Serious infections (SI) are common in patients with ANCA-associated vasculitides (AAV) like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Real-life data regarding their ...incidence and predisposing factors-after the introduction of B cell depleting agents-are limited while data quantifying the risk per treatment modality and year of the disease are missing. Here, we aim to describe in details the incidence and the risk factors for SI in a contemporary AAV cohort.
Multicenter, observational, retrospective study of AAV patients followed in three tertiary referral centers.
We included 162 patients with GPA (63%) and MPA (37%), males 51.9%, mean age 60.9 years, ΑΝCA+ 86%, and generalized disease 80%. During follow-up (891.2 patient-years, mean 5.4 years), 67 SI were recorded in 50 patients at an incidence rate of 7.5 per 100 patient-years. The SI incidence rate was higher during induction with cyclophosphamide (CYC) compared to rituximab (RTX, 19.3 vs. 11.3 per 100 patient-years, respectively) while it was lower and comparable between RTX and other regimens (5.52 vs. 4.54 per 100 patient-years, respectively) in the maintenance phase. By multivariate analysis, plasmapheresis (PLEX) and/or dialysis was a strong predictor for an SI during the 1st year after diagnosis (OR = 3.16, 95% CI 1.001-9.96) and throughout the follow-up period (OR = 5.21, 95% CI 1.93-14.07). In contrast, a higher baseline BVAS (OR = 1.11, 95% CI 1.01-1.21) was associated with SI only during the 1st year.
In this real-life study of patients with AAV, the SI incidence was higher during CYC compared to RTX induction while there was no difference between RTX and other agents used for maintenance therapy. Higher disease activity at baseline and need for PLEX and/or dialysis were independent factors associated with an SI.
The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in ...predicting renal outcomes in AAV.
This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo- or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared.
In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years, p = 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL, p = 0.006), were more often hemodialysis dependent (64% vs. 19%, p = 0.009) and progressed more often to ESRD (55% vs. 11%, p = 0.01) compared to normo-complementemic patients (n = 36). On multivariate analysis, serum creatinine at diagnosis (HR = 16.8, 95%CI: 1.354-208.62, p = 0.028) and low serum C3 (HR = 2.492; 95% CI: 1.537-11.567; p = 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%, p = 0.033), low serum C3 levels (42% vs. 18%, p < 0.001) and serious infections during follow-up (57% vs. 18%, p = 0.047) compared to those with negative (n = 11) IF staining.
Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background/Objectives: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, characterized by dysfunction of glomerular filtration barrier, especially of podocytes. Several ...podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels (p = 0.001 and p = 0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p < 0.05). In addition, the PDC and NEP demonstrated statistically significant correlations with interstitial inflammation (p = 0.018/p = 0.028). Regarding electron microscopy evaluation, PDC levels were correlated with distinct characteristics, such as fibrils and global podocyte foot process fusion, whereas the NEP/CR ratio was uniquely significantly associated with podocyte fusion only in non-immune-complex-mediated glomerulonephritis (p = 0.02). Among the other clinical and histological parameters included in our study, a strong correlation between proteinuria >3 g/24 h and diffuse fusion of podocyte foot processes (p = 0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine are markers of podocyte dysfunction, and in our study, they were associated both with serum creatinine and histological chronicity indices.
