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Background and objectives:
This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever).
Design, setting, participants, & measurements:
We enroll...
Contexts in source publication
Context 1
... characteristics of the 441 eligible and active patients are summarized in Table 1. Patients range in age from 1 to 84 years; 66% were adults (age $18 years) at the time of biopsy. ...
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Abstract Background Proteinuria is known to be associated with both kidney function deterioration and cardiovascular diseases. While proteinuria estimation from 24-h urine samples has traditionally been considered as the standard method for assessment of the degree of urinary protein excretion, sample collection is associated with several technical...
Although various patterns of renal diseases have been reported from different renal biopsy registries worldwide, data from Nigeria remain scanty. A 10-year retrospective review of renal biopsies was conducted in our tertiary health care facility. All cases were reclassified based on their light microscopic features after the application of standard...
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Introduction: Few studies have addressed the genetic spectrum of NPHS1 variants in Chinese children with nephrotic syndrome. In this multicenter study, the clinical manifestations and features of NPHS1 variants in Chinese children with nephrotic syndrome were researched.
Method: Genotypical and phenotypical data from 30 children affected by NPHS1 v...
Citations
... MCD, FSGS, and MN median ages were 31, 39, and 60 years, respectively. and younger than those of included in JNSCS (44, 59, and 67 years, respectively) 19 4 , the present study shows that the prevalence of FSGS in Japan was lower (11.4%) and has not changed in the past decade 21 . These epidemiological differences could be attributed partially to the genetic variants in apolipoprotein L1 (APOL1) among people with sub-Saharan ancestry 22 . ...
The nationwide clinical features of Japanese patients with primary nephrotic syndrome (NS), including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN), have not yet been reported. We collected the clinical personal records of patients with primary NS between 2015 and 2018 from the national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Overall, the demographics, chronic kidney disease classification based on glomerular filtration rate and albuminuria, and treatment of 6036 patients were collected: 3394 (56.2%) with MCD, 677 (11.2%) with FSGS, 1455 (24.1%) with MN, and 510 (8.5%) with others. MN patients were older than MCD and FSGS patients (67 vs. 42 and 47 years, respectively). Steroid-dependent NS or frequently relapsing NS was found in 70.2%, 40.5%, and 24.6%, whereas steroid-resistant NS was found in 6.4%, 36.0%, and 37.9% of patients in the MCD, FSGS, and MN, respectively. The present oral prednisolone use (mean dose, mg/day) was 87.2% (21.2), 80.9% (20.0), and 77.5% (18.8) of patients in the MCD, FSGS, and MN, respectively. The national registry of clinical personal records of primary NS could provide an informative insight into the characteristics, clinical features, and treatment approaches for patients with primary NS in Japan.
... 441 patients with proteinuria more than or equal to 0.5 g/day attributed to MCD, FSGS, MN, and other glomerulopathies in the Nephrotic Syndrome Study Network (NEPTUNE) and found that complete remission of proteinuria was observed in 46% after a median duration of follow-up of 19 months. On the contrary, 4.6% of the patients progressed to ESRD [34]. In the same context, cure glomerulonephritis, a large prospective multicenter observational study of GDs, namely, MCD, FSGS, MN, and IgA nephropathy, is going on with a broad goal to lessen GD burden and improve outcomes [35]. ...
Background
Glomerular diseases (GDs) place a significant burden on patients and health care systems, and they are a leading cause of end-stage renal disease (ESRD) globally. There is no national register for GDs in Egypt, and the outcomes of GDs are not extensively examined. As a result, studying GD patterns and outcomes, as well as the association between chronic renal injury at presentation and GD outcomes, was of great interest.
Patients and methods
Patients with biopsy-proven GDs presenting to an Egyptian tertiary care center were enrolled and prospectively followed up for 6 months, until death or reaching ESRD. Chronic renal damage was assessed at diagnosis by calculating the total renal chronicity.
Results
A total of 66 individuals with biopsy-confirmed GDs were enrolled in the study.
Unexplained decrease in kidney function (62%), subnephrotic (23%), and nephrotic
presentation (15%) were the most common reasons for a renal biopsy. The most common histological patterns were diffuse proliferative glomerulonephritis (GN), membranoproliferative GN, and sclerosing GN. Primary and secondary GDs made up 30.3 and 69.7% of the cases, respectively. At the end of the 6-month follow-up, 28 patients had recovered their renal function, 19 had advanced to ESRD, and seven had died. Hemoglobin level and the total renal chronicity score were the best ways to predict how well the kidneys would get better.
