P0445PREVALENCE AND PREDICTORS OF GLYCOSURIA IN PRIMARY GLOMERULOPATHIES

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.

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

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Carolina Ormonde ◽  
Ivo Laranjinha ◽  
Augusta Gaspar ◽  
Margarida Gonçalves ◽  
Célia Gil ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Glomerular Sclerosis ◽  
Similar Proportion ◽  
Tubular Damage ◽  
Tubular Dysfunction ◽  
Ckd Progression ◽  
Tubular Atrophy ◽  
Glomerular Diseases ◽  
Glomerular Lesion ◽  
Ckd Stage

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.

scholarly journals Glycosuria in primary glomerulopathies: prevalence and prognostic significance

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.

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

2007 ◽  
Vol 293 (4) ◽  
pp. H2064-H2071 ◽  
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.

scholarly journals Evaluation of urinary N-acetyl-beta-D-glucosaminidase as a marker of early renal damage in patients with type 2 diabetes mellitus

2014 ◽  
Vol 58 (8) ◽  
pp. 798-801 ◽  
Author(s):  
Beatriz R. Bouvet ◽  
Cecilia V. Paparella ◽  
Sandra M. M. Arriaga ◽  
Adriana L. Monje ◽  
Ana M. Amarilla ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Creatinine ◽  
Positive Association ◽  
Tubular Damage ◽  
Tubular Dysfunction ◽  
Significant Positive Association ◽  
Estimated Glomerular Filtration Rates

Objective To evaluate the clinical usefulness of urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion for the detection of early tubular damage in type 2 diabetes mellitus (T2DM). Subjects and methods Thirty six patients with T2DM were divided into two groups based on urinary albumin to creatinine ratio (ACR): normoalbuminuria (ACR <30 mg/g; n=19) and microalbuminuria (ACR =30‐300 mg/g; n=17). The following parameters were determined in both groups: urinary NAG and albumin, serum and urine creatinine, fasting plasma glucose and glycated hemoglobin (HbA1c). Results Urinary NAG levels [Units/g creatinine; median (range)] were significantly increased in microalbuminuria group [17.0 (5.9 - 23.3)] compared to normoalbuminuria group [4.4 (1.5 - 9.2)] (P<0.001). No differences between groups were observed in fasting glucose, HbA1c, serum creatinine levels and estimated glomerular filtration rates (eGFR). Urinary NAG positively correlated with ACR (r=0.628; p<0.0001), while no significant association was observed between NAG and glycemia, HbA1c, serum creatinine and eGFR. Conclusions The increase of urinary NAG at the microalbuminuria stage of diabetic nephropathy (DN) suggests that tubular dysfunction is already present in this period. The significant positive association between urinary NAG excretion and ACR indicates the possible clinical application of urinary NAG as a complementary marker for early detection of DN in T2DM.

scholarly journals Explanatory histological findings for urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: A cross-sectional study

2020 ◽  
Author(s):  
Eri Katsuyama ◽  
Yoshia Miyawaki ◽  
Kenei Sada ◽  
Yosuke Asano ◽  
Keigo Hayashi ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Renal Biopsy ◽  
Multiple Regression ◽  
Interstitial Fibrosis ◽  
Urinary Protein ◽  
Glomerular Sclerosis ◽  
Fibrinoid Necrosis ◽  
Class Iii ◽  
The Mean

Abstract Background To evaluate histological active and chronic lesions associated with proteinuria and serum creatinine (SCr) level as common clinical endpoints in many clinical trials for lupus nephritis (LN).Methods One hundred and nineteen patients from 1990 to 2015 with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society classification, were enrolled. Multiple regression analysis was performed to explore semiquantitative histological variables related to urinary protein and SCr levels.Results The mean age of enrolled patients was 45 years and 79% were female. The mean SCr level was 0.87 mg/dl and mean urinary protein was 3.00 g/gCr at the time of the renal biopsy. Class IV (71%) was the most common type, followed by class III (17%) and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29) and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). After excluding fibrinoid necrosis and monocellular infiltration because of multicollinearity, only urinary protein level was correlated with wire loop (β−coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74) by multiple regression analysis.Conclusion As urinary protein and SCr levels could not reflect active lesions quantitatively, they might be difficult to be evaluated for response to induction remission treatments in patients with LN.