Abstract Background and Aims The glomerulonephritis (GN) is a rare and complicated disease with high demand of hospital resources while the chronic kidney disease and end-stage renal disease present ...increased prevalence in these patients. Method We retrospectively assessed the inpatient and outpatient service of a Greek reference centre for glomerular diseases during the pre-Covid-19 period 2018-2020. Results 267 patients (38% female, median age 65 ± 23 years) included. All patients underwent a kidney biopsy by the nephrologist without complications. ANCA associated GN (18%), Focal Segmental Glomerulosclerosis/Minimal Change Disease (17.5%), IgA nephropathy (17%), Membranous Nephropathy (12.6%), Lupus Nephritis (5%), Membranoproliferative GN (3%), Fibrillary GN (3%), Monoclonal Gammopathy of Renal Significance (3.3%) and IgG4-related disease (2%.) are encompassed. We reported median 75 new patients per year. Regarding the inpatient service, we observed an increasing trend to the hospitalizations during this period (274, 452, 461 hospitalizations in 2018, 2019, 2020 respectively). The AAGN was the most common disease of hospitalizations through this period (53% in 2018, 33% in 2019, 39% in 2020), whereas the second most common was the FSGS/MCD (28% in 2018, 13% in 2019, 23.8% in 2020). The outpatient's service review also revealed an increasing number of visits per person per year (279, 456 and 464 total visits in 2018, 2019 and 2020 respectively). The disease with the highest number of visits per person was reported the AAV (median 3.25 visits per patient per year). All the patients were managed in adherence to the latest guidelines for GN in collaboration with a multidisciplinary team, consisting of nephrologist, rheumatologist, cardiologist, and pathologist. Finally, we reported complete response at 76% of the patients and in terms of renal improvement, 46% presented eGFR≥60 ml/min/1.73 m2, 45% eGFR<60 ml/min/1.73 m2 and only 9% progressed to ESRD after the first year of treatment. Conclusion Patients with GN present an increased need for hospitalization and regular outpatient visits. Addressing these diseases necessitates the expertise of a multidisciplinary team to provide comprehensive care that maximizes the potential for sustained positive long-term outcomes.
Abstract
BACKGROUND AND AIMS
Transforming growth factor-β1 (TGF-β1) has long been considered as a potent, multifunctional cytokine that is involved in the pathogenesis of fibrosis and inflammation, ...which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β1/Smad3 signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD).
METHOD
We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression and their role in progression to CKD.
RESULTS
TGF-β1 expression correlated positively with segmental glomerulosclerosis (P = .025) and creatinine level at diagnosis (p = .002), while pSmad3 expression with interstitial inflammation (P = .024). In glomerulus, we recorded different expression patterns of pSmad3 in crescents, while concomitant expressions of strong Smad7 and moderate pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (P = .011), intense interstitial inflammation (P = .029) and lower serum complement 3 (P = .028) and complement 4 (P = .029). We also reported a significant preferable expression between pSmad3 and glomerular endothelial cells of proliferative GN (P = .045) and podocytes of non-proliferative GN (P = .005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (HR = 5.08; 95% CI 1.133–22.78; P = .034) was emerged as independent predictor for CKD.
CONCLUSION
TGF-β1/Smad3 dependent signaling is upregulated, especially in proliferative GN, with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.
Abstract
Background and Aims
Acute Kidney injury (AKI) is a serious disease with a significant social and economic burden worldwide. The epidemiology of AKI is not well defined, nevertheless the ...incidence of AKI in hospitalized patients is deemed to be 10- 15%. AKI is a syndrome provoked from various clinical conditions and has different management depending on the cause, the stage and the comorbidities of the patients.
The aim of this study is to describe the heterogeneity of hospital acquired AKI as it concerns the underlying cause and the applied treatment as well as to emphasize on the high importance of the time of nephrology assessment
Method
This is a retrospective observational single-center study, including 1082 adult patients with hospital acquired AKI according to the KDIGO guidelines, hospitalized in different departments of our hospital from January 2021 to September 2022. Patients with End Stage Renal Disease were excluded from this study.
Results
A total of 1082 adult patients were recorded with median age 77 years. The majority of them had several comorbidities, 457(42%) diabetic, 424(39%) hypertensive and 442(41%) with Chronic Kidney Disease (CKD). Principal causes of AKI were cardiovascular disease (405;38%), infection (198;18%), gastrointestinal disorders (130;12%) and malignancy (103;10%). Other etiologies comprise obstructive nephropathy (45;4%), bleeding (36;3%), surgery (29;3%), cardiovascular surgery (13;1%) and miscellaneous (123;12). Management of AKI included fluid resuscitation applied in 405;37% cases, intravenous diuretic therapy applied in 241;22% patients, while 216;20% cases required hemodialysis.