Conclusion
In this tertiary care center Egyptian cohort, secondary GDs appeared to be more frequent than primary GDs, diffuse proliferative GN was the most common histopathological pattern, and rapid renal recovery was not the rule in this short
period. The renal chronicity score could accurately predict the renal outcome.
... Este hallazgo se opone a las asociaciones descritas en otros estudios realizados en niños. (14,15,16,17,18) encierra el número elevado de pacientes sin respuesta al tratamiento (53 %) resulta mayor que el número de pacientes con respuesta al tratamiento (47 %) lo que contradice a Santin y otros (19) que describió solo el 40 % de los casos como resistentes a los esteroides, los autores consideramos que una de las posibles razones puede ser la no adherencia a los esteroides en la población del hospital, ya que el hospital asiste a una población predominante de clase económica baja. En la regresión lineal realizada con los valores de proteinuria previa y después del tratamiento se demostró una ligera asociación con la edad (r = 0,2) pero con los hallazgos no alcanzó la significancia estadística (valor de p = 0,2). ...
Introducción:
El síndrome nefrótico es una patología que afecta el complejo glomerular del riñón, se caracteriza por una proteinuria mayor 3500 mg/d. De acuerdo a la respuesta de los esteroides se puede clasificar en síndrome nefrótico en esteroide resistente o esteroide sensible.
Objetivo:
Determinar la relación que existe entre la proteinuria y las variantes del síndrome nefrótico en adultos.
Métodos:
Se realizó un estudio descriptivo, retrospectivo, tipo serie de casos, con una población de 28 pacientes. Se recolectaron y se procesaron los datos a través del software Epi-Info 7,2TM; la frecuencia simple, la media estadística, prueba t de Student, y el coeficiente de correlación de Pearson.
Resultados:
En el análisis combinatorio de los fármacos adyuvantes para síndrome nefrótico, el grupo que utilizó antiproteinúricos pero no estatinas, demostró una diferencia estadísticamente significativa entre la proteinuria postratamiento media del grupo de síndrome nefrótico esteroideo resistente (6202 mg/d) vs síndrome nefrótico esteroideo sensible (65,9 mg/d) (valor de p 0,418). Existe una correlación negativa entre los niveles proteinuria postratamiento y el nivel de albúmina sérica postratamiento (r = - 0,7 valor de p < 0,00001).
Conclusiones:
Se demostró la ausencia de asociación entre la proteinuria inicial y las variantes de síndrome nefrótico esteroide sensible y esteroide resistente (valor de p = 0,8).
... proteinuria, and response to empiric therapy. 3 In view of the heterogeneity of the underlying biological mechanisms, the ability to identify specific biomarkers of molecular pathway activation is a critical step that can enable the development of targeted therapies and a precision medicine approach to the treatment of patients with GD. ...
Introduction:
Dysregulation of sphingolipid and cholesterol metabolism contributes to the pathogenesis of glomerular diseases (GDs). Apolipoprotein M (ApoM) promotes cholesterol efflux and modulates the bioactive sphingolipid sphingosine-1-phosphate (S1P). Glomerular ApoM expression is decreased in patients with focal segmental glomerulosclerosis (FSGS). We hypothesized that glomerular ApoM deficiency occurs in GD and that ApoM expression and plasma ApoM correlate with outcomes.
Methods:
Patients with GD from the Nephrotic Syndrome Study Network (NEPTUNE) were studied. We compared glomerular mRNA expression of ApoM (gApoM), sphingosine kinase 1 (SPHK1), and S1P receptors 1 to 5 (S1PR1-5) in patients (n = 84) and controls (n = 6). We used correlation analyses to determine associations between gApoM, baseline plasma ApoM (pApoM), and urine ApoM (uApoM/Cr). We used linear regression to determine whether gApoM, pApoM, and uApoM/Cr were associated with baseline estimated glomerular filtration rate (eGFR) and proteinuria. Using Cox models, we determined whether gApoM, pApoM, and uApoM/Cr were associated with complete remission (CR) and the composite of end-stage kidney disease (ESKD) or ≥40% eGFR decline.
