Tubular Lesions Research Articles

Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? PRO.

Chronic interstitial nephritis in agricultural communities (CINAC), also named CKD of unknown origin (CKDu) or Mesoamerican nephropathy (MeN), is defined as a form of CKD affecting young men and—less often—women. Its etiology is unrelated to diabetes, GN, hypertension, or other known causes of CKD. Patients with CINAC live and work mainly in poor agricultural communities, often in hot tropical regions, and are exposed to potentially toxic agrochemicals through work by ingestion of contaminated food and water, and/or by inhalation (1,2). The epidemic dimension of CINAC was first observed in the 1990s in Sri Lanka and Central America and has since been found to be an important cause of CKD-related deaths in an increasing number of countries (3,4). Patients with CINAC have bilateral, small, irregularly contoured kidneys with mutual size discrepancy of <1.5 cm on ultrasound, as observed in advanced cases of analgesic nephropathy and aristolochic nephropathy (5,6). Almost all patients with CINAC exhibit a proximal tubular lesion: tubular cell atrophy, basement membrane thickening, deficient proximal tubular cell (PTC) regeneration, loss of function, distal tubular proliferation/hypertrophy, and variable extents of interstitial fibrosis and cellular infiltration. Overt glomerular injury is rare in the early stages, whereas secondary glomerulosclerosis develops in later CKD stages. By electron microscopy, PTCs demonstrate enlarged dysmorphic lysosomes (≥1.2 µ m) containing homogenous nonmembrane-bound, electron-dense, rounded/irregular “aggregates” dispersed throughout the light-to-medium, uniform, electron-dense lysosomal matrix (7) (Figure 1). These features are also observed in a number of toxin-induced nephropathies. Figure 1. Overview of the constellation of proximal tubular lesions observed in patients with chronic interstitial nephritis in agricultural communities/CKD of unknown origin. (A) Proximal tubular cells containing many enlarged argyrophilic granules, demonstrated to be lysosomes (arrowheads) (7) (Periodic acid–Schiff methenamine [PASM] staining). (B) Affected proximal tubule demonstrating enlarged lysosomes, flattened atrophic epithelial cells with …

Hemangioma of long tubular bone: imaging characteristics with emphasis on magnetic resonance imaging.

To investigate the imaging findings, especially the MRI findings, of intraosseous hemangioma of long tubular bones and to improve the recognition of this rare tumor. The imaging characteristics of 16 histopathologically diagnosed long tubular bone hemangioma lesions were retrospectively reviewed on radiography (n = 16), CT (n = 16), and MRI (n = 15). Thirteen of 16 lesions were intramedullary, whereas the other three were cortical, subperiosteal, and mixed intracortical and intramedullary, respectively. The radiologic appearance of long bone intraosseous hemangioma was divided into five types: cyst-like (n = 7), mesh- or honeycomb-like (n = 6), medullary sclerosis (n = 1), cortical thickening (n = 1), and cortical lytic type (n = 1). Radiography and CT allowed the identification of sclerotic margins in eight cases, thickened trabeculae in six cases, internal calcification in one case, cortical thickening in one case, and fracture in four cases. Two lesions were confusing on radiography but clearly identifiable on MRI. All intraosseous hemangioma showed high signal intensity on T2-weighted imaging and intermediate signal intensity on T1-weighted imaging. Four cyst-like lesions showed peripheral and filling enhancement, whereas others exhibited diffuse enhancement with an intensity similar to adjacent vessels. Cystic and mesh types are the most common types of hemangioma in long tubular bones. MRI can help to define the location and extent of lesions. The tumor usually shows high signal intensity on T2-weighted imaging and intermediate signal intensity on T1-weighted imaging. Peripheral and filling or diffuse enhancement with an intensity similar to vessels is helpful for the diagnosis of intraosseous hemangioma.

Oxymatrine Inhibits Twist-Mediated Renal Tubulointerstitial Fibrosis by Upregulating Id2 Expression.

The final pathway for the development of diabetic nephropathy (DN) into chronic renal failure in DN is glomerulosclerosis and tubulointerstitial fibrosis. Renal tubular lesions can occur in the early stage of DN renal injury. Cumulative evidence shows that oxymatrine (OMT) has a variety of biological and pharmacological properties. In recent years, more attention has been paid on the preventive and therapeutic influence of OMT on organ fibrosis. In this experiment, db/db mice were intraperitoneally injected with OMT 120 mg/kg for 8 weeks, and NRK-52E cultured with 30 mmol/L glucose and 0.1 mg/mL OMT for 48-hour. We investigated the relationship between Id2 and Twist in NRK-52E cells and the effect of OMT on the expression of E-cadherin, α-SMA, Fibronectin, and Collagen-IV by Western blot, Real-time PCR, Immunofluorescence, cell transfection, Co-Immunoprecipitation, and Luciferase assays. OMT increased the expression of Id2 but decreased that of Twist under high glucose condition in vitro and in vivo. The promoted recovery of Id2 facilitated its binding to Twist and affected E-cadherin activity inhibiting EMT and the excessive proliferation and abnormal deposition of ECM. In brief, OMT promotes Id2 to reverse EMT and exert anti-fibrotic effect in diabetic renal tubular epithelial cells by binding Id2 to Twist and affecting its transcriptional activation of downstream target genes. Or findings provide a new experimental basis for delaying the progress and for treatment of diabetic renal fibrosis.

