Patients with primary focal segmental glomerulosclerosis with detectable urinary CD80 are more similar to patients with minimal change disease in clinicopathological features.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is an important cause of refractory nephrotic syndrome (NS) in children and adults. Urinary CD80 is elevated in some patients with primary FSGS, however, its clinical value is not fully clarified. This study aims to evaluate the clinical and pathological significance of urinary CD80 in patients with primary FSGS. METHODS: Sixty-one adult patients with biopsy-proven primary FSGS, with standard treatment and long-term follow up, were enrolled retrospectively. Urinary CD80, on the day of kidney biopsy, was measured using commercial ELISA kits and adjusted by urinary creatinine excretion. Their associations with clinical and pathological parameters were investigated. RESULTS: Urinary CD80 was detectable in 30/61 (49.2%) patients, who presented with a higher level of proteinuria (10.7 vs. 5.8 g/24h; p = 0.01), a lower level of serum albumin (19.3 ± 3.9 vs. 24.2 ± 8.2 g/L; p = 0.005), a higher prevalence of hematuria (70.0 vs. 38.7%; p = 0.01), and showed a lower percentage of segmental glomerulosclerosis lesion [4.8 (3.7-14.0) vs. 9.1 (5.6-21.1) %; p = 0.06]. The cumulative relapse rate was remarkably high in these patients (log-rank, p = 0.001). Multivariate analysis identified that the elevated urinary CD80 was an independent risk factor for steroid-dependent NS (OR 8.81, 95% CI 1.41-54.89; p = 0.02) and relapse (HR, 2.87; 95% CI 1.29-6.38; p = 0.01). CONCLUSIONS: The elevated urinary CD80 is associated with mild pathological change and steroid-dependent cases of primary FSGS adults, which indicates these patients are more similar to minimal change disease (MCD) in clinicopathological features.

Glomerular endothelial cells and podocytes can express CD80 in patients with minimal change disease during relapse.

BACKGROUND: Urinary CD80 has emerged as potential biomarker in idiopathic nephrotic syndrome (INS). However, its cellular source remains controversial. The aim of the study was to assess whether CD80 is truly expressed by glomerular cells in INS patients during relapse and in the LPS mouse model of podocyte injury. METHODS: The presence of CD80 in glomeruli was evaluated by combining immunostaining, immunogold labeling, and in situ hybridization techniques. RESULTS: CD80 was present along the surface of glomerular endothelial cells (GEC) and rarely in podocytes in six of nine minimal change disease (MCD) patients in relapse, two of eleven patients with focal segmental glomerulosclerosis in relapse, and absent in controls. In mice, CD80 was upregulated at mRNA and protein level in GEC and podocytes, in a similar pattern to that seen in MCD patients. CONCLUSIONS: Glomerular endothelial cells and podocytes can express CD80 in patients with MCD during relapse. A better understanding of the role of CD80 in glomerular cells may provide further insights into the mechanisms of proteinuria in INS.

Evaluation of immunological, inflammatory, and oxidative stress biomarkers in gasoline station attendants.

BACKGROUND: Gasoline is a complex mixture of saturated and unsaturated hydrocarbons, in which aromatic compounds, such as BTX (benzene, toluene, and xylene) feature as the main constituents. Simultaneous exposure to these aromatic hydrocarbons causes a significant impact on benzene toxicity. In order to detect early alterations caused in gasoline station attendants exposed to BTX compounds, immunological, inflammatory, and oxidative stress biomarkers were evaluated. METHODS: A total of 66 male subjects participated in this study. The gasoline station attendants (GSA) group consisted of 38 gasoline station attendants from Rio Grande do Sul, Brazil. The non-exposed group consisted of 28 subjects who were non-smokers and who had no history of occupational exposure. Environmental and biological monitoring of BTX exposure was performed using blood and urine. RESULTS: The GSA group showed increased BTX concentrations in relation to the non-exposed group (p < 0.001). The GSA group showed elevated protein carbonyl (PCO) levels and pro-inflammatory cytokines, decreased expression of CD80 and CD86 in monocytes, and reduced glutathione S-transferase (GST) activity compared to the non-exposed group (p < 0.05). BTX levels and trans,trans-muconic acid levels were positively correlated with pro-inflammatory cytokines and negatively correlated with interleukin-10 contents (p < 0.001). Increased levels of pro-inflammatory cytokines were accompanied by increased PCO contents and decreased GST activity (p < 0.001). Furthermore, according to the multiple linear regression analysis, benzene exposure was the only factor that significantly contributed to the increased pro-inflammatory cytokines (p < 0.05). CONCLUSIONS: Taken together, these findings show the influence of exposure to BTX compounds, especially benzene, on the immunological, inflammatory, and oxidative stress biomarkers evaluated. Furthermore, the data suggest the relationship among the evaluated biomarkers of effect, which could contribute to providing early signs of damage to biomolecules in subjects occupationally exposed to BTX compounds.