P0395DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS IN TURKEY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Zeki Aydin ◽  
Kultigin Turkmen ◽  
Fatih Dede ◽  
Emre Yasar ◽  
Savas Ozturk ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Interstitial Fibrosis ◽  
Rapidly Progressive Glomerulonephritis ◽  
Demographic Characteristics ◽  
Glomerular Diseases ◽  
Nephritic Syndrome ◽  
Number Of Patients ◽  
Type 3

Abstract Background and Aims Rapidly progressive glomerulonephritis (RPGN) is a clinical condition that develops due to different etiologic causes, characterized by a rapid and progressive decrease in renal function and progresses to end-stage renal failure in weeks to months if not treated. In our study, diagnostic and demographic characteristics of patients diagnosed with RPGN by biopsy, clinical and laboratory findings in our country were investigated. Method Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database between May 2009 and June 2019. Demographic characteristics such as age, sex, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. The data presented is cross-sectional and includes application data for the biopsy period. According to their types, RPGN patients were classified as type 1 (anti-GBM related), type 2 (immunocomplex related) and type 3 (immune-negative; “pauci-immune”). Results After exclusion of 46 patients with missing data, 200 patients (mean age 47.9 ± 16.7 years, 44% female) were included in the study which constitutes 5.2% of the total glomerulonephritis database (total number of patients: 3875). Hypertension was present in 62 patients (31.0%) and diabetes was present in 18 patients (9.0%). Renal biopsy was performed in 147 (73.5%) patients due to nephritic syndrome (RPGN included). 80.2% of the patients' biopsies were performed in nephrology clinics and 19.8% of them were performed in radiology clinics. ANCA positivity was found in 121 (60.5%) patients (proteinase 3-ANCA was positive in 55 and myeloperoxidase-ANCA positive in 66 patients). Type 1 RPGN was detected in 11 (5.5%), type 2 RPGN in 42 (21%) and type 3 RPGN in 147 (73.5%) patients. In 21 patients (10.5%), biopsy revealed RPGN with advanced chronic changes (fibrous global sclerotic glomeruli, advanced interstitial fibrosis and tubular atrophy). Mean serum creatinine was 4.2 ± 3.4 mg/dl, median glomerular filtration rate was 18 (10-37) ml/min and proteinuria 2100 (1229-3526) mg/day according to CKD-EPI formula. The mean number of glomeruli in the biopsies was 18.8 ± 10.6 and the number of crescentic glomeruli was 9.9 ± 7.7 (ratio: 52.7%) (Figure). The patients were divided into 3 groups according to their crescentic glomeruli ratios. The proportion of crescentic glomeruli is 10-50% in group 1, 50-80% in group 2, and &gt;80% in group 3. The demographic, laboratory and histopathological characteristics of the groups are given in Figure. It was observed that urea and creatinine increased and calcium and hemoglobin decreased with increasing crescentic glomerular ratio. Conclusion Our study provides valuable demographic, clinical, laboratory and histopathological data about RPGN in our country. Our data are generally compatible with the literature. In our study, advanced chronic histopathological findings were prominent in the biopsy of 21 patients. Early biopsy should be performed to confirm the diagnosis of RPGN and to avoid unnecessary intensive immunosuppressive therapy. In addition to the treatments applied, detailed data, including patient and renal survival are needed.

scholarly journals Morphologic lesions of membranous nephropathy in association with various demographic and laboratory parameters of patients; a single center study

2019 ◽  
Vol 9 (1) ◽  
pp. e09-e09
Author(s):  
Sara Zamani ◽  
Hamid Nasri
Keyword(s):  
Nephrotic Syndrome ◽  
Serum Creatinine ◽  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Glomerular Diseases ◽  
Laboratory Parameters ◽  
Positive Correlation ◽  
End Stage

