scholarly journals Addition of eGFR and Age Improves the Prognostic Absolute Renal Risk-Model in 1,134 Norwegian Patients with IgA Nephropathy

2015 ◽  
Vol 41 (3) ◽  
pp. 210-219 ◽  
Author(s):  
Thomas Knoop ◽  
Ann Merethe Vågane ◽  
Bjørn Egil Vikse ◽  
Einar Svarstad ◽  
Bergrún Tinna Magnúsdóttir ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Prognostic Model ◽  
Risk Model ◽  
Area Under The Curve ◽  
Predicting Outcome ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage ◽  
French Cohort

Background: Predicting outcome in individual patients with IgA nephropathy (IgAN) is difficult but important. For this purpose, the absolute renal risk (ARR) model has been developed in a French cohort to calculate the risk of end-stage renal disease (ESRD) and death. ARR (0-3) is scored in individual IgAN patients based on the presence of proteinuria ≥1 g/24 h, hypertension, and severe histopathological lesions (1 point per risk factor). We have validated the ARR model in a Norwegian cohort of IgAN patients and tested whether adding data on initial estimated glomerular filtration rate (eGFR) and age improved prediction. Methods: IgAN patients diagnosed between 1988 and 2012 were identified in the Norwegian Kidney Biopsy Registry, and endpoints were identified by record linkage with the Norwegian Renal Registry (ESRD) and the Population Registry (deaths). Results: We identified 1,134 IgAN patients. The mean duration of follow-up was 10.2 years (range 0.0 to 25.7 years). Two hundred and fifty one patients developed ESRD and there were 69 pre-ESRD deaths. The ARR model significantly stratified the IgAN cohort according to risk of ESRD/death. The inclusion of eGFR and age significantly improved the ARR prognostic model; in the receiver operator characteristics (ROC) analysis, area under the curve (AUC) at 10-years of follow-up increased from 0.79 to 0.89, p < 0.001. Conclusions: ARR is a suitable prognostic model for stratifying IgAN patients according to the risk of ESRD or death. Including initial eGFR and age in the model substantially improved its accuracy in our nationwide cohort.

MO308COULD THE PRESENCE OF ANCAS IN IGA NEPHROPATHY WITH CRESCENTS HAVE A CLINICAL IMPLICATION?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Zaira Castañeda Amado ◽  
Alejandra Gabaldon ◽  
María Teresa Sanz ◽  
Roxana Bury ◽  
Cinthia Baldallo ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Iga Nephropathy ◽  
Kidney Biopsy ◽  
Clinical Presentation ◽  
Fibrinoid Necrosis ◽  
Oral Steroids ◽  
Common Clinical Presentation ◽  
The Mean ◽  
End Stage