The utility of urinary CD80 as a diagnostic marker in patients with renal diseases.

CD80, which regulates T cell activation, may provide a differential diagnostic marker between minimal change disease (MCD) and other renal diseases, including focal segmental glomerular sclerosis (FSGS). However, recent reports show contrasting results. Therefore, we evaluated the utility of urinary CD80 as a diagnostic biomarker. We collected 65 urine samples from 55 patients with MCD (n = 31), FSGS (n = 4), inherited nephrotic syndrome (n = 4), Alport syndrome (n = 5) and other glomerular diseases (n = 11), and control samples (n = 30). We measured urinary CD80 levels by ELISA. Urinary CD80 (ng/gCr) (median, interquartile range) levels were significantly higher in patients with MCD in relapse (91.5, 31.1-356.0), FSGS (376.2, 62.7-1916.0), and inherited nephrotic syndrome (220.1, 62.9-865.3), than in patients with MCD in remission (29.5, 21.7-52.8) (p < 0.05). Elevation of urinary CD80 was observed, even in patients with inherited nephrotic syndrome unrelated to T cell activation. Additionally, urinary CD80 was positively correlated with urinary protein levels. Our results suggest that urinary CD80 is unreliable as a differential diagnostic marker between MCD in relapse and FSGS or inherited kidney diseases. Increased urinary CD80 excretion was present in all patients with active kidney disease.

Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome.

BACKGROUND: Rituximab, a monoclonal antibody targeting B lymphocytes, effectively sustains remission in steroid-dependent nephrotic syndrome (SDNS). We studied its effects on lymphocyte subsets and urinary CD80 excretion (uCD80) in patients with SDNS. METHODS: Blood and urine samples were collected from 18 SDNS patients before rituximab, and after 1 month and 1 year or at first relapse. T and B lymphocytes and uCD80 were determined by flow cytometry and ELISA, respectively. RESULTS: Treatment was associated with reduction in counts of Th17, Th2, and memory T cells, and increased T-regulatory (Treg) cells. The Th17/Treg ratio declined from baseline (median 0.6) to 1 month (0.2, P = 0.006) and increased during relapse (0.3, P = 0.016). Ratios of Th1/Th2 cells at baseline, 1 month after rituximab, and during relapse were 7.7, 14.0 (P = 0.0102), and 8.7, respectively. uCD80 decreased 1 month following rituximab (45.5 vs. 23.0 ng/g creatinine; P = 0.0039). B lymphocytes recovered earlier in relapsers (60.0 vs.183.0 days; P < 0.001). Memory B cells were higher during relapse than remission (29.7 vs.18.0 cells/µL; P = 0.029). CONCLUSION: Rituximab-induced sustained remission and B-cell depletion was associated with reduced numbers of Th17 and Th2 lymphocytes, and increased Treg cells; these changes reversed during relapses. Recovery of B cells and memory B cells predicted the occurrence of a relapse.

Urinary CD80 as a Replacement for Renal Biopsy for Diagnosis of Pediatric Minimal Change Disease.

