Manifestation Of Chronic Kidney Disease Research Articles

BMPER Ameliorates Renal Fibrosis by Inhibiting Tubular Dedifferentiation and Fibroblast Activation.

Tubulointerstitial fibrosis is both a pathological manifestation of chronic kidney disease and a driving force for the progression of kidney disease. A previous study has shown that bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER) is involved in lung fibrogenesis. However, the role of BMPER in renal fibrosis remains unknown. In the present study, the expression of BMPER was examined by real-time PCR, Western blot and immunohistochemical staining. The in vitro effects of BMPER on tubular dedifferentiation and fibroblast activation were analyzed in cultured HK-2 and NRK-49F cells. The in vivo effects of BMPER were dissected in unilateral ureteral obstruction (UUO) mice by delivery of BMPER gene via systemic administration of plasmid vector. We reported that the expression of BMPER decreased in the kidneys of UUO mice and HK-2 cells. TGF-β1 increased inhibitor of differentiation-1 (Id-1) and induced epithelial mesenchymal transition in HK-2 cells, and knockdown of BMPER aggravated Id-1 up-regulation, E-cadherin loss, and tubular dedifferentiation. On the contrary, exogenous BMPER inhibited Id-1 up-regulation, prevented E-cadherin loss and tubular dedifferentiation after TGF-β1 exposure. In addition, exogenous BMPER suppressed fibroblast activation by hindering Erk1/2 phosphorylation. Knockdown of low-density lipoprotein receptor-related protein 1 abolished the inhibitory effect of BMPER on Erk1/2 phosphorylation and fibroblast activation. Moreover, delivery of BMPER gene improved renal tubular damage and interstitial fibrosis in UUO mice. Therefore, BMPER inhibits TGF-β1-induced tubular dedifferentiation and fibroblast activation and may hold therapeutic potential for tubulointerstitial fibrosis.

Cutaneous Manifestations of Chronic Kidney Disease, Dialysis and Post-Renal Transplant: A Review.

Skin serves as the mirror of underlying systemic problems. The early diagnosis of subtle cutaneous clinical pointers often helps in identifying renal disorders, obviating the delay in diagnosis and treatment. Cutaneous changes can be observed from the beginning of renal impairment until the evolution to terminal stage, in uremia, hemodialysis, and after kidney transplantation. In the review, we have discussed the cutaneous changes, its implicated etiopathogenesis, and their treatment options, as encountered in chronic kidney disease, hemodialysis and post-renal transplantation.

Clinical and Laboratory Profile of Dogs Seroreactive to Ehrlichiosis Treated at the Veterinary Medical Teaching Hospital in Niterói, State of Rio de Janeiro, Brazil

