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<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.

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P0445PREVALENCE AND PREDICTORS OF GLYCOSURIA IN PRIMARY GLOMERULOPATHIES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0445 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Carolina Ormonde ◽

Ivo Laranjinha ◽

Augusta Gaspar ◽

Margarida Gonçalves ◽

Célia Gil ◽

...

Keyword(s):

Serum Creatinine ◽

Serum Albumin ◽

Clinical Laboratory ◽

Interstitial Fibrosis ◽

Glomerular Sclerosis ◽

Tubular Damage ◽

Tubular Dysfunction ◽

Lower Serum ◽

Glomerular Diseases ◽

Glomerular Lesion

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.

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Glycosuria in primary glomerulopathies: prevalence and prognostic significance

Brazilian Journal of Nephrology ◽

10.1590/2175-8239-jbn-2021-0115 ◽

2021 ◽

Author(s):

Carolina Ormonde ◽

Ivo Laranjinha ◽

Célia Gil ◽

Margarida Gonçalves ◽

August a Gaspar

Keyword(s):

Interstitial Fibrosis ◽

Prognostic Significance ◽

Renal Outcome ◽

Diabetic Patients ◽

Tubular Damage ◽

Tubular Dysfunction ◽

Tubular Atrophy ◽

Glomerular Diseases ◽

Transplant Patients

Abstract Introduction: Tubular damage is common in glomerular diseases (GD). Glycosuria is a marker of tubular dysfunction and may be used to detect tubular lesion and CKD progression. The aim of this study was to evaluate the prevalence and prognostic value of glycosuria at the time of diagnosis in primary glomerulopathies (PG). Methods: We conducted a 24-month retrospective study in patients diagnosed with PG in our center between 2009 and 2020. We excluded diabetic patients, use of SGLT2 inhibitors, transplant patients, and secondary GD. Patients were divided in two groups according to their glycosuria status at diagnosis. Results: We studied 115 patients. Global prevalence of glycosuria was 10% (n=11) and membranous nephropathy (MN) had the highest prevalence (n=5, 17.9%). We found that patients with glycosuria had higher serum creatinine (2.4 vs. 1.2 mg/dL, p=0.030), higher albuminuria (4.8 vs. 1.9 g/g, p=0.004), and lower serum albumin (2.3 vs. 3.2 g/dL, p=0.021). We did not find association with histological prognostic factors. At the end of follow-up, patients with glycosuria had higher prevalence of the composite outcome of stage 5D CKD or 50% increase in basal SCr (45.5% vs. 17.3%, p=0.037). In patients with MN, results were similar but we were able to find an association of glycosuria with more severe interstitial fibrosis and tubular atrophy (25.0 vs. 0.0 %, p=0.032). Conclusion: Ten percent of our patients with PG have glycosuria. Glycosuria at the time of diagnosis was associated with more severe clinical presentation and worst renal outcome. The association with higher albuminuria suggests that tubular function has an impact on the severity and outcomes of PG.

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Clinical Relevance of Serum Galactose Deficient IgA1 in Patients with IgA Nephropathy

Journal of Clinical Medicine ◽

10.3390/jcm9113549 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3549

Author(s):

Jin Sug Kim ◽

Hyeon Seok Hwang ◽

Sang Ho Lee ◽

Yang Gyun Kim ◽

Ju-Young Moon ◽

...

