Lymphopenia at diagnosis of ANCA-vasculitis with renal involvement is correlated with severity and renal prognosis

2021 ◽  
Author(s):  
Samuel Wacrenier ◽  
Jérémie Riou ◽  
Pierre Jourdain ◽  
Fanny Guibert ◽  
Nicolas Henry ◽  
...  
Keyword(s):  
Renal Involvement ◽  
Cost Effective ◽  
Renal Outcome ◽  
Small Scale ◽  
Free Survival ◽  
Kidney Replacement Therapy ◽  
Histological Data ◽  
Renal Prognosis ◽  
Cox Analysis ◽  
End Stage

ABSTRACT Background Lymphopenia is commonly observed in autoimmune diseases, where it has been associated with disease activity or prognosis. However, in ANCA-associated vasculitis (AAV) only few, small-scale studies have been targeted to this issue. Research has not yet focused on AAV with renal involvement (AAV-RI) patients. Thus, the aim of this study was to analyze the association between lymphocyte counts and outcomes in a large cohort of AAV-RI patients. Methods We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French Nephrology Centers, recorded since January 2000. We analyzed clinical, biological, and histological data at diagnosis of AAV-RI. Risk factors for end-stage kidney disease (ESKD) were analyzed. Event-free survival was also assessed. Results Among the 145 patients included in the study, those with lymphopenia at diagnosis had a lower renal function at baseline (eGFR 13 mL/min vs 26 mL/min, p = 0.002) and were more likely to require kidney replacement therapy (51% vs 25%, p = 0.003). Lymphopenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (p = 0.0027). ESKD-free survival was lower in lymphopenic patients (p < 0.0001). In multivariate Cox analysis, lymphopenia was an independent risk factor for ESKD (HR 4.47 (95% confidence interval: [2.06–9.72], p < 0.001). Conclusion Lymphopenia correlates with the severity of AAV glomerulonephritis at diagnosis and predicts poor renal outcome. In this view, lymphopenia could be used as a simple and cost-effective biomarker to assess renal prognosis at AAV-RI diagnosis.

MO259LYMPHOPENIA AT ANCA-GLOMERULONEPHRITIS DIAGNOSIS IS CORRELATED WITH SEVERITY AND RENAL PROGNOSIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Samuel Wacrenier ◽  
Jeremie Riou ◽  
Pierre Jourdain ◽  
Fanny Guibert ◽  
NICOLAS HENRY ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Immunosuppressive Treatment ◽  
Cost Effective ◽  
Biological Data ◽  
Renal Outcome ◽  
Small Scale ◽  
Free Survival ◽  
Histological Data ◽  
Renal Prognosis ◽  
Cox Analysis

Abstract Background and Aims Lymphopenia is commonly observed in various autoimmune diseases, such as systemic lupus erythematosus, where it has been associated with disease activity or prognosis. However, in ANCA-associated vasculitis (AAV) only few, small-scale studies have been targeted to this issue. Research has not yet focused on ANCA-glomerulonephritis (ANCA-GN) patients. Thus, the aim of this study was to analyze the association between lymphocyte counts and outcomes in a large cohort of ANCA-GN patients. Method We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French Nephrology Centers, recorded since January 2000. We analyzed clinical, biological, and histological data at diagnosis of ANCA-GN. Biological data, including lymphocyte counts, were collected before the administration of any immunosuppressive treatment. Risk factors for end-stage kidney disease (ESKD) were analyzed. Event-free survival was also assessed. Results Among the 145 patients included in the study, 53 (37%) patients presented with lymphopenia at ANCA-GN diagnosis. Lymphopenic patients were older (72 [63–79] vs 66 [56–73] years old, p = 0.010), had a lower renal function at baseline (eGFR 13 mL/min vs 26 mL/min, p = 0.002), and a higher proteinuria (1.86 [1.21–3.52] g/g vs 1.30 [0.75–2.65] g/g, p = 0.042). There was a trend for a higher BVAS (18 [14–22] vs 15 [12–20], p = 0.076) in lymphopenic patients. Therapeutic management between the two groups was similar. There was no difference in relapse rate between the two groups but lymphopenic patients were more likely to require kidney replacement therapy (51% vs 25%, p = 0.003) and were more likely to die (34% vs 17%, p = 0.039). Lymphopenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (p = 0.0027). ESKD-free survival and overall survival were lower in lymphopenic patients (p < 0.0001 and 0.0051 respectively). In multivariate Cox analysis, lymphopenia, but not death, was an independent risk factor for ESKD (HR 4.47 (95% confidence interval: [2.06–9.72], p < 0.001). Conclusion Lymphopenia correlates with severity of ANCA-GN at diagnosis and predicts poor renal outcome. In this view, lymphopenia could be used as a simple and cost-effective biomarker to assess renal prognosis at ANCA-GN diagnosis.