Background: Ehrlichiosis is a tick-borne disease highly prevalent in Brazil, and is relevant in canine clinical practice due to its high morbidity and mortality. Its clinical signs are nonspecific and its phases are acute, lasting 2 to 4 weeks; subclinical, i.e., asymptomatic; and chronic, resembling an autoimmune disease. The purpose of this study was to identify the occurrence of reactivity to Ehrlichia canis of bitches treated at the Veterinary Medical Teaching Hospital of the Universidade Federal Fluminense (UFF) - Niterói, RJ, Brazil, based on serological examination by iELISA, and to compare the hematological, biochemical, urinary protein-creatinine and urinary density profiles of reactive and non-reactive animals. Materials, Methods & Results: This study involved solely bitches, regardless of breed, starting at 1 year of age. One hundred and thirty bitches, 1 to 16 year-old (mean age 7.02 ± 4.00), weighing 1.5 to 50 kg (mean weight 12.12 ± 10.65) were subjected to clinical examination and abdominal ultrasound. Complete blood count, biochemical measurements, urinalysis and serology for E. canis were also performed. The serum was used in the iELISA to identify immunoglobulin G (IgG), using a canine Ehrlichia Imunotest® diagnostic kit (Imunodot®, Jaboticabal, SP, Brazil) according to the manufacturer’s instructions. Sixty animals (46.20%) were reactive to E. canis. According to their owners, only 5 (8.3%) of the 60 seroreactive animals had a history of tick-borne disease. The most common profile was that of mixed breed animals living with their owners, older than 7 years, who had not been treated preventatively with specific drugs against ectoparasites. Laboratory tests showed significant differences between groups in terms of total protein (TP), and calcium and urinary protein-creatinine ratio (UPC). TP and UPC were elevated in the non-reactive group, while the only significant change in the reactive group was mild hypocalcemia. In this study, 30% (18/60) of the bitches were seroreactive to E. canis and had hypocalcemia. Of these, 50% (9/18) had a UPC above 0.5. Furthermore, 66.7% (12/18) of this group with hypocalcemia also showed urine density (UD) of less than 1024. Among these 18 bitches, 5 had both alterations, i.e., UPC > 0.5 and UD < 1024.Discussion: In this study, a high prevalence of bitches seroreactive to Ehrlichia canis was observed, despite the absence of clinical and/or laboratory signs indicative of the disease. In the investigation of IgG class antibodies, it is not possible to determine the exact time of infection, and titers may remain high for a period of more than 11 months, even after treatment and elimination of the bacterium. The fact that most seroreactive bitches showed no symptoms compatible with the disease either before or during the study suggests that they were in the subclinical phase of ehrlichiosis. The main reason for calcium metabolism disorders is a phosphorus imbalance, a condition that occurs in kidney diseases. Isosthenuria reflects the kidney’s inability to concentrate urine. This finding may be one of the first clinical manifestations of chronic kidney disease (CKD), especially in dogs. On the other hand, the UPC ratio may increase with the progression of CKD. The presence of hypocalcemia, isosthenuria and increased UPC associated with seroreactivity suggests that infection by E. canis may be associated with the onset of CKD. Veterinarians should keep in mind the complexity of the pathophysiology of ehrlichiosis to ensure the disease is not underdiagnosed in any of its phases, thereby ensuring the correct treatment is provided. Such awareness is expected to reduce the chronicity of the disease and underlying sequelae among dogs.Keywords: Ehrlichia canis, serology, tick, clinic, renal.Descritores: Ehrlichia canis, sorologia, carrapato, clínica, renal.Título: Perfil clínico e laboratorial de cadelas sororeativas para erliquiose tratadas em um Hospital Veterinário Universitário em Niterói, Estado do Rio de Janeiro, Brasil

Muco-cutaneous manifestations of chronic kidney disease with or without hemodialysis

<p class="abstract"><strong>Background:</strong> Mucocutaneous manifestations significantly impair the quality of life of patients with chronic kidney disease (CKD) but are usually understudied. Our objective was to study the patterns and prevalence of mucocutaneous and nail involvement in CKD patients and to compare those in patients with or without haemodialysis.</p><p class="abstract"><strong>Methods:</strong> Ninety patients aged 18-80 years having CKD (M: F=1.64:1) since mean duration of 4.43±9.9 months were studied in an observational cross-sectional study. Sixty-two (68.9%) patients were on hemodialysis since 42.64±63.14 months. Detailed history and examination, and relevant investigations like KOH mount, skin biopsy, gram stain and culture were done when required. Data was analyzed using SPSS version 21 software. Relevant tests were applied, p<0.05 was considered statistically significant.<strong></strong></p><p class="abstract"><strong>Results:</strong> Xerosis in 43 (47.7%), pruritus in 26 (28.9%), ichthyosis in 11 (12.2%), and skin pallor in 7 (7.8%) patients were major dermatoses. Xerosis was more commonly found in patients on haemodialysis (37.8%) as compared to those without dialysis (9.9%) (p-0.046). Bullous lesions, perforating folliculitis and foot ulcers occurred in 1 (1.1%) patient each. Common nail abnormalities were longitudinal ridging (21.1%), leukonychia (13.3%), Lindsay’s half‐and‐half nails (4.4%) and dystrophic nails (4.4%). Mucosal manifestations were coated tongue (2.2%%), angular cheilitis (2.2%), and pigmented tongue (1.1%).</p><p class="abstract"><strong>Conclusions:</strong> Xerosis, pruritus, ichthyosis skin pallor, longitudinal ridging, leukonychia, coated tongue, and angular cheilitis were the common mucocutaneous manifestations in our study. Early recognition and management of these dermatoses plays a crucial role in a holistic patient treatment, reduce disease morbidity and improve their quality of lives.</p>