Abstract Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis. The presence of ANCAs in this pathology represents a rare coincidence. However, it is not clear if the presence of IgA or IgG ANCAs in these patients could have clinical significance. We aim to describe the presence of IgA and IgG ANCAs in patients diagnosed with IgAN with crescents, and its possible clinical implications. Method Retrospective study from 2013 to 2020, it included all patients diagnosed by kidney biopsy of IgAN with extracapillary proliferation. Outpatient follow-up time was up to 24 months. Demographics and clinicopathologic data, ANCAs subtype, characteristics of the biopsy and treatment at the time of diagnosis/follow up was recollected. Results From 2013 to 2020, 17 adults were diagnosed with IgAN and extracapillary proliferation. 5 patients presented ANCAs, 3 (17%) were IgA ANCAs and 2 (11%) were IgG ANCAs. At diagnosis, the median age was 48 years old (27-75 years, sd. 15), with 9 women (52%). At the time of diagnosis, the most common clinical presentation was hypertension (71%). The laboratory analysis showed that median hemoglobin was 11.7 mg/dl (8.4-14.9 mg/dL, sd. 1.5), median creatinine was 2.2 mg/dL (0.55-5.7 mg/dL, sd. 1.4) and median proteinuria was 3.5 g/mgCr (0.1-12 g/mgCr, sd. 3.5). 7 patients (41%) presented extracapillary proliferation less than 25%, 7 patients presented it between 25% and 50%, and 3 patients (17%) had it in more than 50%. 5 (30%) patients presented fibrinoid necrosis. 1 (6%) patient needed renal replacement therapy upon admission. In terms of treatment, all patients with ANCAs IgAN received endovenous steroids and cyclophosphamide. The mean follow-up time was 6 months. Oral steroids (59%) and mycophenolate (41%) were the most frequent treatments. At six months, the median creatinine was 1.9 mg/dL (0.4-7, sd. 1.78) and the median proteinuria was 1.45 g/gCr (0.12-5.9, sd. 1.84 g/gCr). 3 patients developed end-stage chronic kidney disease and requiring substitute renal therapy; 4 patients died. Statistical analysis did not show differences in clinical characteristics, demographics, kidney function, proteinuria, need for renal therapy replacement or mortality according to the presence or subtype of ANCA. ANCA negative patients presented less than 25% of extracapillary proliferation in renal biopsy (p = 0.04). ANCA positive patients presented more fibrinoid necrosis than ANCA negative patients (p=0.01). Conclusion Given the limited size of our sample, our results do not allow us to be conclusive, showing no significant differences between the ANCA subtypes. However, from the point of renal biopsy, it is observed that patients with negative ANCAs present less extracapillary proliferation; and that patients ANCA positive presented more fibrinoid necrosis.

A multi-dose pharmacokinetic study of dalteparin in haemodialysis patients

2006 ◽  
Vol 96 (12) ◽  
pp. 750-755 ◽  
Author(s):  
Stephen Byrne ◽  
Lynda Szczech ◽  
Thomas Ortel ◽  
Stephanie Perry ◽  
Susan O’Shea
Keyword(s):  
Body Weight ◽  
Area Under The Curve ◽  
Factor Xa ◽  
Renal Elimination ◽  
Low Molecular Weight Heparins ◽  
Lower Body Weight ◽  
Multiple Blood ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage

SummaryLow-molecular-weight heparins undergo renal elimination, and therefore the proper dosing in hemodialysis (HD) patients is unclear. It was the objective of this study to evaluate the pharmacokinetic (PK) parameters of dalteparin in patients receiving chronic HD for end-stage renal disease. We performeda multidose PK study with prophylactic doses of dalteparin in twelve HD patients. Dalteparin 5,000 IU was administered subcutaneously daily for four consecutive days, with HD performed on day2 and day 4. Anti-factor Xa activity was determined daily and at multiple blood samples after the 3rd and 4th dose. Eleven of 12 patients completed the study. The mean (range) PK parameters determined after the 4th dose were as follows: i) maximum concentration (Cmax) was 0.31 IU/ml (0.06 to 0.55 IU/ml); ii) time to Cmax was 3.55 hours (2.59 to 4.96 hr); iii) area under the curve was 3.24 IU*hr/ml (0.64 to 6.44 IU*hr/ml); iv) half-life was 3.82 hr (2.03 to 9.63 hr); and v) trough anti-factor Xa activity 0.04 IU/ml (0.02 to 0.08 IU/ml). No major bleeding was observed. In general, patients with lower body weight exhibited a higher Cmax. From this pilot PK study, we have determined initial PK parameters for dalteparin in HD patients. Although a standard prophylactic dose was used, we found that in this patient population differences in body weight influenced the Cmax. Future studies to evaluate the PK parameters of dalteparin in patients receiving chronic HD may have to use weight-based dosing and will need to be performed over a longer period of time.

scholarly journals Assessment of the 24-hour profle of blood pressure and arterial stiffness in patients with end-stage renal disease

2019 ◽  
Vol 25 (1) ◽  
pp. 66-73
Author(s):  
I. E. Minyukhina ◽  
E. A. Praskurnichiy
Keyword(s):  
Blood Pressure ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Age Groups ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage ◽  
Design And Methods ◽  
Daily Changes