P0661DIAGNOSTIC VALUE OF FULL AGE SPECTRUM EQUATION AS A PREDICTOR OF MORPHOLOGICAL LESIONS IN PATIENTS WITH GLOMERULONEPHRITIS

Abstract Background and Aims Glomerular filtration rate (GFR) is generally accepted as a best overall index of kidney function. However, it remains controversial to choose the optimal equation to estimate GFR in patients with glomerulonephritis (GN). Recent studies have reported that newly developed full age spectrum equation based on normalized serum creatinine (FASsCr) showed improved validity and was less biased, more accurate than currently recommended sCr-based eGFR equations. Our aim was to assess FASsCr equation as a predictor of various morphological lesions in patients with GN. Method 100 patients [48 female, age Me 39 (27; 54) years] with biopsy proven primary GN and without acute kidney injury, infectious diseases, severe heart failure, respiratory insufficiency, cancer were included in the study. Minimal change disease was diagnosed in 9% of cases based on the results of kidney biopsy, in 28% – focal segmental glomerulosclerosis, in 26% – membranous nephropathy and in 37% – IgA-nephropathy. Serum creatinine (sCr) level was measured by enzymatic method (Uni Cel DxC 800 PRO, «Beckman Coulter»,USA). eGFR was calculated using FASsCr equation. The extent of global glomerulosclerosis (GS) was assessed quantitatively as a sum of full and focal sclerotic glomeruli. Tubulo-interstitial fibrosis (TIF) and tubular atrophy (TA) were assessed semi-quantitatively (0-lesions absent; 1-mild focal tubular and interstitial lesions; 2-moderate tubular and interstitial lesions; 3 - diffuse tubular and interstitial lesions). All patients consistently were separated into 2 groups according to the degree of each morphological lesion (GS, TIF or TA): “mild” (GS&amp;lt;25% or TIF/TA grade 0 or 1) and “severe” (GS ≥ than 25% or TIF/TA grade 2-3). Results eGFR using FASsCr equation positively correlated (p&amp;lt;0,001 in all cases) with GS (r=0,44), TIF (r=0,64) and TA (r=0,61) and was significantly higher in patients with “mild” GS, TIF and TA (p&amp;lt;0,001) in comparison with “severe” group. Using ROC-analysis all patients were separated (p&amp;lt;0.001) in 2 groups using FASsCr equation according to the degree of morphological lesions (“mild” or “severe”): GS (Sn – 48.8%, Sp – 88.1%, ACC – 72.0%, AUC – 0.696, cut-off value – 47 ml/min/1.73m2), TIF (Sn - 75.4%, Sp – 76.9%, ACC – 76.0%, AUC – 0.815, cut-off value – 72 ml/min/1.73m2), TA (Sn – 65.9%, Sp – 88.8%, ACC – 70.0%, AUC – 0.798, cut-off value – 74 ml/min/1.73m2), (Figure). Conclusion Our results show that FASsCr equation is a significant marker of various morphological lesions in patients with GN. FASsCr equation predominantly can be used as a predictor of mild degree of interstitial sclerosis and tubular atrophy with high diagnostic value. Figure: ROC curves with 95% CI of BM panel for A – GS; B – TIF; C – TA

P0099CALCINEURIN INHIBITION, BUT NOT DEHYDRATION, IN RATS MIMICS HUMAN RENAL HISTOPATHOLOGY OF PATIENTS WITH CHRONIC INTERSTITIAL NEPHRITIS IN AGRICULTURAL COMMUNITIES (CINAC)

