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PURPOSE OF REVIEW: The purpose of this review is to discuss the role of the complement system in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as well as the employment of complement inhibitors in AAV treatment. RECENT FINDINGS: AAV has traditionally been considered a pauci-immune disease until recent findings demonstrated the pathogenic role of the complement system. The complement alternative pathway is crucial in AAV, and C5a seems to be a key molecule for AAV to develop. Avacopan, a C5a-receptor (C5aR) antagonist, proved effective in achieving AAV remission and ameliorating kidney function. SUMMARY: The increased circulating levels of some complement components - as well as the consumption of others - in patients with AAV suggested a systemic activation of the complement system. Low C3 levels correlate with a more aggressive disease and a worse renal prognosis. In ANCA-associated glomerulonephritis, renal deposits of C3d and properdin, suggestive of local alternative pathway activation, correlate with glomerular crescents and proteinuria. The interaction between C5a and neutrophil triggers alternative pathway activation, suggesting the central role of C5a in AAV pathogenesis. Avacopan, a C5aR inhibitor, showed beneficial effects in AAV and represents a promising therapy to achieve sustained remission and to spare glucocorticoids.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glomerulonefritis , Humanos , Anticuerpos Anticitoplasma de Neutrófilos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Proteínas del Sistema Complemento , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/complicaciones , Riñón/patologíaRESUMEN
BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.
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Riñón , Humanos , Persona de Mediana Edad , Riñón/patología , Estudios Prospectivos , Estudios Retrospectivos , Creatinina , BiopsiaRESUMEN
BACKGROUND: Medullary sponge kidney (MSK) is a rare disease characterized by cystic dilatation of papillary collecting ducts. Intravenous urography is still considered the gold standard for diagnosis. We identified a cohort of patients from our outpatient clinic with established diagnosis of MSK to outline some ultrasonographic characteristics that may help establish a diagnosis. METHODS: We conducted a retrospective study of patients seen between January 1st 2009 and January 1st 2019 in our clinic. Out of 4321 patients, 18 had a diagnosis of MSK. We reviewed their clinical and family history, laboratory data and imaging studies. Specifically, we focused on ultrasound imaging. RESULTS: Patients were referred to our outpatient clinic because of renal impairment (44%), family history of nephropathy (17%), nephrolithiasis or an established diagnosis of MSK (39%). Seventy-two percent of patients presented with chronic kidney disease, 22% required hemodialysis. Urinary tract infections (44%), nephrolithiasis (33%), microscopic hematuria (50%) and proteinuria (44%) were reported. Seven patients underwent computed tomography; all of them received ultrasound. Ultrasound examination showed bilateral renal cysts, usually small and located in the renal medulla, and microcalcifications located in the medulla or within the cysts. CONCLUSION: We identified a peculiar tetrad associated with MSK: 1) hypoechoic medullary areas, 2) hyperechoic spots, 3) microcystic dilatation of papillary zone, 4) multiple calcifications (linear, small stones or calcified intracystic sediment) in each papilla. The presence of this diagnostic tetrad, added to laboratory data and clinical history, could be helpful in the differential diagnosis to identify patients with MSK.
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Riñón/diagnóstico por imagen , Riñón Esponjoso Medular/diagnóstico por imagen , Ultrasonografía , Adulto , Anciano , Anciano de 80 o más Años , Calcinosis/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Riñón/patología , Cálculos Renales/diagnóstico por imagen , Médula Renal/diagnóstico por imagen , Médula Renal/patología , Masculino , Riñón Esponjoso Medular/patología , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos XAsunto(s)
Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Fallo Renal Crónico/complicaciones , Trasplante de Riñón , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Anciano , Betacoronavirus , COVID-19 , Cobicistat/administración & dosificación , Colchicina/administración & dosificación , Citocinas/metabolismo , Darunavir/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Inmunosupresores/administración & dosificación , Fallo Renal Crónico/cirugía , Lopinavir/administración & dosificación , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Pandemias , Ritonavir/administración & dosificación , SARS-CoV-2 , Tacrolimus/administración & dosificación , Tacrolimus/sangre , Receptores de Trasplantes , Resultado del TratamientoRESUMEN
Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgAN causes end-stage kidney disease (ESKD) in 30-40% of all cases. The activation of the complement system by pathological circulating IgAs, which is often associated with low serum C3 levels (LowC3), seems to play a crucial role. Previous studies have shown an association between histological evidence of TMA, which is the result of alternative complement activation, and poor outcomes. However, it is not known to what extent the decrease in serum C3 levels reflects ongoing TMA injury. Our study aimed at assessing the association between LowC3 and ESKD and whether this association reflects ongoing TMA. Methods: We enrolled all patients with biopsy-proven IgAN and followed-up patients until their last visit, ESKD, or death. Results: Of the 56 patients included in the study, 12 (21%) presented low serum C3 (LowC3) at the time of renal biopsy. TMA was significantly more frequent in the LowC3 group [7/12 (58%) vs. 9/44 (20%), p = 0.02]. After adjusting for potential confounders, LowC3 was strongly associated with an increased hazard of ESKD (hazard ratio [HR]: 5.84 [95%CI: 1.69, 20.15; p = 0.005). The association was not affected by adjusting for TMA. The estimated overall proportion of the relation between C3 and ESKD mediated by TMA was low and not statistically significant. Conclusions: Our study provides evidence that C3 hypocomplementemia is associated with an increased risk of ESKD through mechanisms that are largely independent from TMA.