INTRODUCTION: Early diagnosis of minimal change disease (MCD) is challenging in nephrotic children. CD80 is a protein expressed on the surface of podocytes associated with nephrotic syndrome and it is implicated in the induction of proteinuria. This study aimed to investigate the use of urinary CD80 for the diagnosis of MCD. MATERIALS AND METHODS: Urinary CD80 levels were evaluated in 36 children with nephrotic syndrome and normal glomerular filtration rate. They were divided into three groups of MCD (n = 21), focal segmental glomerulosclerosis (n = 9), and other glomerulopathies (n = 6). The MCD group was subdivided into 2 of those with remission (n = 11) and those in the active stage (n = 10). Forty healthy children were included as controls. RESULTS: The urinary CD80 level was significantly higher in the MCD group (3.5 ± 2.1 ng/mg creatinine) than in the focal segmental glomerulosclerosis group (1.2 ± 0.5 ng/mg creatinine, P < .001), the other glomerulopathies group (1.4 ± 0.7 ng/mg creatinine, P < .001), and the control group (0.7 ± 0.2 ng/mg creatinine, P < .001), while it showed no significant difference among the non-MCD groups. There was no significant difference between MCD in remission and MCD in relapse, either. A urinary CD80 cutoff value of 1.5 ng/gm creatinine showed a sensitivity of 100% and a specificity of 86% for diagnosis of MCD. CONCLUSIONS: Urinary CD80 levels were significantly higher in the children with MCD than in the controls and patients with other causes of nephrotic syndrome.

Urinary CD80 excretion is a predictor of good outcome in children with primary nephrotic syndrome.

BACKGROUND: The level of urinary cluster of differentiation 80 (uCD80) is elevated in most children with minimal change disease (MCD) as opposed to focal segmental glomerulosclerosis (FSGS) during the acute phase. The objective of this follow-up study was to evaluate whether uCD80 elevation is actually associated with MCD and whether it signals better prognosis. METHODS: We evaluated uCD80 levels and a series of putative progression factors in a cohort of 64 patients with nephrotic syndrome (NS) seen between 2011 and 2016. We monitored progression of chronic kidney disease (CKD), assessed as a glomerular filtration rate of < 90 ml/min/1.73 m2 for at least 3 months. Patients were classified according to uCD80 level and to the progression rate as calculated by Kaplan-Meier survival analysis and Cox's regression analysis. RESULTS: During a mean follow-up period of 4.8 ± 0.6 (range 3.5-6.0) years, 13 children (20%) evolved to at least CKD stage 2. The 64 patients with NS and normal baseline renal function were divided into two groups based on uCD80 excretion, i.e. below or above a defined cutoff (< or > 328.98 ng/g creatinine). The predicted response to immunosuppression therapy was 34.5 and 100% in the low- and high-uCD80 excretion, respectively (p < 0.001). Progression to CKD was 41.4 vs. 2.9% in NS patients (p < 0.001). Using the Cox model, only uCD80 excretion (p = 0.013, relative risk 6.171) predicted progression to CKD. CONCLUSIONS: Urinary CD80 predicts progression and remission in children with NS. The use of uCD80 as a prognostic marker facilitates the identification of high-risk patients at an early stage and may lead to better treatment selection.

Predictability of Urinary CD80 in the Relapse of Primary Nephrotic Syndrome.

PURPOSE: The current study is aimed at investigating whether urinary CD80 is reliable to predict the recurrence of pediatric PNS. MATERIALS AND METHODS: A total of 128 children, 105 males and 23 females, were enrolled in this study. Urinary samples were collected from SSNS and SRNS patients and 25 healthy children as controls. Urinary CD80 was measured by ELISA and adjusted for urinary creatinine excretion. RESULTS: Urinary CD80 in relapse stage of SSNS was significantly higher, and the urinary CD80 of paired relapse and remission stages of each SSNS patient were also significantly different. No significant difference was found between the urinary CD80 in SRNS relapse group, SRNS remission group, and the control group. Similarly, there was no significant difference between frequent SSNS and not frequent SSNS in remission group, as well as the relapse group. There is no correlation between urinary CD80 and 24-hour urinary protein. CONCLUSION: The increase of urinary CD80 was closely associated with the relapse of SSNS but was not related to the frequency of relapse. The urinary CD80 changes of concentration were reliable to predict the recurrence of SSNS. However, it cannot be used to predicate the frequent recurrence of PNS.