Abstract Background and Aims CINAC patients present a newly discovered constellation of proximal tubular lysosomal lesions which is also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy involving calcineurin inhibition. An alternate hypothesis advocates chronic heat stress/dehydration as the major etiological factor for CINAC. Here, we evaluated in rats to what extent heat stress/dehydration versus CNI exposure reflects proximal tubular CINAC histopathology. Method Wistar rats were divided in 3 groups. Group 1 (n=6) was given water ad libitum (control group). Group 2 (n=8) was water deprived for 10 hours per 24h, 5 days/week and were placed in an incubator (37°C) for 30 min/hr of water deprivation. Group 3 (n=8) underwent daily oral gavage with cyclosporine (50mg/kg body weight). Animals were weighed daily and urine was collected at day 3, 17 and 28. After 28 days, rats were sacrificed. Kidneys were collected for light (LM) and electron microscopic (EM) histopathological analysis as well as for cortical renal tissue proteomics. Results Cyclosporine rats developed focal cortical lesions mimicking those of CINAC patients: i.e. atrophic proximal tubuli with thickened basement membranes and associated tubulo-interstitial fibrosis, PASM staining demonstrating enlarged argyrophyllic granules in the affected proximal tubuli, LAMP1 immunofluorescent staining identifying a subset of these granules as lysosomes, and EM confirming the presence of enlarged lysosomes, some dysmorphic approaching CINAC lysosomes. In dehydrated rats, confirmed by urinary osmolality and fluctuating body weight associated with water deprivation, none of the cyclosporine features were observed. Proteomic analysis confirmed cellular toxicity by cyclosporine, whereas the dehydration group lacked any markers of such. Conclusion The histopathological analogy between CNI nephrotoxicity in rats and humans and CINAC suggests a toxicological etiology for CINAC. In rats, dehydration/heat stress alone does not lead to the constellation of proximal tubular lesions as observed in CINAC patients.

P0445PREVALENCE AND PREDICTORS OF GLYCOSURIA IN PRIMARY GLOMERULOPATHIES

Abstract Background and Aims Albuminuria is a marker of glomerular lesion, however some studies have suggested that proximal tubule (endocytosis of albumin) is also essential to determine the amount of albumin excreted in the urine. It has been hypothesized that patients with glomerulopathies and concomitant tubular damage might present higher levels of albuminuria. Glycosuria is a marker of proximal tubular dysfunction and may be used as an easy and useful marker of tubular lesion in glomerular diseases. The aim of this transversal study was to evaluate the prevalence of glycosuria in primary glomerulopathies (GP) and identify its predictors. Method We included all patients diagnosed in the last 10 years in our centre with primary GP confirmed by renal biopsy. Clinical, laboratory and biopsy results were collected from patients’ charts. Patients were divided in two groups according to their glycosuric status at the diagnosis. Exclusion criteria: patients with diabetes and glucose intolerance, use of SGLT2 inhibitors, transplant kidney patients and secondary GP. Results We studied 110 patients – 39 (35.5%) IgA Nephropathy (IgAN), 27 (24.5%) Membranous Nephropathy (MN), 26 (23.6%) Focal Segmental Glomerulosclerosis (FSGS) and 18 (16.4%) Minimal Change Disease (MCD). Demographic data were not different between patients with and without glycosuria. Global prevalence of glycosuria was 9.1% (n=10) – patients with MN had higher prevalence of glycosuria (n=4, 17.4%), followed by FSGS (n=3, 15.5%), MCD (n=1, 5.9%) and IgAN (n=2, 5.4%). We found that patients with glycosuria had higher serum creatinine (3.9±5.1 vs 1.7±1.3 mg/dL, p=0.001), higher albuminuria (7.1±6.3 vs 3.2±3.4 g/g, p=0.002), lower serum albumin (2.3±0.7 vs 3.2±1.1 g/dL, p=0.022) and lower hemoglobin (12.0±2.5 vs 13.4±2.0 g/dL, p=0.050). Nevertheless, we did not find differences between glycosuric and non-glycosuric patients in percentage of glomerular sclerosis (%GS) or interstitial fibrosis and tubular atrophy (IFTA). In a multivariate analysis, glycosuria was positively associated with MN diagnosis, serum creatinine and albuminuria, but not with hematuria, %GS and IFTA. Conclusion Glycosuria is not frequent in primary GP. MN is the primary GP that most frequently presents glycosuria. Glycosuria is associated with higher albuminuria and lower serum albumin levels, corroborating the hypothesis that albuminuria as an offender to the tubules will affect the amount of albumin excreted in the urine. We also found that patients with glycosuria presented a more severe renal dysfunction (higher creatinine) at the GP diagnosis.

P0470IS GLYCOSURIA A MARKER OF TUBULO-INTERSTITITAL FIBROSIS AND PROGNOSIS IN PRIMARY GLOMERULOPATHIES?

