Age, gender, ward of admission, primary organ dysfunction at admission, length of hospital stay (LOS), mechanical ventilation, APACHE, SOFA and ISS scores, the use of vasopressors, transfusion, RRT and the number of RRT sessions were extracted. RESULTS: 1703 critically ill patients were divided into two groups: the RRT-group (238 patients) and the non-RRT group (1465 patients). The mean age was 63.58 ± 17.52 (SD) in the final ICU studied patients (64.72 ± 16.64 SD in the RRT-group), 60.5% being male. Patients admitted from general surgery ward needing RRT were 41.4%. The specific scores, the use of vasopressors, transfusions and mortality were higher in the RRT-group. The ICU LOS was superior in the RRT-group, regardless of the primary organ dysfunction. CONCLUSIONS: RRT was practiced in 13.9% of patients (especially after age of 61), with mortality being the outcome for 66.8% of the RRT-group patients. All analyzed data were higher in the RRT group, especially for multiple trauma and surgical patients, or patients presenting cardiac or renal dysfunctions at admission. We found significant increased ISS scores in the RRT-group, a significant association between the need of vasopressors or transfusion requirement and RRT use, and an association in the number of RRT sessions and LOS (p < 0.001).

The Ideal Time for Iron Administration in Anemia Secondary to Blood Loss-An Experimental Animal Model.

BACKGROUND: Anemia and iron deficiency are two of the main public health problems worldwide, associated with negative outcomes in surgical patients. This experimental study aimed to create a model of acute iron deficiency with anemia through blood loss and extensive surgery. Afterwards, intravenous iron was administered to correct the iron deficiency and to improve the hematological parameters in distinct moments regarding the surgical time. To assess the optimum time for therapeutic intervention, experimental subjects were compared, performing clinical, paraclinical, and histological examinations, as well. METHODS: Male rats (n = 35), aged 11-13 months, were randomly designated into six groups. Anemia and iron deficiency were obtained through a 15% blood volume loss, followed by major surgical intervention (femur fracture and osteosynthesis using Kirschner wire). Therapeutic intervention was obtained with an intravenous ferric carboxymaltose infusion, as follows: group II: intraoperative (n = 7), group III: 48 h after surgery (n = 7), group IV: 48 h before surgery (n = 5), and group V: seven days before surgery (n = 6). Group I (n = 5) was left anemic, while group 0 (n = 5) was nonanemic without therapeutic intervention. RESULTS AND DISCUSSION: In group I, serum iron lower than in group 0 (27.04 ± 6.92 µg/dL versus 60.5 ± 2.34 µg/dL), as well as hemoglobin (10.4 ± 0.54 g/dL versus 14.32 ± 2.01 g/dL) and ferritin values (22.52 ± 0.53 ng/mL versus 29.86 ± 3.97 ng/mL), validated the experimental model. Regarding wound healing after surgical trauma, we observed that neovascularization was more significant in group III, followed by group V, with fewer neutrophils, a well-represented and rich in lymphomonocytes inflammatory infiltrate associated with the biggest collagen fiber dimensions. The periosteal reaction and callus area presented thicker trabeculae in groups II and III compared to the anemic group. CONCLUSIONS: This original experimental study assessed the effect of perioperative intravenous iron administration at a specific time by comparing the weight, hematological, and iron status-defining parameters, as well as histological characteristics of the included subjects. The present findings highlight that correcting the iron deficiency in emergency settings through intravenous iron administration intraoperatively or 48 h postoperatively could determine the improved bioumoral parameters, as well as a better evolution of the postoperative wound and bone healing compared to the anemic group or subjects that received therapeutic intervention 48 h before surgery.

Histopathological features of low-dose organophosphate exposure.

Organophosphate (OP) use remains largely available worldwide despite more strict regulatory measures, in agriculture, parks or households, leading to a daily low-dose exposure. The systemic dysfunction appears partly due to acetylcholinesterase inhibition, exhibiting a primary toxic effect on the endocrine system but also on the liver and kidneys, which are responsible for products metabolization and elimination. Prolonged OP exposure can be responsible for histopathological (HP) changes that can either evolve or worsen pre-existing conditions. We conducted an experimental study including six male Wistar rats divided into two groups (four rats in the study group and two in the control group). The subjects in the first group were administered 100 mg∕kg Chlorpyrifos half median lethal dose (LD50) at baseline and at 48 hours, under general anesthesia. Organ harvesting was achieved after one week. HP modifications were discovered in all kidney samples, with dystrophic changes and vacuolization of mesangial cells, dilation of renal tubules and epithelial atrophy. Congestion of vascular structures also occurred. The liver samples showed severe alteration in both vessels and hepatocytes. Adrenal gland impairment was confirmed through an increase in vacuole number in all areas, while a decrease in colloid content was noted in the thyroid gland simultaneously with a modified foamy aspect. This study is the first to certify the extent of organ injury induced by OP exposure, describing both glomerular and tubular involvement in the kidneys, liver necrosis and endocrine disturbances.

