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1.
Kidney Blood Press Res ; 49(1): 1-8, 2024.
Article in English | MEDLINE | ID: mdl-38011842

ABSTRACT

INTRODUCTION: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN. METHODS: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records. RESULTS: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) µmol/L in the conservatively managed group versus 374 (249-558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001). CONCLUSIONS: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.


Subject(s)
Nephritis, Interstitial , Renal Dialysis , Humans , Retrospective Studies , Creatinine , Czech Republic , Renal Dialysis/adverse effects , Nephritis, Interstitial/drug therapy , Nephritis, Interstitial/diagnosis , Adrenal Cortex Hormones/therapeutic use , Kidney/pathology
2.
Front Immunol ; 14: 1122972, 2023.
Article in English | MEDLINE | ID: mdl-37020541

ABSTRACT

Background: Activity and chronicity of kidney involvement in ANCA-associated vasculitis (AAV) can be currently reliably evaluated only by kidney biopsy. In this study, we measured a panel of serum and urinary biomarkers collected at the time of kidney biopsy and hypothesized that they could reflect specific histopathological parameters in the biopsy and help to predict prognosis. Methods: We examined a cohort of 45 patients with AAV and 10 healthy controls. Biomarker levels (DKK-3, CD163, EGF, PRO-C6 and C3M) were measured in this study by ELISA. Biopsies were scored with a scoring system for AAV (focal x crescentic x sclerotic x mixed class) and interstitial fibrosis was quantified. Results: Levels of urinary DKK-3, CD163, EGF, PRO-C6 and C3M significantly differed among biopsy classes in AAV, with urinary DKK-3 and PRO-C6 levels being highest in the sclerotic class and lowest in the focal class, urinary CD163 levels highest in the crescentic class and urinary C3M levels highest in the focal class. Moreover, the urinary biomarkers were able to discriminate focal biopsy class from the other classes. Urinary DKK-3, EGF, PRO-C6 and C3M levels measured at the time of biopsy were also significantly related to the extent of fibrosis and to the final kidney function at the end of follow-up. Conclusions: This small pilot study suggests that selected urinary biomarkers of fibrosis and inflammation may reflect changes in the kidney biopsy and be prognostic of kidney outcome in patients with AAV.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Antibodies, Antineutrophil Cytoplasmic , Humans , Epidermal Growth Factor , Pilot Projects , Kidney/pathology , Inflammation/pathology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Biomarkers/urine , Fibrosis
3.
J Am Soc Nephrol ; 34(3): 505-514, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36446430

ABSTRACT

SIGNIFICANCE STATEMENT: Most patients with anti-glomerular basement membrane (GBM) disease present with rapidly progressive glomerulonephritis, and more than half develop ESKD. Currently, no tools are available to aid in the prognostication or management of this rare disease. In one of the largest assembled cohorts of patients with anti-GBM disease (with 174 patients included in the final analysis), the authors demonstrated that the renal risk score for ANCA-associated vasculitis is transferable to anti-GBM disease and the renal histology is strongly predictive of renal survival and recovery. Stratifying patients according to the percentage of normal glomeruli in the kidney biopsy and the need for RRT at the time of diagnosis improves outcome prediction. Such stratification may assist in the management of anti-GBM disease. BACKGROUND: Prospective randomized trials investigating treatments and outcomes in anti-glomerular basement membrane (anti-GBM) disease are sparse, and validated tools to aid prognostication or management are lacking. METHODS: In a retrospective, multicenter, international cohort study, we investigated clinical and histologic parameters predicting kidney outcome and sought to identify patients who benefit from rescue immunosuppressive therapy. We also explored applying the concept of the renal risk score (RRS), currently used to predict renal outcomes in ANCA-associated vasculitis, to anti-GBM disease. RESULTS: The final analysis included 174 patients (out of a total of 191). Using Cox and Kaplan-Meier methods, we found that the RRS was a strong predictor for ESKD. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-risk, moderate-risk, and high-risk groups, respectively. The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD. The best predictor for renal recovery was the percentage of normal glomeruli, with a cut point of 10% normal glomeruli providing good stratification. A model with the predictors RRT and normal glomeruli ( N ) achieved superior discrimination for significant differences in renal survival. Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N ≥10%), 74.0% (no RRT, N <10%), 42.3% (RRT, N ≥10%), and 14.1% (RRT, N <10%), respectively. CONCLUSIONS: These findings demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Such stratification may assist in the management of anti-GBM disease. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.