Abstract 13655: Chronic Kidney Disease Progression and Prediction of Clinical Cardiovascular Disease and Total Mortality: The Coronary Artery Risk Development in Young Adults (cardia) Study

Introduction: The Kidney Disease Improving Global Outcomes (KDIGO)Guidelines proposed a chronic kidney disease (CKD) risk assessment matrix based on estimated glomerular filtration (eGFR) together with albuminuria categories (urine albumin-to-creatinine (ACR)). This classification system tends to focus on nuances at the severe CKD end of the spectrum among middle-aged and older adults. We expanded the KDIGO risk categories to include less severe manifestations of CKD, applicable to a generally healthy population in young adulthood. Hypothesis: CKD progression in its less severe range is common and predicts CVD and total mortality starting in generally healthy young adults. Methods: In a community-based sample of black and white men and women, both eGFR (creatinine) and spot urine ACR were assayed at study year 10 (age 27-41y) and every 5 y for 20 y through year 30. We expanded the 4 KDIGO risk categories by adding 2 less severe categories (see Figure). We estimated CKD stage prevalence at each exam and transition probabilities, including 4389 participants by year 30. We used proportional hazards regression with time-varying CKD stage, age, sex, and race as predictors of the endpoints any incident CVD or total death. Results: As expected, extreme risk was seen in 131 people (3% prevalence) who reached stages 4-6 (See Figure). Important increases in risk (hazard ratios 1.55 to 3.11) occurred in 1601 people (36% prevalence) who reached stages 2-3. Transition to higher stage (mostly by 1 stage) occurred in 5-10% per 5 years (~30% in 20 years). Conclusions: These data suggest that clinically important changes occur in CKD risk staging throughout middle age, though most of these changes are currently regarded as minor occurrences. Research should explore whether more aggressive, low risk treatment options, which currently exist, would be beneficial in people with small changes in CKD stage, starting in young adulthood.

Novel poricoic acids attenuate renal fibrosis through regulating redox signalling and aryl hydrocarbon receptor activation

BackgroundRenal fibrosis is the final manifestation of chronic kidney disease (CKD). Renal fibrosis is largely driven by oxidative stress and inflammation. PurposeThe aim of the current study was to identify novel poricoic acids from Poria cocos and investigated their antifibrotic effects and the underlying mechanism. MethodsIn this study, we identified six novel poricoic acids from Poria cocos and examined their antifibrotic effect using transforming growth factor-β1- (TGF-β1-) induced cultured human kidney proximal tubular epithelial cells (HK-2) and mice with unilateral ureteral obstruction (UUO). ResultsTreatment with six poricoic acids significantly inhibited TGF-β1-induced α-smooth muscle actin expression at both mRNA and protein levels in HK-2 cells. Three compounds with an intact carboxyl group at C-3 position showed a stronger inhibitory effect than that of other three compounds with esterified carboxyl group at the C-3 position. Mechanistically, poricoic acid ZM (PZM) and poricoic acid ZP (PZP) attenuate renal fibrosis through the modulation of redox signalling including the inhibition of proinflammatory nuclear factor kappa B (NF-κB) signalling and its target genes as well as the activation of antioxidative nuclear factor-erythroid-2-related factor 2 (Nrf2) signalling and its downstream target gene in both TGF-β1-induced HK-2 cells and UUO mice. PZM treatment and PZP treatment inhibit the upregulated aryl hydrocarbon receptor and they target the gene expression in UUO mice. Intriguingly, PZM treatment exhibits a stronger inhibitory effect than that of the PZP treatment. Structure–function relationship reveals that the carboxyl group at C-3 position is the most important bioactive function group in secolanostane tetracyclic triterpenoids against renal fibrosis. ConclusionsPZM and PZP attenuated renal fibrosis through the modulation of redox signalling and the aryl hydrocarbon receptor signalling pathway. Our findings will provide several promising leading compounds against renal fibrosis.