Abstract Background and Aims Multiple studies have shown that tubular damage is common in glomerular diseases and that it correlates better with chronic kidney disease (CKD) progression than glomerular lesion itself. The link between glomerular and tubular damage is not entirely established. Glycosuria can be found in (proximal) tubular dysfunction and may be used as a marker of tubular lesion and CKD progression. The aim of this study was to evaluate the association between glycosuria (at the diagnosis) and known histological prognostic markers (glomerular sclerosis (%GS) and interstitial fibrosis/tubular atrophy (IFTA)) and CKD progression, in patients with primary glomerulopathies (GP). Method We conducted a 36-month retrospective cohort study with 110 patients with primary GP confirmed by renal biopsy in the last 10 years in our centre – 39 (35.5%) IgA Nephropathy, 27 (24.5%) Membranous Nephropathy, 26 (23.6%) Focal Segmental Glomerulosclerosis and 18 (16.4%) Minimal Change Disease. Patients were divided in two groups according to their glycosuric status at the time of the diagnosis. Data was collected from patients’ charts. Exclusion criteria: patients with diabetes or glucose intolerance, use of SGLT2 inhibitors, secondary GP and transplant kidney patients. Results The global prevalence of glycosuria was 9.1% (n=10). Glycosuric patients had, at baseline, higher serum creatinine (3.9±5.1 vs 1.7±1.3mg/dL, p=0.001), higher baseline albuminuria (7.1±6.3 vs 3.2±3.4 g/g, p=0.002) and lower serum albumin (2.3±0.7 vs 3.2±1.1 g/dL, p=0.022). Both groups had similar proportion of patients that underwent immunosuppressive therapy. At the end of the follow-up, in glycosuric patients, only albuminuria was higher (3.3±0.6 vs 0.7±0.8 g/g, p&amp;lt;0.0001); the eGFR decline rate (ml/min/year), 3-year eGFR and 3-year CKD stage 5D incidence were not statistically different. Glomerular sclerosis (%GS) and interstitial fibrosis and tubular atrophy (IFTA) were not different between groups. These results were confirmed by multivariate analysis. Conclusion Patients with primary GP with glycosuria at diagnosis had higher baseline creatinine and albuminuria. Even though a worse clinical presentation, glycosuria was not associated with well-known prognostic factors (%GS and IFTA) or CKD progression. We can hypothesize that patients with primary GP with glycosuria have severe diseases at diagnosis, but the lesions may have greater reversibility. Prospective and longer studies are needed to confirm these results.

Effects of dexmedetomidine on new oxidative stress markers on renal ischaemia-reperfusion injury in rats: thiol/disulphide homeostasis and the ischaemia-modified albumin

Objectives This study investigated the effect of dexmedetomidine on the oxidant–antioxidant (thiol/disulphide) balance. Methods A total of 24 rats were divided into four groups. The renal arteries in groups IR (ischaemia/reperfusion) and IR + D (ischaemia/reperfusion + dexmedetomidine) were clamped for 45 min and reperfused for 180 min. Groups D (Dexmedetomidine) and IR + D were administered 100 μg/kg dexmedetomidine. Oxidant–antioxidant (thiol/disulphide) levels were measured. Kidney tissue was examined histopathologically. Results No statistically difference was found between the groups in terms of thiol–disulphide averages, while IMA, TOS and thiol–disulphide results showed a minimal decrease in Group IR + D compared to Group IR (p > 0.05). Tubular lesions and necrosis were found in 26–50% of tubules in Group IR. Tubular damage and necrosis in Group IR + D declined to 5–25% . Conclusions No statistically difference was found in the study where OSI index, thiol/disulphide balance and IMA were measured together as biochemical values.

New Insights into the Pathogenesis of Diabetic Nephropathy: Proximal Renal Tubules Are Primary Target of Oxidative Stress in Diabetic Kidney.

Diabetic nephropathy is a major source of end-stage renal failure, affecting about one-third cases of diabetes mellitus. It has long been accepted that diabetic nephropathy is mainly characterized by glomerular defects, while clinical observations have implied that renal tubular damage is closely linked to kidney dysfunction at the early stages of diabetic nephropathy. In this study, we conducted pathohistological analyses focusing on renal tubular lesions in the early-stage diabetic kidney with the use of a streptozotocin (STZ)-induced diabetes mellitus mouse model. The results revealed that histological alterations in renal tubules, shown by a vacuolar nucleic structure, accumulations of PAS-positive substance, and accelerated restoration stress, occur initially without the presence of glomerular lesions in the early-stage diabetic kidney, and that these tubular defects are localized mainly in proximal renal tubules. Moreover, enhanced expression of RAGE, suggesting an aberrant activation of AGEs-RAGE signaling pathway, and accumulation of oxidative modified mitochondria through the impaired autophagy/lysosome system, were also seen in the damaged diabetic proximal renal tubules. Our findings indicate that proximal tubular defects are the initial pathological events increasingly linked to the progression of diabetic nephropathy, and that controlling renal tubular damage could be an effective therapeutic strategy for the clinical treatment of diabetic nephropathy.

The study of the content of β-2-microglobulin in blood plasma and urine in modeling acute pyelonephritis and concomitant diabetes mellitus under conditions of drug exposure in the experiment

An indisputable criterion for the chronicity of pyelonephritis is damage to the tubulointerstitial tissue of the kidneys. One of the factors of the adverse course of pyelonephritis is an increase in the level of b-2 microglobulin in the blood and urine of patients. An increase in the concentration of serum b2-MG occurs with impaired renal function at the glomerular level, and an increase in the content of the peptide in the urine indicates tubular lesions. Therefore, studies of the pathogenetic features of the development of inflammatory kidney diseases against the background of concomitant diabetes mellitus in order to study the corrective effect of drugs with the metabolism of the corrective effect is an urgent task. The obtained data on changes in the content of b-2-Microglobulin indicate the important role of concomitant type II diabetes mellitus, and to a greater extent type I in the development of tubulointerstitial lesions in acute pyelonephritis in rats. Etio-pathogenetic drug correction, significantly contributed to the development of a tendency to normalize the level of b-2-Microglobulin in the body of animals with acute pyelonephritis with concomitant diabetes mellitus type I and II, it was noted a possible decrease in type I diabetes in blood plasma by 35, 4 % in urine by 38.7%, with type II diabetes in blood plasma by 39.0% and in urine by 41.4% in relation to the group with etiotropic drug exposure.