Focal segmental glomerulosclerosis histologic variants and renal outcomes based on nephrotic syndrome, immunosuppression, and proteinuria remission

2021 ◽  
Author(s):  
Takehiko Kawaguchi ◽  
Toshiyuki Imasawa ◽  
Moritoshi Kadomura ◽  
Hiroshi Kitamura ◽  
Shoichi Maruyama ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Renal Outcome ◽  
Renal Outcomes ◽  
Not Otherwise Specified ◽  
Segmental Glomerulosclerosis ◽  
Subgroup Analyses ◽  
Renal Prognosis ◽  
End Stage

Abstract Background The associations of focal segmental glomerulosclerosis (FSGS) histologic variants with renal outcomes have rarely been investigated comprehensively by clinically relevant subgroups in this modern age. Methods Data on 304 (173 nephrotic and 131 non-nephrotic) patients with biopsy-confirmed FSGS from 2010 to 2013 were analyzed using the Japanese nationwide renal biopsy registry. The primary outcome was a composite of a 30% decline in estimated glomerular filtration rate or progression to end stage kidney disease 5 years from the biopsy. We compared outcomes of FSGS variants according to the Columbia classification using survival analyses. Subgroup analyses were performed based on nephrotic syndrome (NS), immunosuppression, and proteinuria remission (PR, proteinuria <0.3 g/day) during follow-up. Additionally, associations of NS, immunosuppression, and PR with outcomes were examined for each variant. Results The distribution of variants was 48% (n = 145) FSGS not otherwise specified (NOS), 19% (n = 57) tip, 15% (n = 47) perihilar, 13% (n = 40) cellular, and 5% (n = 15) collapsing. The outcome event occurred in 87 patients (29%). No significant differences in the outcome were found among the variants. Subgroup analyses yielded similar results. However, there was a trend toward improved outcome in patients with PR irrespective of variants (hazard ratio adjusted for histologic variant and potential confounders [adjusted HR]: 0.19 [95% confidence interval (CI), 0.10–0.34]). NS was marginally associated with better outcome compared with non-NS (adjusted HR: 0.50 [95% CI, 0.25–1.01]. Conclusions FSGS variants alone might not have significant impacts on the renal outcome after 5 years, while PR could be predictive of improved renal prognosis for any variant. Specific strategies and interventions to achieve PR for each variant should be implemented for better renal outcomes.

FC 039RENAL OUTCOME AFTER RITUXIMAB IN ADULT-ONSET IGA VASCULITIS AND CRESCENTIC IGA NEPHROPATHY: A MULTICENTRE STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Giorgio Trivioli ◽  
Alice Canzian ◽  
Federica Maritati ◽  
Roberta Fenoglio ◽  
Evangeline Pillebout ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Disease ◽  
Iga Nephropathy ◽  
Immunosuppressive Agents ◽  
Renal Involvement ◽  
Renal Outcome ◽  
Iga Vasculitis ◽  
Adult Onset ◽  
Free Survival