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Background: Chronic kidney disease-associated pruritus (CKD-aP) affects patients on hemodialysis. This study identified hemodialysis patients presumably affected or not affected by CKD-aP and integrated healthcare costs, from the perspective of the Italian administrative healthcare data. Methods: Through cross-linkage of Italian administrative healthcare data collected between 2015 and 2017 (accrual period) in the database of Fondazione ReS (Ricerca e Salute), patients undergoing in-hospital/outpatient hemodialysis were selected. Cohorts with and without CKD-aP were created based on the presence/absence of CKD-aP-related treatment (according to common clinical practice and guidelines) supplies and assessed in terms of CKD-aP-related treatments and mean healthcare costs per capita paid by the Italian National Health Service (INHS). Results: Of 1,239 people on hemodialysis for ≥2 years, CKD-aP affected 218 patients. Patients with CKD-aP were older and with more comorbidities. During the follow-up year, on average, the INHS spent 37,065 per case, 31,286 per control and 35,988 per non-CKD-aP subject. High-efficiency dialytic therapies performed to people on hemodialysis with CKD-aP largely weighed on the overall mean annual cost. Conclusions: This real-world study identified patients on chronic hemodialysis potentially treated for CKD-aP. Interestingly, high-efficiency dialysis seems the most frequent and expensive choice for the treatment of CKD-aP. The discovery of appropriate and effective treatments for this condition might offer cost offsets.
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BACKGROUND: Primary or secondary glomerulonephritis has been anecdotally reported in association with atypical haemolytic uraemic syndrome (aHUS). We here report a series of six patients who developed aHUS and glomerulopathy, and review the literature on aHUS and glomerulonephritis. METHODS: Out of all patients diagnosed at our unit with biopsy-proven glomerular diseases between March 2007 and October 2011, selected cases developing aHUS during the follow-up are presented. The following tests were performed in all six patients: serum C3 and C4 levels, ADAMTS13 activity, CFH levels and anti-CFH autoantibodies and genetic screening for CFH, MCP, CFI, C3 and CFHR1-3 mutations and risk haplotypes associated with aHUS. RESULTS: Two hundred and forty-eight patients received a biopsy-proven diagnosis of glomerulopathy and were followed for a median of 31 months (range 2-58). Of these, six developed aHUS, within a median of 15 months (range 1-36) of their initial diagnosis of glomerulopathy. One of these patients had focal segmental glomerulosclerosis (FSGS), two membranoproliferative glomerulonephritis (MPGN) type I, one C3 glomerulonephritis and two systemic small vessel vasculitis [one granulomatosis with polyangiitis (Wegener's), one Henoch-Schoenlein purpura]. Five patients (one of them heterozygous for a CFH mutation) carried, in homo- or heterozygosity, the risk haplotype CFH-H3 (CFH tgtgt), previously described to be associated with aHUS, while another one patient was homozygous for the MCPggaac risk haplotype predisposing to aHUS when present on both alleles. CONCLUSIONS: Different types of glomerulopathies can be complicated by aHUS. Several mechanisms can contribute to this association, such as nephrotic-range proteinuria, mutations or aHUS-risk haplotypes involving genes encoding alternative complement regulatory proteins in some patients and inflammatory triggers associated with systemic immune-mediated diseases.
