scholarly journals Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252758
Author(s):  
Nicholas A. Maksimowski ◽  
James W. Scholey ◽  
Vanessa R. Williams ◽  
Keyword(s):  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Current Knowledge ◽  
Interstitial Fibrosis ◽  
Linear Regression Analysis ◽  
Renin Angiotensin System ◽  
Multiple Linear Regression Analysis ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Segmental Glomerulosclerosis

Background Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge. Methods We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects. Results ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (CCL2 and TNF) correlated with ACE2 expression in males (TNF: r = -0.65, P < 0.0001; CCL2: r = -0.60, P < 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes. Conclusions Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.

Kidney Outcome in Primary Focal Segmental Glomerulosclerosis (FSGS) by Using a Predictive Model

2020 ◽  
Author(s):  
Shahrzad Ossareh ◽  
Mansoureh Yahyaei ◽  
Mojgan Asgari ◽  
Hanri Afghahi
Keyword(s):  
Kidney Disease ◽  
Predictive Model ◽  
Focal Segmental Glomerulosclerosis ◽  
Interstitial Fibrosis ◽  
Cox Model ◽  
Tubular Atrophy ◽  
Model Interaction ◽  
Segmental Glomerulosclerosis ◽  
End Stage ◽  
Adjusted Model

Abstract Background: Focal segmental glomerulosclerosis (FSGS) is one of the important causes of end stage kidney disease (ESKD). We evaluated the risk factors of progression of primary FSGS to chronic kidney disease (CKD) or ESKD with a predictive model including clinical and histological predictors.Methods: 201 patients with primary FSGS (59% male, mean age: 38±15 years), were studied. Time-dependent Cox model and C statistics were used for the predictive model. Interaction and correlation between independent variables were estimated.Results: During 55±27 months of follow-up, 82 patients (41%) developed CKD (46) or ESKD (36) patients. In adjusted model, 1 unit of higher serum creatinine (SCr) at baseline (HR:1.39, 95%CI: 1.15-1.70) and 1% increase in glomeruli with segmental glomerulosclerosis (SGS) (HR: 1.03, 95% CI: 1.02-1.04) or interstitial fibrosis/tubular atrophy (IF/TA) (HR: 1.03, 95% CI: 1.01-1.05) increased the risk of CKD/ESKD. In adjusted model, higher baseline proteinuria and collapsing variant were not associated with risk of CKD/ESKD. By adding SGS and IF/TA scores to baseline SCr in the model, discrimination by C statistics was 0.83 (95%CI: 0.77-0.90). Median renal survival was 3.1 years (95% CI: 2.2-4.1 years) in patients with highest risks score (baseline eGFR<25 ml/min/1.73 m2+ IF/TA/SGS> 50%), and 8.1 years (95% CI: 7.7-8.6 years).in those with lowest score (baseline eGFR>75 ml/min/1.73 m2+ IF/TA/SGS <5%).Conclusion: In primary FSGS, higher baseline SCr, increased SGS and IF/TA, but not baseline proteinuria and collapsing pathology, were the predictors for CKD/ESKD. These findings indicated the importance of timely detection and referral in prognosis of primary FSGS.

scholarly journals Development of a clinical prediction model of chronic kidney disease in primary Focal Segmental Glomerulosclerosis

2020 ◽  
Author(s):  
Shahrzad Ossareh ◽  
Mansoureh Yahyaei ◽  
Mojgan Asgari ◽  
Hanri Afghahi
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Predictive Model ◽  
Focal Segmental Glomerulosclerosis ◽  
Interstitial Fibrosis ◽  
Cox Model ◽  
Tubular Atrophy ◽  
Model Interaction ◽  
Segmental Glomerulosclerosis ◽  
Adjusted Model