Abstract Background and Aims Glucocorticoids (GC) and/or immunosuppressive agents are the mainstay of therapy for adult-onset IgA Vasculitis (IgAV), but their efficacy is often partial while their toxicity is relevant. Recently, rituximab (RTX) has been reported as a safe and effective option but only few data on renal outcome are available.1 RTX has also been used in a few cases of crescentic IgA Nephropathy (cIgAN), an IgAN subset with vasculitic lesions and poor response to conventional immunosuppressive regimens.2 We present the results of a multicentre cohort of patients with IgAV and cIgAN treated with RTX. Method The databases of 16 consorted European centres were investigated to screen for patients with adult-onset, biopsy-proven IgAV and cIgAN (crescents in ≥25% glomeruli and rapid eGFR worsening at presentation), who received RTX as induction therapy. We selected patients with active renal manifestations at the time of RTX. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS)=0 or <5 if it was due to persistent proteinuria and relapse as an increase in BVAS requiring change in immunosuppressive therapy. Results We identified 38 patients with IgAV and 12 patients with cIgAN who received RTX and had active renal involvement at the time of treatment. The median age at onset was 40 years (interquartile range, IQR, 25-53) and more than two-thirds of patients were male (Table 1). The median follow-up after RTX was 41 months (IQR 18-60). Renal outcomes are reported in Table 2. At the time of treatment, 24 patients (48%) had eGFR ≥60 mL/min/1.73 m2. All had IgAV and their median BVAS was 17 (IQR 10-22). Furthermore, all had microhaematuria and proteinuria. Renal histology showed mesangial or focal endocapillary proliferation in 12/17 (71%) patients who underwent biopsy (class II-IIIA according to Pillebout3). Twenty patients (83%) achieved remission; after a median of 12 months (range 9-14), four experienced a minor relapse and one had a major relapse with significant renal disease progression. Renal function remained stable in all but two patients who developed end-stage renal disease (ESRD). Micro-haematuria subsided in 14/24 (58%) and median 24h proteinuria decreased from 1750 mg (IQR 865-3275) to 175 mg (IQR 100-800) at last follow-up (p=0.029). Of the 26 patients with eGFR <60 mL/min/1.73 m2, 14 had IgAV and 12 had cIgAN. All were biopsied and 20 (77%) had diffuse endo/extra-capillary proliferation (classes IIIB-IV). Five patients required dialysis but recovered soon after treatment start. Remission was achieved by 16/26 (61%); eight (50%) subsequently relapsed and two (12%) reached ESRD. At last follow-up, eGFR was ≥60 mL/min/1.73 m2 in 8/26 (31%), 10/26 (48%) had stable renal function as compared to the time of RTX, while 8/26 (31%) had developed ESRD. Median 24h proteinuria decreased from 3400 mg (IQR 2150-6500) to 770 mg (177-1315) (p=0.016). Remission rate and ESRD-free survival were respectively 86% and 92% in patients with IgAV, while they were respectively 42% and 42% in cIgAN patients. Furthermore, 21/24 (87%) patients who received RTX alone or combined to glucocorticoids but not to immunosuppressive agents achieved remission and 22/24 (92%) were ESRD-free at last follow-up. Of the 26 patients receiving immunosuppressive agents, 17 (65%) obtained remission and 18 (69%) were ESRD-free at last assessment. Over the whole follow-up, only one patient reported a severe adverse effect related to RTX (pneumonia). Conclusion Renal involvement in adult-onset IgAV and cIgAN is frequently severe. RTX, combined or not with other immunosuppressive agents, may improve renal manifestations and is well tolerated. IgAV patients show higher remission rates and a longer ESRD-free survival as compared to cIgAN patients.

scholarly journals Serum IL-18 Is Closely Associated with Renal Tubulointerstitial Injury and Predicts Renal Prognosis in IgA Nephropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Beili Shi ◽  
Zhaohui Ni ◽  
Liou Cao ◽  
Minjie Zhou ◽  
Shan Mou ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Renal Outcome ◽  
Tubulointerstitial Injury ◽  
Baseline Serum ◽  
Protein Excretion ◽  
Kaplan Meier ◽  
Tubulointerstitial Damage ◽  
Renal Prognosis ◽  
Cox Analysis

Background. IgA nephropathy (IgAN) was thought to be benign but recently found it slowly progresses and leads to ESRD eventually. The aim of this research is to investigate the value of serum IL-18 level, a sensitive biomarker for proximal tubule injury, for assessing the histopathological severity and disease progression in IgAN.Methods. Serum IL-18 levels in 76 IgAN patients and 36 healthy blood donors were measured by ELISA. We evaluated percentage of global and segmental sclerosis (GSS) and extent of tubulointerstitial damage (TID). The correlations between serum IL-18 levels with clinical, histopathological features and renal prognosis were evaluated.Results. The patients were38.85±10.95years old, presented with 2.61 (1.43∼4.08) g/day proteinuria. Serum IL-18 levels were significantly elevated in IgAN patients. Baseline serum IL-18 levels were significantly correlated with urinary protein excretion (r=0.494,P=0.002), Scr (r=0.61,P<0.001), and eGFR (r=−0.598,P<0.001). TID scores showed a borderline significance with serum IL-18 levels (r=0.355,P=0.05). During follow-up, 26 patients (34.21%) had a declined renal function. Kaplan-Meier analysis found those patients with elevated IL-18 had a significant poor renal outcome (P=0.03), and Cox analysis further confirmed that serum IL-18 levels were an independent predictor of renal prognosis (β=1.98,P=0.003).