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Proteínas del Sistema Complemento/genética , Glomerulonefritis/complicaciones , Síndrome Hemolítico-Urémico/etiología , Adolescente , Adulto , Anciano , Síndrome Hemolítico Urémico Atípico , Proteínas del Sistema Complemento/inmunología , Femenino , Estudios de Seguimiento , Síndrome Hemolítico-Urémico/patología , Humanos , Masculino , Persona de Mediana Edad , Literatura de Revisión como Asunto , Adulto JovenRESUMEN
OBJECTIVES: PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism (SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. METHODS: PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. RESULTS: The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, χ(2 )= 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, χ(2 )= 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73). CONCLUSION: The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Complement protein factor H (CFH) is a regulatory protein of the alternative complement pathway (AP); CFH mutations lead to a spectrum of different phenotypical manifestations of renal disease. CASE-DIAGNOSIS/TREATMENT: We report the case of a boy with a novel CFH gene mutation who presented with a membranoproliferative (MPGN) pattern of glomerular injury and developed 2 years later atypical hemolytic uremic syndrome (aHUS); this description shows that CFH alteration leads to two different renal diseases in the same patient. CONCLUSIONS: Our case suggests the possibility that complement dysregulation could determine different renal conditions, which may be part of the same disease spectrum. Early recognition of an evolution of glomerulopathies into aHUS may allow appropriate management and prevention of life-threatening consequences.
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Glomerulonefritis Membranoproliferativa/genética , Síndrome Hemolítico-Urémico/genética , Enfermedades Renales/genética , Mutación , Adolescente , Síndrome Hemolítico Urémico Atípico , Biopsia , Factor H de Complemento/deficiencia , Factor H de Complemento/genética , Factor H de Complemento/inmunología , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/terapia , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/inmunología , Síndrome Hemolítico-Urémico/terapia , Enfermedades por Deficiencia de Complemento Hereditario , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico , Enfermedades Renales/inmunología , Masculino , Fenotipo , Intercambio Plasmático , Resultado del TratamientoRESUMEN
Chronic kidney disease-associated pruritus (CKD-aP) has been recognized for over a century. The complex pathophysiology of CKD-aP makes it challenging to find an effective treatment; the proposed therapeutic options come from anecdotal reports and small clinical trials, which at best compare the test drug against placebo. Gabapentinoids have shown relevant efficacy but there are serious safety concerns about their possible central nervous system toxicity. Recently difelikefalin, a κ-opioid receptor agonist, has been the first Food and Drug Administration (FDA)-approved drug for moderate-severe CKD-aP treatment. Approval from other regulatory agencies is expected in 2022. In this article, preclinical, pharmacokinetic and safety studies on difelikefalin are reported, but a great part of the data derive from meeting abstracts and non-peer-review communications and this is a possible cause for concern regarding bias in publication. A review of published and unpublished studies about difelikefalin in CKD-aP treatment is provided. Currently, two published large trials show that difelikefalin offers a new therapeutic opportunity to treat CKD-aP, a condition that leads to both worse survival and quality of life in hemodialysis patients.
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Calidad de Vida , Insuficiencia Renal Crónica , Humanos , Piperidinas , Prurito/tratamiento farmacológico , Prurito/etiología , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Estados UnidosRESUMEN
Background: This retrospective observational study aimed at describing patients on hemodialysis with/without uremic pruritus (UP), their healthcare resource consumption and costs from the perspective of the Italian National Health Service (INHS). Methods: Through the cross-linkage of the healthcare administrative data collected in the ReS (Ricerca e Salute) database from 2015 to 2017, patients undergoing in-hospital/outpatient hemodialysis (index date) for ≥2 years were selected. After the exclusion of subjects with other causes of pruritus, UP/non-UP cohorts were created based on the presence/absence of UP-related treatment supplies and characterized. Treatments, hospitalizations and costs were analyzed. Results: Of 1239 patients on hemodialysis for ≥2 years (20.2% of all hemodialysis subjects), 218 (17.6%) were affected by UP. Both cohorts were mostly males and elderly. One year before and after the index date, 58.1% and 65.1% of UP patients received UP-related treatments, of which >50% were treated with antihistamines (mostly cetirizine), 10% gabapentin and 1.4% ultraviolet light therapy. The mean annual overall cost per patient with/without UP was 37,065/35,988. Outpatient specialist services accounted for 80% (>77% hemodialysis), hospitalizations for 10% (>60% hemodialysis). Conclusions: Though the prevalence of UP and related healthcare costs charged to the INHS were underestimated, the burden of UP was not negligible. High-efficiency dialytic therapies performed 3 to UP patients seemed to largely weigh on the overall mean annual cost. The availability of specific and effective treatments for UP might offer cost and healthcare offsets.