Introduction: Nephrotic syndrome is an important clinical presentation of glomerular diseases that is classified into several types based on the findings of renal biopsy. Membranous neuropathy is the most common cause of nephrotic syndrome, especially in adults over 40 years of age, which may lead to end-stage renal failure. Objectives: The present study aimed to assess the association of morphologic lesions of membranous nephropathy (MN) on renal biopsy with various demographic and laboratory parameters of the patients. Patients and Methods: This study was performed on renal biopsies, which were referred to the laboratory with the diagnosis of MN. To reach a definite diagnosis of MN, an immunofluorescence study (IgG, IgA, IgM, C1q and C3 antibody deposits) was conducted for all patients. Light microscopy was conducted to categorize the morphologic lesions of the glomeruli and interstitial area. The percentage of interstitial fibrosis/tubular atrophy was assessed too. Additionally, age, gender, and 24- hour urinary protein and serum creatinine were recorded. Results: Among 175 idiopathic MN patients, 98 were male (56%). The patients’ age was between 14 and 84 years (mean; 42±15 years). The mean of serum creatinine and 24-hour urine protein were 1.05 ± 0.31 mg/dL and 2779.56± 1495.80 mg/d, respectively. We found a significant correlation between gender and serum creatinine level, which was higher in men (P<0.001). Moreover, there was a significant, positive correlation between serum creatinine and age of patients (P<0.001, r=0.25). Additionally, there was a significant correlation between serum creatinine and interstitial fibrosis (P=0.001). We found a significant correlation between serum creatinine and the pathologic stage of glomeruli (P=0.003). The stages of glomeruli were also associated with the proportion of interstitial fibrosis (P=0.001) and C3 deposition rate (P=0.002). IgG deposition score was also significantly different in age ranges over and under 40 years of age (P=0.001). The 24-hours proteinuria had no correlation with other laboratory parameters and microscopic findings. Conclusion: In accordance with other studies, we found that MN is more common among male patients. The positive correlation between serum creatinine and proportion of interstitial fibrosis is in concordance with previous studies. We found a positive correlation between serum creatinine and glomerular morphologic stages. It may show the importance of glomerular damage intensity in prognosis and survival of patients.

scholarly journals Mitochondrial Dysfunction in Podocytes Caused by CRIF1 Deficiency Leads to Progressive Albuminuria and Glomerular Sclerosis in Mice

2021 ◽  
Vol 22 (9) ◽  
pp. 4827
Author(s):  
Ki Ryang Na ◽  
Jin Young Jeong ◽  
Jin Ah Shin ◽  
Yoon-Kyung Chang ◽  
Kwang-Sun Suh ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Interstitial Fibrosis ◽  
Renal Diseases ◽  
Glomerular Sclerosis ◽  
Loss Of Function ◽  
Inner Mitochondrial Membrane ◽  
Glomerular Diseases ◽  
Glomerular Function ◽  
Tubulointerstitial Lesions ◽  
Deficient Mice

Recent studies have implicated mitochondrial disruption in podocyte dysfunction, which is a characteristic feature of primary and diabetic glomerular diseases. However, the mechanisms by which primary mitochondrial dysfunction in podocytes affects glomerular renal diseases are currently unknown. To investigate the role of mitochondrial oxidative phosphorylation (OxPhos) in podocyte dysfunction, glomerular function was examined in mice carrying a loss of function mutation of the gene encoding CR6-interacting factor-1 (CRIF1), which is essential for intramitochondrial production and the subsequent insertion of OxPhos polypeptides into the inner mitochondrial membrane. Homozygotic deficiency of CRIF1 in podocytes resulted in profound and progressive albuminuria from 3 weeks of age; the CRIF1-deficient mice also developed glomerular and tubulointerstitial lesions by 10 weeks of age. Furthermore, marked glomerular sclerosis and interstitial fibrosis were observed in homozygous CRIF1-deficient mice at 20 weeks of age. In cultured mouse podocytes, loss of CRIF1 resulted in OxPhos dysfunction and marked loss or abnormal aggregation of F-actin. These findings indicate that the OxPhos status determines the integrity of podocytes and their ability to maintain a tight barrier and control albuminuria. Analyses of the glomerular function of the podocyte-specific primary OxPhos dysfunction model mice demonstrate a link between podocyte mitochondrial dysfunction, progressive glomerular sclerosis, and tubulointerstitial diseases.

scholarly journals Hypoalbuminaemia and One-Year Mortality in Haemodialysis Patients with Heart Failure: A Cohort Analysis