Supersonic Shear Wave Ultrasonography for Assessing Tissue Stiffness in Native Kidney.

Recent years have brought shear wave elastography to the attention of nephrologists as a non-invasive method for detecting kidney fibrosis and, therefore, as a potential tool for reducing the need for kidney biopsy. Few studies are performed on native kidney. We aimed to compare cortical stiffness, assessed by measuring Young's modulus (YM, kPa) with SuperSonic Imaging technology, in patients with various degrees of chronic kidney disease (CKD) compared with healthy individuals. Cortical stiffness was measured by two operators, in different sessions, in 32 patients with CKD stages 3-5 and 20 healthy individuals. Comparison between mean YM values in CKD and those in controls and also between the different stages of CKD was our primary objective. The influence of other possible confounders on YM readings was also investigated and analyzed. Mean YM was significantly greater in CKD patients than in controls. Estimated YM was not able to differentiate the stages of CKD, except stage 5. Intra-subject variability was greater in CKD than in controls. Body mass index was the most important confounder in multiple analyses, in both the CKD and control groups. Our results highlight a positive correlation between increased cortical stiffness and presence of CKD. Further studies are needed to validate this method for implementation in daily clinical practice.

Nephrotic syndrome secondary to amyloidosis in a patient with monoclonal gammopathy with renal significance (MGRS).

Monoclonal gammopathy with renal significance (MGRS) is a relative new-described entity, diagnosed especially in older patients and deriving from the group with monoclonal gammopathy of undetermined significance (MGUS). Various renal lesions may arise in MGRS, according to the ultrastructural characteristics of the monoclonal immunoglobulin deposition in the kidney, from proliferative glomerulopathies and amyloidosis to light chain proximal tubulopathy and crystal-storing histiocytosis. Although both are considered premalign or non-malignant hematological conditions, kidney involvement in MGRS aggravates the prognosis of the patients and need to be treated aggressively. We discuss the case of a 44-year-old female patient admitted in our Department of Nephrology for clinical picture of impure nephrotic syndrome and decreased renal function associated with Bence-Jones proteinuria. Renal biopsy was performed, and fibrillar amyloid deposits were demonstrated both in glomerular and tubular basement membranes; the immunofluorescence identified the presence of κ chains. Bone marrow aspiration and biopsy showed <10% plasmocytic proliferation confirming the diagnosis of MGRS.

Coronary risk score for mineral bone disease in chronic non-diabetic hemodialysis patients: results from a prospective pilot study.

INTRODUCTION: Chronic kidney disease-mineral bone disorder enhances coronary artery impairment (often occult and difficult to diagnose) in hemodialysis (HD) patients. The aim of the study was to correlate biochemical and imagistic parameters of MBD with the degree of documented coronary artery disease (CAD) in non-diabetic HD patients, in order to obtain a MBD-coronary risk score as a screening algorithm. METHODS: A 3-year prospective study was conducted on 168 non-diabetic HD patients, evaluating MBD biochemical parameters along with pulse wave velocity (PWV) determination and valve/coronary calcification assessment; coronary angiography was performed in symptomatic patients. Correlations between noninvasive parameters and the degree of coronary obstruction were assessed using IBM SPSS Statistics 20 software, Chi-square test and the determination of odds ratio. RESULTS: Significant differences in serum calcium (p < 0.001), phosphates (p = 0.03), bicarbonate (p < 0.001), albumin and iPTH (p = 0.002), percentage of deviations from PWV normal values (p = 0.004), average doses of phosphate binders and vitamin D and the number of vascular/valve calcifications were noted between the study group (angina, n = 17) and control group (asymptomatic, n = 151). After applying MBD-coronary risk score in control group, coronary angiography was performed in high-score patients. CONCLUSION: A noninvasive screening algorithm for early diagnosis of CAD in asymptomatic HD patients with altered MBD parameters is necessary. Applying MBD-coronary risk score might be an important step in the prevention of major coronary episodes by extending the indication for further investigations, early diagnosis and treatment management.