Abstract Background: Focal segmental glomerulosclerosis (FSGS) is one of the important causes of end stage kidney disease (ESKD). We evaluated the risk factors of progression of primary FSGS to chronic kidney disease (CKD) or ESKD with a predictive model including clinical and histological predictors. Methods: 201 patients with primary FSGS (59% male, mean age: 38±15 years), were studied. Time-dependent Cox model and C statistics were used for the predictive model. Interaction and correlation between independent variables were estimated. Results: During 55±27 months of follow-up, 82 patients (41%) developed CKD (46) or ESKD (36) patients. In adjusted model, 1 unit of higher serum creatinine (SCr) at baseline (HR:1.39, 95%CI: 1.15-1.70) and 1% increase in glomeruli with segmental glomerulosclerosis (SGS) (HR: 1.03, 95% CI: 1.02-1.04) or interstitial fibrosis/tubular atrophy (IF/TA) (HR: 1.03, 95% CI: 1.01-1.05) increased the risk of CKD/ESKD. In adjusted model, higher baseline proteinuria and collapsing variant were not associated with risk of CKD/ESKD. By adding SGS and IF/TA scores to baseline SCr in the model, discrimination by C statistics was 0.83 (95%CI: 0.77-0.90) for prediction of CKD/ESKD . Median renal survival was 3.1 years (95% CI: 2.2-4.1 years) in patients with highest risks score (baseline eGFR<25 ml/min/1.73 m 2 + IF/TA/SGS> 50%), and 8.1 years (95% CI: 7.7-8.6 years).in those with lowest score (baseline eGFR>75 ml/min/1.73 m 2 + IF/TA/SGS <5%). Conclusion: In primary FSGS, higher baseline SCr, increased SGS and IF/TA were the predictors for CKD/ESKD. Baseline proteinuria did not predict the risk of CKD/ESKD. Collapsing variant did not increase the risk of CKD/ESKD after adjustment for IF/TA score. These findings indicated the importance of baseline GFR and the degree of chronicity at biopsy as predictors of kidney outcome .

scholarly journals Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

2013 ◽  
Vol 304 (7) ◽  
pp. C591-C603 ◽  
Author(s):  
Gabriela Campanholle ◽  
Giovanni Ligresti ◽  
Sina A. Gharib ◽  
Jeremy S. Duffield
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Innate Immune ◽  
Cellular Mechanisms ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Capillary Rarefaction ◽  
Peritubular Capillaries

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.

scholarly journals Lithium Nephrotoxicity

2000 ◽  
Vol 11 (8) ◽  
pp. 1439-1448 ◽  
Author(s):  
GLEN S. MARKOWITZ ◽  
JAI RADHAKRISHNAN ◽  
NEERAJA KAMBHAM ◽  
ANTHONY M. VALERI ◽  
WILLIAM H. HINES ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Focal Segmental Glomerulosclerosis ◽  
Interstitial Fibrosis ◽  
Renal Cysts ◽  
Significant Degree ◽  
Fisher Exact Test ◽  
Tubular Atrophy ◽  
Segmental Glomerulosclerosis ◽  
Tubulointerstitial Nephropathy ◽  
Collecting Tubules

Abstract. This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%. Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with >50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria >1.0 g/d (P= 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at biopsy (P= 0.008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.

Kidney Outcome in Primary Focal Segmental Glomerulosclerosis (FSGS) by Using a Predictive Model

2019 ◽  
Author(s):  
Shahrzad Ossareh ◽  
Mansoureh Yahyaei ◽  
Mojgan Asgari ◽  
Hanri Afghahi
Keyword(s):  
Kidney Disease ◽  
Predictive Model ◽  
Focal Segmental Glomerulosclerosis ◽  
Interstitial Fibrosis ◽  
Cox Model ◽  
End Stage Kidney Disease ◽  
Model Interaction ◽  
Segmental Glomerulosclerosis ◽  
End Stage ◽  
Adjusted Model

Abstract Background: Focal segmental glomerulosclerosis (FSGS) is one of the important causes of end stage kidney disease (ESKD). We evaluated the risk factors of progression of primary FSGS to chronic kidney disease (CKD) or ESKD with a predictive model including clinical and histological predictors. Methods: 201 patients with primary FSGS (59% male, mean age: 38±15 years), were studied. Time-dependent Cox model and C statistics were used for the predictive model. Interaction and correlation between independent variables were estimated. Results: During 55±27 months of follow-up, 82 patients (41%) developed CKD (46) or ESKD (36) patients. In adjusted model, 1 unit of higher serum creatinine (SCr) at baseline (HR:1.39, 95%CI: 1.15-1.70) and 1% increase in glomeruli with segmental glomerulosclerosis (SGS) (HR: 1.03, 95% CI: 1.02-1.04) or interstitial fibrosis/tubular atrophy (IF/TA) (HR: 1.03, 95% CI: 1.01-1.05) increased the risk of CKD/ESKD. In adjusted model, higher baseline proteinuria and collapsing variant were not associated with risk of CKD/ESKD. By adding SGS and IF/TA scores to baseline SCr in the model, discrimination by C statistics was 0.83 (95%CI: 0.77-0.90). Median renal survival was 3.1 years (95% CI: 2.2-4.1 years) in patients with highest risks score (baseline eGFR<25 ml/min/1.73 m2+ IF/TA/SGS> 50%), and 8.1 years (95% CI: 7.7-8.6 years).in those with lowest score (baseline eGFR>75 ml/min/1.73 m2+ IF/TA/SGS <5%). Conclusion: In primary FSGS, higher baseline SCr, increased SGS and IF/TA, but not baseline proteinuria and collapsing pathology, were the predictors for CKD/ESKD. These findings indicated the importance of timely detection and referral in prognosis of primary FSGS. Keywords: Focal segmental glomerulosclerosis, End stage kidney disease, Pathology