2021 ◽  
Vol 10 (19) ◽  
pp. 4518
Author(s):  
Ana Cardoso ◽  
Carolina Branco ◽  
Mariana Sant’Ana ◽  
Cláudia Costa ◽  
Bernardo Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Multivariate Analysis ◽  
Serum Creatinine ◽  
Serum Albumin ◽  
Tertiary Care ◽  
Older Age ◽  
Lower Serum ◽  
One Year ◽  
The Impact

Introduction: The prevalence of chronic kidney disease (CKD) and heart failure (HF) has been rising over the past decade, with a prevalence close to 40%. Cardiovascular disease and malnutrition are common comorbidities and known risk factors for mortality in haemodialysis (HD) patients. We aimed to evaluate the one-year mortality rate after dialysis induction, and the impact of serum albumin levels on survival outcomes, in patients with CKD and HF. Methods: This was a retrospective analysis of patients with CKD and HF who underwent chronic HD between January 2016 and December 2019 in a tertiary-care Portuguese hospital. Variables were submitted to univariate and multivariate analysis to determine factors predictive of one-mortality after HD start. Results: In total, 204 patients were analysed (mean age 75.1 ± 10.3 years). Within the first year of HD start, 28.7% of patients died. These patients were significantly older [79.8 ± 7.2 versus 72.9 ± 10.9 years, p < 0.001; OR 1.08 (1.04–1.13), p < 0.001] and had a higher mean Charlson Index [9.0 ± 1.8 versus 8.3 ± 2.0, p = 0.015; OR 1.22 (1.04–1.44), p = 0.017], lower serum creatinine [5.1 ± 1.6 mg/dL versus 5.8 ± 2.0 mg/dL; p = 0.021; OR 0.80 (0.65–0.97), p = 0.022], lower albumin levels [3.1 ± 0.6 g/dL versus 3.4 ± 0.6 g/dL, p < 0.001; OR 0.38 (0.22–0.66), p = 0.001] and started haemodialysis with a central venous catheter more frequently [80.4% versus 66.2%, p = 0.050]. Multivariate analysis identified older age [aOR 1.07 (1.03–1.12), p = 0.002], lower serum creatinine [aOR 0.80 (0.64–0.99), p = 0.049] and lower serum albumin [aOR 0.41 (0.22–0.75), p = 0.004] as predictors of one-year mortality. Conclusion: In our cohort, older age, lower serum creatinine and lower serum albumin were independent risk factors for one-year mortality, highlighting the prognostic importance of malnutrition in patients starting chronic HD.

scholarly journals Podocyte injury: the role of proteinuria, urinary plasminogen, and oxidative stress

2016 ◽  
Vol 311 (6) ◽  
pp. F1308-F1317 ◽  
Author(s):  
Leopoldo Raij ◽  
Runxia Tian ◽  
Jenny S. Wong ◽  
John C. He ◽  
Kirk N. Campbell
Keyword(s):  
Oxidative Stress ◽  
Glomerular Filtration ◽  
Biologically Active ◽  
Current Evidence ◽  
Glomerular Sclerosis ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Filtration Barrier ◽  
Focal Segmental Glomerular Sclerosis

Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA). In vivo inhibition of uPA mitigates Plg activation and development of FSGS in several proteinuric models of renal disease including 5/6 nephrectomy. Here, we show that Plg is markedly increased in the urine in two murine models of proteinuric kidney disease associated with podocyte injury: Tg26 HIV-associated nephropathy and the Cd2ap −/− model of FSGS. We show that human podocytes express uPA and three Plg receptors: uPAR, tPA, and Plg-RKT. We demonstrate that Plg treatment of podocytes specifically upregulates NADPH oxidase isoforms NOX2/NOX4 and increases production of mitochondrial-dependent superoxide anion (O2−) that promotes endothelin-1 synthesis. Plg via O2− also promotes expression of the B scavenger receptor CD36 and subsequent increased intracellular cholesterol uptake resulting in podocyte apoptosis. Taken together, our findings suggest that following disruption of the glomerular filtration barrier at the onset of proteinuric disease, podocytes are exposed to Plg resulting in further injury mediated by oxidative stress. We suggest that chronic exposure to Plg could serve as a “second hit” in glomerular disease and that Plg is potentially an attractive target for therapeutic intervention.

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