Objective. The purpose of our study was to research specifc features the daily changes of the vascular stiffness (VS) in patients with end-stage renal disease (ESRD) and to assess the feasibility of using the 24-hour vascular index Pulse Time Index of Norm (PTIN) (the percentage of the 24-hour period during which the pulse wave velocity (PWVao) does not exceed 10 m/second) in the management of arterial hypertension (HTN) in patients after renal transplantation (RT).Design and methods. We examined 158 people, divided into 4 comparable age groups: those receiving program hemodialysis (PGD), patients after RT, patients with essential HTN and healthy volunteers. All of them underwent 24-hour blood pressure (BP) monitoring with a daily evaluation of VS indices and central BP. At follow-up, 27 patients from the PG group underwent all assessments also 1 week and 6 months after transplantation.Results. Patients with ESRD compared with patients with essential HTN had elevated PWVao, night central BP and decrease PTIN. PTIN changes were the most signifcant. In 27 patients a week after the RT a decrease in the PTIN was found in most cases. After 6 months the mean PTIN in the whole group increased again. Our study demonstrates HTN persistence after kidney transplantation can be predicted. Two PTIN states could be predicted by the cutoff PTIN value that was determined in the study: a state of improvement and a state of decline/unchanged state. PTIN cutoff value at 45 % was characterized by 69 % sensitivity, 76 % specifcity and AUC of 0,65. Therefore, baseline PTIN ≥ 45 % (before RT) is associated with its further growth, and a favourable course of HTN.Conclusions. Patients receiving replacement therapy, compared to patients with essential HTN, showed a marked increase in the daily VS and the night central BP. The daily PTIN is the most accurate predictor of the changes in the VS index, the PTIN values before the RT at the PG stage allow predicting the course of HTN after the RT

scholarly journals P0345THE EFFICACY OF THE CORTICOSTEROIDS COMBINED ORAL CYCLOPHOSPHAMIDE FOR IGA NEPHROPATHY WITH REAL INSUFFICIENCY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Shiren Sun ◽  
Feng Ma ◽  
Xiaoxia Yang ◽  
Ming Bai
Keyword(s):  
Supportive Care ◽  
Renal Biopsy ◽  
Iga Nephropathy ◽  
Cox Regression ◽  
Immunosuppressive Drugs ◽  
Oral Cyclophosphamide ◽  
Renal Survival ◽  
The Mean ◽  
Stage Renal Disease