Chronic Kidney Disease in Children: A Review

Chronic kidney disease (CKD) in children is a life-consuming ailment with a variable but progressive course. CKD, in particular, the end stage kidney disease (ESKD) affects multiple body systems complexed with secondary complications that significantly and adversely affect the growth, development and quality of life. Although uncommon in children, CKD poses unique challenges to the health care delivery system to manage the primary renal disorders and extrarenal manifestations of CKD along with a heavy socioeconomic burden. Despite the availability of better management tools, there is a rise in incidence and prevalence of pediatric CKD for which wide range short- and long-term planning is inevitable that will lure the medicos to acquire the advanced nephrological training and skills, besides providing quality infrastructure and sustained socio-economic support. Our review is aimed to provide recent advances regarding the evaluation and management of pediatric CKD and its complications.

LncRNA PVT1 Suppresses the Progression of Renal Fibrosis via Inactivation of TGF-β Signaling Pathway.

BackgroundRenal fibrosis is a frequent pathway leading to end-stage kidney dysfunction. In addition, renal fibrosis is the ultimate manifestation of chronic kidney diseases (CKD). Long noncoding RNAs (lncRNAs) are known to be involved in occurrence of renal fibrosis, and lncRNA plasmacytoma variant translocation 1 (PVT1) has been reported to act as a key biomarker in renal diseases. However, the role of PVT1 in renal fibrosis remains unclear.Materials and MethodsHK-2 cells were treated with TGF-β1 to mimic renal fibrosis in vitro. Gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of creatinine (CR) and blood urea nitrogen (BUN) in serum of mice. Additionally, unilateral ureteral obstruction (UUO)-induced renal fibrosis mice model was established to investigate the effect of PVT1 on renal fibrosis in vivo.ResultsPVT1 was upregulated in TGF-β1-treated HK-2 cells. In addition, TGF-β1-induced upregulation of α-SMA and fibronectin in HK-2 cells was significantly reversed by PVT1 knockdown. Meanwhile, PVT1 bound to miR-181a-5p in HK-2 cells. Moreover, miR-181a-5p directly targeted TGF-βR1. Furthermore, miR-181a-5p antagonist could significantly reverse the anti-fibrotic effect of PVT1 knockdown. Besides, knockdown of PVT1 notably attenuated the symptom of renal fibrosis in vivo.ConclusionKnockdown of PVT1 significantly inhibited the progression of renal fibrosis in vitro and in vivo. Thus, PVT1 may serve as a potential target for the treatment of renal fibrosis.

Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study.

AimsTo examine the manifestation of cardiovascular or renal disease (CVRD) in patients with type 2 diabetes (T2D) initially free from CVRD as well as the mortality risks associated with these diseases.MethodsPatients free from CVRD were identified from healthcare records in England, Germany, Japan, the Netherlands, Norway and Sweden at a fixed date. CVRD manifestation was defined by first diagnosis of cardiorenal disease, or a stroke, myocardial infarction (MI) or peripheral artery disease (PAD) event. The mortality risk associated with single CVRD history of heart failure (HF), chronic kidney disease (CKD), MI, stroke or PAD was compared with that associated with CVRD‐free status.ResultsOf 1 177 896 patients with T2D, 772 336 (66%) were CVRD‐free and followed for a mean of 4.5 years. A total of 137 081 patients (18%) developed a first CVRD manifestation, represented by CKD (36%), HF (24%), stroke (16%), MI (14%) and PAD (10%). HF or CKD was associated with increased cardiovascular and all‐cause mortality risk: hazard ratio (HR) 2.02 (95% confidence interval [CI] 1.75–2.33) and HR 2.05 (95% CI 1.82–2.32), respectively. HF and CKD were separately associated with significantly increased mortality risks, and the combination was associated with the highest cardiovascular and all‐cause mortality risk: HRs 3.91 (95% CI 3.02–5.07) and 3.14 (95% CI 2.90–3.40), respectively.ConclusionIn a large multinational study of >750 000 CVRD‐free patients with T2D, HF and CKD were consistently the most frequent first cardiovascular disease manifestations and were also associated with increased mortality risks. These novel findings show these cardiorenal diseases to be important and serious complications requiring improved preventive strategies.