Influence of angiotensin-converting enzyme inhibitor ramipril on indicators of tubular kidney lesion in patients with chronic glomerulonephritis

Abstract To research and deepen the understanding of the links between morphological tubular kidney lesion parameters and serum markers – neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18), in patients with chronic glomerulonephritis (CGN) with saved renal function, as well as to estimate therapeutic correction of identified changes using ACE inhibitor ramipril. The diagnosis of “chronic glomerulonephritis” was verified based on clinical, laboratory and morphological data. Patients were divided into 2 clinical groups: patients with CGN and arterial hypertension (AH) and without AH. We used the data of renal biopsies to analyze the indicators of tubular kidney lesion in patients with CGN. Levels of serum NGAL and IL-18 were measured by means of ELISA kits. Treatment of patients was carried out over 24 weeks using the ACE inhibitor ramipril. The average daily dose of ramipril for the entire treatment period for patients with AH was 12.8±5.6 mg, patients of the second group – without AH, were treated with ramipril at a dose of 2.5 mg. On the basis of rank correlation analysis, we demonstrated that the level of serum NGAL is directly correlated with interstitial fibrosis (r=0.65; p&lt;0.05), serum IL-18 – with dystrophic changes in the epithelium of renal tubules (r=0.81; p&lt;0.05). Conclusion. Serum levels of NGAL and IL-18 are one of the most sensitive markers of tubular kidney lesion and have diagnostic efficiency up to 97%. A 24-week treatment with ACE inhibitor ramipril in patients with CGN with and without AH leads to a decrease in the levels of tubular kidney lesion markers.

Retrospective study: clinicopathological features and prognosis of idiopathic membranous nephropathy with seronegative anti-phospholipase A2 receptor antibody.

BackgroundTo discuss the clinicopathological features and prognosis of patients with idiopathic membranous nephropathy (IMN) who are serum-negative for the anti-PLA2R antibody.MethodOverall, 229 IMN patients were retrospectively collected in this study and classified into anti-PLA2R antibody-negative (PLA2R−, 59 cases) and antibody-positive (PLA2R+, 170 cases) groups. The clinical and pathological features of the PLA2R− group were analyzed; 162 patients in both groups were followed up, and the PLA2R antigen was detected in renal biopsies from the PLA2R− group. Kaplan-Meier and survival analyses were used to compare differences in prognosis.ResultsSerum albumin levels were higher and 24-hour urine protein, creatinine, and beta 2-microglobulin (BMG) levels were lower in the PLA2R− group than in the PLA2R+ group; the proportion of acute and chronic tubular lesions was also significantly lower in the PLA2R− group than in in the PLA2R+ group. After treatment, the remission rate was significantly higher in the negative group than in the positive group (93.02% vs 74.78%,), especially the rate of complete remission (51.16% vs 23.47%). Furthermore, the PLA2R antigen-positive staining rate of 43 patients in the PLA2R− group was 62.79%. Although not significant, the survival rate was higher in the PLA2R− group than in the PLA2R+ group. BMG, 24-hour urine protein and acute and chronic tubular lesions were risk factors for kidney death, and 24-hour urine protein was an independent risk factor for kidney death.ConclusionsCompared with the PLA2R+ group, the PLA2R− group had mild clinical manifestations and pathological damage and a higher clinical treatment remission rate. Renal tissue PLA2R antigen testing can be considered for patients with seronegative IMN to increase the diagnostic rate.

Nanofibrillar Decellularized Wharton's Jelly Matrix for Segmental Tracheal Repair

AbstractWharton's jelly (WJ) is considered a potential scaffold in tissue‐engineered trachea for its similar composition and function to cartilage tissue. However, the feasibility of using WJ to construct engineered neocartilage tissue has not been reported, let alone tubular tracheal cartilage regeneration and segmental tracheal lesion repair. Here, electrospun nanofibrous membranes composed of three different decellularized WJ matrix (DWJM)/poly(ε‐caprolactone) (PCL) ratios (8:2, 5:5, and 2:8) are fabricated. The results demonstrate improved degradation speed, absorption, and cell adhesion capacity but weakened mechanical properties with increased DWJM content, but satisfactory homogeneous cartilage regeneration is only achieved in the DWJM/PCL (8:2) group after 12 weeks in vivo culture. Furthermore, homogeneous, 3D, tubular, trachea‐shaped cartilage is constructed with a controllable lumen diameter and wall thickness based on the 2D nanofibrous membrane using a modified sandwich model, in which the chondrocyte‐membrane construct is rolled around a silicon tube. Most importantly, by combining the above schemes with previously established vascularization and epithelialization techniques, chondrification, vascularization, and epithelialization are achieved simultaneously thus realizing long‐term (6 months) circumferential tracheal lesion repair in a rabbit model with a biological structure and function similar to that of native trachea, representing a promising approach for the clinical application of tracheal tissue engineering.