Results:
gApoM was reduced (P < 0.01) and SPHK1 and S1PR1 to 5 expression was increased (P < 0.05) in patients versus controls, consistent with ApoM/S1P pathway modulation. gApoM positively correlated with pApoM in the overall cohort (r = 0.34, P < 0.01) and in the FSGS (r = 0.48, P < 0.05) and minimal change disease (MCD) (r = 0.75, P < 0.05) subgroups. Every unit decrease in gApoM and pApoM (log2) was associated with a 9.77 ml/min per 1.73 m2 (95% confidence interval [CI]: 3.96-15.57) and 13.26 ml/min per 1.73 m2 (95% CI: 3.57-22.96) lower baseline eGFR, respectively (P < 0.01). From Cox models adjusted for age, sex, or race, pApoM was a significant predictor of CR (hazard ratio [HR]: 1.85; 95% CI: 1.06-3.23).
Conclusions:
pApoM is a potential noninvasive biomarker of gApoM deficiency and strongly associates with clinical outcomes in GD.
... [Downloaded free from http://www.jesnt.eg.net on Tuesday, July 4, 2023, IP: 98.220.33.57] 441 patients with proteinuria more than or equal to 0.5 g/day attributed to MCD, FSGS, MN, and other glomerulopathies in the Nephrotic Syndrome Study Network (NEPTUNE) and found that complete remission of proteinuria was observed in 46% after a median duration of follow-up of 19 months. On the contrary, 4.6% of the patients progressed to ESRD [34]. In the same context, cure glomerulonephritis, a large prospective multicenter observational study of GDs, namely, MCD, FSGS, MN, and IgA nephropathy, is going on with a broad goal to lessen GD burden and improve outcomes [35]. ...
... These clinical observations suggest a heterogeneous biology underlying current disease classification. [2][3][4] Because of limited understanding of pathobiology, interpretation of the clinical outcome variability in observational studies and clinical trials is challenging, 5,6 and molecularly-driven, 7,8 personalized 6 treatments for MCD and FSGS are unavailable. ...
The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual’s TNF pathway activation score. Kidney organoids and single nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing.
... Beyond NS, elevated urinary protein excretion in general represents an independent risk factor for increased cardiovascular disease and CKD-progression [10][11][12][13][14]. Interestingly, even subtle differences in very low grade albuminuria were recently shown to effect all-cause and cardiovascular mortality [15]. While the main underlying causes of primary and secondary NS are well characterized in adults [7,16], in subnephrotic and low range proteinuria systematic biopsy data are scarce. This phenomenon is partly explained by the fact that the diagnostic value of native kidney biopsy is still less well-established in patients with subnephrotic range proteinuria (UPCR 300-3500mg/g crea (creatinine)) and little is known about the impact of kidney biopsy on differential diagnosis and prognosis. ...
Background
In nephrotic range proteinuria of adult-onset, kidney biopsy is the diagnostic gold standard in determining the underlying cause of disease. However, in low grade or subnephrotic proteinuria the diagnostic value of kidney biopsy as first-line diagnostics is less well established.
Methods
We conducted a retrospective analysis of all native kidney biopsies at our institution (n = 639) between 01/2012 and 05/2021 for comparison of histological diagnoses and clinical outcomes stratified by amount of proteinuria at the time of kidney biopsy: A: <300mg/g creatinine (low grade), B: 300-3500mg/g creatinine (subnephrotic), C >3500mg/g creatinine (nephrotic).
Results
Nephrotic range proteinuria was associated with the highest frequency (49.3%) of primary glomerulopathies followed by subnephrotic (34.4%) and low grade proteinuria (37.7%). However, within the subnephrotic group, the amount of proteinuria at kidney biopsy was linearly associated with renal and overall survival (HR 1.05 per Δ100mg protein/g creatinine (95% CI: 1.02–1.09, p = 0.001)) independent of present histological diagnoses and erythrocyturia.
Conclusion
Frequency of primary glomerulopathies supports to perform kidney biopsy in patients with subnephrotic proteinuria. These patients have a substantial risk of ESKD and death upon follow-up. Therefore, diagnostic accuracy including histopathology is essential to guide personalized treatment and avert detrimental courses.