Subject(s)
Anti-Glomerular Basement Membrane Disease , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Humans , Retrospective Studies , Cohort Studies , Prospective Studies , Kidney , Renal Replacement Therapy , Risk Assessment
4.
Nephrol Dial Transplant ; 37(6): 1099-1108, 2022 05 25.
Article in English | MEDLINE | ID: mdl-33914059

ABSTRACT

BACKGROUND: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with immunoglobulin A nephropathy (IgAN) and patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the enzyme-linked immunosorbent assay PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores. RESULTS: S-ETP and U-ETP/Cr levels correlated with kidney function, increased CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort. CONCLUSIONS: We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Glomerulonephritis, IGA , Renal Insufficiency, Chronic , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Atrophy/complications , Atrophy/pathology , Collagen Type VI , Fibrosis , Glomerulonephritis, IGA/pathology , Humans , Kidney/pathology , Peptide Fragments , Renal Insufficiency, Chronic/complications
5.
Arthritis Res Ther ; 18: 168, 2016 07 13.
Article in English | MEDLINE | ID: mdl-27412443

ABSTRACT

BACKGROUND: Plasma exchange (PLEX) has been used routinely for treatment of severe renal vasculitis and/or alveolar haemorrhage (AH) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but the long-term benefit of PLEX in AAV remains unclear. We aimed to describe the characteristics and outcomes of patients treated with PLEX in a single centre. METHODS: Patients with AAV were identified by performing a case review of medical records of 705 patients who received PLEX in a single tertiary referral centre between 2000 and 2010. Patient characteristics and outcomes were recorded. The Kaplan-Meier method, log-rank tests and Cox regression analysis were used for survival analyses. RESULTS: A total of 94 patients with AAV were identified (44 men, 50 women; median age 60 years, range 21-90 years; 52 proteinase 3-ANCA, 41 myeloperoxidase-ANCA and 1 ANCA-negative; 8 double-positive for ANCA and anti-glomerular basement membrane; 93 newly diagnosed/1 relapse; 55 [58.5 %] required dialysis). The reasons for initiating PLEX therapy were severe renal involvement alone in 52 %, AH in 10 %, both renal involvement and AH in 35 %, and "other" in 3 %. The patients had 3-27 (median 7) PLEX sessions. At 3 months, 81 (86 %) of 94 were alive and 62 (66 %) of 94 were alive and dialysis-independent. The median follow-up was 41 months (minimum-maximum 0.5-137 months), when 56 (59.6 %) of 94 patients were alive and 47 (50 %) were dialysis-independent. The estimated overall survival rates were 75.3 % at 1 year and 61.1 % at 5 years. Patient survival decreased with increasing age at presentation (5-year survival 85 % for age <50 years, 64.4 % for ages 50-65 years, and 41 % for >65 years; p < 0.01 for comparison between all groups). Estimated renal survival rates were 65.5 % at 1 year and 43 % at 5 years. Renal survival was worse in patients aged >65 years than in the younger patients (5-year survival 25.1 % in patients >65 years vs. 50.8 % for those ≤65 years, p < 0.01). The estimated renal survival was better in patients with higher Disease Extent Index (DEI) >6 than in patients with DEI ≤6 (5-year survival 52.1 % vs. 39.4 %, p = 0.04), even though this was not confirmed in multivariate analysis. CONCLUSIONS: The mortality of patients presenting with severe manifestations of AAV remains high despite the use of PLEX. Older age at presentation is associated with worse overall and renal prognosis.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/therapy , Adult , Aged , Aged, 80 and over , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Plasma Exchange/methods , Proportional Hazards Models , Retrospective Studies , Time , Young Adult
6.
Ren Fail ; 30(9): 890-5, 2008.
Article in English | MEDLINE | ID: mdl-18925529

ABSTRACT

The natural course of as-yet-untreated ANCA-associated vasculitis (AAV) or complications of immunosuppressive treatment may result in rapid clinical deterioration with the need of admission to an intensive care unit (ICU). The aim of this retrospective study was to assess the outcome of patients with renal AAV admitted to the ICU in a single center. We reviewed the medical records of all 218 patients with AAV followed in our department between January 2001 and December 2006 and selected those admitted to the ICU. To assess the severity of critical illness, the Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) score on the first ICU day were calculated. Birmingham Vasculitis Activity Score (BVAS) was calculated to represent the total disease activity. Thirty patients with AAV (11 women, 19 men; mean age 61.5 +/- 13.2 years; 20 x cANCA, 10 x pANCA positive) were included. The most common reasons for ICU admission were as follows: active vasculitis (13 patients, 43.3 %), infections (7 patients, 23.3%), and other causes (10 patients, 33.3%). The in-ICU mortality was 33.3% (10 patients). The most common cause of death was septic shock (in 5 patients). The APACHE II (33.5 vs. 23.8) and SOFA scores (11.9 vs. 6.6), but not BVAS (11.5 vs. 16.1), were statistically significantly higher in non-survivors than in survivors (p < 0.01). In conclusion, the in-ICU mortality in AAV patients may be predicted by APACHE II and SOFA scores. While active vasculitis is the most frequent reason for ICU admission, the mortality rate is highest in patients with infectious complications.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic , Churg-Strauss Syndrome/therapy , Critical Care , Granulomatosis with Polyangiitis/therapy , Hospitalization , Kidney Diseases/therapy , Aged , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/mortality , Cohort Studies , Female , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/mortality , Health Status Indicators , Hospital Mortality , Humans , Kidney Diseases/etiology , Kidney Diseases/mortality , Male , Middle Aged , Retrospective Studies , Treatment Outcome
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