Structural and ultrastructural renal lesions in rats fed high-fat and high-phosphorus diets.

BackgroundFoods prone to deteriorate renal function are rich in fat and in phosphorus (P), but the interaction between these two factors is not well studied.MethodDetailed structural and ultrastructural histopathological studies were performed on the kidneys of rats fed different amounts of fat and P: low (4%) fat (LF) and normal (0.6%) P (NP), LF and high (1.2%) P (HP), high (35%) fat (HF) and NP, HF and HP, and HF with low (0.2%) P (LP) for 28 weeks.ResultsGlomeruli of the HF groups showed segmental areas of retraction, sclerosis and thickening of the Bowman’s capsule and basal membranes, which were more accentuated in the HF–HP group. Ultrastructural lesions in the glomeruli also were prominent in rats fed HF, particularly in the HF–HP group, and included thickening of the capillary membrane, endothelial damage, mesangial matrix hypercellularity and podocyte effacement. P restriction reduced the severity of endothelial damage, mesangial matrix hypercellularity, thickening of capillary basement membrane and podocyte effacement. The kidneys of rats fed HP showed significant tubular atrophy and dilatation, focal tubular hyperplasia, thickening of the tubular basal membrane, interstitial edema, inflammation and calcification. All groups fed HF also showed tubular lesions that were more prominent in the HF–HP group. P restriction had a beneficial effect on inflammation and calcification.ConclusionsIntake of both HF and HP damages the kidneys and their noxious effects are additive. HF intake was preferentially associated with glomerular lesions, while lesions related to HP intake were located mainly in the tubuli and in the interstitium.

Biochemical and histopathological changes in Wistar rats after consumption of boiled and un-boiled water from high and low disease prevalent areas for chronic kidney disease of unknown etiology (CKDu) in north Central Province (NCP) and its comparison with low disease prevalent Colombo, Sri Lanka

BackgroundChronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka. Consumption of un-boiled dug well water has been identified as one of the causative factors. This in-vivo study was performed to investigate some of the suspected factors associated with the pathogenesis of CKDu mediated via ground water.MethodRats were given water, collected from high and low disease prevalent areas from the NCP of Sri Lanka and the results compared with those obtained from previously identified low disease prevalent area; Colombo. Blood Urea Nitrogen, creatinine, urinary microalbumin:creatinine ratio together with ALT and AST levels were analyzed and results were compared using one-way ANOVA and paired t-Test. Histopathology was analyzed using non-parametric method.ResultsRats that ingested water from New Town Medirigiriya (NTM) from high disease prevalent NCP reported significantly elevated microalbumin:creatinine ratios compared to other water sources after 8 months, whilst boiled water from NTM had been able to significantly reduce it. Histopathological findings after the 14 months experimental period revealed significantly high tubular lesion index in rats that ingested water from NCP compared to Colombo. Rats that ingested water from high disease prevalent Divuldamana (DD) from NCP showed the highest kidney lesion index though the fluoride content was relatively low in this area compared to other water sources from high disease prevalent NCP. Rats that ingested boiled and un-boiled water from NTM also developed severe lesions whilst the group from Colombo reported the lowest. Low disease prevalent area from NCP, Huruluwewa (HW) also reported elevated liver enzymes and altered renal histopathology. Association of Na+:Ca2+ ratio in the disease progression was not reflected by the current study. Compared to Colombo, high fluoride, calcium and sodium contents were observed in water from high disease prevalent areas. All the water samples were negative for heavy metals.ConclusionsThough Fluoride is a known kidney toxic agent it cannot be the sole reason for CKDu in NCP, Sri Lanka. Various toxic elements present in NCP water may contribute to different grade of kidney and liver lesions in Wistar rats.