Abstract Background and Aims IgA nephropathy (IgAN) is the most type of primary glomerulonephritis and one of the major causes of end-stage renal disease (ESRD). The KDIGO clinical practice guidelines for glomerulonephritis suggest not the use of immunosuppressive drugs in IgAN patients with estimated glomerular filtration rate (eGFR) ≤50 mL/min/1.73m2. However, VALIGA study showed that immunosuppressive drugs were more frequently used in IgAN patients with eGFR &lt; 30 mL/min/1.73m2 than in those with eGFR ≥ 30 ml/ min/1.73m2 (60% vs. 44 %; p = 0.004). The immunosuppressive drugs could be effective for IgAN with renal insufficiency in few studies, such as corticosteroids combined oral cyclophosphamide (CS + oral CTX). Therefore, in our present study, we evaluated the efficacy and treatment-related complications of the patients with eGFR from 15 ml/min/1.73m2 to 59 ml/min/1.73m2 who receive supportive care, or CS, or CS + oral CTX. Method 1602 renal biopsy–proven patients were reviewed between January 2008 and December 2016 in the Xijing Hospital. Patients were excluded from the study if they had secondary IgAN. The inclusion criteria were the primary IgAN with eGFR from 15 ml/min/1.73m2 to 59 ml/min/1.73m2 (n = 389). We extracted the patients with receive supportive care, or corticosteroids, or corticosteroids combined oral cyclophosphamide (n = 212). We further excluded patients: &lt; 8 glomeruli (n = 10), diabetes mellitus (n = 4), a follow-up less than 6 months (n = 22), and incomplete data (n = 7). The remaining 169 patients were included in the study (Figure 1). The data included baseline demographic at renal biopsy, renal biopsy, treatment, follow-up parameters and outcomes. The primary endpoint was the combined event of a ≥ 50% reduction in eGFR and/or ESRD. Univariate and multivariate Cox regression analyses were conducted to determine which variables were associated with renal survival. Variables were entered into a multivariate Cox regression model using an Enter method, which were derived from adjusted models: model 1 was adjusted for age, sex, MAP, proteinuria, and eGFR; model 2 was adjusted for the variables in model 1 plus RAS; model 3 was adjusted for the variables in model 1 plus M1, E1, S1, T1-2, and C1-2; model 4 was adjusted for the variables in model 3 plus RAS. Results In all patients, the mean age was 36.0 years, the median proteinuria at the time of the biopsy was 1.6 g/day, the mean MAP was 108.7 mmHg, and eGFR was 40.4 ml/min/per 1.73 m2, the mean follow-up period was 43.3 months, 75 (44.9%) patients had reached combined event. The cumulative 5-year and 10-year renal survival rate were 39.3% and 9.3%, respectively, in the no-IS group ; 56.5% and 25.1%, respectively, in the CS group and 63.4% and 27.1%, respectively, in the CS + CTX group (Figure 2). Both univariate and multivariate Cox analyses shown that CS did not reduce the risk of combined event, whereas CS + CTX significantly reduced the risk of combined event. CS + CTX (HR = 0.367, 95%CI 0.198-0.682, P = 0.002) was notably associated with the risk of combined event after adjusted for age, sex, MAP, proteinuria, eGFR, M1, E1, S1, T1-2, C1-2, and ARB. The two groups did not differ significantly in treatment-related complications. Conclusion CS + oral CTX is possibly more effective than supportive care, or CS for IgAN patients with eGFR from 15 ml/min/1.73m2 to 59 ml/min/1.73m2. Furthermore, randomized controlled trials further verified the findings of the present study.

Outcomes of Simultaneous Peritoneal Dialysis and Arteriovenous Fistula Placement in End-Stage Renal Disease Patients

2017 ◽  
Vol 37 (6) ◽  
pp. 658-661 ◽  
Author(s):  
Nosratollah Nezakatgoo ◽  
Albert Ndzengue ◽  
Manhunath Ramaiah ◽  
Elvira O. Gosmanova
Keyword(s):  
Peritoneal Dialysis ◽  
Renal Disease ◽  
Arteriovenous Fistula ◽  
End Stage Renal Disease ◽  
Catheter Insertion ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Peritoneal dialysis (PD) interruption requiring hemodialysis (HD) is not uncommon and its frequently abrupt nature prevents timely creation of permanent HD access and avoidance of central venous catheters (CVC). We retrospectively studied a cohort of 24 end-stage renal disease (ESRD) patients (mean age 50.7 years, 83.3% African-Americans, 58.3% females, time on dialysis interquartile range [IQR] 0 - 65 days) who had simultaneous PD catheter insertion and backup arteriovenous fistula (AVF) creation between January 1, 2012, and December 31, 2013. The primary outcome of interest was the percent of patients receiving HD through the backup AVF at the time of PD interruption. A median (IQR) for PD catheter use after its insertion was 10.5 (2 - 20) days. After the mean follow-up of 19.6 months, 12 patients remained on PD, 2 patients received a kidney transplant, and 1 patient died. The overall AVF patency was 66.7%. A total of 9 (37.5%) patients had PD interruption requiring permanent (8 patients) or temporary (1 patient) HD after the mean (standard deviation [SD]) follow-up of 12.3 (8.2) months. Arteriovenous fistula was used as the initial access in 4 patients, and in 3 patients the original AVF was used after additional surgical revision. Forty-four percent of patients with a backup AVF fistula avoided CVC at the time of PD interruption requiring HD. The simultaneous AVF creation at the time of PD catheter insertion reduced but did not fully eliminate CVC at the time of PD interruption. Larger studies are needed to evaluate the utility of a backup AVF in PD patients.