Sublingual desmopressin is efficient and safe in the therapy of lithiasic renal colic.

PURPOSE: To evaluate the effects of newer sublingual desmopressin administration in lithiasic renal colic, alone or combined with a nonsteroidal anti-inflammatory drug (NSAID). METHODS: Prospective single-blind study including an initial number of 249 patients with lithiasic renal colic was randomized as follows: group NSAID (71 patients) received ketorolac tromethamine (ketorolac) 30 mg im and sublingual placebo (vitamin C), groups D1 and D2 (57 and 62 patients) received sublingual desmopressin (Minirin Melt), 60 and 120 µg, respectively, whereas group C (59 patients) received a combination of 30 mg im ketorolac and 60 µg sublingual desmopressin. Pain intensity was assessed using the visual analogue scale before and thirty minutes after drug administration. Patients experiencing pain aggravation were rescued and excluded from the study. RESULTS: Dropout incidence was higher in the NSAID group than in the groups treated with desmopressin in monotherapy or combined with ketorolac (p < 0.05). Pain intensity was diminished at least as potently by the monotherapy with desmopressin and ketorolac. The higher dose of desmopressin and the combination therapy decreased pain intensity with 56 and 59%, respectively, significantly more than the 47% decrease obtained with ketorolac alone (p < 0.05 and p < 0.001). Mean pain decrease was higher in the combination group (C) than in the NSAID or D1 groups (p < 0.001 and p < 0.05, respectively), suggesting drug additivity. Patients did not experience severe side effects. CONCLUSIONS: Sublingual desmopressin is at least as potent as NSAID in the treatment of lithiasic renal colic. The combination of sublingual desmopressin and NSAID has additive analgesic effects.

New molecular insights in diabetic nephropathy.

Diabetes mellitus represents one of the major causes of functional kidney impairment. The review highlights the most significant steps made over the last decades in understanding the molecular basis of diabetic nephropathy (DN), which may provide reliable biomarkers for early diagnosis and prognosis, along with new molecular targets for personalized medicine. There is an increased interest in developing new therapeutic strategies to slow DN progression for improving patients' quality of life and reducing all-cause morbidity and disease-associated mortality. It is highly important to have a science-based medical attitude when facing diabetic patients with associated comorbidities and risk of rapid evolution toward end-stage renal disease. The data discussed herein were mainly from MEDLINE and PubMed articles published in English from 1990 to 2015 and from up-to-date. The search term was "diabetic nephropathy and oxidative stress".

Uterus neuroendocrine tumor - a severe prognostic factor in a female patient with alcoholic cirrhosis undergoing chronic hemodialysis.

There is increased evidence that end-stage renal disease patients, especially the hemodialyzed population, may present various unexpected forms of complications, contributing to a poor prognosis. Furthermore, neuroendocrine tumors, rarely encountered in daily practice, present in dialyzed individuals can significantly exacerbate the inflammatory condition with negative impact on patients' quality of life. We present an unusual case of uterus neuroendocrine tumor with multiple metastases in a 49-year-old female hemodialyzed patient with a history of alcoholic liver cirrhosis and uterus fibromatous. Multiple endoscopic techniques (e.g., upper endoscopy, colonoscopy, upper and lower echoendoscopy), histological evaluation of biopsy samples from involved areas (the operatory piece) were performed in order to complete and refine the diagnosis.

An overview of permanent vascular access in hemodialyzed patients.

In the last decade, because of significant number of end-stage renal disease individuals in need of renal therapy replacement and permanent quest of nephrologist to optimize kidney disease patients' quality of life, there is an increased interest in achieving a suitable permanent vascular access, essential for an efficient dialysis. Furthermore, it is of high importance to preserve arteriovenous fistula in optimal condition and therefore, it is vital to correctly understand the histopathology and pathophysiological mechanisms implicated in maturation and well function of dialysis vascular access.

Vascular calcification in continuous ambulatory peritoneal dialysis patients.

Vascular calcifications represent a severe complication of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) stage 5. The factors influencing the development of this complication are in close relation with the pathology of chronic dialysis premorbid condition, and with therapy as well. The present article highlights the association between several factors and the development or the aggravation of vascular calcifications in continuous ambulatory peritoneal dialysis (CAPD) patients. The results are not always in accordance with similar literature data, but there is a lack of researches regarding mineral metabolism in peritoneal dialysis patients versus those on chronic hemodialysis.