Major adverse renal events (MARE): A proposal to unifying renal endpoints

2019 ◽  
Author(s):  
Friedrich C Prischl ◽  
Peter Rossing ◽  
George Bakris ◽  
Gert Mayer ◽  
Christoph Wanner
Keyword(s):  
Kidney Disease ◽  
Kidney Injury ◽  
Renal Outcome ◽  
Reporting Standard ◽  
Renal Outcomes ◽  
Patient Reported ◽  
Individualize Care ◽  
Kidney Replacement Therapy ◽  
Meta Analyses ◽  
End Stage

Abstract Background In renal studies, various outcome endpoints are used with variable definitions, making it nearly impossible to perform meta-analyses and deduce meaningful conclusions. Increasing attention is directed towards standardization of renal outcome reporting. Methods A working group was formed to produce a unifying definition of renal outcomes that can be used by all investigators. We propose major adverse renal events (MARE) as the term for a standardized composite of hard renal outcomes. We discuss the components for inclusion in MARE from existing evidence. Results MARE could include three to five items, considered relevant to patients and regulators. New onset of kidney injury, that is persistent albuminuria/proteinuria and/or decreasing glomerular filtration rate (GFR) <60 ml/min/1.73 m2, persistent signs of worsening kidney disease, development of end-stage kidney disease with estimated GFR <15 ml/min/1.73 m2 without or with initiation of kidney replacement therapy, and death from renal cause are core items of MARE. Additionally, patient reported outcomes should be reported in parallel to MARE as a standard set of primary (or secondary) endpoints in studies on kidney disease of diabetic, hypertensive-vascular, or other origin. Conclusions MARE as a reporting standard will enhance the ability to compare studies and thus, facilitate meaningful meta-analyses. This will result in standardized endpoints that should result in guideline improvement to better individualize care of patients with kidney disease.

Urban pollution control strategy: SBR technology to treat agricultural waste from pig farm in Indonesia

2019 ◽  
Vol 2 (2) ◽  
pp. 21
Author(s):  
Lindawati Lindawati
Keyword(s):  
Cost Estimation ◽  
Batch Reactor ◽  
Agricultural Waste ◽  
Cost Effective ◽  
Land Application ◽  
Pig Manure ◽  
Small Scale ◽  
Piggery Wastewater ◽  
Pig Farm ◽  
Number Of Customers

Reduction of food rations and shortages is one of the impacts of the increasing human population. Food sector industries then try to cope with the fast growing number of customers. Agribusiness sector gains its popularity in these recent years, including pig farm. The increase trend of animal farming industry is likely to bring increasing pollution problem unless effective treatment methods are used. The main problems related to the pig farm include odor nuisance and pig manure disposal. The existing land application of piggery wastewater is the traditional way to discharge the wastewater. This may yield in land and water contamination, due to the accumulation of unused nutrients by crop plant. A case study of a large commercial pig farm from Australia is proposed to apply in smaller scale in Indonesia. Operational strategies for the small-scale SBR (Sequencing Batch Reactor) treating piggery effluent were developed based on lab-scale experiments. Due to SBR characteristics, which are money-saving and space-saving, it is very suitable to be applied in urban area. An economic evaluation was made of various process options. The cost estimation showed that SBR is a cost effective process, allowing operational batches to be adjusted to reduce unnecessary aeration cost. A reduction in the aeration cost was achieved by shortening the batch time from 24-h to 8-h. A comparison of three different SBR options showed that smaller size reactors could be more flexible and cost effective when compared with the larger ones.

scholarly journals AB0820 INFLUENCE OF ANCA ANTIBODIES ON DEMOGRAPHIC AND CLINICAL CHARACTERISTIC OF AAV

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1434.1-1434
Author(s):  
K. Wójcik ◽  
A. Masiak ◽  
Z. Zdrojewski ◽  
R. Jeleniewicz ◽  
M. Majdan ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Clinical Characteristics ◽  
Renal Involvement ◽  
Organ Involvement ◽  
Unknown Etiology ◽  
Anca Associated Vasculitis ◽  
Stage Renal Disease ◽  
End Stage ◽  
Male To Female