scholarly journals Crescents and Global Glomerulosclerosis in Chinese IgA Nephropathy Patients: A Five-Year Follow-Up

2019 ◽  
Vol 44 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Wei Peng ◽  
Yi Tang ◽  
Li Tan ◽  
Wei Qin
Keyword(s):  
Serum Creatinine ◽  
Iga Nephropathy ◽  
Treatment Modalities ◽  
Renal Outcome ◽  
Urine Protein ◽  
Lower Egfr ◽  
Global Glomerulosclerosis ◽  
Stage Renal Disease ◽  
End Stage

Background/Aims: This study aims to evaluate the clinical significance of crescent and global glomerulosclerosis formation on renal outcome in patients with IgA nephropathy (IgAN). Methods: Biopsy-proven primary IgAN patients from West China Hospital of Sichuan University were studied retrospectively between 2008 and 2015. Clinicopathological features and treatment modalities were recorded. The patients were divided into several groups on the basis of cellular and/or fibrocellular crescents scores and global glomerulosclerosis scores. Crescent (C) was scored according to the updated Oxford classification (C0/C1/C2). Global glomerulosclerosis (G) was scored according to the frequency of global glomerulosclerosis: G0 (≤25% of glomeruli), G1 (26–50% of glomeruli), and G2 (> 50% of glomeruli). The primary endpoint was defined as a 50% reduction in renal function or end stage renal disease. Patients were followed up for at least 12 months, or shorter if they reached study endpoints. 1328 patients with IgAN were recruited. Mean follow-up time was 46.1±23.6 months. The percentage of patients with C1 and C2 was 19.3% and 5.9% respectively. Higher crescent scores was associated with lower estimated glomerular filtration rates (eGFR), decreased serum albumin levels, increased amounts of urine protein, higher serum creatinine, as well as greater proportions of M1 and E1. The percentage of patients with G0, G1 and G2 was 70.5%, 20.7% and 8.8%, respectively. Elevated glomerulosclerosis scores were associated with lower eGFR levels, increased amounts of urine protein, higher levels of serum creatinine, higher incidences of arterial hypertension, as well as greater proportions of M1. There was a significantly higher proportion of T1/2 in patients with G2. In a multivariate model, crescent and global glomerulosclerosis were identified as independent predictors of decreased renal survival. Conclusion: Global glomerulosclerosis and crescents, as detected in renal biopsies, are strong predictors of long-term renal outcome of IgAN.

Nierenbeteiligung bei Spondylarthritiden: Spezifisch oder unabhängig?

2021 ◽  
pp. 1-3
Author(s):  
Sibylle von Vietinghoff
Keyword(s):  
Renin Angiotensin System ◽  
Renal Outcome ◽  
Frequent Use ◽  
Tnf Α ◽  
Ckd Stage ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage ◽  
Egfr Decline

<b>Introduction:</b> IgA nephropathy (IgAN) can be associated with spondyloarthritis (SpA). The course of SpA-associated IgAN remains largely unknown due to the absence of large cohorts. <b>Methods:</b> This retrospective study included patients with biopsy-proven IgAN and definite SpA. Kidney biopsies were centrally examined and scored according to the IgAN Oxford Classification. Thirty-two patients fulfilled the inclusion criteria, with a male:female ratio of 9:1 and median age of 27 and 37 years at SpA and IgAN diagnosis, respectively. HLA-B27 was positive in 90% of cases, and most patients (60%) presented with ankylosing spondylitis. The mean baseline estimated glomerular filtration rate (eGFR) was 84 ± 26 ml/min per 1.73 m<sup>2</sup>, and the urine protein-to-creatinine ratio was 0.19 g/mmol. <b>Results:</b> Renal biopsy revealed frequent presence of crescents (33%) and interstitial inflammation (18%). Despite almost constant use of renin-angiotensin system inhibitors, combined with steroids in 13 of 32 patients, renal outcome was particularly poor. After a median follow-up of 5.9 years, 4 patients (12.5%) reached end-stage renal disease and 41% of patients experienced a &#x3e;50% decrease of eGFR. The mean annual eGFR decline rate was –4.3 ± 6.7 ml/min per 1.73 m<sup>2</sup>. The risk of reaching class IV or V chronic kidney disease (CKD) stage during follow-up was associated with the presence of hypertension, level of proteinuria, and baseline S- and T-scores of the Oxford. <b>Conclusion:</b> SpA-associated IgAN is associated with a poor renal outcome, despite frequent use of steroids. Tumor necrosis factor (TNF)-α blockade did not appear to influence the rate of eGFR decline in this setting.