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Medicina Estatal , Enfermedades Urológicas , Anciano , Femenino , Costos de la Atención en Salud , Humanos , Masculino , Prurito/epidemiología , Prurito/etiología , Prurito/terapia , Diálisis Renal/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: IgA nephropathy (IgAN) has been anecdotally reported in association with atypical hemolytic uremic syndrome (aHUS). The association likely portends poor renal outcome, and the possible relationship with complement overactivation has yet to be elucidated. We evaluated a series of IgAN patients with aHUS and reviewed the available literature. METHODS: Adult patients who received a diagnosis of IgAN and developed aHUS between January 2009 and December 2019 were included in this retrospective review. RESULTS: We identified six IgAN-aHUS patients, all of whom developed end-stage kidney disease. At aHUS presentation all patients had decreased serum C3 levels. Predisposing pathogenetic variants and risk haplotypes for aHUS in CFH gene heterozygosity were documented in four out of six patients. Anti-CFH antibodies were found to be negative in the five tested patients. In the literature we identified 21 case reports involving aHUS-IgAN and six retrospective studies evaluating the presence of TMA at the time of renal biopsy. Hypertension, severe proteinuria, reduced sC3 and a worse renal prognosis were the common features of most cases. CONCLUSION: Our case series and literature review show that the onset of either aHUS or renal TMA in the course of IgAN are associated with very poor renal outcome. Activation of the alternative pathway revealed by consumption of serum C3 seems to play a major role. Our hypothesis is that the presence of a predisposing factor (e.g. dysregualtion of complement alternative pathway and/or other intrarenal precipitating factors) might be at the heart of aHUS-IgAN pathophysiology.
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Síndrome Hemolítico Urémico Atípico , Glomerulonefritis por IGA , Fallo Renal Crónico , Adulto , Síndrome Hemolítico Urémico Atípico/diagnóstico , Síndrome Hemolítico Urémico Atípico/genética , Proteínas del Sistema Complemento , Femenino , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/genética , Humanos , Fallo Renal Crónico/etiología , Masculino , Estudios RetrospectivosRESUMEN
Background: Polycystic kidney diseases (PKD) are an important cause of chronic kidney disease (CKD). Autosomal dominant polycystic kidney disease (ADPKD) due to PKD1 or PKD2 mutations is the most common form, but other genes can be responsible for ADPKD and its phenocopies. Among them, a form of atypical ADPKD caused by DNAJB11 mutations (DNAJB11-PKD) has been recently described. Methods: We retrospectively recruited a cohort of 27 patients from six different families sharing common ancestries and harboring the same DNAJB11 mutation (c.100C>T, p.Arg34*) and we compared it with a cohort of 42 typical ADPKD patients. Results: DNAJB11-PKD patients show small/normal-sized kidneys, with significantly smaller cysts and a slower progression to end-stage kidney disease (ESKD) than ADPKD patients. In the DNAJB11-PKD cohort, the cystic phenotype could not be detected by ultrasound in about half of the patients, but all cases with available computed tomography/magnetic resonance scans displayed cysts. Clinically, DNAJB11-PKD patients displayed proteinuria (mostly albuminuria). Compared with ADPKD, DNAJB11-PKD patients were older and had a higher prevalence of type 2 diabetes mellitus (19% versus 0%; P = 0.007) and nephrolithiasis (62% versus 29%; P = 0.01), whereas the prevalence of cardiac valvular defects was lower (4% versus 51%; P < 0.001). Conclusions: Overall, clinical features of DNAJB11-PKD were more subtle compared with those of ADPKD. DNAJB11-PKD shows a unique renal and extrarenal phenotype, clinical presentation and natural history. Therefore our data support that this genetic disease is classified separately from ADPKD.