Background:ANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology and the broad clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Unfortunately the clinical classification, ANCA specificity or genetic characteristics alone is not able to categorize AAV patients in a satisfactory manner. As a consequence advanced statistical techniques were used to identify and stratify AAV subphenotypes [1, 2]. Here we have analyzed influence of the ANCA type on clinical manifestations and demographic characteristics in various types of AAV, based on data from the POLVAS registryObjectives:We decided to retrospectively analyze a large cohort of Polish AAV patients deriving from several referral centers – members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS) – and concentrate on demographic and clinical characteristics of anti-PR3 and anti-MPO positive patients regardless of their clinical diagnosis.Methods:We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016. Patients were enrolled by 9 referral centers. We analyzed dichotomous variables: gender; ANCA status – anti-PR3+ or anti-MPO+, ANCA negative; organ involvement - skin, eye, ENT, respiratory, heart, GI, renal, urinary, CNS, peripheral nerves and polytomous variable (number of relapses), supported by quantitative covariates (e.g., age at diagnosis, CRP at diagnosis, maximal serum creatinine concentration ever)[3].Results:MPO-positive patients (both GPA and EGPA phenotype) were older at the time of diagnosis with a substantial percentage diagnosed > 65 years of age, and with high rate of renal involvement. Interestingly, while in the whole group of patients diagnosed with EGPA male to female ratio was 1:2, the MPO+ EGPA patients showed M:F ratio of 1:1.The analysis of ANCA negative AAV reveled significant differences in GPA, ANCA negative group is characterized with significantly lower frequency of renal involvement compared to rest GPA (11,5% vs 63,7%) p<0,05 what should be emphasized ANCA negative AAV never lead to ESRD (end stage renal disease) or even transient dialysis.Conclusion:ANCA specificity is indispensable as a separate variable in any clinically relevant analysis of AAV subcategories. MPO+ group is characterized by older age at time of diagnosis, male to female ration 1:1, kidney involvement, and shows more homogenous clinical phenotype than PR3+ AAV patients. In our group ANCA negative AAV never lead to ESRD (end stage renal disease) or even transient dialysis.References:[1]Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatol Oxf Engl 2019;58:1707–9. https://doi.org/10.1093/rheumatology/kez148.[2]Wójcik K, Biedroń G, Wawrzycka-Adamczyk K, Bazan-Socha S, Ćmiel A, Zdrojewski Z et al. Subphenotypes of ANCA-associated vasculitis identified by latent class analysis. Clin Exp Rheumatol. 2020 Sep 1. Epub PMID: 32896241.[3]Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A, et al. Clinical characteristics of Polish patients with ANCA-associated vasculitides—retrospective analysis of POLVAS registry. Clinical Rheumatology. 1 wrzesień 2019;38(9):2553–63.Disclosure of Interests:None declared

Association of coexisting anti-ribosomal P and anti-dsDNA antibodies with histology and renal prognosis in lupus nephritis patients

Lupus ◽  
2021 ◽  
pp. 096120332098390
Author(s):  
Ayako Wakamatsu ◽  
Hiroe Sato ◽  
Yoshikatsu Kaneko ◽  
Takamasa Cho ◽  
Yumi Ito ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Outcome ◽  
Class V ◽  
Double Stranded Dna ◽  
Number Of Patients ◽  
Renal Histology ◽  
Renal Prognosis ◽  
Incidence Of Ckd ◽  
Ribosomal P

Objectives Anti-ribosomal P protein autoantibodies (anti-P) specifically develop in patients with systemic lupus erythematosus. Associations of anti-P with lupus nephritis (LN) histological subclass and renal outcome remain inconclusive. We sought to determine the association of anti-P and anti-double-stranded DNA antibody (anti-dsDNA) with renal histology and prognosis in LN patients. Methods Thirty-four patients with LN, having undergone kidney biopsy, were included. The 2018 revised ISN/RPS classification system was used for pathophysiological evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for > 3 months. Results Six patients (17.6%) were positive for anti-P and 26 (76.5%) for anti-dsDNA. Among the six patients with anti-P, one did not have anti-dsDNA, but did have anti-Sm antibody, and showed a histological subtype of class V. This patient maintained good renal function for over 14 years. The remaining five patients, who had both anti-P and anti-dsDNA, exhibited proliferative nephritis and were associated with prolonged hypocomplementemia, and the incidence of CKD did not differ from patients without anti-P. Conclusion Although this study included a small number of patients, the results indicated that histology class and renal prognosis associated with anti-P depend on the coexistence of anti-dsDNA. Further studies with a large number of patients are required to confirm this conclusion.

scholarly journals Protection of Residual Renal Function and Nutritional Treatment: First Step Strategy for Reduction of Uremic Toxins in End-Stage Kidney Disease Patients

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 289
Author(s):  
Adamasco Cupisti ◽  
Piergiorgio Bolasco ◽  
Claudia D’Alessandro ◽  
Domenico Giannese ◽  
Alice Sabatino ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Residual Renal Function ◽  
The Body ◽  
Uremic Toxins ◽  
End Stage Kidney Disease ◽  
Waste Products ◽  
Hemodialysis Treatment ◽  
Life Saving ◽  
Kidney Replacement Therapy ◽  
End Stage

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

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