... m 2 were significantly associated with remission at the similar level (adjusted HRs of eGFR of < 30.0, 30.0-59.9, 60.0-89.9, and ≥ 90.0 mL/min/1.73 m 2 Table 3). The non-linear association between eGFR and remission was verified in a multivariable-adjusted restricted cubic spline model (Fig. 2b). ...
Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.
... AUC indicates the area under the receiver operating curves. (Gipson et al., 2016). Immunomodulatory agents, including glucocorticoids, are well-recognized therapeutic choices. ...
Tremors have been reported even with a low dose of tacrolimus in patients with nephrotic syndrome and are responsible for hampering the day-to-day work of young active patients with nephrotic syndrome. This study proposes a neural network model based on seven variables to predict the development of tremors following tacrolimus. The sensitivity and specificity of this algorithm are high. A total of 252 patients were included in this study, out of which 39 (15.5%) experienced tremors, 181 patients (including 32 patients who experienced tremors) were randomly assigned to a training dataset, and the remaining were assigned to an external validation set. We used a recursive feature elimination algorithm to train the training dataset, in turn, through 10-fold cross-validation. The classification performance of the classifer was then used as the evaluation criterion for these subsets to find the subset of optimal features. A neural network was used as a classification algorithm to accurately predict tremors using the subset of optimal features. This model was subsequently tested in the validation dataset. The subset of optimal features contained seven variables (creatinine, D-dimer, total protein, calcium ion, platelet distribution width, serum kalium, and fibrinogen), and the highest accuracy obtained was 0.8288. The neural network model based on these seven variables obtained an area under the curve (AUC) value of 0.9726, an accuracy of 0.9345, a sensitivity of 0.9712, and a specificity of 0.7586 in the training set. Meanwhile, the external validation achieved an accuracy of 0.8214, a sensitivity of 0.8378, and a specificity of 0.7000 in the validation dataset. This model was capable of predicting tremors caused by tacrolimus with an excellent degree of accuracy, which can be beneficial in the treatment of nephrotic syndrome patients.
... For example, a prospective cohort study enrolled 441 patients with proteinuria ≥0.5 g/day attributed to MCD, FSGS, MN and other glomerulopathies in the Nephrotic Syndrome Study Network (NEPTUNE) found that complete remission of proteinuria was observed in 46% after a median duration of follow up for 19 months. On the other hand, 4.6% of the patients progressed to ESRD [34]. In the same context, cure glomerulonephritis (CureGN), a large prospective multicenter observational study of GDs namely; MCD, FSGS, MN and IgAN, is going on with a broad goal to lessen GDs burden and improve outcomes [35]. ...
Background
Glomerular diseases (GDs) place a significant burden on patients and health-care systems, and they are a leading cause of end-stage renal disease (ESRD) globally. There is no national register for GDs in Egypt, and the outcomes of GDs are not extensively examined. As a result, studying GDs patterns and outcomes, as well as the association between chronic renal injury at presentation and GDs outcome, was of great interest.
Methods
Patients with biopsy-proven GDs, presenting to an Egyptian tertiary care center were enrolled and prospectively followed-up for 6 months, death or reaching ESRD. Chronic renal damage was assessed at diagnosis by the total renal chronicity.
Results
Sixty-six individuals with biopsy-confirmed GDs were enrolled in the study. The most common reasons for a renal biopsy were unexplained kidney function decrease (62%), followed by subnephrotic (23%) and nephrotic presentation (15%). The most common histological patterns were diffuse proliferative glomerulonephritis (GN), membranoproliferative GN (MPGN), and sclerosing GN. Primary and secondary GDs made up 30.3% and 69.7% of the cases, respectively. At the end of the 6-month follow-up, 28 patients had recovered their renal function, 19 had advanced to ESRD, and 7 had died. The most significant predictors of renal recovery were hemoglobin level and the total renal chronicity score.
Conclusion
In this tertiary care center Egyptian cohort, secondary GDs appear to be more frequent than primary GDs, diffuse proliferative GN was the most common histopathological pattern, and rapid renal recovery was not the rule in this short period. The renal chronicity score could accurately predict the renal outcome.
Trial Registration
Approval for this study was granted by the Mansoura Faculty of Medicine Institutional Research Board (IRB) (approval no. MD/17.05.13).