The mean creatinine value at assessment was 3.9±2 mg/dl while 15% of the patients had a normal admission creatinine (<1.3mg/dl). The patients were classified in three groups according to the creatine levels rise: A) 345 patients at baseline had a creatinine rise of 0.3-0.5 mg/dl, B) 343 had a rise of 0.6-1 mg/dl and C) 394 had a rise of type="Periodical" type="Periodical">1 mg/dl. The mean value of hospitalization days for each of the 3 above groups was calculated as 10.8 ± 10.3, 10.7 ± 8.1 and 14.7 ± 11.4 respectively, p<0.05 for the comparisons with the 3rd group.
In comparison, there was no significant difference in the treatment method of AKI between the first 2 groups, but Hemodialysis was applied more frequent in the 3rd group (44 vs 46 vs 124 patients, p<0.05 for the comparisons with the 3rd group). Regarding the difference between the creatinine levels on admission and the creatinine levels on discharge, a statistically significant difference was found between the 3 groups (p<0.05) with prevalence of worst discharge creatine levels to the third group. 15% exited with creatinine <1.3 mg/dl. In a multivariate linear regression model, it was also found that for the difference in admission-discharge creatinine levels, diabetes mellitus was an independent factor (p = 0.035) as well as the group categorized based on the increase in creatinine during assessment (p<0.01).
Conclusion
Hospitalized patients in non-nephrology clinics may develop AKI and require different treatment plan as well as management of the primary cause. The heterogeneity of AKI and the need for dialysis as well as the days of hospitalization, underlines the need for close observation, personalized care, vigilance of other specialists and the cooperation with nephrologists.
As it is shown from this study the early nephrology assessment is associated with fewer days of hospitalization and better outcome for the patient's renal function, as well as the severity of the treatment. As the prevalence of chronic kidney disease is rising around the world is of great importance for the patients with AKI to be able to maintain their kidney function.
Abstract
Background and Aims
Acute Kidney Injury (AKI) is a frequent clinical entity. There are three AKI definition clasifications: RIFLE, AKIN and KDIGO. The endpoint of this study is to compare ...KDIGO and RIFLE regarding the prediction of AKI stage and adverse outcomes and to evaluate the renal prognosis of patients with a history of chronic kidney disease (CKD), who develop AKI during hospitalization. It is a well-known fact that Diabetes mellitus (DM) is the most common cause of end-stage chronic kidney disease (CKD). The epidemiology and outcome of diabetic patients with AKI during hospitalization, needs further study and comparison with the data of non-diabetic patients. As a secondary end point of this study we observed the progression of kidney function and severity of treatment in diabetic patients with stage III AKI (KDIGO) in comparison with the non-diabetic patients.
Method
This is a retrospective epidemiological study where data of 1083 adult patients were examined with AKI, who were hospitalized in various clinics at General Hospital of Athens Hippokratio between January 2021-September 2022.