Recent advances in understanding the role of hypoxia-inducible factor 1α in renal fibrosis.

Renal fibrosis is the most common pathological manifestation of chronic kidney disease (CKD), and with numerous influencing factors, its pathogenesis is complex. Epithelial-mesenchymal transition (EMT) is known to promote the progression of renal fibrosis via alterations in the secreted proteome. Moreover, blocking or even reversing EMT can effectively reduce the degree of fibrosis. As such, targeting the key molecules responsible for promoting EMT may be an effective strategy for inhibiting renal fibrosis. Research in recent years has demonstrated that hypoxia-inducible factor 1α (HIF-1α) acts to promote renal fibrosis through regulation of EMT. However, the relationship between HIF-1α and EMT remains incompletely understood. In the present review, the underlying mechanism of the interaction between HIF-1α and EMT is explored to provide novel insight into the pathogenesis of renal fibrosis and new ideas for early targeted intervention.

Protective role of renal proximal tubular alpha-synuclein in the pathogenesis of kidney fibrosis

Kidney fibrosis is a highly deleterious process and a final manifestation of chronic kidney disease. Alpha-(α)-synuclein (SNCA) is an actin-binding neuronal protein with various functions within the brain; however, its role in other tissues is unknown. Here, we describe the expression of SNCA in renal epithelial cells and demonstrate its decrease in renal tubules of murine and human fibrotic kidneys, as well as its downregulation in renal proximal tubular epithelial cells (RPTECs) after TGF-β1 treatment. shRNA-mediated knockdown of SNCA in RPTECs results in de novo expression of vimentin and α-SMA, while SNCA overexpression represses TGF-β1-induced mesenchymal markers. Conditional gene silencing of SNCA in RPTECs leads to an exacerbated tubulointerstitial fibrosis (TIF) in two unrelated in vivo fibrotic models, which is associated with an increased activation of MAPK-p38 and PI3K-Akt pathways. Our study provides an evidence that disruption of SNCA signaling in RPTECs contributes to the pathogenesis of renal TIF by facilitating partial epithelial-to-mesenchymal transition and extracellular matrix accumulation.

Chronodisruption: A Poorly Recognized Feature of CKD.

Multiple physiological variables change over time in a predictable and repetitive manner, guided by molecular clocks that respond to external and internal clues and are coordinated by a central clock. The kidney is the site of one of the most active peripheral clocks. Biological rhythms, of which the best known are circadian rhythms, are required for normal physiology of the kidneys and other organs. Chronodisruption refers to the chronic disruption of circadian rhythms leading to disease. While there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate chronic kidney disease (CKD) progression, there is no comprehensive review on chronodisruption and chronodisruptors in CKD and its manifestations. Indeed, the term chronodisruption has been rarely applied to CKD despite chronodisruptors being potential therapeutic targets in CKD patients. We now discuss evidence for chronodisruption in CKD and the impact of chronodisruption on CKD manifestations, identify potential chronodisruptors, some of them uremic toxins, and their therapeutic implications, and discuss current unanswered questions on this topic.

MULTIPLE MYELOMA: CHALLENGES OF DIFFERENTIAL DIAGNOSIS (CLINICAL CASE)

The objective of our study was to interpret and discuss atypical multiple myeloma case. The article describes the case of clinical observation of a patient K, in which manifestations of chronic kidney disease and circulatory failure prevailed in clinical picture of the disease. The authors recommended an X-ray examination of skull and pelvic bones as a screening method suitable for elderly people with symptoms of chronic renal insufficiency and chronic bone and muscle pain resistant to treatment.