Keyword(s):

Iga Nephropathy ◽

Clinical Relevance ◽

Interstitial Fibrosis ◽

Healthy Controls ◽

Ckd Progression ◽

Serum Samples ◽

Tubular Atrophy ◽

Appropriate Treatment ◽

Cox Proportional Hazard Models ◽

New Biomarkers

New biomarkers of IgA nephropathy (IgAN) are needed for non-invasive diagnosis and appropriate treatment. There is emerging evidence that galactose deficient IgA1 (Gd-IgA1) is a pivotal molecule in the pathogenesis of IgAN. However, few studies have investigated the role of Gd-IgA1 as a biomarker in IgAN. In this study, we investigated the clinical relevance of serum Gd-IgA1 levels in patients with IgAN. Two hundred and thirty biopsy-proven IgAN patients, 74 disease controls (patients with non-IgAN nephropathy), and 15 healthy controls were enrolled in this study. Levels of serum Gd-IgA1 were measured using an ELISA kit in serum samples obtained the day of renal biopsy. We compared levels of serum Gd-IgA1 according to the type of glomerular disease and analyzed the association between Gd-IgA1 levels and clinical and pathological parameters in patients with IgAN. We then divided IgAN patients into two groups according to Gd-IgA1 level and investigated the predictive value of Gd-IgA1 for progression of chronic kidney disease (CKD). Serum Gd-IgA1 levels were significantly higher in IgAN patients than disease controls and healthy controls. In patients with IgAN, serum Gd-IA1 levels were significantly correlated with estimated glomerular filtration rate, serum IgA level, and tubular atrophy/interstitial fibrosis. CKD progression was more frequent in IgAN patients with higher serum Gd-IgA1 levels than in those with lower serum Gd-IgA1 levels. Cox proportional hazard models showed that high GdIgA1 level was an independent risk factor for CKD progression after adjusting for several confounders. Our results suggest that serum Gd-IgA1 level is a useful diagnostic and prognostic marker in IgAN patients. Further studies with a larger sample size and longer follow-up duration are needed.

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P0417THE ABSENCE OF C3 DEPOSIT IN MEMBRANOUS NEPHROPATHY IS ASSOCIATED WITH SPONTANEOUS REMISSION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0417 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Cristina Rabasco ◽

Ana Martínez ◽

Rosa Ortega ◽

Mario Espinosa

Keyword(s):

Membranous Nephropathy ◽

Interstitial Fibrosis ◽

Immunosuppressive Treatment ◽

Spontaneous Remission ◽

Glomerular Sclerosis ◽

Tubular Atrophy ◽

Positive Group ◽

Stage Renal Disease ◽

End Stage

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of biopsied nephrotic syndrome in adults. Recently, it has been reported that the pathogenesis of MN may be associated with an activation of the complement system. The pathway of activation is not clearly established. The intensity of C3 deposition could be a good marker of this activation in MN as has been shown in other diseases (IgA nephropathy, crescentic GN). The aim of this study is to evaluate clinical-pathological data in a cohort of patients with MN and the significance of glomerular C3 staining as a possible predictor of renal outcomes. Method We analysed patients with idiopathic MN biopsied in our department between January 2000 and December 2019, excluding those who had no material for IF (n = 115). The patients were divided into positive (87 cases) and negative (28 cases) based on glomerular C3 deposition. We assessed the clinical and histological characteristics and the percentage of spontaneous remission (SR) and end-stage renal disease (ESRD). Results A total of 115 patients with MN were followed with a median follow-up of 65 (25-161) months. We found no differences in baseline characteristics between both groups, with the exception that patients with C3 deposit had less albumin at the time of biopsy that negative patients [2.4 (2-2.9) vs 2.8 (2.3-3.1) g/dl, P=0.011)]. Patients with C3-negative had a higher percentage of SR than patients with C3-positive (75 vs 24%, P = 0.000) and less need for immunosuppressive treatment (18 vs 56%, P =0.001). At the most recent follow-up, C3-positive group had higher creatinine [1.42 (0.8-1.7) vs 0.97 (0.71-1) mg/dl, P=0.045] and proteinuria [1.64 (0.08-3.2) vs. 0.62 (0.05-0.79) g / 24h, P = 0.039]. Regarding histology, we found no differences in glomerular sclerosis, tubular atrophy and interstitial fibrosis. The renal survival analysis showed no statistically significant differences between both groups (P = 0.091). We analysed a subgroup of patients (n = 23) with antibodies against the phospholipase receptor on blood at the time of the biopsy (13/23 were positive). 84% of this positive group presented C3-positive in the renal biopsy vs 25% of the C3-negative group (P =0.008). Conclusion Patients without C3 staining show a higher rate of SR and less need for immunosuppressive treatment than patients with C3-positive. These results would support the theory that complement activation in this entity can play an important role. It is possible that these patients with negative C3 deposit represent a MN with evolution to SR and in these patients and that these patients do not need immunosuppressive treatment.