[Shendi granules regulates the balance of T cell subsets and down-regulates podocalyxin in rats with mesangial proliferative glomerulonephritis].

Objective To observe the effect of Shendi granules on T cell subsets and podocyte marker protein in rats with mesangial proliferative glomerulonephritis (MsPGN), and study possible mechanism. Methods Totally 40 SD rats were randomly divided into the model group, valsartan group, Shendi granule group and normal group. The Shendi granule group were given 4 g/(kg.d) of Shendi granule by gavage; the valsartan group were given 10.3 mg/(kg.d) of valsartan by gavage; the model group and normal group were given the same amount of saline per day by gavage. The treatments lasted 12 weeks. Routine biochemical method was used to quantify 24-hour urine protein; the numbers of CD4+ and CD8+ T cells were detected by flow cytometry; the serum levels of interleukin 2 (IL-2), IL-4 and IL-17, the levels of urinary podocalyxin (PCX) and B7-1, the renal calcineurin (CaN) content were determined by ELISA. Results Compared with the normal group, the levels of 24-hour urine protein, CD8+ T cells, serum IL-2 and IL-17, urinary PCX and B7-1, CaN in the model group were higher. The above indexes in the valsartan group and control group were lower than those in the model group, they were lower in the Shendi granule group than in the valsartan group. The whole blood CD4+ T cell number and serum IL-4 level in the model group were lower than those in the normal group, they were higher in the valsartan group and control group than in the model group. Compared with the valsartan group, the Shendi granule group had a better improvement. Conclusion Shendi granule could reduce 24-hour urine protein effectively. The mechanism may be related to the regulation of CD4+ T and CD8+ T cell numbers, the down-regulated expressions of serum IL-2, IL-17, the decreased levels of PCX and B7-1 in urine, CaN in kidney tissue, and the up-regulated level of serum IL-4.

Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome.

BACKGROUND: The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS). METHODS: The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls. TLR-3, TLR- 4 and CD80 mRNA expression levels in PBMCs were determined and the urinary CD80 level estimated. RESULTS: Median TLR-3, TLR-4 and CD80 mRNA expression levels were higher in patients with active SSNS than in those with SRNS, and the latter patient group also had significantly lower expression levels than the controls. The expression levels of these markers were associated with reductions in remission. Patients with biopsy-proven MCD had higher median expression levels of these markers than those with FSGS, but the differences were not statistically significant. Median urinary CD80/creatinine values were significantly higher in patients with SSNS and SRNS than in the controls and steroid-sensitive patients in remission (p < 0.001). CD80 levels were also significantly higher in patients with MCD than in those with FSGS (p = 0.002). A cut-off level of >914.5 ng/g had a sensitivity of 86.6%, specificity 71.4% and area under the curve of 0.828 (95% confidence interval 0.678-0.978, p = 0.002) for the diagnosis of MCD. CONCLUSIONS: Increased expressions of TLR-3, TLR-4 and CD80 mRNA and the level of urinary CD80/creatinine could be useful markers to differentiate patients of SSNS in relapse from those with SRNS. Further these markers can also distinguish biopsy proven MCD from FSGS in SRNS patients.

Increased urinary CD80 excretion and podocyturia in Fabry disease.