scholarly journals The Relationship of Vitamin D Level with Renal Prognosis in Focal Segmental Glomerulosclerosis Patients- A Retrospective Study

2021 ◽  
Author(s):  
Cagdas Kucukerdogan ◽  
Ebru Gok Oguz ◽  
Gulay Ulusal Okyay ◽  
Hatice Sahin ◽  
Tamer Selen ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Interstitial Fibrosis ◽  
Binary Logistic Regression ◽  
Binary Logistic Regression Analysis ◽  
First Year ◽  
Tubular Atrophy ◽  
Segmental Glomerulosclerosis ◽  
Renal Prognosis ◽  
One Year ◽  
The Relationship

Introduction: The level of 25-hydroxyvitamin D3 is an independent predictor of disease progression and death in Chronic Kidney Disease (CKD) patients. However, there are insufficient data to evaluate the possible effects of plasma 25(OH)D3 levels on the prognosis of Focal Segmental Glomerulosclerosis (FSGS). Aim: To analyse the relationship between renal prognosis and serum 25(OH)D3 status in FSGS. Materials and Methods: The study was conducted on 56 patients, who were followed-up for at least one year and diagnosed with primary FSGS. Participants were grouped according to their baseline 25(OH)D3 levels (≤15 or >15 ng/mL) and treatment response at the end of one year (remission group or no remission group) was evaluated. Results: Mean age of the 56 participants was 44±13.92 years and 27 (48.2%) were male. Remission achievement in the first year was significantly higher and interstitial fibrosis was significantly lower for the group with a 25(OH)D3 above >15 ng/ mL (p<0.001, p=0.002, respectively). Basal serum 25(OH)D3 level was significantly lower and interstitial fibrosis and tubular atrophy percentages were higher for the ‘no remission’ group (p<0.001, p<0.001, p=0.005, respectively). Results of the binary logistic regression analysis revealed that low 25(OH)D3 level and higher interstitial fibrosis were independent predictive factors that increased the risk of no remission in the first year (p=0.036, p=0.004, respectively). Conclusion: In primary FSGS patients, low baseline 25(OH)D3 level at the time of biopsy and high interstitial fibrosis are independent predictors that reduce remission rates in the first year.

scholarly journals Moxibustion Alleviates Injury in a Rat Focal Segmental Glomerulosclerosis Model

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yi Li ◽  
Yuxia Sun ◽  
Chunling Zhang ◽  
Ke Wang ◽  
Peicheng Shen ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Rat Model ◽  
Interstitial Fibrosis ◽  
Similar Efficacy ◽  
Glomerular Sclerosis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Repeated Injection ◽  
Moxibustion Group ◽  
Segmental Glomerulosclerosis

Objectives. To evaluate the therapeutic effects of moxibustion at Shenshu (BL-23) and Geshu (BL-17) acupoints in a focal segmental glomerulosclerosis (FSGS) model in rats. Methods. A FSGS rat model was established by single nephrectomy and repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, losartan (positive control) group, Shenshu moxibustion group, and Geshu moxibustion group. Molecular indicators of kidney function and renal pathological changes were monitored. Results. Urinary protein, serum creatinine, urea nitrogen, and serum uric acid were significantly reduced after 12-week intervention with losartan, Shenshu, or Geshu moxibustion. Renal α-SMA, FN, and TGF-β were also decreased, while podocin and nephrin protein and mRNA were increased. The pathological damage in renal tissue was obviously alleviated by all three treatments, which suggests that moxibustion may have similar efficacy to losartan in the treatment of FSGS. Conclusion. Moxibustion alleviates podocyte injury and inhibits renal interstitial fibrosis in the FSGS rat model, thereby minimizing the progression of glomerular sclerosis and improving renal function.