NON-DIABETIC GLUCOSURIA AS ONE OF THE POSSIBLE FACTORS OF FORMATION OF CHRONIC KIDNEY DISEASE

Relevance. The reason for this study was the discovery of patients with clinical and laboratory manifestations of chronic kidney disease (CKD) in the lumen of the tubules of red blood cells and their decay products during nephrobiopsy1. It is known that the appearance of glucose in urine makes an ideal nutrient base for microorganisms that provoke chronic microbial inflammatory damage to the kidneys. Glycated hemoglobin is included in 5% of red blood cells in healthy adults. Its increase is associated with episodes of glycemia exceeding 6.5 mmol/l. which occuts in diabetes decompensation. Moreover, glycated hemoglobin has toxic properties with respect to the viability of the surrounding cytomembranes. This explains the large number of multiple organ diabetic complications 2,3. At the same time, it was found that the biochemical process of glycation of not only hemoglobin, but also other cellular glucoproteins is accompanied by oxidative damage to cytomembranes leading to their structural and functional failure 4,5. However, the role of glycated hemoglobin and glucose released during the deteriation of erythrocytes in the renal tubules, as one of the possible pathogenetic factors in the occurrence of chronic kidney disease, no one has previously analyzed.

Involvement of hydrogen sulfide in the progression of renal fibrosis.

ObjectiveRenal fibrosis is the most common manifestation of chronic kidney disease (CKD). Noting that existing treatments of renal fibrosis only slow disease progression but do not cure it, there is an urgent need to identify novel therapies. Hydrogen sulfide (H2S) is a newly discovered endogenous small gas signaling molecule exerting a wide range of biologic actions in our body. This review illustrates recent experimental findings on the mechanisms underlying the therapeutic effects of H2S against renal fibrosis and highlights its potential in future clinical application.Data sourcesLiterature was collected from PubMed until February 2019, using the search terms including “Hydrogen sulfide,” “Chronic kidney disease,” “Renal interstitial fibrosis,” “Kidney disease,” “Inflammation factor,” “Oxidative stress,” “Epithelial-to-mesenchymal transition,” “H2S donor,” “Hypertensive kidney dysfunction,” “Myofibroblasts,” “Vascular remodeling,” “transforming growth factor (TGF)-beta/Smads signaling,” and “Sulfate potassium channels.”Study selectionLiterature was mainly derived from English articles or articles that could be obtained with English abstracts. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors’ files.ResultsThe experimental data confirmed that H2S is widely involved in various renal pathologies by suppressing inflammation and oxidative stress, inhibiting the activation of fibrosis-related cells and their cytokine expression, ameliorating vascular remodeling and high blood pressure, stimulating tubular cell regeneration, as well as reducing apoptosis, autophagy, and hypertrophy. Therefore, H2S represents an alternative or additional therapeutic approach for renal fibrosis.ConclusionsWe postulate that H2S may delay the occurrence and progress of renal fibrosis, thus protecting renal function. Further experiments are required to explore the precise role of H2S in renal fibrosis and its application in clinical treatment.

Effects of single and dual RAAS blockade therapy on progressive kidney disease transition to CKD in rats.

Ischemic reperfusion (I/R) is the primary cause of acute kidney injury (AKI) in hospitalized patients. Although AKI resolution occurs in few days, it predisposes kidneys to progressive renal injury. Previously, administration of rennin-angiotensin-aldosterone system (RAAS) blocker spironolactone in acute phase was reported to attenuate various manifestations of chronic kidney disease (CKD) in rats. The present study investigates the effects of RAAS blockade during progressive kidney disease (30 days onwards) on CKD outcomes in rodent model of I/R injury. CKD was induced by clamping both renal pedicles for 45 min followed by 90 days of reperfusion in rats. Single and dual RAAS blocker therapy was initiated at 30 days post-I/R injury and continued until the end of the study period. Evaluation of proteinuria and creatinine levels was done every 30 days in various study groups. Assessment of CKD was done by analyzing renal tissue oxidative stress, inflammatory biomarker levels, and histological changes after 90 days of I/R injury. After 90 days, I/R rat kidneys displayed hypertrophy, reduced body weight, increased oxidative stress, elevated inflammatory biomarker levels, and histological abnormalities such as glomerulosclerosis, mesangial expansion, and tubulointerstitial fibrosis. Treatment with losartan or spironolactone alone significantly reduced various CKD-associated features. Remarkably, combined treatment with dual RAAS blocker in low dose or high dose exhibited highest beneficial effects on various parameters in CKD model, with low-dose combination showing fewer side effects. Therefore, we propose that combined low-dose RAAS blockade therapy might serve as a better therapeutic approach for retarding progressive kidney disease transition to CKD.