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P0729AKARDI: A NEW PREDICTIVE MODEL FOR RENAL DECAY AFTER NEPHRECTOMY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0729 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

FEDERICO DI MARCO ◽

Umberto Capitanio ◽

Arianna Bettiga ◽

Riccardo Vago ◽

Alessandra Cinque ◽

...

Keyword(s):

Multivariate Analysis ◽

Radical Nephrectomy ◽

Interstitial Fibrosis ◽

Chronic Kidney Disease Stage ◽

Univariate Analysis ◽

Disease Stage ◽

P Value ◽

Compensatory Mechanism ◽

Tubular Atrophy ◽

Ckd Stage

Abstract Background and Aims Radical Nephrectomy is usually associated to the risk of future development of a mild to severe chronic kidney disease stage especially for those patients who already present early stages of CKD (e.g CKD class II and IIIa). Any insight on this topic could influence the clinical decision about the surgery. But how can we know for sure the magnitude of the renal function’s decay? In this preliminary work, our aim was to identify a new model able to predict at time surgery the renal function’s variation at 1 year from the operation Method We collected prospectively clinical data of a group of consecutive 114 patients who underwent radical nephrectomy (RN) for the presence of a benign or malignant renal mass. We estimated Glomerular Filtration Rate (eGFR) with MDRD formula. We considered the following clinical varibles: AKI onset (according to RIFLE criteria), age, gender, presence of blood hypertension, diabetes type II and BMI. Moreover, to investigate a possible correlation between renal basal histology and renal functional decay, renal biopsies were performed on each on the healthy part of the removed kidney > 3cm far from tumor. A pathological evaluation using a chronicity score (Remuzzi Score) was subsequently carried out evaluating damage on four parameters: (a) glomerular global sclerosis, (b) tubular atrophy, (c) interstitial fibrosis and (d) arterial narrowing. Statistical analysis were performed using generalized linear model (GLM), Kruskal-Wallis test and chi-square test. Multivariate analysis were applied using stepwise regressions method in order to select the best fitting model. Statistically significant correlations were considered for p-value<0.05. Results At t0, 21% of the patients had an eGFR>90ml/min/1.73m2, 45% between 60 and 90, 23% between 30 and 45, and 11% under 45. Median observed decay after 12 months was 32.8% (IQR= 17.9%:41.9%).Taking in account the eGFR decay’s percentage there was a strong correlation with AKI onset (decay increased by 22.4%, CI= 14%:30.8%, p<0.0001), with Diabetes ( decay increased by 13%, CI= 2%: 24.5%, p=0.02) and with the CKD stages at t0 (p=0.0007). Considering the histology, a significative negative correlation was found with the presence of arterial narrowing (-14%, CI=-23%:-6%, p<0.01) even though the whole chronicity score did not correlate (p=0.5). No significative correlations were found between the decay of eGFR and other variables such as age, gender or comorbidities. The multivariate analysis by stepwise regression, including all the significative variables from the univariate analysis, proposed as best model to predict the decay the use of AKI onset (14%, CI=6%:22%, p=0.001), arterial narrowing (-13%, CI=-22%:-5%, p=0.001) and diabetes (p=0.14) as variables. Conclusion A precise and reliable prediction of renal function decrease after RN represents a cornerstone for urologist and nephrologist in order to create a personalized medical approach and management.In our cohort of study, CKD stage I and II patients displayed a huge decrease of eGFR in respect to CKD stages III-IV over time. One possible biological explanation can be that the healthy kidney of the patients affected by moderate and severe CKD starts working with a compensatory mechanism before the entire removal of the kidney with cancer so that the surgical acute nephron loss does not represent a shock in comparison to healthy patients with an eGFR >90 ml/min. Our preliminary study identified a new clinical and pathological panel of variables able to predict at time zero the magnitude of eGFR decay after 1 year from surgical operation. Further studies are needed in order to validate and improve this model.