scholarly journals Kidney and Urinary Tract Involvement in Epidermolysis Bullosa: Is Routine Follow-Up Necessary?

2021 ◽  
pp. 2021051
Author(s):  
Neslihan Cicek ◽  
Nurdan Yildiz ◽  
Ruslan Asadov ◽  
Ayse Deniz Yucelten ◽  
Halil Tugtepe ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Renal Disease ◽  
Epidermolysis Bullosa ◽  
End Stage Renal Disease ◽  
Creatinine Ratio ◽  
Tract Involvement ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage

Background: Several renal and urinary tract complications have been reported in patients with epidermolysis bullosa. Objective: This study investigated kidney and urinary tract involvement in patients with epidermolysis bullosa. Patients and Methods: Patients with epidermolysis bullosa in treatment at the Dermatology Unit were included in the study. Glomerular and tubular functions were investigated. Results: The study included 16 patients (4 females, 12 males) of mean 11.1 years (SD = 8.1 years). Estimated GFR was normal in all patients except one with end-stage renal disease. Excluding this patient, the urinary albumin/creatinine ratio and the fractional excretion of sodium were normal. The mean beta-2 microglobulin/creatinine ratio was 278.8 µg/g, and it was abnormally high in 2 patients. The mean tubular phosphorus reabsorption was 92.6%; it was abnormally low in 1 patient. Severe kidney or urinary tract involvement was present in 2 patients with recessive dystrophic EB-generalized severe (RDEB-GS): one patient had obstructive bullous lesions in the urethra; the other had end-stage renal disease secondary to focal segmental glomerulosclerosis and was on peritoneal dialysis for 3 years.   Conclusions:  Assessment for renal and urinary tract involvement should become a routine part of the evaluation of patients with any type of EB, but especially of patients with RDEB-GS. Patients with mild tubular dysfunction need long-term follow-up to detect early deterioration of renal function.

P0228THE NEFIGARD TRIAL: THE EFFECT OF NEFECON® (BUDESONIDE) IN PATIENTS WITH PRIMARY IGA NEPHROPATHY AT RISK OF DEVELOPING END-STAGE RENAL DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jonathan Barratt ◽  
Andrew Stone ◽  
Jens Kristensen
Keyword(s):  
Placebo Group ◽  
Renal Disease ◽  
Iga Nephropathy ◽  
End Stage Renal Disease ◽  
Primary Outcome ◽  
Stage Renal Disease ◽  
End Stage ◽  
Full Approval