Characterization of Matricellular Protein Expression Signatures in Mechanistically Diverse Mouse Models of Kidney Injury

Fibrosis is the most common pathophysiological manifestation of Chronic Kidney Disease (CKD). It is defined as excessive deposition of extracellular matrix (ECM) proteins. Embedded within the ECM are a family of proteins called Matricellular Proteins (MCPs), which are typically expressed during chronic pathologies for ECM processing. As such, identifying potential MCPs in the pathological secretome of a damaged kidney could serve as diagnostic/therapeutic targets of fibrosis. Using published RNA-Seq data from two kidney injury mouse models of different etiologies, Folic Acid (FA) and Unilateral Ureteral Obstruction (UUO), we compared and contrasted the expression profile of various members from well-known MCP families during the Acute and Fibrotic injury phases. As a result, we identified common and distinct MCP expression signatures between both injury models. Bioinformatic analysis of their differentially expressed MCP genes revealed similar top annotation clusters from Molecular Function and Biological Process networks, which are those commonly involved in fibrosis. Using kidney lysates from FA- and UUO-injured mice, we selected MCP genes from our candidate list to confirm mRNA expression by Western Blot, which correlated with injury progression. Understanding the expressions of MCPs will provide important insight into the processes of kidney repair, and may validate MCPs as biomarkers and/or therapeutic targets of CKD.

Renal Dysplasia in a Maltese dog

Background: Renal dysplasia (RD) is a common cause of renal failure in young dogs. It is defined as a disorganization in renal parenchymal development, with abnormal differentiation. In all domestic animal species, RD may be hereditary or acquired. The affected animals show clinical signs of early chronic kidney disease, usually between 3 months to 3 years of age. The alterations include persistent metanephric ducts surrounded by primitive mesenchyme, glomeruli and fetal tubules, and abnormal interstitial fibrous tissue. We aimed to report the case of a 1-year-old canine with renal dysplasia.Case: A 1-year-old male Maltese dog experiencing polyuria, polydipsia, recurrent episodic vomiting, bloody diarrhea, weight loss, apathy, and anorexia was referred to a private clinic in the municipality of Itabuna-Bahia. Physical examination revealed hypochromic mucosa, dehydration estimated at 8%, rectal temperature of 37.5º C, halitosis, and a body score of 3 out of 9. Laboratory abnormalities included hematocrit of 18%, with hypochromic normocytic aregenerative anemia, azotemia (urea - 530 mg/dL, creatinine - 10.5 mg/dL), hyperglobulinemia (4.7 g/dL), low urinary density (1005), proteinuria (300 mg/dL), and urinary pH - 7.0. Ultrasonography revealed bilateral small kidneys with loss of cortico-medullary definition, cystic formations of different sizes on the renal surface, and hyperechoic areas in the parenchyma; these alterations were suggestive of bilateral chronic nephropathy. Considering the clinical, hematological, biochemical, and ultrasonographic presentation associated with the age of the patient, renal dysplasia was suspected. The patient's clinical condition progressed to loss of consciousness and convulsions, followed by death. Necropsy revealed pale, hypotrophic kidneys with firm consistency, irregular capsular surface containing multiple cortical cysts of different sizes, and altered cortico-medullar proportion. . Kidney fragments were sent to the Laboratory of Histopathology of the State University of Santa Cruz. Histopathological analysis revealed a marked alteration of renal architecture with glomeruli and immature tubules (adenomatous aspect), persistent primitive mesenchyme, and remnants of the metanephric ducts, as well as tubular dilatation associated with marked interstitial fibrosis, discrete lymphohistiocytic interstitial nephritis, and multifocal areas of mineralization.Discussion: The clinical changes observed in the present case occurred as a consequence of chronic kidney failure caused by RD and included anorexia, apathy, vomiting, bloody diarrhea, polyuria, polydipsia, and dehydration. These alterations were also found in other reported cases. The macroscopic findings were similar to those described in the literature and are characteristic of chronic kidney disease: small, firm, pale-colored kidneys. Microscopic changes of renal dysplasia include persistent metanephric ducts surrounded by primitive mesenchyme, glomeruli and fetal tubules, and abnormal interstitial fibrous tissue. In the histopathological renal evaluation in the present report, morphological alterations compatible with the described alterations in the literature were observed, thus allowing the diagnosis of renal dysplasia. Renal dysplasia can affect young dogs of different breeds, causing clinical manifestations of chronic kidney disease. In view of this, this disease should be included as a differential diagnosis in patients under 3 years old who present signs of chronic nephropathy.