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Ovariectomy is protective against renal injury in the high-salt-fed older mRen2.Lewis rat

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00427.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. H2064-H2071 ◽

Cited By ~ 16

Author(s):

Liliya M. Yamaleyeva ◽

Karl D. Pendergrass ◽

Nancy T. Pirro ◽

Patricia E. Gallagher ◽

Leanne Groban ◽

...

Keyword(s):

Renal Injury ◽

Interstitial Fibrosis ◽

Kidney Injury ◽

High Salt ◽

Glomerular Sclerosis ◽

Tubular Damage ◽

Lewis Rat ◽

Lewis Rats ◽

Ovx Rats ◽

Igf I

Studies in experimental animals and younger women suggest a protective role for estrogen; however, clinical trials may not substantiate this effect in older females. Therefore, the present study assessed the outcome of ovariectomy in older mRen2.Lewis rats subjected to a high-salt diet for 4 wk. Intact or ovariectomized (OVX, 15 wk of age) mRen2.Lewis rats were aged to 60 wk and then placed on a high-salt (HS, 8% sodium chloride) diet for 4 wk. Systolic blood pressures were similar between groups [OVX 169 ± 6 vs. Intact 182 ± 7 mmHg; P = 0.22] after the 4-wk diet; however, proteinuria [OVX 0.8 ± 0.2 vs. Intact 11.5 ± 2.6 mg/mg creatinine; P < 0.002, n = 6], renal interstitial fibrosis, glomerular sclerosis, and tubular casts were lower in OVX vs. Intact rats. Kidney injury molecule-1 mRNA, a marker of tubular damage, was 53% lower in the OVX HS group. Independent from blood pressure, OVX HS rats exhibited significantly lower cardiac (24%) and renal (32%) hypertrophy as well as lower C-reactive protein (28%). Circulating insulin-like growth factor-I (IGF-I) levels were not different between the Intact and OVX groups; however, renal cortical IGF-I mRNA and protein were attenuated in OVX rats [ P < 0.05, n = 6]. We conclude that ovariectomy in the older female mRen2.Lewis rat conveys protection against salt-dependent increase in renal injury.

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Urinary Periostin Excretion Predicts Renal Outcome in IgA Nephropathy

American Journal of Nephrology ◽

10.1159/000452228 ◽

2016 ◽

Vol 44 (6) ◽

pp. 481-492 ◽

Cited By ~ 12

Author(s):

Jin Ho Hwang ◽

Jung Pyo Lee ◽

Clara Tammy Kim ◽

Seung Hee Yang ◽

Jin Hyuk Kim ◽

...

Keyword(s):