Abstract Background and Aims Since the first description of IgA nephropathy (IgAN) over 50 years ago, it has been recognised that the mucosal immune system plays a crucial role in the pathogenesis of this common global cause of kidney failure. Recently, particular attention has focussed on the importance of the gut-associated lymphoid tissue (GALT) as the potential source of the poorly O-galactosylated IgA1 that triggers the formation of nephritogenic immune complexes in IgAN. Pathway analysis based on a large meta-analysis of genome wide association studies identified the intestinal immune network for IgA production as the most enriched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway in IgAN. Furthermore, separate studies have shown that the IgA in glomerular IgA deposits is indistinguishable from mucosal IgA. The therapeutic potential of selectively targeting GALT was demonstrated in the NEFIGAN trial (NCT01738035), which assessed the safety and efficacy of a novel targeted-release formulation of budesonide (NEFECON®), designed to deliver budesonide to the GALT-rich distal ileum in patients with IgAN. After 9 months’ treatment, urine protein–creatinine ratio (UPCR) was reduced by 29.3% in the NEFECON® 16 mg group compared with the placebo group. Estimated glomerular filtration rate (eGFR) dropped 4.7 ml/min/1.73 m2 in the placebo group with no deterioration seen in the NEFECON® 16 mg group. Incidence of patients reporting adverse events was similar in all groups. These data led to the design of the NefIgArd study which aims to assess the efficacy, safety, and tolerability of NEFECON® 16 mg in patients with IgAN at risk of end-stage renal disease. Method The NefIgArd study is a randomised, double-blind, placebo-controlled Phase 3 trial, with two parts – PART A a 15–35-day screening period, 9-month treatment and 3-month follow-up period; and PART B a 12-month no-treatment follow-up period (Figure). The study is recruiting across 146 nephrology clinics in 19 countries. Patients must be at least 18 years old with biopsy-confirmed primary IgAN and persistent proteinuria &gt;1 g/24 h and eGFR between 35 and 90 ml/min per 1.73 m2 (CKD-EPI) despite optimised renin–angiotensin system blockade. Patients are randomised on a 1:1 ratio to NEFECON® 16 mg/day or placebo. Consistent with the Kidney Health Initiative White Paper “Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy” published in early 2019, the primary outcome of Part A is to assess the effect of NEFECON® 16 mg on 24 h UPCR at 9 months compared with placebo. The Part B primary outcome is based on data presented at the NKF/FDA/EMA workshop in March 2018 that supported eGFR slope as an endpoint for full approval and will assess the effect of NEFECON® 16 mg on a 2-year eGFR-based endpoint compared with placebo. In comparison with other studies that are recruiting, we believe that the relatively short period required to provide validation of the surrogacy of proteinuria reduction will significantly reduce the risks of non-protocol treatments and loss of patients from the study that could dilute the true treatment effect of NEFECON®. Results As of 1 January 2020, 207 patients have been randomised, and Part A is expected to complete in Q4 2020, with Part B completing in 2022. To ensure the NefIgArd study results are fully translatable to the global IgAN population, NefIgArd will also open in China in 2020. Conclusion The NefIgArd study builds on the experience of the NEFIGAN trial, the largest commercially sponsored study ever completed in IgAN. The design of the NefIgArd study has used state-of-the-art data to evaluate kidney outcomes, using proteinuria as a reasonably likely surrogate of the effect of NEFECON® on long-term kidney outcomes and confirming long-term renoprotection using an NKF/FDA/EMA-suggested eGFR-based endpoint as a basis for full approval.

Predictors for the Healing of Transmetatarsal Amputations: Retrospective Study of 91 Amputations

Vascular ◽  
2007 ◽  
Vol 15 (3) ◽  
pp. 126-133 ◽  
Author(s):  
Peter Blume ◽  
Christine Salonga ◽  
Juan Garbalosa ◽  
Daphne Pierre-Paul ◽  
Jonathon Key ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Final Examination ◽  
The Mean ◽  
Group 2 ◽  
Stage Renal Disease ◽  
End Stage ◽  
Group 1

This retrospective study reviewed 80 consecutive patients (mean age 62 years; range 21–91 years) who underwent 91 transmetatarsal amputations (TMAs) between 1995 and 2003. The mean follow-up was 12 ± 1.36 months. Sixty-two TMAs healed initially (group 1), whereas 29 TMAs did not heal by 3 months (group 2). At the final examination, in groups 1 and 2, 63 of 91 (69%) limbs were healed. Of the 28 limbs that did not heal, 25 of 28 (89%) required further proximal amputation. Initial healing correlated significantly with the ability to ambulate ( p < .0001) and overall limb salvage ( p < .0001). In group 1, 20 of 27 (74%) limbs that were revascularized healed ( p = .0336). Nonhealing amputations were associated with end-stage renal disease (13 of 19; 68%) ( p = .0209) and leukocytosis (13 of 19; 68%) ( p = .0052).

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