BACKGROUND: Certain glomerulopathies are associated with increased levels of CD80 (B7-1). We measured the urinary excretion of CD80, podocyturia and proteinuria in controls and in subjects with Fabry disease either untreated or on enzyme replacement therapy (ERT). METHODS: Cross-sectional study including 65 individuals: controls (n = 20) and Fabry patients (n = 45, 23 of them not on ERT and 22 on ERT). Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), urinary uCD80/creatinine ratio (uCD80) and podocyturia. CD80 mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes. RESULTS: Controls and Fabry patients did not differ in age, eGFR and gender. However, UPCR, uCD80 and podocyturia were significantly higher in Fabry patients than in controls. As expected, Fabry patients not on ERT were younger and a higher percentage were females. Non-ERT Fabry patients had less advanced kidney disease than ERT Fabry patients: UPCR was lower and eGFR higher, but uCD80 and podocyturia did not differ between non-ERT or ERT Fabry patients. There was a significant correlation between uCD80 and UPCR in the whole population (r 0.44, p 0.0005) and in Fabry patients (r 0.42, p 0.0046). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uCD80 expression in cultured podocytes. CONCLUSIONS: Fabry disease is characterized by early occurrence of increased uCD80 excretion that appears to be a consequence of glycolipid accumulation. The potential for uCD80 excretion to reflect early, subclinical renal Fabry involvement should be further studied.

Urine and serum ghrelin, sCD80 and sCTLA-4 levels in doxorubicin-induced experimental nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is an immune-mediated disorder associated with hyperlipidemia. NS has been proposed to be mediated through CD80-related T cell immune response, which could be blocked using soluble cytotoxic T lymphocyte-associated s(CTLA)-4. Although ghrelin is a hormone-modulating lipid metabolism and suppressing immune system, the precise role of ghrelin in NS is not well established. METHODS: We evaluated the levels of ghrelin, soluble CD80 (sCD80) and sCTLA4 in serum and urine in doxorubicin-induced NS in rats. We also investigated the relation between their levels and the levels of serum total cholesterol (TC), triglyceride, albumin and urine protein. RESULTS: While urinary ghrelin levels were significantly lower in the nephrotic rats compared to the control group, serum ghrelin levels were comparable in the nephrotic and control rats. In contrast, serum and urinary sCD80 and sCTLA4 levels were higher in the nephrotic rats than the controls. The urinary ghrelin levels were negatively correlated with the levels of serum triglyceride, TC and urine protein, sCD80 and sCTLA4. The urine sCD80 levels were positively correlated with the TC, urine protein and urine sCTLA4 levels, and negatively correlated with the serum albumin. The urine sCTLA4 levels were positively correlated with the TC and urine protein levels and negatively correlated with the serum albumin levels. In regression analysis, the urine ghrelin levels significantly relate to urine sCD80 levels. Besides, hyperlipidemia in NS did not appear to be related to serum ghrelin levels. CONCLUSION: Low urine ghrelin levels might be relevant to pathogenesis of doxorubicin-induced NS. The reduction in urine ghrelin levels might also be associated with increased levels of urine sCTLA4 and sCD80 which reflect proteinuria.

Urinary CD80 levels as a diagnostic biomarker of minimal change disease.

BACKGROUND: Early diagnosis of minimal change disease (MCD) in nephrotic syndrome (NS) patients remains challenging. Doctors often make a diagnosis of MCD using invasive renal biopsy. CD80, a transmembrane protein, is present on podocytes in a number of experimental models of NS. Urinary CD80 levels are significantly elevated in MCD but not in focal segmental glomerulosclerosis (FSGS) or other glomerulopathies. The purpose of this study was to investigate the feasibility of using urinary CD80 levels as a biomarker for the diagnosis of MCD. MATERIALS AND METHODS: A total of 165 subjects, 129 men and 36 women, were enrolled in this study. Urinary samples were collected from 37 patients with MCD, 27 patients with FSGS, 30 patients with other glomerulopathies, and 71 healthy people. Using ELISA, experimental values were compared with those produced by kidney biopsy samples. RESULTS: The concentration of urinary CD80 was significantly higher in the active MCD group (689.66 ± 378.21 ng/g creatinine) than in the FSGS group (123.49 ± 167. 88 ng/g creatinine, P < 0.00), other glomerulopathies group (152.37 ± 220. 14 ng/g creatinine, P < 0.001) and the control group (81.83 ± 23.01 ng/g creatinine; P < 0.001). A cutoff value of 328.98 (ng/g creatinine) was proposed, with a sensitivity of 81.1 % and specificity of 94.4 %. The area under the receiver operating characteristic (ROC) curve for the urinary CD80 to diagnose MCD was 0.925 (95 % confidence interval: 0.873-0.978). CONCLUSIONS: This experiment has preliminarily confirmed urinary CD80 as a non-invasive diagnostic biomarker. It may have significant value in the diagnosis of MCD.