Iga Nephropathy ◽

Renal Fibrosis ◽

Interstitial Fibrosis ◽

Renal Outcome ◽

Glomerular Sclerosis ◽

Enzyme Linked Immunosorbent Assay ◽

Matricellular Protein ◽

Tubular Atrophy ◽

Renal Outcomes ◽

Group 3

Background: Periostin is a matricellular protein and plays a vital role in tissue regeneration, fibrosis and wound healing. However, data about its significance in nephrology are limited. We investigated the correlation between urinary periostin excretion and its clinical significance including renal histologic findings and prognosis in IgA nephropathy (IgAN). Methods: Of 399 patients from a glomerulonephritis cohort recruited between January 2009 and December 2014, 314 were enrolled. Serum and urine periostin (uPOSTN) were measured using enzyme-linked immunosorbent assay. We divided the patients into 3 groups by uPOSTN/creatinine (uPOSTN/Cr): group 1 (undetectable), group 2 (lower than the median) and group 3 (higher than the median). Results: The uPOSTN level was correlated with pathologic classifications and both initial and final IDMS-MDRD estimated glomerular filtration rates (eGFRs; p < 0.001). Histologically, group 3 patients were correlated with severe interstitial fibrosis/tubular atrophy (p = 0.004), interstitial inflammation (p = 0.007), hyaline arteriolosclerosis (p = 0.001) and glomerular sclerosis (p < 0.001). A higher initial uPOSTN/Cr level was associated with a greater decline in eGFR during follow-up (p = 0.043 when initial eGFR ≥60; p = 0.025 when eGFR <60 ml/min/1.73 m2), and the renal outcomes with end-stage renal disease (ESRD; p = 0.003), ESRD and/or eGFR decrease of >30% (p = 0.033) and ESRD and/or eGFR decrease of >50% (p = 0.046) occurred significantly more in group 3. In multivariate analysis, uPOSTN group 3 (hazards ratio 2.839, 95% CI 1.013-7.957; p = 0.047) was independently associated with ESRD in IgAN patients. Conclusion: uPOSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.

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Increased urinary miR-196a level predicts the progression of renal injury in patients with diabetic nephropathy

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy326 ◽

2018 ◽

Vol 35 (6) ◽

pp. 1009-1016 ◽

Cited By ~ 1

Author(s):

Yu An ◽

Changming Zhang ◽

Feng Xu ◽

Wei Li ◽

Caihong Zeng ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Renal Injury ◽

Cox Regression ◽

Interstitial Fibrosis ◽

Glomerular Sclerosis ◽

Tubular Atrophy ◽

Cox Regression Analysis ◽

Stage Renal Disease ◽

End Stage

Abstract Background Recent data suggest that miR-196a is predominantly expressed in the kidney and plays an inhibitory role in the progress of renal interstitial fibrosis (IF). However, the predictive value of miR-196a in diabetic nephropathy (DN) remains unknown. We validated the role of urinary miR-196a in the progression of renal injury in a cohort of patients with type 2 diabetes mellitus. Methods Our study included 209 patients with biopsy-proven DN. The mean follow-up time was 54.03 ± 32.94 months. Histological lesions were assessed using the pathological classification established by the Renal Pathology Society. Percentages of IF and tubular atrophy were assessed using the Aperio ScanScope system. We measured the correlation of urinary miR-196a with clinical and pathological parameters using the Spearman’s correlation test. The influence of urinary miR-196a on renal outcomes was assessed using Cox regression analysis. Results Urinary miR-196a levels correlated positively with proteinuria (ρ = 0.385, P < 0.001), duration of diabetes mellitus (ρ = 0.255, P < 0.001) and systolic blood pressure (ρ = 0.267, P < 0.001). The baseline estimated glomerular filtration rate (eGFR) and hemoglobin level showed a negative correlation with urinary miR-196a (ρ = −0.247, P < 0.001 and ρ = −0.236, P = 0.001, respectively). Pathologically, urinary miR-196a levels correlated with glomerular sclerosis and IF in patients with DN. Urinary miR-196a was significantly associated with progression to end-stage renal disease [hazard ratio (HR) 2.03, P < 0.001] and a 40% reduction of baseline eGFR (HR 1.75, P = 0.001), independent of age, gender, body mass index, mean arterial pressure and hemoglobinA1c level. However, urinary miR-196a did not improve predictive power to proteinuria and eGFR in DN patients. Conclusions Increased urinary miR-196a was significantly associated with the progression of renal injury and might be a noninvasive prognostic marker of renal fibrosis in DN patients.