Outcome of “Renal Diet Therapy and Deep Breathing Exercises” on Biochemical Parameters in Chronic Kidney Disease Patients of Shere Kashmir Institute of Medical Sciences (SKIMS) Soura Srinagar Kashmir

Chronic Kidney Disease (CKD) is an irreversible and progressive reduction of renal tissue function which affects almost all other systems of the body. It often goes undiagnosed and therefore remains undertreated. For this reason, various biochemical parameters such as: serum creatinine and blood urea nitrogen, urinary protein, urinary albumin, urinary creatinine and Glomerular Filtration Rate (GFR) act as baseline predictors in early detection and management of CKD manifestations. Hence the present study was undertaken to find out the outcome of “Renal diet therapy and Deep breathing exercises” on 21 kidney related biochemical parameters among adult CKD patients who were admitted in SKIMS from 5th March 2012 to 31st July 2013.A total of 200 adult CKD patients being randomly selected were studied in two groups (experimental=100; control=100). The findings of the study revealed that CKD patients in the experimental group who received “Renal diet therapy and Deep breathing exercises” reported a considerable improvement (p≤0.05) in 11 biochemical parameters including: fasting serum glucose, cholesterol, triglycerides, HDL, LDL, calcium, phosphorus, potassium, chloride, hematocrit and platelets as compared to CKD patients in control group who received routine care, had shown a considerable improvement (p≤0.05) in only 5 biochemical parameters such as: fasting serum glucose, cholesterol, triglycerides, calcium and phosphorus. Hence, it can be inferred that “Renal diet therapy and Deep breathing exercises” were effective in regulating various biochemical parameters within normal level in CKD patients. However, the long-term efficacy of these non-pharmacological therapies need to be investigated.

Biomarkers and the role of mast cells as facilitators of inflammation and fibrosis in chronic kidney disease.

Chronic kidney disease (CKD) is a clinical syndrome with many adverse sequelae and is currently a major global health and economic burden. Regardless of aetiology, inflammation and fibrosis are common manifestations of CKD. Unfortunately, the underlying pathophysiological mechanisms are poorly understood, and robust prognostic and early diagnostic biomarkers of CKD are lacking. One immune cell population that has received little attention in the context of CKD is mast cells (MCs). This mini review will examine the role of MCs as facilitators of kidney inflammation and fibrosis, propose a mechanistic structure for MCs in CKD, and give consideration to biomarkers specific for MC activation that can be deployed clinically. MCs are derived from haematopoietic stem cells. They are characterised by electron-dense granules in the cytoplasm, filled with preformed mediators. MCs can synthesise a range of bio-active compounds. Activation of MCs modulates an innate immune and adaptive effector response. Increased MC counts have been observed in animal models of kidney disease and a range of kidney diseases in humans where MC presence has been linked to biomarkers of kidney function and tissue damage. To further implicate MCs in CKD, several chemokines, cytokines and proteases released by MCs have been observed in their own right in various kidney diseases and linked to progressive CKD. One compound released by MCs that is of particular interest is the MC-specific protease tryptase. This protease is capable of activating the G-protein coupled receptor (GPCR) protease activated receptor-2 (PAR-2). PAR-2 is widely expressed throughout the kidney and highly expressed in the tubular epithelial cells where its activation induces robust inflammatory and fibrotic responses. Novel prognostic and diagnostic biomarkers of CKD are needed. MC-specific proteases [tryptase, chymase and carboxypeptidase A3 (CPA3)] are easily detectable in the blood but questionably in the urine. This review aims to promote these as prognostic and diagnostic biomarkers in the context of CKD.