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Introduction: Proliferative lupus nephritis (LN) progresses to end-stage kidney disease (ESKD) in roughly 10% of the cases despite treatment. Other than achieving <0.8 g/24h proteinuria at 12 months after treatment, early biomarkers predicting ESKD or death are lacking. Recent studies encompassing not only LN have highlighted the central role of the alternative complement pathway (ACP), with or without histological evidence of thrombotic microangiopathy (TMA), as a key promotor of renal death. Methods: We assessed whether persistent isolated C3 hypocomplementemia (PI-LowC3), that is not accompanied by C4 hypocomplementemia, 6 months after kidney biopsy, is associated with an increased risk of death or ESKD in proliferative LN. Results: We retrospectively followed-up 197 patients with proliferative LN (51 with PI-LowC3) for a median of 4.5 years (interquartile-range: 1.9-9.0), 11 of whom died and 22 reached ESKD. After adjusting for age, gender, ethnicity, hypertension, mycophenolate, or cyclophosphamide use, PI-LowC3 was associated with a hazard ratio [HR] of the composite outcome ESKD or death of 2.46 (95% confidence interval [CI]: 1.22-4.99, P = 0.012). These results were confirmed even after controlling for time-varying estimated glomerular filtration rate (eGFR) measurements in joint longitudinal-survival multiple regression models. After accounting for the competing risk of death, PI-LowC3 patients showed a strikingly increased risk of ESKD (adjusted HR 3.41, 95% CI: 1.31-8.88, P = 0.012). Conclusion: Our findings support the use of PI-LowC3 as a low-cost readily available biomarker, allowing clinicians to modify treatment strategies early in the course of disease and offering a rationale for complement blockade trials in this particularly at-risk subgroup of LN patients.
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Chronic kidney disease-associated pruritus (CKD-aP) is a potentially distressing condition that affects a significant proportion of patients with end-stage kidney disease undergoing dialysis. CKD-aP may lead to worsening of patients' physical and mental health-related quality of life (HRQoL) and has also been linked with worse clinical outcomes, including increased mortality. Despite these detrimental effects, evidence from real-world studies shows that CKD-aP still remains overlooked by nephrologists and underreported by patients in clinical practice. Itch is subjective and therefore its diagnosis is often dependent on patients reporting this symptom. There is an opportunity to reduce the burden of CKD-aP on dialysis patients by increasing awareness about this condition and the availability of effective treatments. It is particularly important that nephrologists and other healthcare providers routinely ask their patients if they are experiencing itch. The differential diagnosis of CKD-aP requires a step-by-step identification and exclusion of possible alternative or concomitant causes of itch. Several simple validated self-reported assessment scales are available to evaluate the presence and severity of itch in a time-efficient manner, making them suitable for use in everyday clinical practice. The impact of CKD-aP on haemodialysis patients' HRQoL should also be assessed on a regular basis. This review provides a comprehensive overview of the differential diagnosis of CKD-aP and the diagnostic tools that are available to identify itch and quantify its severity and impact on patient HRQoL. A suggested algorithm to guide the screening, diagnosis and assessment of CKD-aP among dialysis patients in real-world practice is provided.
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OBJECTIVES: Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. We hypothesized that colchicine, by counteracting proinflammatory pathways implicated in the uncontrolled inflammatory response of COVID-19 patients, reduces pulmonary complications, and improves survival. METHODS: This retrospective study included 71 consecutive COVID-19 patients (hospitalized with pneumonia on CT scan or outpatients) who received colchicine and compared with 70 control patients who did not receive colchicine in two serial time periods at the same institution. We used inverse probability of treatment propensity-score weighting to examine differences in mortality, clinical improvement (using a 7-point ordinary scale), and inflammatory markers between the two groups. RESULTS: Amongst the 141 COVID-19 patients (118 [83.7%] hospitalized), 70 (50%) received colchicine. The 21-day crude cumulative mortality was 7.5% in the colchicine group and 28.5% in the control group (P = 0.006; adjusted hazard ratio: 0.24 [95%CI: 0.09 to 0.67]); 21-day clinical improvement occurred in 40.0% of the patients on colchicine and in 26.6% of control patients (adjusted relative improvement rate: 1.80 [95%CI: 1.00 to 3.22]). The strong association between the use of colchicine and reduced mortality was further supported by the diverging linear trends of percent daily change in lymphocyte count (P = 0.018), neutrophil-to-lymphocyte ratio (P = 0.003), and in C-reactive protein levels (P = 0.009). Colchicine was stopped because of transient side effects (diarrhea or skin rashes) in 7% of patients. CONCLUSION: In this retrospective cohort study colchicine was associated with reduced mortality and accelerated recovery in COVID-19 patients. This support the rationale for current larger randomized controlled trials testing the safety/efficacy profile of colchicine in COVID-19 patients.