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Effect of resveratrol on tubular damage and interstitial fibrosis in kidneys of rats exposed to cigarette smoke

Toxicology and Industrial Health ◽

10.1177/0748233709346755 ◽

2009 ◽

Vol 25 (8) ◽

pp. 539-544 ◽

Cited By ~ 22

Author(s):

Meltem Kuruş ◽

Murat Ugras ◽

Mukaddes Esrefoglu

Keyword(s):

Cigarette Smoke ◽

Interstitial Fibrosis ◽

Periodic Acid ◽

Control Group ◽

Albino Rats ◽

Tubular Damage ◽

Tubular Atrophy ◽

Hydropic Degeneration ◽

Group 4 ◽

Group 2

The aim of this study was to evaluate the effect of resveratrol on kidney tissue of rats exposed to cigarette smoke. Forty adult male Wistar Albino rats were divided into four groups. Animals in group 1 was the control group. For 6 weeks, group 2 was exposed to cigarette smoke; group 3 received daily intraperitoneal injections of resveratrol (10 mg/kg/d); and group 4 was exposed to both cigarette smoke and intraperitoneal resveratrol. All rats were sacrificed with cervical dislocation. The kidney tissues were obtained, fixed in Bouin’s fixative and embeded in paraffin blocks. Samples were sectioned to 4-5 microns thickness, stained with hematoxylin/eosin (H/E), Masson’s trichromic, periodic acid-schiff (PAS) and were examined by light microscopy for tubular injury and interstitial fibrosis. Results were compared by non-parametric tests. Hydropic degeneration, tubular atrophy, tubulo-interstitial fibrosis, interstitial cell infiltration, vacuolar degeneration and desquamation were prominent in group 2. In group 4, hydropic degeneration, epithelial cell vacuolization and desquamation was not observed, but occasional tubular atrophy and dilation were observed. Our study suggests that, some morphological alterations in the rat kidney, due to cigarette smoke may be prevented by resveratrol.

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Kidney Pathology and Outcomes in Anca-Associated Vasculitis: Retrospective Analysis of 85 Patients

10.20944/preprints202108.0210.v1 ◽

2021 ◽

Author(s):

Elena Zakharova ◽

Anastasiia Zykova ◽

Tatyana Makarova ◽

Eugenia Leonova ◽

Ekaterina Stolyarevich

Keyword(s):

Interstitial Fibrosis ◽

Significant Risk ◽

High Risk Group ◽

Additional Parameter ◽

Tubular Atrophy ◽

Anca Associated Vasculitis ◽

Pathology Classification ◽

Ckd Stage ◽

Significant Difference

ANCA-associated vasculitis (AAV) pose a significant risk of kidney failure, kidney biopsy remains a key prognostic tool. Pathology classification of the AAV glomerulonephritis (GN) developed by Berden et al showed correlation between GN classes and kidney outcomes; ANCA Renal Risk Score (ARRS) included tubular atrophy and interstitial fibrosis (TA/IF) as an additional parameter for risk assessment. We aimed to evaluate kidney survival across AAV GN classes and ARRS groups. A single-center retrospective study included 85 adult patients with biopsy-proven AAV kidney disease followed in 2000-2020. Primary outcome was kidney survival at the end of 18 [5; 66] months follow-up, kidney death considered as CKD stage 5. We found significant difference in the kidney survival for sclerotic, mixed, crescentic and focal AAV GN classes: 19%, 76.2%, 91.7% and 100% respectively (p=0.009). Kidney survival was 0%, 75.6% and 100% for the high, median and low risk ARRS groups respectively (p&lt;0.001); TA/IF analysis showed kidney survival 49.6% vs 87.7% for widespread and mild TA/IF respectively (р=0.003). Kidney survival was significantly lower in anti-MPO-ANCA versus anti-PR3-ANCA carriers (50.3% and 78.1% respectively, р=0.045). We conclude that unfavorable AAV kidney outcomes associated with sclerotic GN class by Berden’s classification, ARRS high risk group, and anti-MPO-ANCA subtype.

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