Minimal change disease: a dysregulation of the podocyte CD80-CTLA-4 axis?

BACKGROUND: Minimal Change Disease (MCD) is associated with CD80 expression in podocytes and elevated urinary CD80 excretion during active renal disease. We have evaluated the urinary excretion of CTLA-4 and CD80 during different stages of the nephrotic syndrome in patients with MCD to test the hypothesis that persistent increased urinary CD80 excretion in patients with MCD in relapse is due to an ineffectual CTLA-4 response of the host to curtail the activation of CD80. METHODS: Thirty-two children with biopsy-proven MCD were studied during relapse and/or remission. Eleven healthy subjects served as controls. RESULTS: Urinary CD80 excretion was significantly increased in MCD patients in relapse relative to that in MCD patients in remission (p < 0.001) and controls (p < 0.001). Although urinary CTLA-4 excretion was higher in MCD patients in relapse than in MCD patients in remission (p = 0.01) and controls (p = 0.03), no significant correlation was observed between urinary CD80 excretion and urinary CTLA-4 level in MCD patients at the time of relapse (p = 0.06). At the time of remission, CD80 had decreased significantly in all patients, but CTLA-4 levels either decreased or remained unchanged in all but five patients, and no correlation was observed between urinary CD80 excretion and CTLA-4 level (p = 0.7). CONCLUSIONS: Urinary CTLA-4 levels do not correlate with urinary CD80 excretion, suggesting the possibility that the CTLA4 response may be suboptimal in this disease during relapse.

CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance.

BACKGROUND: Minimal change disease (MCD) is characterized by increased urinary excretion of CD80, whereas focal segmental glomerulosclerosis (FSGS) is associated with increased serum soluble urokinase-type plasminogen activator receptor (suPAR). The aim of the study was to assess whether the simultaneous measurement of urinary CD80 and serum suPAR helps differentiate MCD and FSGS. METHODS: Urine and sera were collected from patients with MCD in relapse or in remission, from FSGS patients with nephrotic syndrome, and from healthy individuals. CD80 and suPAR were measured by ELISA. RESULTS: Urinary CD80 was significantly increased in MCD patients in relapse compared with those in remission and with FSGS patients and control individuals. Serum suPAR levels were significantly higher in patients with FSGS when compared with MCD patients in relapse. Urinary suPAR showed a positive correlation with proteinuria in MCD in relapse and FSGS patients, whereas urinary CD80 correlated with proteinuria only in MCD patients in relapse. CONCLUSION: Urinary CD80 is elevated in MCD patients in relapse compared with FSGS patients. In contrast, serum suPAR is significantly elevated in FSGS patients. The consistent pattern of these two biomarkers in MCD and FSGS suggests that these two conditions represent different entities rather than a continuum spectrum of one disease.

CD80, suPAR and nephrotic syndrome in a case of NPHS2 mutation.