Results
A total of 1083 patients were registered (63% male, mean age 74.5 ±12.6 years). 42% suffered from diabetes mellitus, 39% from arterial hypertension and 41% from CKD. RIFLE identified fewer patients with AKI than KDIGO (69.7% vs. 100%, p<0.001). Of all patients, 45.1% corresponded to AKI stage 1 (AKI-1), 7.3% to AKI stage 2 (AKI-2) and 47.6% to AKI stage 3 (AKI-3) according to KDIGO. 41.9% of AKI-3 patients underwent hemodialysis. Of the 214 patients on dialysis, 31.8% were not identified as AKI by RIFLE. In addition, patients with a history of CKD showed a higher percentage of AKI-3 (47.1% vs. 39.3% AKI-1, p=0.003 and 13.6% AKI-2, p=0.001) and underwent hemodialysis in a higher percentage (56.6% vs. 43.4%, p= 0.002). On the secondary end point 1083 patients, 458 (42.3%) diabetic and 625 (57.7%) non-diabetic were recognized. Hemodialysis was required in 83(18%) diabetic patients and in 132(21.1%) non-diabetic patients. Patients who ended up on end stage CKD requiring chronic hemodialysis or with GFR<15ml/min/1.73 m2 one month after hospital discharge were 37.7% and 51, 1% respectively. More specifically patients with the worst prognosis, who developed end stage CKD or ended up with GFR<15ml/min/1.73 m2 one month after hospital discharge, were categorized in three groups according to CKD Stage at hospital admission : in group A) CKD STAGE II out of 29, 8 (27.3%) non-diabetics and out of 19, 4 (21%) diabetic, in group B) STAGE IIIa out of 30 patients 5 (16.6%) non-diabetic and out of 15 3 (20%) diabetic and in group C) STAGE IIIb out of 17 patients 8 (47%) non-diabetic and out of 20 6 (30%) diabetics. It should be mentioned that the worst prognosis was observed in patients who were hospitalized for infection out of 30, 16(63%), with prerenal AKI out of 19 patients, 10(53%) and with a cardiovascular event out of 18 patients, 6(33%).
Conclusion
RIFLE criteria identified a lower proportion of patients with AKI compared to KDIGO, while not classifying a proportion of patients undergoing hemodialysis as AKI. Additionally, CKD was associated with worse renal prognosis in hospitalized patients with AKI. Patients with AKI on CKD who required hemodialysis during their hospitalization did not appear to have a worse prognosis at one month after discharge,compering diabetic with non-diabetic in group A and B. On the contrary there was a significant difference between patients in group C.
Abstract
Background and Aims
Interstitial inflammatory infiltrates in ANCA associated glomerulonephritis (AAGN) are frequently observed but their correlation to clinicopathological parameters remains ...elusive.
Method
Retrospective study of 40 patients with newly diagnosed AAGN. Histological assessments using the presence of interstitial inflammatory cells were performed. Biopsy tissues were investigated by CD3, CD20, CD4, CD8, CD68+ (PG-M1), CD138 immunohistochemical staining. We assessed the presence of inflammatory cells in terms of clinical, histopathological parameters as well as the renal prognosis in a large follow-up period 47.87 months (12-216).
Results
The interstitial infiltrates were consisted of lymphocytes (CD3 T cell> CD 20 B cell) at 83%, followed by plasma cells at 43%, neutrophils at 43%, macrophages at 40% and eosinophils at 20% of the biopsies. CD8 T cells dominated the interstitial area in focal and sclerotic class, while CD8 and CD4 tended to have different expression patterns in the interstitial area (figures 1,2). Interestingly, we reported that the presence of macrophages was correlated with higher chronicity index interstitial fibrosis (39% vs 24%, p = 0.015) and creatinine at diagnosis (4.4 vs 2.6 mg/dL, p = 0.01), while the presence of neutrophils, lymphocytes and eosinophils was correlated with higher activity index cellular crescents (37% vs 6%, p<0.001, 26% vs 9%, p = 0.021, 49% vs 24%, p = 0.021, respectively). In terms of short-term renal prognosis, only the macrophages were correlated with worst renal function at the 1st year (Cre 3.2 vs 1.8 mg/dL, p = 0.042). Regarding the long-term renal prognosis, we validated as the most reliably predictive score, amongst Berden classification and Mayo Clinic chronicity score, the ANCA renal risk score (AUC 0.694, p = 0.05) and we found that the low-risk group tended to present less severe inflammation (p = 0.029), while the presence of macrophages and eosinophils was less often present (p = 0.03 and 0.05, respectively) compared to the higher risk groups.
Conclusion
Identifying the differences in histopathological subtypes, in yet underestimated active tubulointerstitial lesions, could be the first step toward improving our understanding of distinct pathophysiological mechanisms and anticipating to specific treatment regimens.
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