scholarly journals Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study

2018 ◽  
Vol 314 (3) ◽  
pp. F412-F422 ◽  
Author(s):  
Harindra Rajasekeran ◽  
Heather N. Reich ◽  
Michelle A. Hladunewich ◽  
Daniel Cattran ◽  
Julie A. Lovshin ◽  
...  
Keyword(s):  
Pilot Study ◽  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Short Term Treatment ◽  
Segmental Glomerulosclerosis ◽  
Renal Hemodynamic ◽  
Hemodynamic Function ◽  
The Impact

Focal segmental glomerulosclerosis (FSGS) is an important cause of nondiabetic chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in nondiabetic CKD such as FSGS. The primary aim of this pilot study was to determine the effect of 8 wk of dapagliflozin on glomerular filtration rate (GFR) in humans and in experimental FSGS. Secondary end points were related to changes in renal hemodynamic function, proteinuria, and blood pressure (BP). GFR (inulin) and renal plasma flow (para-aminohippurate), proteinuria, and BP were measured in patients with FSGS ( n = 10), and similar parameters were measured in subtotally nephrectomized (SNx) rats. In response to dapagliflozin, changes in GFR, renal plasma flow, and 24-h urine protein excretion were not statistically significant in humans or rats. Systolic BP (SBP) decreased in SNx rats (196 ± 26 vs. 165 ± 33 mmHg; P < 0.001), whereas changes were not statistically significant in humans (SBP 112.7 ± 8.5 to 112.8 ± 11.2 mmHg, diastolic BP 71.8 ± 6.5 to 69.6 ± 8.4 mmHg; P = not significant), although hematocrit increased (0.40 ± 0.05 to 0.42 ± 0.05%; P = 0.03). In archival kidney tissue from a separate patient cohort, renal parenchymal SGLT2 mRNA expression was decreased in individuals with FSGS compared with controls. Short-term treatment with the SGLT2i dapagliflozin did not modify renal hemodynamic function or attenuate proteinuria in humans or in experimental FSGS. This may be related to downregulation of renal SGLT2 expression. Studies examining the impact of SGLT2i on markers of kidney disease in patients with other causes of nondiabetic CKD are needed.

scholarly journals Depression and Quality of Life among the Chronic Kidney Disease Patients

2020 ◽  
Vol 18 (3) ◽  
pp. 459-465
Author(s):  
Dipak Kunwar ◽  
Rajyashree Kunwar ◽  
Barsha Shrestha ◽  
Richa Amatya ◽  
Ajay Risal
Keyword(s):  
Quality Of Life ◽  
Chronic Kidney Disease ◽  
Socioeconomic Status ◽  
Kidney Disease ◽  
Low Socioeconomic Status ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
P Value ◽  
Low Socioeconomic

Background: Depression and other mental illness are very common among chronic kidney disease and also Quality of life has been found significantly impaired in chronic kidney disease. The objective of our study is to study Depression, Quality of life and its associations in chronic kidney disease. Methods: This was a descriptive cross-sectional study. We used convenient method of sampling for data collection. The World Health Organization Quality-of-Life 8-question scale was used for estimating quality of life and Beck Depression Inventory  was used for the assessment of depression.  Independent samples t-test was conducted to analysed bivariate relationship of sociodemographic factors with depression and Quality of life scores and multiple linear regression analysis was performed to determine predictors of Quality of life. Results: The 75.5% participants found to have depression. Depression was found statistically significant across socioeconomic status (p value 0.04) and other medical comorbidities (p value 0.04). Variables found to be significantly associated with total quality of life in multiple linear regression analysis were caste (p value 0.03), socioeconomic status (p value 0.009) and depression (p value 0.001). Conclusions: Depression and reduced quality of life is very common among chronic kidney patients. Low socioeconomic status and comorbid medical conditions were associated with depression and caste, low socioeconomic status and depression were associated with low quality of life. Screening and management of depression should be included in the routine care and it could help improving the quality of life of patients with chronic kidney disease. Keywords: chronic kidney disease; depression; quality of life

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