Assessment of Renal Functions and Lesions in Dogs with Serological Diagnosis of Canine Visceral Leishmaniasis

Background: Visceral leishmaniasis is a complex vector-borne disease caused by the protozoan Leishmania infantum. In urban centers of South America, where this zoonotic cycle occurs, dogs seem to be the main reservoirs and infection sources. Animals with canine visceral leishmaniasis (CVL) may have a wide clinical spectrum, and dogs are usually classified as asymptomatic, oligosymptomatic, and symptomatic. Several organs are affected in canine CVL, and renal involvement is often a determining factor in dog prognosis. Nevertheless, serum markers are slow to indicate loss of renal function. The aim of this studywas to evaluate kidney impairment in dogs diagnosed with CVL.Material, Methods &amp; Results: Blood and urine samples were collected from 45 dogs from Barra Mansa-RJ, and used for urinalysis, urine protein/creatinine (UPC) ratio, and serum concentrations of urea and creatinine. The animals were classified as symptomatic (42.2%), oligosymptomatic (37.8%), and asymptomatic (20.0%). Some alterations were found in the urine samples; pale-yellow color in 17.8%, low specific gravity in 6.7%, turbidity in 51.1%, proteinuria in 80%, occult blood in 46.7%, bilirubin in 8.89%, and glucose in 6.7% of the samples. According to the UPC ratio, 60% of dogs were proteinuric, and UPC &gt; 2.0 was high in symptomatic dogs. Azotemia was observed only in three dogs with CVL.Discussion: The majority of dogs presented one or more symptoms of CVL, as expected in an endemic area from Brazil. Pale-yellow urine was observed in some samples, and this change, when accompanied by the decreased urine specific gravity in dogs with CVL, suggests some degree of kidney disease. The presence of epithelial and red blood cells, leukocytes, bacteria, suspended mucus, and phosphate crystals that precipitate in alkaline urines could be associated, to some degree, with the urine turbidity found in the present study. The alkaline urine identified in some dogs could be related to the animals’ diet, but renal tubular acidosis (RTA) is another possible cause when referring to animals with CVL. The abnormal presence of bilirubin and glycosuria can be justified by liver damage and glomerular and tubular damage, respectively. Occult blood was found in the urine of almost half of the tested dogs, which occurred because of the presence of red blood cells in the urine sediment and hematuria in some animals, could be caused by tubular and glomerular lesions. The presence of granular and hyaline casts found in the samples reinforce the possibility of tubular injury. We found different levels of proteinuria; it was an important result, possibly caused by immune complex deposition in addition to tubular disease. Most tested dogs, including animals without clinical manifestation, were classified as proteinuric or borderline proteinuric, showing that the renal disease could be the only clinical manifestation of CVL and that it could progress from slight proteinuria to end-stage renal disease, resulting in chronic renal failure, which is the main cause of death. The UPC ratio &gt; 2.0 was significantly the more frequent finding in this study, mainly in symptomatic dogs. This result indicates a glomerular disease in these animals, reinforcing that the progression of renal disease follows the clinical progression of CVL. A few serum samples showed increased urea and creatinine levels, proving that azotemia is an uncommon finding in CVL-infected dogs. In conclusion, urinalysis helped in the early identification of renal injury in CVL-infected dogs, highlighting elements that reinforce the presence of tubular or glomerular lesions, or both, even in non-azotemic dogs. The high frequency of symptomatic dogs with UPC ratio &gt; 2.0 suggests a relationship between the progression of renal disease and the clinical progression of CVL.

Evaluation of urine N-acetyl-β-D-glucosaminidase in renal tubular interstitial lesions of IgA nephropathy

Objective To explore the clinical significance of urine NAG in judging the condition of renal tubular interstitial lesions in patients with IgA nephropathy (IgAN). Methods The data of 82 IgAN patients who had been clinical and pathological diagnosed in our hospital from February 2014 to June 2018 were collected. According to NAG normal level, all patients were divided into NAG normal group and high NAG group. The difference of clinic index and pathological scores between two groups were compared, and the clinical and pathological risk factor which have correlation with urine NAG were assessed. Results There had significant differences in Cr, micro-albumin(mALB), Cys-C, and NAG between two groups(P<0.05). The pathological lesion scores of mesangial cell proliferation, interstitial inflammatory cell infiltration, renal interstitial fibrosis, and tubular atrophy comparison between groups were compared. There were statistically significant differences(P<0.05). The correlation analysis showed that there were positive correlations of NAG with mALB, eGFR , renal interstitial inflammatory cell infiltration, renal tubular atrophy, renal fibrosis and the mesangial cell proliferation. Conclusions Urinary NAG levels are closely related to renal function, proteinuria and tubule-interstitial lesions, which can be used as clinical indicators to evaluate and monitor the degree of tubule-interstitial lesions in IgAN. Key words: Glomerulonephritis, IGA; Uridine Diphosphate N-Acetylglucosamine; Nephritis, Interstitial

Renal tubular Bim mediates the tubule-podocyte crosstalk via NFAT2 to induce podocyte cytoskeletal dysfunction.