BACKGROUND: Podocin mutations are characterized by progression to end stage renal disease and histologic findings of Focal Segmental Glomerulosclerosis (FSGS). CD80 is a podocytes protein that may play a role in proteinuria, particularly in Minimal Change Disease whereas the soluble urokinase receptor (suPAR) is characteristically elevated in the serum of FSGS patients. METHODS: In a patient with nephrotic syndrome and podocin mutation, urinary and serum CD80 as well as suPAR were measured using commercially available kits. Urinary CD80 molecular size was determined by western blot analysis. Glomerular staining for CD80 and podocin was performed. RESULTS: Patient displayed marked elevated CD80 and mildly increased suPAR urinary levels compared to controls. Serum CD80 level was within the range observed in normal controls. Serum suPAR level was elevated, albeit in the lower range reported for patients with primary FSGS. Immunofluorescence examination of kidney biopsy revealed glomerular CD80 expression. CONCLUSION: The combination of serum and urinary biomarkers can help differentiate various forms of FSGS. High urinary CD80 and elevated serum and urinary suPAR might represent a profile to differentiate this genetic form of FSGS from primary FSGS.

CD80, suPAR and Nephrotic Syndrome in a case of NPHS2 mutation

Background: Podocin mutations are characterized by progression to end stage renal disease and histologic findings of Focal Segmental Glomerulosclerosis (FSGS). CD80 is a podocytes protein that may play a role in proteinuria, particularly in Minimal Change Disease whereas the soluble urokinase receptor (suPAR) is characteristically elevated in the serum of FSGS patients. Methods: In a patient with nephrotic syndrome and podocin mutation, urinary and serum CD80 as well as suPAR were measured using commercially available kits. Urinary CD80 molecular size was determined by western blot analysis. Glomerular staining for CD80 and podocin was performed. Results: Patient displayed marked elevated CD80 and mildly increased suPAR urinary levels compared to controls. Serum CD80 level was within the range observed in normal controls. Serum suPAR level was elevated, albeit in the lower range reported for patients with primary FSGS. Immunofluorescence examination of kidney biopsy revealed glomerular CD80 expression. Conclusion: The combination of serum and urinary biomarkers can help differentiate various forms of FSGS. High urinary CD80 and elevated serum and urinary suPAR might represent a profile to differentiate this genetic form of FSGS from primary FSGS (AU)

Antecedentes: Las mutaciones de la podocina están caracterizadas por la progresión hacia enfermedad renal terminal y por hallazgos histológicos de glomeruloesclerosis segmentaria y focal (GSF). CD80 es una proteína podocitaria que parece tener un papel en la proteinuria de la enfermedad de cambios mínimos, mientras que el receptor soluble de la uroquinasa (suPAR) es característicamente elevado en el suero de pacientes con GSF. Métodos: En un paciente con síndrome nefrótico y mutación de la podocina, se cuantificó CD80 y suPAR en suero y orina usando los kits disponibles en el mercado. El peso molecular del CD80 urinario fue determinado mediante Western blot. Se realizó la tinción para CD80 y podocina en el glomérulo. Resultados: El paciente presentó niveles urinarios marcadamente elevados de CD80 y ligeramente elevados de suPAR en comparación con controles. El nivel sérico de CD80 se encontró dentro del rango observado en controles. El nivel sérico de suPAR fue elevado, aunque en el límite inferior del rango publicado para pacientes con GSF primaria. La inmunofluorescencia de la biopsia renal mostró expresión glomerular de CD80. Conclusión: La combinación de biomarcadores séricos y urinarios quizás ayude a diferenciar entre diferentes formas de GSF. Niveles elevados de CD80 en orina y suPAR en suero quizás representen un perfil característico que permita diferenciar entre esta forma genética de GSF y GSF de causa primaria (AU)

Minimal change disease in graft versus host disease: a podocyte response to the graft?

Nephrotic syndrome is a rare complication of hematopoietic cell transplantation. It has been suggested that nephrotic syndrome may represent a limited form of graft-versus-host disease although the pathological link between these two entities remains unclear. In this paper, we report a case of a 61-year-old female who underwent nonmyeloablative allogenic stem cell transplantation for T-cell prolymphocytic leukemia and subsequently developed biopsy proven minimal change disease shortly after cessation of her immunosuppression therapy. Urinary CD80 was markedly elevated during active disease and disappeared following corticosteroid-induced remission. We hypothesize that alloreactive donor T cells target the kidney and induce podocyte expression of CD80 that results in proteinuria from limited 'graft versus host' disease.