Diabetic nephropathy (DN) is mainly regarded as diabetic glomerulopathy, and its progression is tightly correlated with tubular epithelial lesions. However, the underlying molecular mechanisms linking tubular damage and glomerulopathy are poorly understood.Methods: We previously reported that the upregulation of Bim mediated proximal tubular epithelial cell (PTEC) apoptosis and was crucial in the early stages of DN. Herein we modulated Bim expression in PTECs and subsequently determined podocyte (PC) cytoskeletal arrangement by building a Transwell co-culture system in high glucose (HG).Results: Compared to normal glucose, exposure to 40 mM of HG for 48 h induced significant expression of Bim in PTECs and disorganization in the PC cytoskeleton. When cocultured with PTECs in HG, exacerbated filamentous actin (F-actin) rearrangement and reduced synaptopodin levels were detected in PCs. In contrast, gene knockdown of Bim in PTECs was correlated with the absence of PC cytoskeletal disorganization. NFAT2 level and its nuclear translocation in PTECs were decreased by suppressing Bim expression. Upregulating NFAT2 disrupted the beneficial effects on F-actin organization in PCs obtained by inhibiting Bim. LncRNA microarray analysis identified NONHSAT179542.1, which was implicated in Bim-mediated PC cytoskeletal disorder.Conclusion: Our study clarified the functional role of Bim, a pro-apoptotic factor, which is involved in the crosstalk between PTECs and PCs. Bim promotes NFAT2 activation in PTECs, inducing the downregulation of lncRNA NONHSAT179542.1 in PCs, contributing to the cytoskeletal damage. Identification of the role of the Bim/NFAT2 pathway may represent a promising research direction for a better understanding of DN development.

Nephroprotective activity of the enriched polyphenol extract of Euterpe edulis Martius

Contrast-induced nephropathy (NIC) is directly related to increased morbidity and mortality, and its treatment and prevention might be achieved by the administration of antioxidant products. The jucara palmetto (Euterpe edulis Martius) has fruits rich in phenolic compounds, which are known for their antioxidant activity. This work aimed to evaluate the nephroprotective activity of E. edulis pulp in the NIC animal model. The collected fruits were pulped, their contents of polyphenols and anthocyanins were quantified, and their antioxidant activity were evaluated. The nephroprotective effects were determined based on iodine contrast induction and evaluated by biochemical and histological analyses. The results showed that E. edulis pulp was rich in polyphenols (811 ± 16.7 mg EAG/g) and anthocyanins (181.25 mg/100 g) and had very strong antioxidant activity, as demonstrated by the DPPH (2,2-diphenyl-1-picryl-hydrazyl) method, which revealed an antioxidant activity index (AAI) of 3.4, and the 2,29-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) method, which revealed an IC50 of 0.59 ± 0.03 mg/mL. In the in vivo experiments, E. edulis pulp tended to provide renal protection and reduce renal dysfunction and tubular morphological lesions in mice after the induction of NIC, and these effects were obtained through the antioxidant activities of the polyphenols in the pulp.

Idiopathic granulomatous mastitis in a pregnant woman

Introduction: Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease of unknown etiology. It was described in 1972 by Kessler and Wolloch, who reported cases of granulomatous lobulitis with no established relationship with trauma, foreign body, or specific infection. This study aimed at reporting a case of IGM in a pregnant patient. Clinical case: A 36-year-old pregnant woman, with a gestational age of 27 weeks, was admitted with a complaint of right breast pain for 7 days. She denied comorbidities. Clinical examination showed a dense area in the junction of the right inner quadrants, associated with mild hyperemia without signs of fluctuation. Lymphadenopathy was not identified. Ultrasound revealed a non-homogeneous fluid of 4.9x1.7x5.2 cm in the right upper inner quadrant, with a consequent surgical approach and collection of fragments for analysis. Cultures with antibiogram and for fungi and the venereal disease research laboratory (VDRL) tested negative. Histopathological examination showed a chronic inflammatory process with abundant granulation tissue and isolated giant cells, suggesting granulomatous mastitis. Corticosteroid therapy was indicated after the birth, with prednisone 40 mg/day for 3 months, with complete resolution of the symptoms. Discussion: Usually, IGM affects women aged 17 to 42 years. Recent history of pregnancy is common, with identified cases ranging from 2 months to 15 years after the last delivery, rarely occurring during gestation. It manifests as a breast mass of 0.5 to 9 cm in diameter, often unilateral and on the left side. Signs of inflammation and local lymphadenopathy can also be identified. Mammography is not ideal for detecting IGM, with findings of low specificity, and false negatives are frequent in dense breasts. The most frequent ultrasound findings are irregular hypoechoic mass and tubular hypoechoic lesion. IGM can be confirmed by detecting a histological pattern of chronic granulomatous lobulitis, non-caseating granuloma with infiltration of histiocytes, few polymorphonuclear cells, and multinucleated giant cells. Ruling out syphilis, fungi, and breast tuberculosis is important. The recommended treatment is excisional biopsy, preferably a wide excision. However, surgical management has a negative cosmetic impact and is associated with up to 50% of cases of persistence and recurrence of the disease, in addition to complications such as abscesses, fistulas, and ulceration. Corticosteroids are an effective option for controlling the disease, but active surveillance can also be chosen. Considering the above, we underline the importance of early diagnosis with appropriate scientific and technical foundations to provide a better prognosis for patients.